User login
Blood Tests for Alzheimer’s Are Here... Are Clinicians Ready?
With the approval of anti-amyloid monoclonal antibodies to treat early-stage Alzheimer’s disease, the need for accurate and early diagnosis is crucial.
Recently, an expert workgroup convened by the Global CEO Initiative on Alzheimer’s Disease published recommendations for the clinical implementation of Alzheimer’s disease blood-based biomarkers.
“Our hope was to provide some recommendations that clinicians could use to develop the best pathways for their clinical practice,” said workgroup co-chair Michelle M. Mielke, PhD, with Wake Forest University School of Medicine, Winston-Salem, North Carolina.
Triage and Confirmatory Pathways
The group recommends two implementation pathways for Alzheimer’s disease blood biomarkers — one for current use for triaging and another for future use to confirm amyloid pathology once blood biomarker tests have reached sufficient performance for this purpose.
In the triage pathway, a negative blood biomarker test would flag individuals unlikely to have detectable brain amyloid pathology. This outcome would prompt clinicians to focus on evaluating non–Alzheimer’s disease-related causes of cognitive impairment, which may streamline the diagnosis of other causes of cognitive impairment, the authors said.
A positive triage blood test would suggest a higher likelihood of amyloid pathology and prompt referral to secondary care for further assessment and consideration for a second, more accurate test, such as amyloid PET or CSF for amyloid confirmation.
In the confirmatory pathway, a positive blood biomarker test result would identify amyloid pathology without the need for a second test, providing a faster route to diagnosis, the authors noted.
Mielke emphasized that these recommendations represent a “first step” and will need to be updated as experiences with the Alzheimer’s disease blood biomarkers in clinical care increase and additional barriers and facilitators are identified.
“These updates will likely include community-informed approaches that incorporate feedback from patients as well as healthcare providers, alongside results from validation in diverse real-world settings,” said workgroup co-chair Chi Udeh-Momoh, PhD, MSc, with Wake Forest University School of Medicine and the Brain and Mind Institute, Aga Khan University, Nairobi, Kenya.
The Alzheimer’s Association published “appropriate use” recommendations for blood biomarkers in 2022.
“Currently, the Alzheimer’s Association is building an updated library of clinical guidance that distills the scientific evidence using de novo systematic reviews and translates them into clear and actionable recommendations for clinical practice,” said Rebecca M. Edelmayer, PhD, vice president of scientific engagement, Alzheimer’s Association.
“The first major effort with our new process will be the upcoming Evidence-based Clinical Practice Guideline on the Use of Blood-based Biomarkers (BBMs) in Specialty Care Settings. This guideline’s recommendations will be published in early 2025,” Edelmayer said.
Availability and Accuracy
Research has shown that amyloid beta and tau protein blood biomarkers — especially a high plasma phosphorylated (p)–tau217 levels — are highly accurate in identifying Alzheimer’s disease in patients with cognitive symptoms attending primary and secondary care clinics.
Several tests targeting plasma p-tau217 are now available for use. They include the PrecivityAD2 blood test from C2N Diagnostics and the Simoa p-Tau 217 Planar Kit and LucentAD p-Tau 217 — both from Quanterix.
In a recent head-to-head comparison of seven leading blood tests for AD pathology, measures of plasma p-tau217, either individually or in combination with other plasma biomarkers, had the strongest relationships with Alzheimer’s disease outcomes.
A recent Swedish study showed that the PrecivityAD2 test had an accuracy of 91% for correctly classifying clinical, biomarker-verified Alzheimer’s disease.
“We’ve been using these blood biomarkers in research for a long time and we’re now taking the jump to start using them in clinic to risk stratify patients,” said Fanny Elahi, MD, PhD, director of fluid biomarker research for the Barbara and Maurice Deane Center for Wellness and Cognitive Health at Icahn Mount Sinai in New York City.
New York’s Mount Sinai Health System is among the first in the northeast to offer blood tests across primary and specialty care settings for early diagnosis of AD and related dementias.
Edelmayer cautioned, “There is no single, stand-alone test to diagnose Alzheimer’s disease today. Blood testing is one piece of the diagnostic process.”
“Currently, physicians use well-established diagnostic tools combined with medical history and other information, including neurological exams, cognitive and functional assessments as well as brain imaging and spinal fluid analysis and blood to make an accurate diagnosis and to understand which patients are eligible for approved treatments,” she said.
There are also emerging biomarkers in the research pipeline, Edelmayer said.
“For example, some researchers think retinal imaging has the potential to detect biological signs of Alzheimer’s disease within certain areas of the eye,” she explained.
“Other emerging biomarkers include examining components in saliva and the skin for signals that may indicate early biological changes in the brain. These biomarkers are still very exploratory, and more research is needed before these tests or biomarkers can be used more routinely to study risk or aid in diagnosis,” Edelmayer said.
Ideal Candidates for Alzheimer’s Disease Blood Testing?
Experts agree that blood tests represent a convenient and scalable option to address the anticipated surge in demand for biomarker testing with the availability of disease-modifying treatments. For now, however, they are not for all older adults worried about their memory.
“Current practice should focus on using these blood biomarkers in individuals with cognitive impairment rather than in those with normal cognition or subjective cognitive decline until further research demonstrates effective interventions for individuals considered cognitively normal with elevated levels of amyloid,” the authors of a recent JAMA editorial noted.
At Mount Sinai, “we’re not starting with stone-cold asymptomatic individuals. But ultimately, this is what the blood tests are intended for — screening,” Elahi noted.
She also noted that Mount Sinai has a “very diverse population” — some with young onset cognitive symptoms, so the entry criteria for testing are “very wide.”
“Anyone above age 40 with symptoms can qualify to get a blood test. We do ask at this stage that either the individual report symptoms or someone in their life or their clinician be worried about their cognition or their brain function,” Elahi said.
Ethical Considerations, Counseling
Elahi emphasized the importance of counseling patients who come to the clinic seeking an Alzheimer’s disease blood test. This should include how the diagnostic process will unfold and what the next steps are with a given result.
Elahi said patients need to be informed that Alzheimer’s disease blood biomarkers are still “relatively new,” and a test can help a patient “know the likelihood of having the disease, but it won’t be 100% definitive.”
To ensure the ethical principle of “do no harm,” counseling should ensure that patients are fully prepared for the implications of the test results and ensure that the decision to test aligns with the patient’s readiness and well-being, Elahi said.
Edelmayer said the forthcoming clinical practice guidelines will provide “evidence-based recommendations for physicians to help guide them through the decision-making process around who should be tested and when. In the meantime, the Alzheimer’s Association urges providers to refer to the 2022 appropriate use recommendations for blood tests in clinical practice and trial settings.”
Mielke has served on scientific advisory boards and/or having consulted for Acadia, Biogen, Eisai, LabCorp, Lilly, Merck, PeerView Institute, Roche, Siemens Healthineers, and Sunbird Bio. Edelmayer and Elahi had no relevant disclosures.
A version of this article appeared on Medscape.com.
With the approval of anti-amyloid monoclonal antibodies to treat early-stage Alzheimer’s disease, the need for accurate and early diagnosis is crucial.
Recently, an expert workgroup convened by the Global CEO Initiative on Alzheimer’s Disease published recommendations for the clinical implementation of Alzheimer’s disease blood-based biomarkers.
“Our hope was to provide some recommendations that clinicians could use to develop the best pathways for their clinical practice,” said workgroup co-chair Michelle M. Mielke, PhD, with Wake Forest University School of Medicine, Winston-Salem, North Carolina.
Triage and Confirmatory Pathways
The group recommends two implementation pathways for Alzheimer’s disease blood biomarkers — one for current use for triaging and another for future use to confirm amyloid pathology once blood biomarker tests have reached sufficient performance for this purpose.
In the triage pathway, a negative blood biomarker test would flag individuals unlikely to have detectable brain amyloid pathology. This outcome would prompt clinicians to focus on evaluating non–Alzheimer’s disease-related causes of cognitive impairment, which may streamline the diagnosis of other causes of cognitive impairment, the authors said.
A positive triage blood test would suggest a higher likelihood of amyloid pathology and prompt referral to secondary care for further assessment and consideration for a second, more accurate test, such as amyloid PET or CSF for amyloid confirmation.
In the confirmatory pathway, a positive blood biomarker test result would identify amyloid pathology without the need for a second test, providing a faster route to diagnosis, the authors noted.
Mielke emphasized that these recommendations represent a “first step” and will need to be updated as experiences with the Alzheimer’s disease blood biomarkers in clinical care increase and additional barriers and facilitators are identified.
“These updates will likely include community-informed approaches that incorporate feedback from patients as well as healthcare providers, alongside results from validation in diverse real-world settings,” said workgroup co-chair Chi Udeh-Momoh, PhD, MSc, with Wake Forest University School of Medicine and the Brain and Mind Institute, Aga Khan University, Nairobi, Kenya.
The Alzheimer’s Association published “appropriate use” recommendations for blood biomarkers in 2022.
“Currently, the Alzheimer’s Association is building an updated library of clinical guidance that distills the scientific evidence using de novo systematic reviews and translates them into clear and actionable recommendations for clinical practice,” said Rebecca M. Edelmayer, PhD, vice president of scientific engagement, Alzheimer’s Association.
“The first major effort with our new process will be the upcoming Evidence-based Clinical Practice Guideline on the Use of Blood-based Biomarkers (BBMs) in Specialty Care Settings. This guideline’s recommendations will be published in early 2025,” Edelmayer said.
Availability and Accuracy
Research has shown that amyloid beta and tau protein blood biomarkers — especially a high plasma phosphorylated (p)–tau217 levels — are highly accurate in identifying Alzheimer’s disease in patients with cognitive symptoms attending primary and secondary care clinics.
Several tests targeting plasma p-tau217 are now available for use. They include the PrecivityAD2 blood test from C2N Diagnostics and the Simoa p-Tau 217 Planar Kit and LucentAD p-Tau 217 — both from Quanterix.
In a recent head-to-head comparison of seven leading blood tests for AD pathology, measures of plasma p-tau217, either individually or in combination with other plasma biomarkers, had the strongest relationships with Alzheimer’s disease outcomes.
A recent Swedish study showed that the PrecivityAD2 test had an accuracy of 91% for correctly classifying clinical, biomarker-verified Alzheimer’s disease.
“We’ve been using these blood biomarkers in research for a long time and we’re now taking the jump to start using them in clinic to risk stratify patients,” said Fanny Elahi, MD, PhD, director of fluid biomarker research for the Barbara and Maurice Deane Center for Wellness and Cognitive Health at Icahn Mount Sinai in New York City.
New York’s Mount Sinai Health System is among the first in the northeast to offer blood tests across primary and specialty care settings for early diagnosis of AD and related dementias.
Edelmayer cautioned, “There is no single, stand-alone test to diagnose Alzheimer’s disease today. Blood testing is one piece of the diagnostic process.”
“Currently, physicians use well-established diagnostic tools combined with medical history and other information, including neurological exams, cognitive and functional assessments as well as brain imaging and spinal fluid analysis and blood to make an accurate diagnosis and to understand which patients are eligible for approved treatments,” she said.
There are also emerging biomarkers in the research pipeline, Edelmayer said.
“For example, some researchers think retinal imaging has the potential to detect biological signs of Alzheimer’s disease within certain areas of the eye,” she explained.
“Other emerging biomarkers include examining components in saliva and the skin for signals that may indicate early biological changes in the brain. These biomarkers are still very exploratory, and more research is needed before these tests or biomarkers can be used more routinely to study risk or aid in diagnosis,” Edelmayer said.
Ideal Candidates for Alzheimer’s Disease Blood Testing?
Experts agree that blood tests represent a convenient and scalable option to address the anticipated surge in demand for biomarker testing with the availability of disease-modifying treatments. For now, however, they are not for all older adults worried about their memory.
“Current practice should focus on using these blood biomarkers in individuals with cognitive impairment rather than in those with normal cognition or subjective cognitive decline until further research demonstrates effective interventions for individuals considered cognitively normal with elevated levels of amyloid,” the authors of a recent JAMA editorial noted.
At Mount Sinai, “we’re not starting with stone-cold asymptomatic individuals. But ultimately, this is what the blood tests are intended for — screening,” Elahi noted.
She also noted that Mount Sinai has a “very diverse population” — some with young onset cognitive symptoms, so the entry criteria for testing are “very wide.”
“Anyone above age 40 with symptoms can qualify to get a blood test. We do ask at this stage that either the individual report symptoms or someone in their life or their clinician be worried about their cognition or their brain function,” Elahi said.
Ethical Considerations, Counseling
Elahi emphasized the importance of counseling patients who come to the clinic seeking an Alzheimer’s disease blood test. This should include how the diagnostic process will unfold and what the next steps are with a given result.
Elahi said patients need to be informed that Alzheimer’s disease blood biomarkers are still “relatively new,” and a test can help a patient “know the likelihood of having the disease, but it won’t be 100% definitive.”
To ensure the ethical principle of “do no harm,” counseling should ensure that patients are fully prepared for the implications of the test results and ensure that the decision to test aligns with the patient’s readiness and well-being, Elahi said.
Edelmayer said the forthcoming clinical practice guidelines will provide “evidence-based recommendations for physicians to help guide them through the decision-making process around who should be tested and when. In the meantime, the Alzheimer’s Association urges providers to refer to the 2022 appropriate use recommendations for blood tests in clinical practice and trial settings.”
Mielke has served on scientific advisory boards and/or having consulted for Acadia, Biogen, Eisai, LabCorp, Lilly, Merck, PeerView Institute, Roche, Siemens Healthineers, and Sunbird Bio. Edelmayer and Elahi had no relevant disclosures.
A version of this article appeared on Medscape.com.
With the approval of anti-amyloid monoclonal antibodies to treat early-stage Alzheimer’s disease, the need for accurate and early diagnosis is crucial.
Recently, an expert workgroup convened by the Global CEO Initiative on Alzheimer’s Disease published recommendations for the clinical implementation of Alzheimer’s disease blood-based biomarkers.
“Our hope was to provide some recommendations that clinicians could use to develop the best pathways for their clinical practice,” said workgroup co-chair Michelle M. Mielke, PhD, with Wake Forest University School of Medicine, Winston-Salem, North Carolina.
Triage and Confirmatory Pathways
The group recommends two implementation pathways for Alzheimer’s disease blood biomarkers — one for current use for triaging and another for future use to confirm amyloid pathology once blood biomarker tests have reached sufficient performance for this purpose.
In the triage pathway, a negative blood biomarker test would flag individuals unlikely to have detectable brain amyloid pathology. This outcome would prompt clinicians to focus on evaluating non–Alzheimer’s disease-related causes of cognitive impairment, which may streamline the diagnosis of other causes of cognitive impairment, the authors said.
A positive triage blood test would suggest a higher likelihood of amyloid pathology and prompt referral to secondary care for further assessment and consideration for a second, more accurate test, such as amyloid PET or CSF for amyloid confirmation.
In the confirmatory pathway, a positive blood biomarker test result would identify amyloid pathology without the need for a second test, providing a faster route to diagnosis, the authors noted.
Mielke emphasized that these recommendations represent a “first step” and will need to be updated as experiences with the Alzheimer’s disease blood biomarkers in clinical care increase and additional barriers and facilitators are identified.
“These updates will likely include community-informed approaches that incorporate feedback from patients as well as healthcare providers, alongside results from validation in diverse real-world settings,” said workgroup co-chair Chi Udeh-Momoh, PhD, MSc, with Wake Forest University School of Medicine and the Brain and Mind Institute, Aga Khan University, Nairobi, Kenya.
The Alzheimer’s Association published “appropriate use” recommendations for blood biomarkers in 2022.
“Currently, the Alzheimer’s Association is building an updated library of clinical guidance that distills the scientific evidence using de novo systematic reviews and translates them into clear and actionable recommendations for clinical practice,” said Rebecca M. Edelmayer, PhD, vice president of scientific engagement, Alzheimer’s Association.
“The first major effort with our new process will be the upcoming Evidence-based Clinical Practice Guideline on the Use of Blood-based Biomarkers (BBMs) in Specialty Care Settings. This guideline’s recommendations will be published in early 2025,” Edelmayer said.
Availability and Accuracy
Research has shown that amyloid beta and tau protein blood biomarkers — especially a high plasma phosphorylated (p)–tau217 levels — are highly accurate in identifying Alzheimer’s disease in patients with cognitive symptoms attending primary and secondary care clinics.
Several tests targeting plasma p-tau217 are now available for use. They include the PrecivityAD2 blood test from C2N Diagnostics and the Simoa p-Tau 217 Planar Kit and LucentAD p-Tau 217 — both from Quanterix.
In a recent head-to-head comparison of seven leading blood tests for AD pathology, measures of plasma p-tau217, either individually or in combination with other plasma biomarkers, had the strongest relationships with Alzheimer’s disease outcomes.
A recent Swedish study showed that the PrecivityAD2 test had an accuracy of 91% for correctly classifying clinical, biomarker-verified Alzheimer’s disease.
“We’ve been using these blood biomarkers in research for a long time and we’re now taking the jump to start using them in clinic to risk stratify patients,” said Fanny Elahi, MD, PhD, director of fluid biomarker research for the Barbara and Maurice Deane Center for Wellness and Cognitive Health at Icahn Mount Sinai in New York City.
New York’s Mount Sinai Health System is among the first in the northeast to offer blood tests across primary and specialty care settings for early diagnosis of AD and related dementias.
Edelmayer cautioned, “There is no single, stand-alone test to diagnose Alzheimer’s disease today. Blood testing is one piece of the diagnostic process.”
“Currently, physicians use well-established diagnostic tools combined with medical history and other information, including neurological exams, cognitive and functional assessments as well as brain imaging and spinal fluid analysis and blood to make an accurate diagnosis and to understand which patients are eligible for approved treatments,” she said.
There are also emerging biomarkers in the research pipeline, Edelmayer said.
“For example, some researchers think retinal imaging has the potential to detect biological signs of Alzheimer’s disease within certain areas of the eye,” she explained.
“Other emerging biomarkers include examining components in saliva and the skin for signals that may indicate early biological changes in the brain. These biomarkers are still very exploratory, and more research is needed before these tests or biomarkers can be used more routinely to study risk or aid in diagnosis,” Edelmayer said.
Ideal Candidates for Alzheimer’s Disease Blood Testing?
Experts agree that blood tests represent a convenient and scalable option to address the anticipated surge in demand for biomarker testing with the availability of disease-modifying treatments. For now, however, they are not for all older adults worried about their memory.
“Current practice should focus on using these blood biomarkers in individuals with cognitive impairment rather than in those with normal cognition or subjective cognitive decline until further research demonstrates effective interventions for individuals considered cognitively normal with elevated levels of amyloid,” the authors of a recent JAMA editorial noted.
At Mount Sinai, “we’re not starting with stone-cold asymptomatic individuals. But ultimately, this is what the blood tests are intended for — screening,” Elahi noted.
She also noted that Mount Sinai has a “very diverse population” — some with young onset cognitive symptoms, so the entry criteria for testing are “very wide.”
“Anyone above age 40 with symptoms can qualify to get a blood test. We do ask at this stage that either the individual report symptoms or someone in their life or their clinician be worried about their cognition or their brain function,” Elahi said.
Ethical Considerations, Counseling
Elahi emphasized the importance of counseling patients who come to the clinic seeking an Alzheimer’s disease blood test. This should include how the diagnostic process will unfold and what the next steps are with a given result.
Elahi said patients need to be informed that Alzheimer’s disease blood biomarkers are still “relatively new,” and a test can help a patient “know the likelihood of having the disease, but it won’t be 100% definitive.”
To ensure the ethical principle of “do no harm,” counseling should ensure that patients are fully prepared for the implications of the test results and ensure that the decision to test aligns with the patient’s readiness and well-being, Elahi said.
Edelmayer said the forthcoming clinical practice guidelines will provide “evidence-based recommendations for physicians to help guide them through the decision-making process around who should be tested and when. In the meantime, the Alzheimer’s Association urges providers to refer to the 2022 appropriate use recommendations for blood tests in clinical practice and trial settings.”
Mielke has served on scientific advisory boards and/or having consulted for Acadia, Biogen, Eisai, LabCorp, Lilly, Merck, PeerView Institute, Roche, Siemens Healthineers, and Sunbird Bio. Edelmayer and Elahi had no relevant disclosures.
A version of this article appeared on Medscape.com.
Pediatric Myasthenia Gravis: Don’t Treat Children Like Adults
SAVANNAH, GEORGIA — At a pathophysiological level, juvenile myasthenia gravis (MG) seems to be identical to the adult form, neuromuscular specialists learned. But there are still important differences between children and their elders that affect pediatric care.
For example, “we have to think a little bit differently about the side effect profiles of the medications and their toxicity because children may react to medications differently,” said Matthew Ginsberg, MD, a pediatric neurologist based in Akron, Ohio, in a presentation at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
And then there’s the matter of adherence. “It’s hard to get adults to take medication, but a teenager is sometimes an exceptional challenge,” Ginsberg said.
Case In Point: A 13-Year-Old With MG
Pediatric MG is rare. Cases in children are estimated to account for 10% of MG cases diagnosed each year. According to a 2020 report, “the majority will present with ptosis and a variable degree of ophthalmoplegia [paralysis of eye muscles].”
Ginsberg highlighted a case of a 13-year-old girl who’d been healthy but developed fatigable ptosis and mild restriction of extraocular movements. The patient’s acetylcholine receptor antibodies were very elevated, but she didn’t have MuSK antibodies.
“This isn’t a diagnostic conundrum. She has autoimmune myasthenia gravis with ocular manifestations,” Ginsberg said. “For someone like this, whether it’s an adult or a child, many people would start symptomatic treatment with an acetylcholinesterase inhibitor like pyridostigmine.”
The use of the drug in children is similar to that in adults, he said, although weight-based dosing is used. “Usually it’s around 3-7 mg/kg/d, but it’s still very individualized based on patient response.” The timing of symptoms can affect the distribution of doses throughout the day, he said.
“There are extended-release formulations of the medication, and I think some people use them more than I do,” he said. “The side effects are basically similar to adults. Most of the patients I have on it tolerate it really well and don’t have a lot of the muscarinic side effects that you would expect.”
Consider Prescription Eye Drops for Ptosis
Alpha-1A agonists oxymetazoline and apraclonidine in the form of topical eye drops can help with ptosis. “They potentially avoid some of the systemic toxicity of the other medications,” Ginsberg said. “So they might be an option if you’re really just trying to target ptosis as a symptom.”
However, it can be difficult to get insurers to cover these medications, he said.
The 13-year-old patient initially improved but developed difficulty walking. “Her hands began to feel heavy, and she had difficulty chewing and nasal regurgitation. On her exam, she still had fatigable ptosis plus hypernasal speech and generalized weakness. At this point, we’re starting to see that she has generalized myasthenia gravis that may be an impending crisis.”
The Young Patient Worsens. Now What?
The patient was admitted and given intravenous immunoglobulin at 2 g/kg over a couple days. But her symptoms worsened following initial improvement.
Glucocorticoids can play a larger role in treatment at this stage, and the patient was initially on prednisone. But there are reasons for caution, including effects on bone growth and interference with live vaccines.
However, live vaccines aren’t common in children, with the exception of the MMRV vaccine, he said. “It’s worth noting that you can give that second dose as early as 3 months after the initial one, so most patients really should be able to complete a course before they start on immunosuppression,” he said.
Another option is immunotherapy. “There’s a really large menu of options for immunotherapy in myasthenia gravis right now,” Ginsberg said. “It’s great that we have all these options, but it adds to the complexity.”
Rituximab may be considered based on early data, he said. And thymectomy — removal of the thymus gland — should be considered early.
Don’t Neglect Supportive Care
Ginsberg urged colleagues to consider supportive care measures. Advocacy groups such as the Myasthenia Gravis Foundation of America can help with weight management and diet/exercise counseling, especially in patients taking glucocorticoids.
He added that “school accommodations are very important in this age group. They might need a plan, for example, to have modified gym class or an excuse not to carry a book bag between classes.”
How did the 13-year-old do? She underwent thymectomy, and her disease remained stable after 6 months. “Her rituximab was discontinued,” Ginsberg said. “She considered participating in a clinical trial but then started seeing improvements. About a year after the thymectomy, she just stopped her steroids on her own, and she was fine.”
Ginsberg had no disclosures.
A version of this article appeared on Medscape.com.
SAVANNAH, GEORGIA — At a pathophysiological level, juvenile myasthenia gravis (MG) seems to be identical to the adult form, neuromuscular specialists learned. But there are still important differences between children and their elders that affect pediatric care.
For example, “we have to think a little bit differently about the side effect profiles of the medications and their toxicity because children may react to medications differently,” said Matthew Ginsberg, MD, a pediatric neurologist based in Akron, Ohio, in a presentation at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
And then there’s the matter of adherence. “It’s hard to get adults to take medication, but a teenager is sometimes an exceptional challenge,” Ginsberg said.
Case In Point: A 13-Year-Old With MG
Pediatric MG is rare. Cases in children are estimated to account for 10% of MG cases diagnosed each year. According to a 2020 report, “the majority will present with ptosis and a variable degree of ophthalmoplegia [paralysis of eye muscles].”
Ginsberg highlighted a case of a 13-year-old girl who’d been healthy but developed fatigable ptosis and mild restriction of extraocular movements. The patient’s acetylcholine receptor antibodies were very elevated, but she didn’t have MuSK antibodies.
“This isn’t a diagnostic conundrum. She has autoimmune myasthenia gravis with ocular manifestations,” Ginsberg said. “For someone like this, whether it’s an adult or a child, many people would start symptomatic treatment with an acetylcholinesterase inhibitor like pyridostigmine.”
The use of the drug in children is similar to that in adults, he said, although weight-based dosing is used. “Usually it’s around 3-7 mg/kg/d, but it’s still very individualized based on patient response.” The timing of symptoms can affect the distribution of doses throughout the day, he said.
“There are extended-release formulations of the medication, and I think some people use them more than I do,” he said. “The side effects are basically similar to adults. Most of the patients I have on it tolerate it really well and don’t have a lot of the muscarinic side effects that you would expect.”
Consider Prescription Eye Drops for Ptosis
Alpha-1A agonists oxymetazoline and apraclonidine in the form of topical eye drops can help with ptosis. “They potentially avoid some of the systemic toxicity of the other medications,” Ginsberg said. “So they might be an option if you’re really just trying to target ptosis as a symptom.”
However, it can be difficult to get insurers to cover these medications, he said.
The 13-year-old patient initially improved but developed difficulty walking. “Her hands began to feel heavy, and she had difficulty chewing and nasal regurgitation. On her exam, she still had fatigable ptosis plus hypernasal speech and generalized weakness. At this point, we’re starting to see that she has generalized myasthenia gravis that may be an impending crisis.”
The Young Patient Worsens. Now What?
The patient was admitted and given intravenous immunoglobulin at 2 g/kg over a couple days. But her symptoms worsened following initial improvement.
Glucocorticoids can play a larger role in treatment at this stage, and the patient was initially on prednisone. But there are reasons for caution, including effects on bone growth and interference with live vaccines.
However, live vaccines aren’t common in children, with the exception of the MMRV vaccine, he said. “It’s worth noting that you can give that second dose as early as 3 months after the initial one, so most patients really should be able to complete a course before they start on immunosuppression,” he said.
Another option is immunotherapy. “There’s a really large menu of options for immunotherapy in myasthenia gravis right now,” Ginsberg said. “It’s great that we have all these options, but it adds to the complexity.”
Rituximab may be considered based on early data, he said. And thymectomy — removal of the thymus gland — should be considered early.
Don’t Neglect Supportive Care
Ginsberg urged colleagues to consider supportive care measures. Advocacy groups such as the Myasthenia Gravis Foundation of America can help with weight management and diet/exercise counseling, especially in patients taking glucocorticoids.
He added that “school accommodations are very important in this age group. They might need a plan, for example, to have modified gym class or an excuse not to carry a book bag between classes.”
How did the 13-year-old do? She underwent thymectomy, and her disease remained stable after 6 months. “Her rituximab was discontinued,” Ginsberg said. “She considered participating in a clinical trial but then started seeing improvements. About a year after the thymectomy, she just stopped her steroids on her own, and she was fine.”
Ginsberg had no disclosures.
A version of this article appeared on Medscape.com.
SAVANNAH, GEORGIA — At a pathophysiological level, juvenile myasthenia gravis (MG) seems to be identical to the adult form, neuromuscular specialists learned. But there are still important differences between children and their elders that affect pediatric care.
For example, “we have to think a little bit differently about the side effect profiles of the medications and their toxicity because children may react to medications differently,” said Matthew Ginsberg, MD, a pediatric neurologist based in Akron, Ohio, in a presentation at the American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) 2024.
And then there’s the matter of adherence. “It’s hard to get adults to take medication, but a teenager is sometimes an exceptional challenge,” Ginsberg said.
Case In Point: A 13-Year-Old With MG
Pediatric MG is rare. Cases in children are estimated to account for 10% of MG cases diagnosed each year. According to a 2020 report, “the majority will present with ptosis and a variable degree of ophthalmoplegia [paralysis of eye muscles].”
Ginsberg highlighted a case of a 13-year-old girl who’d been healthy but developed fatigable ptosis and mild restriction of extraocular movements. The patient’s acetylcholine receptor antibodies were very elevated, but she didn’t have MuSK antibodies.
“This isn’t a diagnostic conundrum. She has autoimmune myasthenia gravis with ocular manifestations,” Ginsberg said. “For someone like this, whether it’s an adult or a child, many people would start symptomatic treatment with an acetylcholinesterase inhibitor like pyridostigmine.”
The use of the drug in children is similar to that in adults, he said, although weight-based dosing is used. “Usually it’s around 3-7 mg/kg/d, but it’s still very individualized based on patient response.” The timing of symptoms can affect the distribution of doses throughout the day, he said.
“There are extended-release formulations of the medication, and I think some people use them more than I do,” he said. “The side effects are basically similar to adults. Most of the patients I have on it tolerate it really well and don’t have a lot of the muscarinic side effects that you would expect.”
Consider Prescription Eye Drops for Ptosis
Alpha-1A agonists oxymetazoline and apraclonidine in the form of topical eye drops can help with ptosis. “They potentially avoid some of the systemic toxicity of the other medications,” Ginsberg said. “So they might be an option if you’re really just trying to target ptosis as a symptom.”
However, it can be difficult to get insurers to cover these medications, he said.
The 13-year-old patient initially improved but developed difficulty walking. “Her hands began to feel heavy, and she had difficulty chewing and nasal regurgitation. On her exam, she still had fatigable ptosis plus hypernasal speech and generalized weakness. At this point, we’re starting to see that she has generalized myasthenia gravis that may be an impending crisis.”
The Young Patient Worsens. Now What?
The patient was admitted and given intravenous immunoglobulin at 2 g/kg over a couple days. But her symptoms worsened following initial improvement.
Glucocorticoids can play a larger role in treatment at this stage, and the patient was initially on prednisone. But there are reasons for caution, including effects on bone growth and interference with live vaccines.
However, live vaccines aren’t common in children, with the exception of the MMRV vaccine, he said. “It’s worth noting that you can give that second dose as early as 3 months after the initial one, so most patients really should be able to complete a course before they start on immunosuppression,” he said.
Another option is immunotherapy. “There’s a really large menu of options for immunotherapy in myasthenia gravis right now,” Ginsberg said. “It’s great that we have all these options, but it adds to the complexity.”
Rituximab may be considered based on early data, he said. And thymectomy — removal of the thymus gland — should be considered early.
Don’t Neglect Supportive Care
Ginsberg urged colleagues to consider supportive care measures. Advocacy groups such as the Myasthenia Gravis Foundation of America can help with weight management and diet/exercise counseling, especially in patients taking glucocorticoids.
He added that “school accommodations are very important in this age group. They might need a plan, for example, to have modified gym class or an excuse not to carry a book bag between classes.”
How did the 13-year-old do? She underwent thymectomy, and her disease remained stable after 6 months. “Her rituximab was discontinued,” Ginsberg said. “She considered participating in a clinical trial but then started seeing improvements. About a year after the thymectomy, she just stopped her steroids on her own, and she was fine.”
Ginsberg had no disclosures.
A version of this article appeared on Medscape.com.
FROM AANEM 2024
FDA OKs Novel Levodopa-Based Continuous Sub-Q Regimen for Parkinson’s Disease
Due to the progressive nature of Parkinson’s disease, “oral medications are eventually no longer as effective at motor symptom control and surgical treatment may be required. This new, non-surgical regimen provides continuous delivery of levodopa morning, day, and night,” Robert A. Hauser, MD, MBA, director of the Parkinson’s and Movement Disorder Center at the University of South Florida, Tampa, said in a news release.
The FDA approval was supported by results of a 12-week, phase 3 study evaluating the efficacy of continuous subcutaneous infusion foscarbidopa/foslevodopa in adults with advanced Parkinson’s disease compared with oral immediate-release carbidopa/levodopa.
The study showed that patients treated with foscarbidopa/foslevodopa had superior improvement in motor fluctuations, with increased “on” time without troublesome dyskinesia and decreased “off” time, compared with peers receiving oral immediate-release carbidopa/levodopa.
At week 12, the increase in “on” time without troublesome dyskinesia was 2.72 hours for foscarbidopa/foslevodopa continuous infusion versus 0.97 hours for carbidopa/levodopa (P =.0083).
Improvements in “on” time were observed as early as the first week and persisted throughout the 12 weeks.
The approval of foscarbidopa/foslevodopa for advanced Parkinson’s disease was also supported by a 52-week, open-label study which evaluated the long-term safety and efficacy of the drug.
Most adverse reactions with foscarbidopa/foslevodopa were non-serious and mild or moderate in severity. The most frequent adverse reactions were infusion site events, hallucinations, and dyskinesia.
Full prescribing information is available online.
AbbVie said coverage for Medicare patients is expected in the second half of 2025.
A version of this article appeared on Medscape.com.
Due to the progressive nature of Parkinson’s disease, “oral medications are eventually no longer as effective at motor symptom control and surgical treatment may be required. This new, non-surgical regimen provides continuous delivery of levodopa morning, day, and night,” Robert A. Hauser, MD, MBA, director of the Parkinson’s and Movement Disorder Center at the University of South Florida, Tampa, said in a news release.
The FDA approval was supported by results of a 12-week, phase 3 study evaluating the efficacy of continuous subcutaneous infusion foscarbidopa/foslevodopa in adults with advanced Parkinson’s disease compared with oral immediate-release carbidopa/levodopa.
The study showed that patients treated with foscarbidopa/foslevodopa had superior improvement in motor fluctuations, with increased “on” time without troublesome dyskinesia and decreased “off” time, compared with peers receiving oral immediate-release carbidopa/levodopa.
At week 12, the increase in “on” time without troublesome dyskinesia was 2.72 hours for foscarbidopa/foslevodopa continuous infusion versus 0.97 hours for carbidopa/levodopa (P =.0083).
Improvements in “on” time were observed as early as the first week and persisted throughout the 12 weeks.
The approval of foscarbidopa/foslevodopa for advanced Parkinson’s disease was also supported by a 52-week, open-label study which evaluated the long-term safety and efficacy of the drug.
Most adverse reactions with foscarbidopa/foslevodopa were non-serious and mild or moderate in severity. The most frequent adverse reactions were infusion site events, hallucinations, and dyskinesia.
Full prescribing information is available online.
AbbVie said coverage for Medicare patients is expected in the second half of 2025.
A version of this article appeared on Medscape.com.
Due to the progressive nature of Parkinson’s disease, “oral medications are eventually no longer as effective at motor symptom control and surgical treatment may be required. This new, non-surgical regimen provides continuous delivery of levodopa morning, day, and night,” Robert A. Hauser, MD, MBA, director of the Parkinson’s and Movement Disorder Center at the University of South Florida, Tampa, said in a news release.
The FDA approval was supported by results of a 12-week, phase 3 study evaluating the efficacy of continuous subcutaneous infusion foscarbidopa/foslevodopa in adults with advanced Parkinson’s disease compared with oral immediate-release carbidopa/levodopa.
The study showed that patients treated with foscarbidopa/foslevodopa had superior improvement in motor fluctuations, with increased “on” time without troublesome dyskinesia and decreased “off” time, compared with peers receiving oral immediate-release carbidopa/levodopa.
At week 12, the increase in “on” time without troublesome dyskinesia was 2.72 hours for foscarbidopa/foslevodopa continuous infusion versus 0.97 hours for carbidopa/levodopa (P =.0083).
Improvements in “on” time were observed as early as the first week and persisted throughout the 12 weeks.
The approval of foscarbidopa/foslevodopa for advanced Parkinson’s disease was also supported by a 52-week, open-label study which evaluated the long-term safety and efficacy of the drug.
Most adverse reactions with foscarbidopa/foslevodopa were non-serious and mild or moderate in severity. The most frequent adverse reactions were infusion site events, hallucinations, and dyskinesia.
Full prescribing information is available online.
AbbVie said coverage for Medicare patients is expected in the second half of 2025.
A version of this article appeared on Medscape.com.
ASA Releases New Primary Stroke Prevention Guideline
The first update in a decade, the 2024 Guideline for the Primary Prevention of Stroke, replaces the 2014 version and is intended to be a resource for clinicians to help them implement a variety of prevention strategies in patients with no previous history of stroke. It aligns with the American Heart Association’s Life’s Essential 8.
“This guideline is an important and timely update from 2014 for multiple reasons. First, there have been groundbreaking clinical trials that have been published with new medications to not only treat the target disease [including] diabetes/obesity and high cholesterol], but also lower the risk of stroke and heart disease,” said chair of the guideline writing group, Cheryl D. Bushnell, MD, MHS, FAHA, and vice chair of the research, Department of Neurology, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
It was published online on October 21 in Stroke.
Up to 80% of Strokes Preventable
Estimates show that every year in the United States, more than 500,000 individuals have a first stroke. However, the guideline authors noted that up to 80% of strokes may be preventable. As a result, they called for better primary stroke prevention that includes improved screening and lifestyle changes.
This includes adoption of the Mediterranean diet, which has been shown to significantly reduce stroke risk, especially when supplemented with consumption of nuts and olive oil.
The guideline recommendations also emphasize the need for physical activity, which is “essential” for cardiovascular health and stroke reduction. The authors underscored this point and provided a new recommendation to screen for sedentary behavior and advise patients to avoid inactivity and engage in regular moderate to vigorous physical activity.
Another new recommendation is based on “robust” data that glucagon-like peptide 1 receptor agonists (GLP-1s) significantly improve the management of type 2 diabetes, weight loss, and lower the risk for cardiovascular disease. As a result, guideline authors called for the use of GLP-1s in patients with diabetes and high cardiovascular risk or established cardiovascular disease.
“The glucagon-like peptide receptor agonists have been shown to not only drastically reduce blood sugars in patients with diabetes, but they also lead to significant weight loss in these patients, which has many downstream benefits. Together, this reduces the risk of stroke and other complications of diabetes,” said Bushnell.
She also noted that another drug class introduced since the 2014 guidelines were published, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, have proven to be highly effective in lowering low-density lipoprotein cholesterol. These medications have also been shown to reduce the risk for stroke.
At Least Two Meds Needed to Reduce BP
Effective blood pressure (BP) management is crucial for stroke prevention. Randomized controlled trials show that a single antihypertensive medication helps only about 30% of participants reach their BP target.
Most patients only achieve the desired BP target with two to three medications. In line with these data, the committee recommends using at least two antihypertensives for primary stroke prevention in most patients who require BP-lowering medications for hypertension.
In patients with antiphospholipid syndrome or systemic lupus erythematosus and no history of stroke or unprovoked venous thromboembolism, the authors recommended antiplatelet therapy to prevent stroke. They added that patients with antiphospholipid syndrome who have had a prior unprovoked venous thrombosis will likely benefit from vitamin K antagonist therapy (target international normalized ratio, 2-3) over direct oral anticoagulants.
Emphasis on Women’s Health
Preventing pregnancy-related stroke is achieved primarily by managing hypertension, the guideline authors noted. They recommended treating verified systolic BP over 160 mm Hg or diastolic BP over 110 mm Hg during pregnancy and up to 6 weeks postpartum to lower the risk for fatal maternal intracerebral hemorrhage.
They noted that adverse pregnancy outcomes are also common and linked to chronic hypertension, which increases stroke risk later in life. Therefore, they recommended screening for these outcomes to assess and manage vascular risk factors. The guideline includes a screening tool to help with this in clinical practice.
Endometriosis, premature ovarian failure (before age 40 years), and early-onset menopause (before age 45 years) are all associated with increased stroke risk. As a result, the guideline authors said screening for all three of these conditions is a “reasonable step in the evaluation and management of vascular risk factors in these individuals to reduce stroke risk.”
Finally, the guideline authors addressed primary stroke prevention in transgender individuals, noting that transgender women undergoing estrogen therapy for gender affirmation are at increased risk. They emphasized that evaluating and modifying risk factors could be beneficial for reducing stroke risk in this patient population.
Challenges Lie Ahead
Now that the guideline has been published, the challenge lies in determining how best to implement “its screening recommendations in primary care and other practices when these clinicians are already pushed to see as many patients as possible,” Bushnell said.
Development of screening tools that can be easily incorporated into the clinic visit or the electronic health record, as well as additional personnel to provide counseling, are probably needed to disseminate them, she added.
Bushnell also emphasized that the guideline includes a strong focus on social determinants of health and related social needs.
“We worked hard to use inclusive language and to consider populations historically excluded from research. In acknowledging that social determinants of health including access to healthcare, access to education, economic stability, neighborhood and geographic location, and social and community context have a tremendous influence on stroke risk, we describe how these factors are closely tied to the prevalence and management of many medical risks like obesity, hypertension, and diabetes.
“Our recommendations offer practical steps for screening and addressing essential health-related social needs, including access to nutritious food, stable housing, and reliable transportation, within clinical practice. By considering these factors more comprehensively, we believe we can make meaningful strides toward reducing the disparities in stroke risk,” said Bushnell.
A version of this article appeared on Medscape.com.
The first update in a decade, the 2024 Guideline for the Primary Prevention of Stroke, replaces the 2014 version and is intended to be a resource for clinicians to help them implement a variety of prevention strategies in patients with no previous history of stroke. It aligns with the American Heart Association’s Life’s Essential 8.
“This guideline is an important and timely update from 2014 for multiple reasons. First, there have been groundbreaking clinical trials that have been published with new medications to not only treat the target disease [including] diabetes/obesity and high cholesterol], but also lower the risk of stroke and heart disease,” said chair of the guideline writing group, Cheryl D. Bushnell, MD, MHS, FAHA, and vice chair of the research, Department of Neurology, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
It was published online on October 21 in Stroke.
Up to 80% of Strokes Preventable
Estimates show that every year in the United States, more than 500,000 individuals have a first stroke. However, the guideline authors noted that up to 80% of strokes may be preventable. As a result, they called for better primary stroke prevention that includes improved screening and lifestyle changes.
This includes adoption of the Mediterranean diet, which has been shown to significantly reduce stroke risk, especially when supplemented with consumption of nuts and olive oil.
The guideline recommendations also emphasize the need for physical activity, which is “essential” for cardiovascular health and stroke reduction. The authors underscored this point and provided a new recommendation to screen for sedentary behavior and advise patients to avoid inactivity and engage in regular moderate to vigorous physical activity.
Another new recommendation is based on “robust” data that glucagon-like peptide 1 receptor agonists (GLP-1s) significantly improve the management of type 2 diabetes, weight loss, and lower the risk for cardiovascular disease. As a result, guideline authors called for the use of GLP-1s in patients with diabetes and high cardiovascular risk or established cardiovascular disease.
“The glucagon-like peptide receptor agonists have been shown to not only drastically reduce blood sugars in patients with diabetes, but they also lead to significant weight loss in these patients, which has many downstream benefits. Together, this reduces the risk of stroke and other complications of diabetes,” said Bushnell.
She also noted that another drug class introduced since the 2014 guidelines were published, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, have proven to be highly effective in lowering low-density lipoprotein cholesterol. These medications have also been shown to reduce the risk for stroke.
At Least Two Meds Needed to Reduce BP
Effective blood pressure (BP) management is crucial for stroke prevention. Randomized controlled trials show that a single antihypertensive medication helps only about 30% of participants reach their BP target.
Most patients only achieve the desired BP target with two to three medications. In line with these data, the committee recommends using at least two antihypertensives for primary stroke prevention in most patients who require BP-lowering medications for hypertension.
In patients with antiphospholipid syndrome or systemic lupus erythematosus and no history of stroke or unprovoked venous thromboembolism, the authors recommended antiplatelet therapy to prevent stroke. They added that patients with antiphospholipid syndrome who have had a prior unprovoked venous thrombosis will likely benefit from vitamin K antagonist therapy (target international normalized ratio, 2-3) over direct oral anticoagulants.
Emphasis on Women’s Health
Preventing pregnancy-related stroke is achieved primarily by managing hypertension, the guideline authors noted. They recommended treating verified systolic BP over 160 mm Hg or diastolic BP over 110 mm Hg during pregnancy and up to 6 weeks postpartum to lower the risk for fatal maternal intracerebral hemorrhage.
They noted that adverse pregnancy outcomes are also common and linked to chronic hypertension, which increases stroke risk later in life. Therefore, they recommended screening for these outcomes to assess and manage vascular risk factors. The guideline includes a screening tool to help with this in clinical practice.
Endometriosis, premature ovarian failure (before age 40 years), and early-onset menopause (before age 45 years) are all associated with increased stroke risk. As a result, the guideline authors said screening for all three of these conditions is a “reasonable step in the evaluation and management of vascular risk factors in these individuals to reduce stroke risk.”
Finally, the guideline authors addressed primary stroke prevention in transgender individuals, noting that transgender women undergoing estrogen therapy for gender affirmation are at increased risk. They emphasized that evaluating and modifying risk factors could be beneficial for reducing stroke risk in this patient population.
Challenges Lie Ahead
Now that the guideline has been published, the challenge lies in determining how best to implement “its screening recommendations in primary care and other practices when these clinicians are already pushed to see as many patients as possible,” Bushnell said.
Development of screening tools that can be easily incorporated into the clinic visit or the electronic health record, as well as additional personnel to provide counseling, are probably needed to disseminate them, she added.
Bushnell also emphasized that the guideline includes a strong focus on social determinants of health and related social needs.
“We worked hard to use inclusive language and to consider populations historically excluded from research. In acknowledging that social determinants of health including access to healthcare, access to education, economic stability, neighborhood and geographic location, and social and community context have a tremendous influence on stroke risk, we describe how these factors are closely tied to the prevalence and management of many medical risks like obesity, hypertension, and diabetes.
“Our recommendations offer practical steps for screening and addressing essential health-related social needs, including access to nutritious food, stable housing, and reliable transportation, within clinical practice. By considering these factors more comprehensively, we believe we can make meaningful strides toward reducing the disparities in stroke risk,” said Bushnell.
A version of this article appeared on Medscape.com.
The first update in a decade, the 2024 Guideline for the Primary Prevention of Stroke, replaces the 2014 version and is intended to be a resource for clinicians to help them implement a variety of prevention strategies in patients with no previous history of stroke. It aligns with the American Heart Association’s Life’s Essential 8.
“This guideline is an important and timely update from 2014 for multiple reasons. First, there have been groundbreaking clinical trials that have been published with new medications to not only treat the target disease [including] diabetes/obesity and high cholesterol], but also lower the risk of stroke and heart disease,” said chair of the guideline writing group, Cheryl D. Bushnell, MD, MHS, FAHA, and vice chair of the research, Department of Neurology, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
It was published online on October 21 in Stroke.
Up to 80% of Strokes Preventable
Estimates show that every year in the United States, more than 500,000 individuals have a first stroke. However, the guideline authors noted that up to 80% of strokes may be preventable. As a result, they called for better primary stroke prevention that includes improved screening and lifestyle changes.
This includes adoption of the Mediterranean diet, which has been shown to significantly reduce stroke risk, especially when supplemented with consumption of nuts and olive oil.
The guideline recommendations also emphasize the need for physical activity, which is “essential” for cardiovascular health and stroke reduction. The authors underscored this point and provided a new recommendation to screen for sedentary behavior and advise patients to avoid inactivity and engage in regular moderate to vigorous physical activity.
Another new recommendation is based on “robust” data that glucagon-like peptide 1 receptor agonists (GLP-1s) significantly improve the management of type 2 diabetes, weight loss, and lower the risk for cardiovascular disease. As a result, guideline authors called for the use of GLP-1s in patients with diabetes and high cardiovascular risk or established cardiovascular disease.
“The glucagon-like peptide receptor agonists have been shown to not only drastically reduce blood sugars in patients with diabetes, but they also lead to significant weight loss in these patients, which has many downstream benefits. Together, this reduces the risk of stroke and other complications of diabetes,” said Bushnell.
She also noted that another drug class introduced since the 2014 guidelines were published, proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, have proven to be highly effective in lowering low-density lipoprotein cholesterol. These medications have also been shown to reduce the risk for stroke.
At Least Two Meds Needed to Reduce BP
Effective blood pressure (BP) management is crucial for stroke prevention. Randomized controlled trials show that a single antihypertensive medication helps only about 30% of participants reach their BP target.
Most patients only achieve the desired BP target with two to three medications. In line with these data, the committee recommends using at least two antihypertensives for primary stroke prevention in most patients who require BP-lowering medications for hypertension.
In patients with antiphospholipid syndrome or systemic lupus erythematosus and no history of stroke or unprovoked venous thromboembolism, the authors recommended antiplatelet therapy to prevent stroke. They added that patients with antiphospholipid syndrome who have had a prior unprovoked venous thrombosis will likely benefit from vitamin K antagonist therapy (target international normalized ratio, 2-3) over direct oral anticoagulants.
Emphasis on Women’s Health
Preventing pregnancy-related stroke is achieved primarily by managing hypertension, the guideline authors noted. They recommended treating verified systolic BP over 160 mm Hg or diastolic BP over 110 mm Hg during pregnancy and up to 6 weeks postpartum to lower the risk for fatal maternal intracerebral hemorrhage.
They noted that adverse pregnancy outcomes are also common and linked to chronic hypertension, which increases stroke risk later in life. Therefore, they recommended screening for these outcomes to assess and manage vascular risk factors. The guideline includes a screening tool to help with this in clinical practice.
Endometriosis, premature ovarian failure (before age 40 years), and early-onset menopause (before age 45 years) are all associated with increased stroke risk. As a result, the guideline authors said screening for all three of these conditions is a “reasonable step in the evaluation and management of vascular risk factors in these individuals to reduce stroke risk.”
Finally, the guideline authors addressed primary stroke prevention in transgender individuals, noting that transgender women undergoing estrogen therapy for gender affirmation are at increased risk. They emphasized that evaluating and modifying risk factors could be beneficial for reducing stroke risk in this patient population.
Challenges Lie Ahead
Now that the guideline has been published, the challenge lies in determining how best to implement “its screening recommendations in primary care and other practices when these clinicians are already pushed to see as many patients as possible,” Bushnell said.
Development of screening tools that can be easily incorporated into the clinic visit or the electronic health record, as well as additional personnel to provide counseling, are probably needed to disseminate them, she added.
Bushnell also emphasized that the guideline includes a strong focus on social determinants of health and related social needs.
“We worked hard to use inclusive language and to consider populations historically excluded from research. In acknowledging that social determinants of health including access to healthcare, access to education, economic stability, neighborhood and geographic location, and social and community context have a tremendous influence on stroke risk, we describe how these factors are closely tied to the prevalence and management of many medical risks like obesity, hypertension, and diabetes.
“Our recommendations offer practical steps for screening and addressing essential health-related social needs, including access to nutritious food, stable housing, and reliable transportation, within clinical practice. By considering these factors more comprehensively, we believe we can make meaningful strides toward reducing the disparities in stroke risk,” said Bushnell.
A version of this article appeared on Medscape.com.
AHA Scientific Statement Links Three Common Cardiovascular Diseases to Cognitive Decline, Dementia
The statement includes an extensive research review and offers compelling evidence of the inextricable link between heart health and brain health, which investigators said underscores the benefit of early intervention.
The cumulative evidence “confirms that the trajectories of cardiac health and brain health are inextricably intertwined through modifiable and nonmodifiable factors,” the authors wrote.
Investigators say the findings reinforce the message that addressing cardiovascular health early in life may deter the onset or progression of cognitive impairment later on.
And the earlier this is done, the better, said lead author Fernando D. Testai, MD, PhD, a professor of neurology and the vascular neurology section head, Department of Neurology and Rehabilitation, University of Illinois, Chicago.
The statement was published online in Stroke.
Bridging the Research Gap
It’s well known that there’s a bidirectional relationship between heart and brain function. For example, heart failure can lead to decreased blood flow that can damage the brain, and stroke in some areas of the brain can affect the heart.
However, that’s only part of the puzzle and doesn’t address all the gaps in the understanding of how cardiovascular disease contributes to cognition, said Testai.
“What we’re trying to do here is to go one step further and describe other connections between the heart and the brain,” he said.
Investigators carried out an extensive PubMed search for heart failure, atrial fibrillation, and coronary heart disease. Researchers detailed the frequency of each condition, mechanisms by which they might cause cognitive impairment, and prospects for prevention and treatment to maintain brain health.
A recurring theme in the paper is the role of inflammation. Evidence shows there are “remarkable similarities in the inflammatory response that takes place,” with both cardiac disease and cognitive decline, said Testai.
Another potential shared mechanism relates to biomarkers, particularly amyloid, which is strongly linked to Alzheimer’s disease.
“But some studies show amyloid can also be present in the heart, especially in patients who have decreased ejection fraction,” said Testai.
Robust Heart-Brain Connection
The statement’s authors collected a substantial amount of evidence showing vascular risk factors such as hypertension and diabetes “can change how the brain processes and clears up amyloid,” Testai added.
The paper also provides a compilation of evidence of shared genetic predispositions when it comes to heart and brain disorders.
“We noticed that some genetic signatures that have historically been associated with heart disease seem to also correlate with structural changes in the brain. That means that at the end of the day, some patients may be born with a genetic predisposition to developing both conditions,” said Testai.
This indicates that the link between the two organs “begins as early as conception” and underscores the importance of adopting healthy lifestyle habits as early as possible, he added.
“That means you can avoid bad habits that eventually lead to hypertension, diabetes, and cholesterol, that eventually will lead to cardiac disease, which eventually will lead to stroke, which eventually will lead to cognitive decline,” Testai noted.
However, cardiovascular health is more complicated than having good genes and adhering to a healthy lifestyle. It’s not clear, for example, why some people who should be predisposed to developing heart disease do not develop it, something Testai refers to as enhanced “resilience.”
For example, Hispanic or Latino patients, who have relatively poor cardiovascular risk factor profiles, seem to be less susceptible to developing cardiac disease.
More Research Needed
While genetics may partly explain the paradox, Testai believes other protective factors are at play, including strong social support networks.
Testai referred to the AHA’s “Life’s Essential 8” — the eight components of cardiovascular health. These include a healthy diet, participation in physical activity, nicotine avoidance, healthy sleep, healthy weight, and healthy levels of blood lipids, blood glucose, and blood pressure.
More evidence is needed to show that effective management of cardiac disease positively affects cognition. Currently, cognitive measures are rarely included in studies examining various heart disease treatments, said Testai.
“There should probably be an effort to include brain health outcomes in some of the cardiac literature to make sure we can also measure whether the intervention in the heart leads to an advantage for the brain,” he said.
More research is also needed to determine whether immunomodulation has a beneficial effect on the cognitive trajectory, the statement’s authors noted.
They point out that the interpretation and generalizability of the studies described in the statement are confounded by disparate methodologies, including small sample sizes, cross-sectional designs, and underrepresentation of Black and Hispanic individuals.
‘An Important Step’
Reached for a comment, Natalia S. Rost, MD, Chief of the Stroke Division at Massachusetts General Hospital and professor of neurology at Harvard Medical School, both in Boston, said this paper “is an important step” in terms of pulling together pertinent information on the topic of heart-brain health.
She praised the authors for gathering evidence on risk factors related to atrial fibrillation, heart failure, and coronary heart disease, which is “the part of the puzzle that is controllable.”
This helps reinforce the message that controlling vascular risk factors helps with brain health, said Rost.
But brain health is “much more complex than just vascular health,” she said. It includes other elements such as freedom from epilepsy, migraine, traumatic brain injury, and adult learning disabilities.
No relevant conflicts of interest were disclosed.
A version of this article first appeared on Medscape.com.
The statement includes an extensive research review and offers compelling evidence of the inextricable link between heart health and brain health, which investigators said underscores the benefit of early intervention.
The cumulative evidence “confirms that the trajectories of cardiac health and brain health are inextricably intertwined through modifiable and nonmodifiable factors,” the authors wrote.
Investigators say the findings reinforce the message that addressing cardiovascular health early in life may deter the onset or progression of cognitive impairment later on.
And the earlier this is done, the better, said lead author Fernando D. Testai, MD, PhD, a professor of neurology and the vascular neurology section head, Department of Neurology and Rehabilitation, University of Illinois, Chicago.
The statement was published online in Stroke.
Bridging the Research Gap
It’s well known that there’s a bidirectional relationship between heart and brain function. For example, heart failure can lead to decreased blood flow that can damage the brain, and stroke in some areas of the brain can affect the heart.
However, that’s only part of the puzzle and doesn’t address all the gaps in the understanding of how cardiovascular disease contributes to cognition, said Testai.
“What we’re trying to do here is to go one step further and describe other connections between the heart and the brain,” he said.
Investigators carried out an extensive PubMed search for heart failure, atrial fibrillation, and coronary heart disease. Researchers detailed the frequency of each condition, mechanisms by which they might cause cognitive impairment, and prospects for prevention and treatment to maintain brain health.
A recurring theme in the paper is the role of inflammation. Evidence shows there are “remarkable similarities in the inflammatory response that takes place,” with both cardiac disease and cognitive decline, said Testai.
Another potential shared mechanism relates to biomarkers, particularly amyloid, which is strongly linked to Alzheimer’s disease.
“But some studies show amyloid can also be present in the heart, especially in patients who have decreased ejection fraction,” said Testai.
Robust Heart-Brain Connection
The statement’s authors collected a substantial amount of evidence showing vascular risk factors such as hypertension and diabetes “can change how the brain processes and clears up amyloid,” Testai added.
The paper also provides a compilation of evidence of shared genetic predispositions when it comes to heart and brain disorders.
“We noticed that some genetic signatures that have historically been associated with heart disease seem to also correlate with structural changes in the brain. That means that at the end of the day, some patients may be born with a genetic predisposition to developing both conditions,” said Testai.
This indicates that the link between the two organs “begins as early as conception” and underscores the importance of adopting healthy lifestyle habits as early as possible, he added.
“That means you can avoid bad habits that eventually lead to hypertension, diabetes, and cholesterol, that eventually will lead to cardiac disease, which eventually will lead to stroke, which eventually will lead to cognitive decline,” Testai noted.
However, cardiovascular health is more complicated than having good genes and adhering to a healthy lifestyle. It’s not clear, for example, why some people who should be predisposed to developing heart disease do not develop it, something Testai refers to as enhanced “resilience.”
For example, Hispanic or Latino patients, who have relatively poor cardiovascular risk factor profiles, seem to be less susceptible to developing cardiac disease.
More Research Needed
While genetics may partly explain the paradox, Testai believes other protective factors are at play, including strong social support networks.
Testai referred to the AHA’s “Life’s Essential 8” — the eight components of cardiovascular health. These include a healthy diet, participation in physical activity, nicotine avoidance, healthy sleep, healthy weight, and healthy levels of blood lipids, blood glucose, and blood pressure.
More evidence is needed to show that effective management of cardiac disease positively affects cognition. Currently, cognitive measures are rarely included in studies examining various heart disease treatments, said Testai.
“There should probably be an effort to include brain health outcomes in some of the cardiac literature to make sure we can also measure whether the intervention in the heart leads to an advantage for the brain,” he said.
More research is also needed to determine whether immunomodulation has a beneficial effect on the cognitive trajectory, the statement’s authors noted.
They point out that the interpretation and generalizability of the studies described in the statement are confounded by disparate methodologies, including small sample sizes, cross-sectional designs, and underrepresentation of Black and Hispanic individuals.
‘An Important Step’
Reached for a comment, Natalia S. Rost, MD, Chief of the Stroke Division at Massachusetts General Hospital and professor of neurology at Harvard Medical School, both in Boston, said this paper “is an important step” in terms of pulling together pertinent information on the topic of heart-brain health.
She praised the authors for gathering evidence on risk factors related to atrial fibrillation, heart failure, and coronary heart disease, which is “the part of the puzzle that is controllable.”
This helps reinforce the message that controlling vascular risk factors helps with brain health, said Rost.
But brain health is “much more complex than just vascular health,” she said. It includes other elements such as freedom from epilepsy, migraine, traumatic brain injury, and adult learning disabilities.
No relevant conflicts of interest were disclosed.
A version of this article first appeared on Medscape.com.
The statement includes an extensive research review and offers compelling evidence of the inextricable link between heart health and brain health, which investigators said underscores the benefit of early intervention.
The cumulative evidence “confirms that the trajectories of cardiac health and brain health are inextricably intertwined through modifiable and nonmodifiable factors,” the authors wrote.
Investigators say the findings reinforce the message that addressing cardiovascular health early in life may deter the onset or progression of cognitive impairment later on.
And the earlier this is done, the better, said lead author Fernando D. Testai, MD, PhD, a professor of neurology and the vascular neurology section head, Department of Neurology and Rehabilitation, University of Illinois, Chicago.
The statement was published online in Stroke.
Bridging the Research Gap
It’s well known that there’s a bidirectional relationship between heart and brain function. For example, heart failure can lead to decreased blood flow that can damage the brain, and stroke in some areas of the brain can affect the heart.
However, that’s only part of the puzzle and doesn’t address all the gaps in the understanding of how cardiovascular disease contributes to cognition, said Testai.
“What we’re trying to do here is to go one step further and describe other connections between the heart and the brain,” he said.
Investigators carried out an extensive PubMed search for heart failure, atrial fibrillation, and coronary heart disease. Researchers detailed the frequency of each condition, mechanisms by which they might cause cognitive impairment, and prospects for prevention and treatment to maintain brain health.
A recurring theme in the paper is the role of inflammation. Evidence shows there are “remarkable similarities in the inflammatory response that takes place,” with both cardiac disease and cognitive decline, said Testai.
Another potential shared mechanism relates to biomarkers, particularly amyloid, which is strongly linked to Alzheimer’s disease.
“But some studies show amyloid can also be present in the heart, especially in patients who have decreased ejection fraction,” said Testai.
Robust Heart-Brain Connection
The statement’s authors collected a substantial amount of evidence showing vascular risk factors such as hypertension and diabetes “can change how the brain processes and clears up amyloid,” Testai added.
The paper also provides a compilation of evidence of shared genetic predispositions when it comes to heart and brain disorders.
“We noticed that some genetic signatures that have historically been associated with heart disease seem to also correlate with structural changes in the brain. That means that at the end of the day, some patients may be born with a genetic predisposition to developing both conditions,” said Testai.
This indicates that the link between the two organs “begins as early as conception” and underscores the importance of adopting healthy lifestyle habits as early as possible, he added.
“That means you can avoid bad habits that eventually lead to hypertension, diabetes, and cholesterol, that eventually will lead to cardiac disease, which eventually will lead to stroke, which eventually will lead to cognitive decline,” Testai noted.
However, cardiovascular health is more complicated than having good genes and adhering to a healthy lifestyle. It’s not clear, for example, why some people who should be predisposed to developing heart disease do not develop it, something Testai refers to as enhanced “resilience.”
For example, Hispanic or Latino patients, who have relatively poor cardiovascular risk factor profiles, seem to be less susceptible to developing cardiac disease.
More Research Needed
While genetics may partly explain the paradox, Testai believes other protective factors are at play, including strong social support networks.
Testai referred to the AHA’s “Life’s Essential 8” — the eight components of cardiovascular health. These include a healthy diet, participation in physical activity, nicotine avoidance, healthy sleep, healthy weight, and healthy levels of blood lipids, blood glucose, and blood pressure.
More evidence is needed to show that effective management of cardiac disease positively affects cognition. Currently, cognitive measures are rarely included in studies examining various heart disease treatments, said Testai.
“There should probably be an effort to include brain health outcomes in some of the cardiac literature to make sure we can also measure whether the intervention in the heart leads to an advantage for the brain,” he said.
More research is also needed to determine whether immunomodulation has a beneficial effect on the cognitive trajectory, the statement’s authors noted.
They point out that the interpretation and generalizability of the studies described in the statement are confounded by disparate methodologies, including small sample sizes, cross-sectional designs, and underrepresentation of Black and Hispanic individuals.
‘An Important Step’
Reached for a comment, Natalia S. Rost, MD, Chief of the Stroke Division at Massachusetts General Hospital and professor of neurology at Harvard Medical School, both in Boston, said this paper “is an important step” in terms of pulling together pertinent information on the topic of heart-brain health.
She praised the authors for gathering evidence on risk factors related to atrial fibrillation, heart failure, and coronary heart disease, which is “the part of the puzzle that is controllable.”
This helps reinforce the message that controlling vascular risk factors helps with brain health, said Rost.
But brain health is “much more complex than just vascular health,” she said. It includes other elements such as freedom from epilepsy, migraine, traumatic brain injury, and adult learning disabilities.
No relevant conflicts of interest were disclosed.
A version of this article first appeared on Medscape.com.
FROM STROKE
White Matter Shows Decline After Bipolar Diagnosis
based on data from 88 individuals.
Patients with bipolar disorder demonstrate cognitive impairment and brain structure abnormalities, including global white matter loss, that have been associated with poor outcomes, but data on the stability or progression of neuroanatomical changes are limited, wrote Julian Macoveanu, PhD, of Copenhagen University Hospital, Denmark, and colleagues.
In a study published in The Journal of Affective Disorders, the researchers identified 97 adults aged 18 to 60 years with recently diagnosed bipolar disorder and matched them with 66 healthy controls. Participants were enrolled in the larger Bipolar Illness Onset (BIO) study. All participants underwent structural MRI and neuropsychological testing at baseline and were in full or partial remission based on total scores of 14 or less on the Hamilton Depression Rating Scale and the Young Mania Rating Scale. Approximately half of the participants (50 bipolar patients and 38 controls) participated in follow-up scans and testing after 6-27 months (mean 16 months), because of limited resources, according to the researchers.
The researchers compared changes in cortical gray matter volume and thickness, total cerebral white matter, hippocampal and amygdala volumes, estimated brain age, and cognitive functioning over time. In addition, they examined within-patient associations between baseline brain structure abnormalities and later mood episodes.
Overall, bipolar patients (BD) showed a significant decrease in total cerebral white matter from baseline, compared with healthy controls (HC) in mixed models (P = .006). “This effect was driven by BD patients showing a decrease in WM volume over time compared to HC who remained stable,” the researchers wrote, and the effect persisted in a post hoc analysis adjusting for subsyndromal symptoms and body mass index.
BD patients also had a larger amygdala volume at baseline and follow-up than HC, but no changes were noted between the groups. Changes in hippocampal volume also remained similar between the groups.
Analysis of cognitive data showed no significant differences in trajectories between BD patients and controls across cognitive domains or globally; although BD patients performed worse than controls at both time points.
BD patients in general experienced lower functioning and worse quality of life, compared with controls, but the trajectories of each group were similar for both functional and quality of life.
The researchers found no significant differences over time in total white matter, hippocampus, or amygdala volumes between BD patients who experienced at least one mood episode during the study period and those who remained in remission.
The findings were limited by several factors including the small sample size and limited generalizability of the findings because of the restriction to patients in full or partial remission, the researchers noted. Other limitations included the variation in follow-up time and the potential impact of psychotropic medication use.
However, the results were strengthened by the use of neuropsychiatric testing in addition to MRI to compare brain structure and cognitive function, the researchers said. The data suggest that both amygdala volume and cognitive impairment may be stable markers of BD soon after diagnosis, but that decreases in white matter may stem from disease progression.
The BIO study is funded by the Mental Health Services, Capital Region of Denmark, the Danish Council for Independent Research, Medical Sciences, Weimans Fund, Markedsmodningsfonden, Gangstedfonden, Læge Sofus Carl Emil og hustru Olga Boris Friis’ legat, Helsefonden, Innovation Fund Denmark, Copenhagen Center for Health Technology (CACHET), EU H2020 ITN, Augustinusfonden, and The Capital Region of Denmark. Macoveanu had no financial conflicts to disclose.
based on data from 88 individuals.
Patients with bipolar disorder demonstrate cognitive impairment and brain structure abnormalities, including global white matter loss, that have been associated with poor outcomes, but data on the stability or progression of neuroanatomical changes are limited, wrote Julian Macoveanu, PhD, of Copenhagen University Hospital, Denmark, and colleagues.
In a study published in The Journal of Affective Disorders, the researchers identified 97 adults aged 18 to 60 years with recently diagnosed bipolar disorder and matched them with 66 healthy controls. Participants were enrolled in the larger Bipolar Illness Onset (BIO) study. All participants underwent structural MRI and neuropsychological testing at baseline and were in full or partial remission based on total scores of 14 or less on the Hamilton Depression Rating Scale and the Young Mania Rating Scale. Approximately half of the participants (50 bipolar patients and 38 controls) participated in follow-up scans and testing after 6-27 months (mean 16 months), because of limited resources, according to the researchers.
The researchers compared changes in cortical gray matter volume and thickness, total cerebral white matter, hippocampal and amygdala volumes, estimated brain age, and cognitive functioning over time. In addition, they examined within-patient associations between baseline brain structure abnormalities and later mood episodes.
Overall, bipolar patients (BD) showed a significant decrease in total cerebral white matter from baseline, compared with healthy controls (HC) in mixed models (P = .006). “This effect was driven by BD patients showing a decrease in WM volume over time compared to HC who remained stable,” the researchers wrote, and the effect persisted in a post hoc analysis adjusting for subsyndromal symptoms and body mass index.
BD patients also had a larger amygdala volume at baseline and follow-up than HC, but no changes were noted between the groups. Changes in hippocampal volume also remained similar between the groups.
Analysis of cognitive data showed no significant differences in trajectories between BD patients and controls across cognitive domains or globally; although BD patients performed worse than controls at both time points.
BD patients in general experienced lower functioning and worse quality of life, compared with controls, but the trajectories of each group were similar for both functional and quality of life.
The researchers found no significant differences over time in total white matter, hippocampus, or amygdala volumes between BD patients who experienced at least one mood episode during the study period and those who remained in remission.
The findings were limited by several factors including the small sample size and limited generalizability of the findings because of the restriction to patients in full or partial remission, the researchers noted. Other limitations included the variation in follow-up time and the potential impact of psychotropic medication use.
However, the results were strengthened by the use of neuropsychiatric testing in addition to MRI to compare brain structure and cognitive function, the researchers said. The data suggest that both amygdala volume and cognitive impairment may be stable markers of BD soon after diagnosis, but that decreases in white matter may stem from disease progression.
The BIO study is funded by the Mental Health Services, Capital Region of Denmark, the Danish Council for Independent Research, Medical Sciences, Weimans Fund, Markedsmodningsfonden, Gangstedfonden, Læge Sofus Carl Emil og hustru Olga Boris Friis’ legat, Helsefonden, Innovation Fund Denmark, Copenhagen Center for Health Technology (CACHET), EU H2020 ITN, Augustinusfonden, and The Capital Region of Denmark. Macoveanu had no financial conflicts to disclose.
based on data from 88 individuals.
Patients with bipolar disorder demonstrate cognitive impairment and brain structure abnormalities, including global white matter loss, that have been associated with poor outcomes, but data on the stability or progression of neuroanatomical changes are limited, wrote Julian Macoveanu, PhD, of Copenhagen University Hospital, Denmark, and colleagues.
In a study published in The Journal of Affective Disorders, the researchers identified 97 adults aged 18 to 60 years with recently diagnosed bipolar disorder and matched them with 66 healthy controls. Participants were enrolled in the larger Bipolar Illness Onset (BIO) study. All participants underwent structural MRI and neuropsychological testing at baseline and were in full or partial remission based on total scores of 14 or less on the Hamilton Depression Rating Scale and the Young Mania Rating Scale. Approximately half of the participants (50 bipolar patients and 38 controls) participated in follow-up scans and testing after 6-27 months (mean 16 months), because of limited resources, according to the researchers.
The researchers compared changes in cortical gray matter volume and thickness, total cerebral white matter, hippocampal and amygdala volumes, estimated brain age, and cognitive functioning over time. In addition, they examined within-patient associations between baseline brain structure abnormalities and later mood episodes.
Overall, bipolar patients (BD) showed a significant decrease in total cerebral white matter from baseline, compared with healthy controls (HC) in mixed models (P = .006). “This effect was driven by BD patients showing a decrease in WM volume over time compared to HC who remained stable,” the researchers wrote, and the effect persisted in a post hoc analysis adjusting for subsyndromal symptoms and body mass index.
BD patients also had a larger amygdala volume at baseline and follow-up than HC, but no changes were noted between the groups. Changes in hippocampal volume also remained similar between the groups.
Analysis of cognitive data showed no significant differences in trajectories between BD patients and controls across cognitive domains or globally; although BD patients performed worse than controls at both time points.
BD patients in general experienced lower functioning and worse quality of life, compared with controls, but the trajectories of each group were similar for both functional and quality of life.
The researchers found no significant differences over time in total white matter, hippocampus, or amygdala volumes between BD patients who experienced at least one mood episode during the study period and those who remained in remission.
The findings were limited by several factors including the small sample size and limited generalizability of the findings because of the restriction to patients in full or partial remission, the researchers noted. Other limitations included the variation in follow-up time and the potential impact of psychotropic medication use.
However, the results were strengthened by the use of neuropsychiatric testing in addition to MRI to compare brain structure and cognitive function, the researchers said. The data suggest that both amygdala volume and cognitive impairment may be stable markers of BD soon after diagnosis, but that decreases in white matter may stem from disease progression.
The BIO study is funded by the Mental Health Services, Capital Region of Denmark, the Danish Council for Independent Research, Medical Sciences, Weimans Fund, Markedsmodningsfonden, Gangstedfonden, Læge Sofus Carl Emil og hustru Olga Boris Friis’ legat, Helsefonden, Innovation Fund Denmark, Copenhagen Center for Health Technology (CACHET), EU H2020 ITN, Augustinusfonden, and The Capital Region of Denmark. Macoveanu had no financial conflicts to disclose.
FROM THE JOURNAL OF AFFECTIVE DISORDERS
Long-Term Cognitive Monitoring Warranted After First Stroke
A first stroke in older adults is associated with substantial immediate and accelerated long-term cognitive decline, suggested a new study that underscores the need for continuous cognitive monitoring in this patient population.
Results from the study, which included 14 international cohorts of older adults, showed that stroke was associated with a significant acute decline in global cognition and a small, but significant, acceleration in the rate of cognitive decline over time.
Cognitive assessments in primary care are “crucial, especially since cognitive impairment is frequently missed or undiagnosed in hospitals,” lead author Jessica Lo, MSc, biostatistician and research associate with the Center for Healthy Brain Aging, University of New South Wales, Sydney, Australia, told this news organization.
She suggested clinicians incorporate long-term cognitive assessments into care plans, using more sensitive neuropsychological tests in primary care to detect early signs of cognitive impairment. “Early detection would enable timely interventions to improve outcomes,” Lo said.
She also noted that poststroke care typically includes physical rehabilitation but not cognitive rehabilitation, which many rehabilitation centers aren’t equipped to provide.
The study was published online in JAMA Network Open.
Mapping Cognitive Decline Trajectory
Cognitive impairment after stroke is common, but the trajectory of cognitive decline following a first stroke, relative to prestroke cognitive function, remains unclear.
The investigators leveraged data from 14 population-based cohort studies of 20,860 adults (mean age, 73 years; 59% women) to map the trajectory of cognitive function before and after a first stroke.
The primary outcome was global cognition, defined as the standardized average of four cognitive domains (language, memory, processing speed, and executive function).
During a mean follow-up of 7.5 years, 1041 (5%) adults (mean age, 79 years) experienced a first stroke, a mean of 4.5 years after study entry.
In adjusted analyses, stroke was associated with a significant acute decline of 0.25 SD in global cognition and a “small but significant” acceleration in the rate of decline of −0.038 SD per year, the authors reported.
Stroke was also associated with acute decline in all individual cognitive domains except for memory, with effect sizes ranging from −0.17 to −0.22 SD. Poststroke declines in Mini-Mental State Examination scores (−0.36 SD) were also noted.
In terms of cognitive trajectory, the rate of decline before stroke in survivors was similar to that seen in peers who didn’t have a stroke (−0.048 and −0.049 SD per year in global cognition, respectively).
The researchers did not identify any vascular risk factors moderating cognitive decline following a stroke, consistent with prior research. However, cognitive decline was significantly more rapid in individuals without stroke, regardless of any future stroke, who had a history of diabetes, hypertension, high cholesterol, cardiovascular disease, depression, smoking, or were APOE4 carriers.
“Targeting modifiable vascular risk factors at an early stage may reduce the risk of stroke but also subsequent risk of stroke-related cognitive decline and cognitive impairment,” the researchers noted.
A ‘Major Step’ in the Right Direction
As previously reported by this news organization, in 2023 the American Heart Association (AHA) issued a statement noting that screening for cognitive impairment should be part of multidisciplinary care for stroke survivors.
Commenting for this news organization, Mitchell Elkind, MD, MS, AHA chief clinical science officer, said these new data are consistent with current AHA guidelines and statements that “support screening for cognitive and functional decline in patients both acutely and over the long term after stroke.”
Elkind noted that the 2022 guideline for intracerebral hemorrhage states that cognitive screening should occur “across the continuum of inpatient care and at intervals in the outpatient setting” and provides recommendations for cognitive therapy.
“Our 2021 scientific statement on the primary care of patients after stroke also recommends screening for both depression and cognitive impairment over both the short- and long-term,” said Elkind, professor of neurology and epidemiology at Columbia University Irving Medical Center in New York City.
“These documents recognize the fact that function and cognition can continue to decline years after stroke and that patients’ rehabilitation and support needs may therefore change over time after stroke,” Elkind added.
The authors of an accompanying commentary called it a “major step” in the right direction for the future of long-term stroke outcome assessment.
“As we develop new devices, indications, and time windows for stroke treatment, it may perhaps be wise to ensure trials steer away from simpler outcomes to more complex, granular ones,” wrote Yasmin Sadigh, MSc, and Victor Volovici, MD, PhD, with Erasmus University Medical Center, Rotterdam, the Netherlands.
The study had no commercial funding. The authors and commentary writers and Elkind have declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
A first stroke in older adults is associated with substantial immediate and accelerated long-term cognitive decline, suggested a new study that underscores the need for continuous cognitive monitoring in this patient population.
Results from the study, which included 14 international cohorts of older adults, showed that stroke was associated with a significant acute decline in global cognition and a small, but significant, acceleration in the rate of cognitive decline over time.
Cognitive assessments in primary care are “crucial, especially since cognitive impairment is frequently missed or undiagnosed in hospitals,” lead author Jessica Lo, MSc, biostatistician and research associate with the Center for Healthy Brain Aging, University of New South Wales, Sydney, Australia, told this news organization.
She suggested clinicians incorporate long-term cognitive assessments into care plans, using more sensitive neuropsychological tests in primary care to detect early signs of cognitive impairment. “Early detection would enable timely interventions to improve outcomes,” Lo said.
She also noted that poststroke care typically includes physical rehabilitation but not cognitive rehabilitation, which many rehabilitation centers aren’t equipped to provide.
The study was published online in JAMA Network Open.
Mapping Cognitive Decline Trajectory
Cognitive impairment after stroke is common, but the trajectory of cognitive decline following a first stroke, relative to prestroke cognitive function, remains unclear.
The investigators leveraged data from 14 population-based cohort studies of 20,860 adults (mean age, 73 years; 59% women) to map the trajectory of cognitive function before and after a first stroke.
The primary outcome was global cognition, defined as the standardized average of four cognitive domains (language, memory, processing speed, and executive function).
During a mean follow-up of 7.5 years, 1041 (5%) adults (mean age, 79 years) experienced a first stroke, a mean of 4.5 years after study entry.
In adjusted analyses, stroke was associated with a significant acute decline of 0.25 SD in global cognition and a “small but significant” acceleration in the rate of decline of −0.038 SD per year, the authors reported.
Stroke was also associated with acute decline in all individual cognitive domains except for memory, with effect sizes ranging from −0.17 to −0.22 SD. Poststroke declines in Mini-Mental State Examination scores (−0.36 SD) were also noted.
In terms of cognitive trajectory, the rate of decline before stroke in survivors was similar to that seen in peers who didn’t have a stroke (−0.048 and −0.049 SD per year in global cognition, respectively).
The researchers did not identify any vascular risk factors moderating cognitive decline following a stroke, consistent with prior research. However, cognitive decline was significantly more rapid in individuals without stroke, regardless of any future stroke, who had a history of diabetes, hypertension, high cholesterol, cardiovascular disease, depression, smoking, or were APOE4 carriers.
“Targeting modifiable vascular risk factors at an early stage may reduce the risk of stroke but also subsequent risk of stroke-related cognitive decline and cognitive impairment,” the researchers noted.
A ‘Major Step’ in the Right Direction
As previously reported by this news organization, in 2023 the American Heart Association (AHA) issued a statement noting that screening for cognitive impairment should be part of multidisciplinary care for stroke survivors.
Commenting for this news organization, Mitchell Elkind, MD, MS, AHA chief clinical science officer, said these new data are consistent with current AHA guidelines and statements that “support screening for cognitive and functional decline in patients both acutely and over the long term after stroke.”
Elkind noted that the 2022 guideline for intracerebral hemorrhage states that cognitive screening should occur “across the continuum of inpatient care and at intervals in the outpatient setting” and provides recommendations for cognitive therapy.
“Our 2021 scientific statement on the primary care of patients after stroke also recommends screening for both depression and cognitive impairment over both the short- and long-term,” said Elkind, professor of neurology and epidemiology at Columbia University Irving Medical Center in New York City.
“These documents recognize the fact that function and cognition can continue to decline years after stroke and that patients’ rehabilitation and support needs may therefore change over time after stroke,” Elkind added.
The authors of an accompanying commentary called it a “major step” in the right direction for the future of long-term stroke outcome assessment.
“As we develop new devices, indications, and time windows for stroke treatment, it may perhaps be wise to ensure trials steer away from simpler outcomes to more complex, granular ones,” wrote Yasmin Sadigh, MSc, and Victor Volovici, MD, PhD, with Erasmus University Medical Center, Rotterdam, the Netherlands.
The study had no commercial funding. The authors and commentary writers and Elkind have declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
A first stroke in older adults is associated with substantial immediate and accelerated long-term cognitive decline, suggested a new study that underscores the need for continuous cognitive monitoring in this patient population.
Results from the study, which included 14 international cohorts of older adults, showed that stroke was associated with a significant acute decline in global cognition and a small, but significant, acceleration in the rate of cognitive decline over time.
Cognitive assessments in primary care are “crucial, especially since cognitive impairment is frequently missed or undiagnosed in hospitals,” lead author Jessica Lo, MSc, biostatistician and research associate with the Center for Healthy Brain Aging, University of New South Wales, Sydney, Australia, told this news organization.
She suggested clinicians incorporate long-term cognitive assessments into care plans, using more sensitive neuropsychological tests in primary care to detect early signs of cognitive impairment. “Early detection would enable timely interventions to improve outcomes,” Lo said.
She also noted that poststroke care typically includes physical rehabilitation but not cognitive rehabilitation, which many rehabilitation centers aren’t equipped to provide.
The study was published online in JAMA Network Open.
Mapping Cognitive Decline Trajectory
Cognitive impairment after stroke is common, but the trajectory of cognitive decline following a first stroke, relative to prestroke cognitive function, remains unclear.
The investigators leveraged data from 14 population-based cohort studies of 20,860 adults (mean age, 73 years; 59% women) to map the trajectory of cognitive function before and after a first stroke.
The primary outcome was global cognition, defined as the standardized average of four cognitive domains (language, memory, processing speed, and executive function).
During a mean follow-up of 7.5 years, 1041 (5%) adults (mean age, 79 years) experienced a first stroke, a mean of 4.5 years after study entry.
In adjusted analyses, stroke was associated with a significant acute decline of 0.25 SD in global cognition and a “small but significant” acceleration in the rate of decline of −0.038 SD per year, the authors reported.
Stroke was also associated with acute decline in all individual cognitive domains except for memory, with effect sizes ranging from −0.17 to −0.22 SD. Poststroke declines in Mini-Mental State Examination scores (−0.36 SD) were also noted.
In terms of cognitive trajectory, the rate of decline before stroke in survivors was similar to that seen in peers who didn’t have a stroke (−0.048 and −0.049 SD per year in global cognition, respectively).
The researchers did not identify any vascular risk factors moderating cognitive decline following a stroke, consistent with prior research. However, cognitive decline was significantly more rapid in individuals without stroke, regardless of any future stroke, who had a history of diabetes, hypertension, high cholesterol, cardiovascular disease, depression, smoking, or were APOE4 carriers.
“Targeting modifiable vascular risk factors at an early stage may reduce the risk of stroke but also subsequent risk of stroke-related cognitive decline and cognitive impairment,” the researchers noted.
A ‘Major Step’ in the Right Direction
As previously reported by this news organization, in 2023 the American Heart Association (AHA) issued a statement noting that screening for cognitive impairment should be part of multidisciplinary care for stroke survivors.
Commenting for this news organization, Mitchell Elkind, MD, MS, AHA chief clinical science officer, said these new data are consistent with current AHA guidelines and statements that “support screening for cognitive and functional decline in patients both acutely and over the long term after stroke.”
Elkind noted that the 2022 guideline for intracerebral hemorrhage states that cognitive screening should occur “across the continuum of inpatient care and at intervals in the outpatient setting” and provides recommendations for cognitive therapy.
“Our 2021 scientific statement on the primary care of patients after stroke also recommends screening for both depression and cognitive impairment over both the short- and long-term,” said Elkind, professor of neurology and epidemiology at Columbia University Irving Medical Center in New York City.
“These documents recognize the fact that function and cognition can continue to decline years after stroke and that patients’ rehabilitation and support needs may therefore change over time after stroke,” Elkind added.
The authors of an accompanying commentary called it a “major step” in the right direction for the future of long-term stroke outcome assessment.
“As we develop new devices, indications, and time windows for stroke treatment, it may perhaps be wise to ensure trials steer away from simpler outcomes to more complex, granular ones,” wrote Yasmin Sadigh, MSc, and Victor Volovici, MD, PhD, with Erasmus University Medical Center, Rotterdam, the Netherlands.
The study had no commercial funding. The authors and commentary writers and Elkind have declared no conflicts of interest.
A version of this article first appeared on Medscape.com.
FROM JAMA NETWORK OPEN
What Are the Best Tools for Early Childhood Developmental Concerns?
Early recognition of neurodevelopmental concerns and timely access to services have been shown to result in better outcomes for young children. But not all instruments are of equal value, and new research has sought to identify the most useful among them.
For their research, published online in Developmental Medicine & Child Neurology, Andrea Burgess, PhD, of the University of Queensland in Brisbane, Australia, and her colleagues looked at two decades’ worth of systematic reviews of screening, assessment, and diagnostic tools used in children younger than 6 years.
Eighty-six clinical reviews and six practice guidelines, all published between 2000 and 2023, were included in the scoping review, which covered nearly 250 different multi-domain and domain- and disorder-specific tools.
The diagnostic instruments were those used to diagnose the most common early childhood disorders, including intellectual disability, global developmental delay, communication disorders, autism spectrum disorder, attention-deficit/hyperactivity disorder, cerebral palsy, movement disorders, and fetal alcohol spectrum disorder. Burgess and her colleagues sought to determine which tools had the strongest evidence behind them, noting that comparisons were inherently limited by differences in the tested populations, cutoff values, and other factors.
Burgess and her colleagues identified 67 instruments — about a third of those analyzed in the study — “with good discriminative or predictive validity for the screening and assessment of developmental concerns or disability.” Recommended tools were classified by tool type and by patient age groups.
The reason a tool might not be recommended, Burgess said in an email, was for lack of psychometric testing or published evidence, or because the tool was very narrow in scope (eg, covering only a single aspect of a domain), had a small time window for use, or was too new to have been captured in published systematic reviews.
Top Recommendations
Among multi-domain assessment tools, the Bayley Scales of Infant and Toddler Development, the Battelle Developmental Inventory, and the Mullen Scales of Early Learning all emerged as highly recommended. The top diagnostic screening tool for autism was the revised version of Social Attention and Communication Surveillance. For cerebral palsy, the top-rated diagnostic assessment tools were Prechtl’s Qualitative Assessment of General Movements and the Hammersmith Infant Neurological Examination.
Ratifying findings by other groups, the researchers determined the Ages & Stages Questionnaires, Third Edition (ASQ-3) to be the best overall multi-domain screening instrument for early childhood development, thanks to its simplicity and ease of use by a wide range of practitioner types. Burgess and her colleagues noted, however, that the ASQ-3 “will not identify all children with developmental concerns and may incorrectly identify others,” and that it may be more accurate in children 2 years or older.
Patient Care Setting and Cultural, Socioeconomic Factors Are Key
This news organization spoke to two clinicians working with these and similar tools in the United States. Both said that the care setting can also influence the utility of tools, with cultural and socioeconomic factors playing important roles.
Liz Schwandt, PsyD, an early intervention specialist in Los Angeles, said in an interview that children living in high-risk communities in the United States have a larger burden of developmental delays. But for many families in these communities, accessing care can be complex, which is why well-designed, efficient screening tools like ASQ-3 are especially valuable in practice.
“The reality is you have 10 minutes with a lot of families, and if it’s an emergency, you need to know,” she said. “The ASQ-3 has a very broad age range for this type of instrument and can be used by different practitioner types. The reason it’s successful lies in its parent-centric approach and inherent ease of use. It’s quick, and you can score it using pencil and paper while chatting with the parent, and you can use it for multiple siblings in the space of one appointment.”
With very young children, in whom neurodevelopmental concerns often overlap domains, Schwandt said it can be more important to flag a potential problem early and initiate a nonspecific developmental intervention than wait for results from more precise assessments using more specialized tools. These often require multiple, multi-hour appointments, which can be difficult to attain in lower-resource settings in the United States and can delay care, she said.
Liza Mackintosh, MD, a pediatrician at a federally funded healthcare center in Los Angeles that serves mostly publicly insured families, called validated first-line screening tools “incredibly important.” While rates of developmental screenings in pediatric clinics are increasing, there is still room for improvement, she said.
Mackintosh’s institution does not currently use the ASQ-3 but a different screening tool, called the Survey of Well-Being of Young Children (SWYC), that is embedded into the electronic health record. (The SWYC was not among the tools highlighted in Burgess and colleagues’ review.) Like the ASQ-3, it is short and efficient, she said, and it is used in all children in the recommended age ranges.
“Our visits are on average only 20 minutes,” Mackintosh said. “There’s not enough time for an in-depth developmental assessment. We will flag things such as a speech delay, gross motor delay, or fine motor delay” and refer to early intervention centers for more in-depth developmental assessments as needed, she said.
“The biggest job of pediatricians working in communities that are under-resourced is advocating for those early intervention services,” Mackintosh added. “We really see our job as doing the recommended screening, putting that together with what we’re seeing clinically and on history, and then advocating for the right next step or early intervention. Because sometimes the diagnosis is — I don’t want to say irrelevant, but your treatment plan is still going to be the same. So while I don’t have a formal diagnosis yet, the child definitely needs therapies and we’re still going to get those therapies.”
Burgess and her colleagues stressed in their paper the importance of selecting tools that are culturally appropriate for Indigenous communities in Australia, noting that “inappropriate tools may lead to over- or under-recognition of children with developmental concerns.”
Schwandt and Mackintosh said that the same applies in US settings.
“We’ve done a good job translating screening tools into Chinese, Spanish, Vietnamese, and Russian,” Schwandt said. “But some of them assume a way of taking care of children that is not always shared across cultures. The expectations of how children should play and interact with adults can be very different, and there needs to be an understanding of that. Just putting something in Vietnamese doesn’t mean that there are obvious analogues to understanding what the questionnaire is asking.”
Mackintosh concurred. “A lot of times our patients will not do well on screening, even though they’re fine, because they don’t have the exposure to that activity that’s being asked about. So — is the child scribbling with crayons? Is she climbing up a ladder at a playground? In order to be able to do that, you need to have an environment that you are doing it in. The screeners have to really be appropriate for what the child is exposed to. And sometimes our patients just don’t have that exposure.”
Burgess and colleagues’ study was funded by the Australian government and the Merchant Charitable Foundation. The authors disclosed no financial conflicts of interest. Schwandt and Mackintosh disclosed no conflicts of interest related to their comments.
A version of this article appeared on Medscape.com.
Early recognition of neurodevelopmental concerns and timely access to services have been shown to result in better outcomes for young children. But not all instruments are of equal value, and new research has sought to identify the most useful among them.
For their research, published online in Developmental Medicine & Child Neurology, Andrea Burgess, PhD, of the University of Queensland in Brisbane, Australia, and her colleagues looked at two decades’ worth of systematic reviews of screening, assessment, and diagnostic tools used in children younger than 6 years.
Eighty-six clinical reviews and six practice guidelines, all published between 2000 and 2023, were included in the scoping review, which covered nearly 250 different multi-domain and domain- and disorder-specific tools.
The diagnostic instruments were those used to diagnose the most common early childhood disorders, including intellectual disability, global developmental delay, communication disorders, autism spectrum disorder, attention-deficit/hyperactivity disorder, cerebral palsy, movement disorders, and fetal alcohol spectrum disorder. Burgess and her colleagues sought to determine which tools had the strongest evidence behind them, noting that comparisons were inherently limited by differences in the tested populations, cutoff values, and other factors.
Burgess and her colleagues identified 67 instruments — about a third of those analyzed in the study — “with good discriminative or predictive validity for the screening and assessment of developmental concerns or disability.” Recommended tools were classified by tool type and by patient age groups.
The reason a tool might not be recommended, Burgess said in an email, was for lack of psychometric testing or published evidence, or because the tool was very narrow in scope (eg, covering only a single aspect of a domain), had a small time window for use, or was too new to have been captured in published systematic reviews.
Top Recommendations
Among multi-domain assessment tools, the Bayley Scales of Infant and Toddler Development, the Battelle Developmental Inventory, and the Mullen Scales of Early Learning all emerged as highly recommended. The top diagnostic screening tool for autism was the revised version of Social Attention and Communication Surveillance. For cerebral palsy, the top-rated diagnostic assessment tools were Prechtl’s Qualitative Assessment of General Movements and the Hammersmith Infant Neurological Examination.
Ratifying findings by other groups, the researchers determined the Ages & Stages Questionnaires, Third Edition (ASQ-3) to be the best overall multi-domain screening instrument for early childhood development, thanks to its simplicity and ease of use by a wide range of practitioner types. Burgess and her colleagues noted, however, that the ASQ-3 “will not identify all children with developmental concerns and may incorrectly identify others,” and that it may be more accurate in children 2 years or older.
Patient Care Setting and Cultural, Socioeconomic Factors Are Key
This news organization spoke to two clinicians working with these and similar tools in the United States. Both said that the care setting can also influence the utility of tools, with cultural and socioeconomic factors playing important roles.
Liz Schwandt, PsyD, an early intervention specialist in Los Angeles, said in an interview that children living in high-risk communities in the United States have a larger burden of developmental delays. But for many families in these communities, accessing care can be complex, which is why well-designed, efficient screening tools like ASQ-3 are especially valuable in practice.
“The reality is you have 10 minutes with a lot of families, and if it’s an emergency, you need to know,” she said. “The ASQ-3 has a very broad age range for this type of instrument and can be used by different practitioner types. The reason it’s successful lies in its parent-centric approach and inherent ease of use. It’s quick, and you can score it using pencil and paper while chatting with the parent, and you can use it for multiple siblings in the space of one appointment.”
With very young children, in whom neurodevelopmental concerns often overlap domains, Schwandt said it can be more important to flag a potential problem early and initiate a nonspecific developmental intervention than wait for results from more precise assessments using more specialized tools. These often require multiple, multi-hour appointments, which can be difficult to attain in lower-resource settings in the United States and can delay care, she said.
Liza Mackintosh, MD, a pediatrician at a federally funded healthcare center in Los Angeles that serves mostly publicly insured families, called validated first-line screening tools “incredibly important.” While rates of developmental screenings in pediatric clinics are increasing, there is still room for improvement, she said.
Mackintosh’s institution does not currently use the ASQ-3 but a different screening tool, called the Survey of Well-Being of Young Children (SWYC), that is embedded into the electronic health record. (The SWYC was not among the tools highlighted in Burgess and colleagues’ review.) Like the ASQ-3, it is short and efficient, she said, and it is used in all children in the recommended age ranges.
“Our visits are on average only 20 minutes,” Mackintosh said. “There’s not enough time for an in-depth developmental assessment. We will flag things such as a speech delay, gross motor delay, or fine motor delay” and refer to early intervention centers for more in-depth developmental assessments as needed, she said.
“The biggest job of pediatricians working in communities that are under-resourced is advocating for those early intervention services,” Mackintosh added. “We really see our job as doing the recommended screening, putting that together with what we’re seeing clinically and on history, and then advocating for the right next step or early intervention. Because sometimes the diagnosis is — I don’t want to say irrelevant, but your treatment plan is still going to be the same. So while I don’t have a formal diagnosis yet, the child definitely needs therapies and we’re still going to get those therapies.”
Burgess and her colleagues stressed in their paper the importance of selecting tools that are culturally appropriate for Indigenous communities in Australia, noting that “inappropriate tools may lead to over- or under-recognition of children with developmental concerns.”
Schwandt and Mackintosh said that the same applies in US settings.
“We’ve done a good job translating screening tools into Chinese, Spanish, Vietnamese, and Russian,” Schwandt said. “But some of them assume a way of taking care of children that is not always shared across cultures. The expectations of how children should play and interact with adults can be very different, and there needs to be an understanding of that. Just putting something in Vietnamese doesn’t mean that there are obvious analogues to understanding what the questionnaire is asking.”
Mackintosh concurred. “A lot of times our patients will not do well on screening, even though they’re fine, because they don’t have the exposure to that activity that’s being asked about. So — is the child scribbling with crayons? Is she climbing up a ladder at a playground? In order to be able to do that, you need to have an environment that you are doing it in. The screeners have to really be appropriate for what the child is exposed to. And sometimes our patients just don’t have that exposure.”
Burgess and colleagues’ study was funded by the Australian government and the Merchant Charitable Foundation. The authors disclosed no financial conflicts of interest. Schwandt and Mackintosh disclosed no conflicts of interest related to their comments.
A version of this article appeared on Medscape.com.
Early recognition of neurodevelopmental concerns and timely access to services have been shown to result in better outcomes for young children. But not all instruments are of equal value, and new research has sought to identify the most useful among them.
For their research, published online in Developmental Medicine & Child Neurology, Andrea Burgess, PhD, of the University of Queensland in Brisbane, Australia, and her colleagues looked at two decades’ worth of systematic reviews of screening, assessment, and diagnostic tools used in children younger than 6 years.
Eighty-six clinical reviews and six practice guidelines, all published between 2000 and 2023, were included in the scoping review, which covered nearly 250 different multi-domain and domain- and disorder-specific tools.
The diagnostic instruments were those used to diagnose the most common early childhood disorders, including intellectual disability, global developmental delay, communication disorders, autism spectrum disorder, attention-deficit/hyperactivity disorder, cerebral palsy, movement disorders, and fetal alcohol spectrum disorder. Burgess and her colleagues sought to determine which tools had the strongest evidence behind them, noting that comparisons were inherently limited by differences in the tested populations, cutoff values, and other factors.
Burgess and her colleagues identified 67 instruments — about a third of those analyzed in the study — “with good discriminative or predictive validity for the screening and assessment of developmental concerns or disability.” Recommended tools were classified by tool type and by patient age groups.
The reason a tool might not be recommended, Burgess said in an email, was for lack of psychometric testing or published evidence, or because the tool was very narrow in scope (eg, covering only a single aspect of a domain), had a small time window for use, or was too new to have been captured in published systematic reviews.
Top Recommendations
Among multi-domain assessment tools, the Bayley Scales of Infant and Toddler Development, the Battelle Developmental Inventory, and the Mullen Scales of Early Learning all emerged as highly recommended. The top diagnostic screening tool for autism was the revised version of Social Attention and Communication Surveillance. For cerebral palsy, the top-rated diagnostic assessment tools were Prechtl’s Qualitative Assessment of General Movements and the Hammersmith Infant Neurological Examination.
Ratifying findings by other groups, the researchers determined the Ages & Stages Questionnaires, Third Edition (ASQ-3) to be the best overall multi-domain screening instrument for early childhood development, thanks to its simplicity and ease of use by a wide range of practitioner types. Burgess and her colleagues noted, however, that the ASQ-3 “will not identify all children with developmental concerns and may incorrectly identify others,” and that it may be more accurate in children 2 years or older.
Patient Care Setting and Cultural, Socioeconomic Factors Are Key
This news organization spoke to two clinicians working with these and similar tools in the United States. Both said that the care setting can also influence the utility of tools, with cultural and socioeconomic factors playing important roles.
Liz Schwandt, PsyD, an early intervention specialist in Los Angeles, said in an interview that children living in high-risk communities in the United States have a larger burden of developmental delays. But for many families in these communities, accessing care can be complex, which is why well-designed, efficient screening tools like ASQ-3 are especially valuable in practice.
“The reality is you have 10 minutes with a lot of families, and if it’s an emergency, you need to know,” she said. “The ASQ-3 has a very broad age range for this type of instrument and can be used by different practitioner types. The reason it’s successful lies in its parent-centric approach and inherent ease of use. It’s quick, and you can score it using pencil and paper while chatting with the parent, and you can use it for multiple siblings in the space of one appointment.”
With very young children, in whom neurodevelopmental concerns often overlap domains, Schwandt said it can be more important to flag a potential problem early and initiate a nonspecific developmental intervention than wait for results from more precise assessments using more specialized tools. These often require multiple, multi-hour appointments, which can be difficult to attain in lower-resource settings in the United States and can delay care, she said.
Liza Mackintosh, MD, a pediatrician at a federally funded healthcare center in Los Angeles that serves mostly publicly insured families, called validated first-line screening tools “incredibly important.” While rates of developmental screenings in pediatric clinics are increasing, there is still room for improvement, she said.
Mackintosh’s institution does not currently use the ASQ-3 but a different screening tool, called the Survey of Well-Being of Young Children (SWYC), that is embedded into the electronic health record. (The SWYC was not among the tools highlighted in Burgess and colleagues’ review.) Like the ASQ-3, it is short and efficient, she said, and it is used in all children in the recommended age ranges.
“Our visits are on average only 20 minutes,” Mackintosh said. “There’s not enough time for an in-depth developmental assessment. We will flag things such as a speech delay, gross motor delay, or fine motor delay” and refer to early intervention centers for more in-depth developmental assessments as needed, she said.
“The biggest job of pediatricians working in communities that are under-resourced is advocating for those early intervention services,” Mackintosh added. “We really see our job as doing the recommended screening, putting that together with what we’re seeing clinically and on history, and then advocating for the right next step or early intervention. Because sometimes the diagnosis is — I don’t want to say irrelevant, but your treatment plan is still going to be the same. So while I don’t have a formal diagnosis yet, the child definitely needs therapies and we’re still going to get those therapies.”
Burgess and her colleagues stressed in their paper the importance of selecting tools that are culturally appropriate for Indigenous communities in Australia, noting that “inappropriate tools may lead to over- or under-recognition of children with developmental concerns.”
Schwandt and Mackintosh said that the same applies in US settings.
“We’ve done a good job translating screening tools into Chinese, Spanish, Vietnamese, and Russian,” Schwandt said. “But some of them assume a way of taking care of children that is not always shared across cultures. The expectations of how children should play and interact with adults can be very different, and there needs to be an understanding of that. Just putting something in Vietnamese doesn’t mean that there are obvious analogues to understanding what the questionnaire is asking.”
Mackintosh concurred. “A lot of times our patients will not do well on screening, even though they’re fine, because they don’t have the exposure to that activity that’s being asked about. So — is the child scribbling with crayons? Is she climbing up a ladder at a playground? In order to be able to do that, you need to have an environment that you are doing it in. The screeners have to really be appropriate for what the child is exposed to. And sometimes our patients just don’t have that exposure.”
Burgess and colleagues’ study was funded by the Australian government and the Merchant Charitable Foundation. The authors disclosed no financial conflicts of interest. Schwandt and Mackintosh disclosed no conflicts of interest related to their comments.
A version of this article appeared on Medscape.com.
A New Way to ‘Smuggle’ Drugs Through the Blood-Brain Barrier
Getting drugs to the brain is difficult. The very thing designed to protect the brain’s environment — the blood-brain barrier (BBB) — is one of the main reasons diseases like Alzheimer’s are so hard to treat.
And even if a drug can cross the BBB, it’s difficult to ensure it reaches specific areas of the brain like the hippocampus, which is located deep within the brain and notoriously difficult to target with conventional drugs.
However, new research shows that novel bioengineered proteins can target neurons in the hippocampus. Using a mouse model, the researchers found that these proteins could be delivered to the hippocampus intranasally — through the nose via a spray.
“This is an urgent topic because many potential therapeutic agents do not readily cross the blood-brain barrier or have limited effects even after intranasal delivery,” said Konrad Talbot, PhD, professor of neurosurgery and pathology at Loma Linda University, Loma Linda, California, who was not involved in the study.
This is the first time a protein drug, which is larger than many drug molecules, has been specifically delivered to the hippocampus, said Noriyasu Kamei, PhD, a professor of pharmaceutical science at Kobe Gakuin University in Kobe, Japan, and lead author of the study.
How Did They Do It?
“Smuggle” may be a flip term, but it’s not inaccurate.
Insulin has the ability to cross the BBB, so the team began with insulin as the vehicle. By attaching other molecules to an insulin fragment, researchers theorized they could create an insulin fusion protein that can be transported across the BBB and into the brain via a process called macropinocytosis.
They executed this technique in mice by fusing florescent proteins to insulin. To treat Alzheimer’s or other diseases, they would want to fuse therapeutic molecules to the insulin for brain delivery — a future step for their research.
Other groups are studying a similar approach using transferrin receptor instead of insulin to shuttle molecules across the BBB. However, the transferrin receptor doesn’t make it to the hippocampus, Kamei said.
A benefit of their system, Kamei pointed out, is that because the method just requires a small piece of insulin to work, it’s straightforward to produce in bacteria. Importantly, he said, the insulin fusion protein should not affect blood glucose levels.
Why Insulin?
Aside from its ability to cross the BBB, the team thought to use insulin as the basis of a fusion protein because of their previous work.
“I found that insulin has the unique characteristics to be accumulated specifically in the hippocampal neuronal layers,” Kamei explained. That potential for accumulation is key, as they can deliver more of a drug that way.
In their past work, Kamei and colleagues also found that it could be delivered from the nose to the brain, indicating that it may be possible to use a simple nasal spray.
“The potential for noninvasive delivery of proteins by intranasal administration to the hippocampal neurons is novel,” said John Varghese, PhD, professor of neurology at University of California Los Angeles (he was not involved in the study). He noted that it’s also possible that this method could be harnessed to treat other brain diseases.
There are other drugs that treat central nervous system diseases, such as desmopressin and buserelin, which are available as nasal sprays. However, these drugs are synthetic hormones, and though relatively small molecules, they do not cross the BBB.
There are also antibody treatments for Alzheimer’s, such as aducanumab (which will soon be discontinued), lecanemab, and donanemab; however, they aren’t always effective and they require an intravenous infusion, and while they cross the BBB to a degree, to bolster delivery to the brain, studies have proposed additional methods like focused ultrasound.
“Neuronal uptake of drugs potentially therapeutic for Alzheimer’s may be significantly enhanced by fusion of those drugs with insulin. This should be a research priority,” said Talbot.
While this is exciting and has potential, such drugs won’t be available anytime soon. Kamei would like to complete the research at a basic level in 5 years, including testing insulin fused with larger proteins such as therapeutic antibodies. If all goes well, they’ll move on to testing insulin fusion drugs in people.
A version of this article first appeared on Medscape.com.
Getting drugs to the brain is difficult. The very thing designed to protect the brain’s environment — the blood-brain barrier (BBB) — is one of the main reasons diseases like Alzheimer’s are so hard to treat.
And even if a drug can cross the BBB, it’s difficult to ensure it reaches specific areas of the brain like the hippocampus, which is located deep within the brain and notoriously difficult to target with conventional drugs.
However, new research shows that novel bioengineered proteins can target neurons in the hippocampus. Using a mouse model, the researchers found that these proteins could be delivered to the hippocampus intranasally — through the nose via a spray.
“This is an urgent topic because many potential therapeutic agents do not readily cross the blood-brain barrier or have limited effects even after intranasal delivery,” said Konrad Talbot, PhD, professor of neurosurgery and pathology at Loma Linda University, Loma Linda, California, who was not involved in the study.
This is the first time a protein drug, which is larger than many drug molecules, has been specifically delivered to the hippocampus, said Noriyasu Kamei, PhD, a professor of pharmaceutical science at Kobe Gakuin University in Kobe, Japan, and lead author of the study.
How Did They Do It?
“Smuggle” may be a flip term, but it’s not inaccurate.
Insulin has the ability to cross the BBB, so the team began with insulin as the vehicle. By attaching other molecules to an insulin fragment, researchers theorized they could create an insulin fusion protein that can be transported across the BBB and into the brain via a process called macropinocytosis.
They executed this technique in mice by fusing florescent proteins to insulin. To treat Alzheimer’s or other diseases, they would want to fuse therapeutic molecules to the insulin for brain delivery — a future step for their research.
Other groups are studying a similar approach using transferrin receptor instead of insulin to shuttle molecules across the BBB. However, the transferrin receptor doesn’t make it to the hippocampus, Kamei said.
A benefit of their system, Kamei pointed out, is that because the method just requires a small piece of insulin to work, it’s straightforward to produce in bacteria. Importantly, he said, the insulin fusion protein should not affect blood glucose levels.
Why Insulin?
Aside from its ability to cross the BBB, the team thought to use insulin as the basis of a fusion protein because of their previous work.
“I found that insulin has the unique characteristics to be accumulated specifically in the hippocampal neuronal layers,” Kamei explained. That potential for accumulation is key, as they can deliver more of a drug that way.
In their past work, Kamei and colleagues also found that it could be delivered from the nose to the brain, indicating that it may be possible to use a simple nasal spray.
“The potential for noninvasive delivery of proteins by intranasal administration to the hippocampal neurons is novel,” said John Varghese, PhD, professor of neurology at University of California Los Angeles (he was not involved in the study). He noted that it’s also possible that this method could be harnessed to treat other brain diseases.
There are other drugs that treat central nervous system diseases, such as desmopressin and buserelin, which are available as nasal sprays. However, these drugs are synthetic hormones, and though relatively small molecules, they do not cross the BBB.
There are also antibody treatments for Alzheimer’s, such as aducanumab (which will soon be discontinued), lecanemab, and donanemab; however, they aren’t always effective and they require an intravenous infusion, and while they cross the BBB to a degree, to bolster delivery to the brain, studies have proposed additional methods like focused ultrasound.
“Neuronal uptake of drugs potentially therapeutic for Alzheimer’s may be significantly enhanced by fusion of those drugs with insulin. This should be a research priority,” said Talbot.
While this is exciting and has potential, such drugs won’t be available anytime soon. Kamei would like to complete the research at a basic level in 5 years, including testing insulin fused with larger proteins such as therapeutic antibodies. If all goes well, they’ll move on to testing insulin fusion drugs in people.
A version of this article first appeared on Medscape.com.
Getting drugs to the brain is difficult. The very thing designed to protect the brain’s environment — the blood-brain barrier (BBB) — is one of the main reasons diseases like Alzheimer’s are so hard to treat.
And even if a drug can cross the BBB, it’s difficult to ensure it reaches specific areas of the brain like the hippocampus, which is located deep within the brain and notoriously difficult to target with conventional drugs.
However, new research shows that novel bioengineered proteins can target neurons in the hippocampus. Using a mouse model, the researchers found that these proteins could be delivered to the hippocampus intranasally — through the nose via a spray.
“This is an urgent topic because many potential therapeutic agents do not readily cross the blood-brain barrier or have limited effects even after intranasal delivery,” said Konrad Talbot, PhD, professor of neurosurgery and pathology at Loma Linda University, Loma Linda, California, who was not involved in the study.
This is the first time a protein drug, which is larger than many drug molecules, has been specifically delivered to the hippocampus, said Noriyasu Kamei, PhD, a professor of pharmaceutical science at Kobe Gakuin University in Kobe, Japan, and lead author of the study.
How Did They Do It?
“Smuggle” may be a flip term, but it’s not inaccurate.
Insulin has the ability to cross the BBB, so the team began with insulin as the vehicle. By attaching other molecules to an insulin fragment, researchers theorized they could create an insulin fusion protein that can be transported across the BBB and into the brain via a process called macropinocytosis.
They executed this technique in mice by fusing florescent proteins to insulin. To treat Alzheimer’s or other diseases, they would want to fuse therapeutic molecules to the insulin for brain delivery — a future step for their research.
Other groups are studying a similar approach using transferrin receptor instead of insulin to shuttle molecules across the BBB. However, the transferrin receptor doesn’t make it to the hippocampus, Kamei said.
A benefit of their system, Kamei pointed out, is that because the method just requires a small piece of insulin to work, it’s straightforward to produce in bacteria. Importantly, he said, the insulin fusion protein should not affect blood glucose levels.
Why Insulin?
Aside from its ability to cross the BBB, the team thought to use insulin as the basis of a fusion protein because of their previous work.
“I found that insulin has the unique characteristics to be accumulated specifically in the hippocampal neuronal layers,” Kamei explained. That potential for accumulation is key, as they can deliver more of a drug that way.
In their past work, Kamei and colleagues also found that it could be delivered from the nose to the brain, indicating that it may be possible to use a simple nasal spray.
“The potential for noninvasive delivery of proteins by intranasal administration to the hippocampal neurons is novel,” said John Varghese, PhD, professor of neurology at University of California Los Angeles (he was not involved in the study). He noted that it’s also possible that this method could be harnessed to treat other brain diseases.
There are other drugs that treat central nervous system diseases, such as desmopressin and buserelin, which are available as nasal sprays. However, these drugs are synthetic hormones, and though relatively small molecules, they do not cross the BBB.
There are also antibody treatments for Alzheimer’s, such as aducanumab (which will soon be discontinued), lecanemab, and donanemab; however, they aren’t always effective and they require an intravenous infusion, and while they cross the BBB to a degree, to bolster delivery to the brain, studies have proposed additional methods like focused ultrasound.
“Neuronal uptake of drugs potentially therapeutic for Alzheimer’s may be significantly enhanced by fusion of those drugs with insulin. This should be a research priority,” said Talbot.
While this is exciting and has potential, such drugs won’t be available anytime soon. Kamei would like to complete the research at a basic level in 5 years, including testing insulin fused with larger proteins such as therapeutic antibodies. If all goes well, they’ll move on to testing insulin fusion drugs in people.
A version of this article first appeared on Medscape.com.
FROM PNAS
Is Pimavanserin a Better Option for Parkinson’s Psychosis?
PHILADELPHIA —
In the first prospective comparison of the two antipsychotics in this patient population, pimavanserin yielded significant improvement across all parameters of efficacy without worsening motor symptoms and was very well tolerated, said study investigator Amey Mane, MD, Sun Pharma Laboratories, Mumbai, India.
Psychosis occurs in about 50% patients with Parkinson’s disease and is a major risk factor for hospitalization, nursing home placement, and mortality.
Antipsychotics are used to treat Parkinson’s disease psychosis, but evidence for the efficacy of quetiapine is inconsistent and clozapine requires regular monitoring for agranulocytosis, said Dr. Mane. Cholinergic blockade by these drugs can also increase non-motor symptoms such as constipation, drooling, and cognitive impairment.
Pimavanserin is an oral 5-HT2A inverse agonist and antagonist and the only Food and Drug Administration–approved medication for Parkinson’s disease psychosis, he said. The drug was approved in 2016, and its label was updated in 2023 to clarify that it can be used to treat patients with Parkinson’s disease psychosis, who also have dementia.
“To the best of our understanding, this is the first completed prospective study of pimavanserin with an active comparator, quetiapine,” in Parkinson’s disease psychosis, he said.
The findings were presented in a late-breaking abstract session at the International Congress of Parkinson’s Disease and Movement Disorders (MDS) 2024.
Primary Outcome at 56 Days
The assessor-blinded study enrolled 247 patients with Parkinson’s disease for at least 1 year, who were Hoehn and Yahr stage 3 or higher, with hallucinations and/or delusions on a stable dose of Parkinson’s disease medication for at least 4 weeks. The average duration of psychosis was 1.2 years.
Patients were randomly assigned to receive daily pimavanserin 34 mg or quetiapine 25-200 mg for 56 days and evaluated at baseline and days 14, 28, 42, and 56.
The mean change in Scale for the Assessment of Positive Symptoms–Parkinson’s disease (SAPS-PD) nine-item total scores improved from baseline in both groups at all visits (P < .0001) and was significantly greater at 42 days with pimavanserin than with quetiapine (−7.15 vs −6.33; P = .029).
The primary outcome of mean change in SAPS-PD total score at day 56 was −9.64 in the pimavanserin group and −8.37 in the quetiapine group (P = .008). The between-group difference was −1.27, and the upper bound of the 95% CI (−2.77 to 0.24) was lower than the prespecified margin of 0.9, demonstrating noninferiority, Dr. Mane said.
Secondary Endpoints and Safety
Pimavanserin was associated with significantly greater improvement than quetiapine for the following secondary outcomes:
- SAPS-Hallucinations and Delusions at day 42 (mean, −12.70 vs −11.40; P = .009) and day 56 (mean, −17.00 vs −15.60; P = .007)
- SAPS-Hallucinations at day 42 (mean, −5.61 vs −4.75; P = .01) and day 56 (mean, −7.33 vs −6.52; P = .02)
- Clinical Global Impression-Improvement score at day 56 (−1.90 vs −1.59; P = .01)
- Scales for Outcomes in Parkinson’s disease (SCOPA) scores for nighttime sleep at day 14 (−1.12 vs −0.85; P = .03) and SCOPA daytime wakefulness at day 28 (−2.42 vs −1.70; P = .01)
Treatment-emergent adverse events (TEAEs) were reported in 7.5% and 13.5% of the pimavanserin and quetiapine groups, respectively.
Five TEAEs, all of mild intensity, were reported as related to study drugs: Pyrexia (1), headache (1), and nasopharyngitis (2) with pimavanserin and headache (1) with quetiapine, Dr. Mane said. There was one unrelated fatal stroke in the quetiapine group. No drug discontinuations occurred because of TEAEs.
Delayed Onset of Action?
During a discussion of the results, Hubert Fernandez, MD, director, Center for Neurological Restoration, Cleveland Clinic in Ohio, asked whether the investigators observed a difference in onset between the two drugs.
“Our general impression in the United States is that pimavanserin has a slower uptake in efficacy as compared with quetiapine. If it [quetiapine] works, it works the next day or the day after, whereas with pimavanserin you have to wait for a week or 2. I was just wondering if that’s validated or just anecdotal experience,” he said.
Dr. Mane said the study showed no difference in efficacy at 14 days and greater improvement in efficacy between days 14 and 56.
Another attendee pointed out that quetiapine is particularly good at inducing sleep and asked whether some of the observed differences, especially early on, were due to the need to rapidly titrate quetiapine to induce sleep and get the sleep-wake cycle back on track.
“We did discuss this with most of our investigators, and they gave the same reason. It’s the titration with the quetiapine, and that’s why it’s seen in the early parts,” said Dr. Mane.
Reached for comment, Regina Katzenschlager, MD, Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders, Klinik Donaustadt, Vienna, Austria, said the majority of drugs commonly used for other types of psychosis cannot be used in PD because of motor worsening.
“Quetiapine is one of the very, very few options we have to treat people with Parkinson’s psychosis because it leads to little, if any, worsening and is the best tolerated,” she said. “Everything else is almost absolutely contraindicated. So that’s why an additional drug — this one has a slightly different mechanism — is incredibly helpful in the clinic because not everyone responds to quetiapine.”
Dr. Katzenschlager pointed out that pimavanserin is not approved in Europe and that the present study was conducted for regulatory purposes in India.
Dr. Mane is an employee of Sun Pharma Laboratories. Dr. Katzenschlager reported having no relevant financial relationships.
A version of this article appeared on Medscape.com.
PHILADELPHIA —
In the first prospective comparison of the two antipsychotics in this patient population, pimavanserin yielded significant improvement across all parameters of efficacy without worsening motor symptoms and was very well tolerated, said study investigator Amey Mane, MD, Sun Pharma Laboratories, Mumbai, India.
Psychosis occurs in about 50% patients with Parkinson’s disease and is a major risk factor for hospitalization, nursing home placement, and mortality.
Antipsychotics are used to treat Parkinson’s disease psychosis, but evidence for the efficacy of quetiapine is inconsistent and clozapine requires regular monitoring for agranulocytosis, said Dr. Mane. Cholinergic blockade by these drugs can also increase non-motor symptoms such as constipation, drooling, and cognitive impairment.
Pimavanserin is an oral 5-HT2A inverse agonist and antagonist and the only Food and Drug Administration–approved medication for Parkinson’s disease psychosis, he said. The drug was approved in 2016, and its label was updated in 2023 to clarify that it can be used to treat patients with Parkinson’s disease psychosis, who also have dementia.
“To the best of our understanding, this is the first completed prospective study of pimavanserin with an active comparator, quetiapine,” in Parkinson’s disease psychosis, he said.
The findings were presented in a late-breaking abstract session at the International Congress of Parkinson’s Disease and Movement Disorders (MDS) 2024.
Primary Outcome at 56 Days
The assessor-blinded study enrolled 247 patients with Parkinson’s disease for at least 1 year, who were Hoehn and Yahr stage 3 or higher, with hallucinations and/or delusions on a stable dose of Parkinson’s disease medication for at least 4 weeks. The average duration of psychosis was 1.2 years.
Patients were randomly assigned to receive daily pimavanserin 34 mg or quetiapine 25-200 mg for 56 days and evaluated at baseline and days 14, 28, 42, and 56.
The mean change in Scale for the Assessment of Positive Symptoms–Parkinson’s disease (SAPS-PD) nine-item total scores improved from baseline in both groups at all visits (P < .0001) and was significantly greater at 42 days with pimavanserin than with quetiapine (−7.15 vs −6.33; P = .029).
The primary outcome of mean change in SAPS-PD total score at day 56 was −9.64 in the pimavanserin group and −8.37 in the quetiapine group (P = .008). The between-group difference was −1.27, and the upper bound of the 95% CI (−2.77 to 0.24) was lower than the prespecified margin of 0.9, demonstrating noninferiority, Dr. Mane said.
Secondary Endpoints and Safety
Pimavanserin was associated with significantly greater improvement than quetiapine for the following secondary outcomes:
- SAPS-Hallucinations and Delusions at day 42 (mean, −12.70 vs −11.40; P = .009) and day 56 (mean, −17.00 vs −15.60; P = .007)
- SAPS-Hallucinations at day 42 (mean, −5.61 vs −4.75; P = .01) and day 56 (mean, −7.33 vs −6.52; P = .02)
- Clinical Global Impression-Improvement score at day 56 (−1.90 vs −1.59; P = .01)
- Scales for Outcomes in Parkinson’s disease (SCOPA) scores for nighttime sleep at day 14 (−1.12 vs −0.85; P = .03) and SCOPA daytime wakefulness at day 28 (−2.42 vs −1.70; P = .01)
Treatment-emergent adverse events (TEAEs) were reported in 7.5% and 13.5% of the pimavanserin and quetiapine groups, respectively.
Five TEAEs, all of mild intensity, were reported as related to study drugs: Pyrexia (1), headache (1), and nasopharyngitis (2) with pimavanserin and headache (1) with quetiapine, Dr. Mane said. There was one unrelated fatal stroke in the quetiapine group. No drug discontinuations occurred because of TEAEs.
Delayed Onset of Action?
During a discussion of the results, Hubert Fernandez, MD, director, Center for Neurological Restoration, Cleveland Clinic in Ohio, asked whether the investigators observed a difference in onset between the two drugs.
“Our general impression in the United States is that pimavanserin has a slower uptake in efficacy as compared with quetiapine. If it [quetiapine] works, it works the next day or the day after, whereas with pimavanserin you have to wait for a week or 2. I was just wondering if that’s validated or just anecdotal experience,” he said.
Dr. Mane said the study showed no difference in efficacy at 14 days and greater improvement in efficacy between days 14 and 56.
Another attendee pointed out that quetiapine is particularly good at inducing sleep and asked whether some of the observed differences, especially early on, were due to the need to rapidly titrate quetiapine to induce sleep and get the sleep-wake cycle back on track.
“We did discuss this with most of our investigators, and they gave the same reason. It’s the titration with the quetiapine, and that’s why it’s seen in the early parts,” said Dr. Mane.
Reached for comment, Regina Katzenschlager, MD, Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders, Klinik Donaustadt, Vienna, Austria, said the majority of drugs commonly used for other types of psychosis cannot be used in PD because of motor worsening.
“Quetiapine is one of the very, very few options we have to treat people with Parkinson’s psychosis because it leads to little, if any, worsening and is the best tolerated,” she said. “Everything else is almost absolutely contraindicated. So that’s why an additional drug — this one has a slightly different mechanism — is incredibly helpful in the clinic because not everyone responds to quetiapine.”
Dr. Katzenschlager pointed out that pimavanserin is not approved in Europe and that the present study was conducted for regulatory purposes in India.
Dr. Mane is an employee of Sun Pharma Laboratories. Dr. Katzenschlager reported having no relevant financial relationships.
A version of this article appeared on Medscape.com.
PHILADELPHIA —
In the first prospective comparison of the two antipsychotics in this patient population, pimavanserin yielded significant improvement across all parameters of efficacy without worsening motor symptoms and was very well tolerated, said study investigator Amey Mane, MD, Sun Pharma Laboratories, Mumbai, India.
Psychosis occurs in about 50% patients with Parkinson’s disease and is a major risk factor for hospitalization, nursing home placement, and mortality.
Antipsychotics are used to treat Parkinson’s disease psychosis, but evidence for the efficacy of quetiapine is inconsistent and clozapine requires regular monitoring for agranulocytosis, said Dr. Mane. Cholinergic blockade by these drugs can also increase non-motor symptoms such as constipation, drooling, and cognitive impairment.
Pimavanserin is an oral 5-HT2A inverse agonist and antagonist and the only Food and Drug Administration–approved medication for Parkinson’s disease psychosis, he said. The drug was approved in 2016, and its label was updated in 2023 to clarify that it can be used to treat patients with Parkinson’s disease psychosis, who also have dementia.
“To the best of our understanding, this is the first completed prospective study of pimavanserin with an active comparator, quetiapine,” in Parkinson’s disease psychosis, he said.
The findings were presented in a late-breaking abstract session at the International Congress of Parkinson’s Disease and Movement Disorders (MDS) 2024.
Primary Outcome at 56 Days
The assessor-blinded study enrolled 247 patients with Parkinson’s disease for at least 1 year, who were Hoehn and Yahr stage 3 or higher, with hallucinations and/or delusions on a stable dose of Parkinson’s disease medication for at least 4 weeks. The average duration of psychosis was 1.2 years.
Patients were randomly assigned to receive daily pimavanserin 34 mg or quetiapine 25-200 mg for 56 days and evaluated at baseline and days 14, 28, 42, and 56.
The mean change in Scale for the Assessment of Positive Symptoms–Parkinson’s disease (SAPS-PD) nine-item total scores improved from baseline in both groups at all visits (P < .0001) and was significantly greater at 42 days with pimavanserin than with quetiapine (−7.15 vs −6.33; P = .029).
The primary outcome of mean change in SAPS-PD total score at day 56 was −9.64 in the pimavanserin group and −8.37 in the quetiapine group (P = .008). The between-group difference was −1.27, and the upper bound of the 95% CI (−2.77 to 0.24) was lower than the prespecified margin of 0.9, demonstrating noninferiority, Dr. Mane said.
Secondary Endpoints and Safety
Pimavanserin was associated with significantly greater improvement than quetiapine for the following secondary outcomes:
- SAPS-Hallucinations and Delusions at day 42 (mean, −12.70 vs −11.40; P = .009) and day 56 (mean, −17.00 vs −15.60; P = .007)
- SAPS-Hallucinations at day 42 (mean, −5.61 vs −4.75; P = .01) and day 56 (mean, −7.33 vs −6.52; P = .02)
- Clinical Global Impression-Improvement score at day 56 (−1.90 vs −1.59; P = .01)
- Scales for Outcomes in Parkinson’s disease (SCOPA) scores for nighttime sleep at day 14 (−1.12 vs −0.85; P = .03) and SCOPA daytime wakefulness at day 28 (−2.42 vs −1.70; P = .01)
Treatment-emergent adverse events (TEAEs) were reported in 7.5% and 13.5% of the pimavanserin and quetiapine groups, respectively.
Five TEAEs, all of mild intensity, were reported as related to study drugs: Pyrexia (1), headache (1), and nasopharyngitis (2) with pimavanserin and headache (1) with quetiapine, Dr. Mane said. There was one unrelated fatal stroke in the quetiapine group. No drug discontinuations occurred because of TEAEs.
Delayed Onset of Action?
During a discussion of the results, Hubert Fernandez, MD, director, Center for Neurological Restoration, Cleveland Clinic in Ohio, asked whether the investigators observed a difference in onset between the two drugs.
“Our general impression in the United States is that pimavanserin has a slower uptake in efficacy as compared with quetiapine. If it [quetiapine] works, it works the next day or the day after, whereas with pimavanserin you have to wait for a week or 2. I was just wondering if that’s validated or just anecdotal experience,” he said.
Dr. Mane said the study showed no difference in efficacy at 14 days and greater improvement in efficacy between days 14 and 56.
Another attendee pointed out that quetiapine is particularly good at inducing sleep and asked whether some of the observed differences, especially early on, were due to the need to rapidly titrate quetiapine to induce sleep and get the sleep-wake cycle back on track.
“We did discuss this with most of our investigators, and they gave the same reason. It’s the titration with the quetiapine, and that’s why it’s seen in the early parts,” said Dr. Mane.
Reached for comment, Regina Katzenschlager, MD, Karl Landsteiner Institute for Neuroimmunological and Neurodegenerative Disorders, Klinik Donaustadt, Vienna, Austria, said the majority of drugs commonly used for other types of psychosis cannot be used in PD because of motor worsening.
“Quetiapine is one of the very, very few options we have to treat people with Parkinson’s psychosis because it leads to little, if any, worsening and is the best tolerated,” she said. “Everything else is almost absolutely contraindicated. So that’s why an additional drug — this one has a slightly different mechanism — is incredibly helpful in the clinic because not everyone responds to quetiapine.”
Dr. Katzenschlager pointed out that pimavanserin is not approved in Europe and that the present study was conducted for regulatory purposes in India.
Dr. Mane is an employee of Sun Pharma Laboratories. Dr. Katzenschlager reported having no relevant financial relationships.
A version of this article appeared on Medscape.com.
FROM MDS 2024