Cognitive impairment predicts worsening multiple sclerosis




Cognitive impairment in individuals at the time of multiple sclerosis diagnosis imparts a significantly higher risk for disability progression, transition to secondary progressive disease, and cortical thinning, according to results from a retrospective, 8-year, longitudinal observational study.

The results, note first author Marco Pitteri, PhD, of the University of Verona (Italy) and his colleagues, “confirm and extend previous studies showing that cognitive impairment could represent a clinical marker of more aggressive gray matter pathology,” and also identified cortical thinning as a neuroimaging correlate of cognitive impairment that was detected only at follow-up between the cognitively impaired and cognitively normal patients who were otherwise similar at baseline.


The study involved 78 consecutive patients with relapsing-remitting multiple sclerosis who underwent neurologic exams during 2015 at a single center in Italy. They all had a cognitive assessment and an MRI scan at the time of diagnosis and at least 8 years of clinical follow-up, including neurologic examination every 6 months. At the time of enrollment into the study, most patients were taking immunomodulatory therapy: 38 were treated with interferon beta-1a, 14 with interferon beta-1b, 15 with glatiramer acetate, and 6 with azathioprine, and 5 were untreated.

At baseline, 39 cognitively normal patients had a mean age of about 36 years, none had conversion to secondary progressive disease, and just 15% had disability progression on the Expanded Disability Status Scale (EDSS). Cortical thickness changed a mean of 3.6%.

The 26 patients with mild cognitive impairment (classified as failure of up to two tests on the Brief Repeatable Battery) were 38 years old at baseline, and only 4 transitioned to secondary progressive disease. Just over half experienced EDSS progression (an average of 0.85 points) and cortical thickness changed by an average of 17%.

The 13 remaining patients with severe cognitive impairment at baseline (three or more failed tests) were about 44 years of age on average and nearly all (92%) experienced EDSS progression, which averaged 1.31 points. Cortical thickness also changed a mean of 34%. Relapsing disease converted to secondary progressive disease in a total of six patients with severe cognitive impairment.

Patients with severe cognitive impairment at baseline had more severe white matter lesion volume at baseline than did others, but there was no difference in the accumulation of white matter lesions during follow-up between patients with normal cognition, mild cognitive impairment, and severe cognitive impairment, which corroborates previous studies. However, the predictive ability of early cognitive impairment in identifying patients with disability progression on the EDSS and cortical thinning “is in line with several previous longitudinal studies showing a strong relationship between gray matter damage and the development of cognitive impairment,” the authors wrote (Brain. 2012 Oct;135[Pt 10]:2952-61 and Neurology. 2013 Nov 12;81[20]:1759-67).

Although the administration of neuropsychological batteries is time consuming and requires expertise, the authors argued that their results “underline the need of using extended screening neuropsychological batteries instead of brief screening batteries, at least at the time of diagnosis, in order to increase the probability to detect even mild forms of cognitive impairment as early as possible in the disease course.”

Read the full paper online in Multiple Sclerosis (2016 Aug 15. doi: 10.1177/1352458516665496).

Recommended Reading

Zinbryta approved by FDA for relapsing forms of multiple sclerosis
MDedge Internal Medicine
Smoking causes worse outcome in MS
MDedge Internal Medicine
Teriflunomide effective for faster-advancing MS
MDedge Internal Medicine
Oral contraceptive efficacy unaffected by dimethyl fumarate
MDedge Internal Medicine
Real-world data favor dimethyl fumarate, fingolimod for MS
MDedge Internal Medicine
Exercise improves sleep and may improve cognitive/physical function in MS
MDedge Internal Medicine
Alemtuzumab beneficial for MS patients of African descent
MDedge Internal Medicine
Real-world MS relapse rate is low for dimethyl fumarate
MDedge Internal Medicine
Siponimod shows promise through 24 months in relapsing-remitting MS
MDedge Internal Medicine
Hemophilia drugs top Medicaid spending per prescription
MDedge Internal Medicine