Cortical atrophy and cognitive decline accelerate together during the course of multiple sclerosis (MS), according to study findings published in Neurology. The researchers found cognitive decline shifted from worsening lesional pathology in stable relapsing-remitting MS (RRMS) to deep gray matter atrophy in converting RRMS and to accelerated cortical atrophy in progressive MS (PMS) only.

A total of 230 patients with MS, including patients with RRMS (n=179) and PMS (n=51), and 59 healthy controls were included in this prospective cohort study. At baseline, mean patient age was 47.7±11.1 years and mean symptom duration was 14.8±8.5 years. Between 2008 and 2012 and between 2014 and 2017, patients were examined using magnetic resonance imaging (MRI) and cognitive evaluations. Per-year cortical and deep gray matter atrophy rates and increases in lesion volumes were correlated to the per-year cognitive decline rate. The Expanded Disability Status Scale was used to assess overall disability in patients with MS.

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There was no difference between patients with PMS and stable RRMS in terms of the annual rate of deep gray matter atrophy (−0.82%/year vs −0.71%/year, respectively; P =.11). A faster cortical atrophy was seen in patients with PMS vs stable RRMS (−0.87%/year vs −0.48%/year, respectively; P <.01). Patients with PMS also had an approximately 3 times higher per-year rate of cognitive decline vs patients with stable, non-converting RRMS (−0.10/year vs −0.03/year, respectively; P <.01).

In patients with stable RRMS, the annual cognitive decline rate was associated with the annual rate of lesion volume increase (r = −0.17; P =.03). Cognitive decline was also associated with the annual deep gray matter atrophy rate in patients with converting RRMS (r = 0.50; P =.02) and the annual cortical atrophy rate in patients with PMS (r = 0.35; P =.01).

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Study limitations included focusing measurements of cortical atrophy and lesions based on T1-weighted and fluid-attenuated inversion recovery imaging, rather than more advanced MRI sequences. The researchers also suggest that it is unclear whether additional factors — other than MS — contributed to the acceleration of cortical atrophy and cognitive decline.

The researcher concluded that these findings expand upon previous findings by longitudinally analyzing changes in MRI measures and portraying a progressive shift in the underlying pathologic substrate of cognitive decline. They add that “future studies should further investigate whether network-guided or local pathologic processes primarily drive the acceleration of cortical neurodegeneration in PMS,” as this future direction may aid in identifying “neuroprotective treatment targets that could slow or even halt this process to preserve cognitive function.”

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Eijlers AJC, Dekker I, Steenwijk MD, et al. Cortical atrophy accelerates as cognitive decline worsens in multiple sclerosis. Neurology. 2019;93(14):e1348-e1359.