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Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Cortical atrophy accelerates as cognitive decline worsens in multiple sclerosis
Anand J C Eijlers1, Iris Dekker2, Martijn D Steenwijk2
1From the Departments of Anatomy & Neurosciences (A.J.C.E., M.D.S., K.A.M., H.E.H., M.M.S., J.J.G.G.), Radiology and Nuclear Medicine (I.D., J.W.P., F.B., H.V.), and Neurology (I.D., B.M.J.U.), Amsterdam Neuroscience, MS Center Amsterdam, Amsterdam UMC, Location VUmc, the Netherlands; and Institutes of Neurology and Healthcare Engineering (F.B.), UCL, London, UK. a.eijlers@amsterdamumc.nl.
Objective:
To determine which pathologic process could be responsible for the acceleration of cognitive decline during the course of multiple sclerosis (MS), using longitudinal structural MRI, which was related to cognitive decline in relapsing-remitting MS (RRMS) and progressive MS (PMS).
Methods:
A prospective cohort of 230 patients with MS (179 RRMS and 51 PMS) and 59 healthy controls was evaluated twice with 5-year (mean 4.9, SD 0.94) interval during which 22 patients with RRMS converted to PMS. Annual rates of cortical and deep gray matter atrophy as well as lesion volume increase were computed on longitudinal (3T) MRI data and correlated to the annual rate of cognitive decline as measured using an extensive cognitive evaluation at both time points.
Results:
The deep gray matter atrophy rate did not differ between PMS and RRMS (-0.82%/year vs -0.71%/year, p = 0.11), while faster cortical atrophy was observed in PMS (-0.87%/year vs -0.48%/year, p < 0.01). Similarly, faster cognitive decline was observed in PMS compared to RRMS (p < 0.01). Annual cognitive decline was related to the rate of annual lesion volume increase in stable RRMS (r = -0.17, p = 0.03) to the rate of annual deep gray matter atrophy in converting RRMS (r = 0.50, p = 0.02) and annual cortical atrophy in PMS (r = 0.35, p = 0.01).
Conclusions:
These results indicate that cortical atrophy and cognitive decline accelerate together during the course of MS. Substrates of cognitive decline shifted from worsening lesional pathology in stable RRMS to deep gray matter atrophy in converting RRMS and to accelerated cortical atrophy in PMS only.
Insights
Cognitive decline in multiple sclerosis (MS) accelerates with disease progression. Cortical atrophy is linked to faster cognitive decline in progressive MS, shifting from lesion volume and deep gray matter atrophy in earlier stages.
Area of Science:
- Neuroscience
- Neurology
- Radiology
Background:
- Multiple Sclerosis (MS) is a chronic neurological disease.
- Cognitive decline is a significant disability in MS patients.
- Understanding the pathological drivers of cognitive decline is crucial for MS management.
Purpose of the Study:
- To identify the pathological processes driving accelerated cognitive decline in Multiple Sclerosis (MS).
- To investigate the relationship between structural MRI changes and cognitive decline in relapsing-remitting MS (RRMS) and progressive MS (PMS).
Main Methods:
- A prospective cohort study of 230 MS patients and 59 controls was conducted.
- Longitudinal 3T MRI scans were used to measure gray matter atrophy and lesion volume over a 5-year interval.
- Cognitive function was assessed extensively at two time points and correlated with MRI-derived rates of change.
Main Results:
- Faster cortical atrophy was observed in PMS compared to RRMS patients.
- Cognitive decline was significantly faster in PMS than in RRMS.
- Cognitive decline correlated with lesion volume increase in stable RRMS, deep gray matter atrophy in converting RRMS, and cortical atrophy in PMS.
Conclusions:
- Cortical atrophy and cognitive decline accelerate concurrently in MS.
- The pathological substrate for cognitive decline evolves throughout the MS disease course.
- These findings highlight the distinct pathological mechanisms underlying cognitive impairment in different MS phenotypes.
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