Cognitive impairment and structural brain changes in patients with clinically isolated syndrome at high risk for multiple sclerosis

Abstract

Patients with clinically isolated syndrome (CIS), unlike those with multiple sclerosis (MS), have a selective cognitive impairment which is not consistently related to structural brain changes. Our objective was to characterize a profile of cognitive impairment and its association with structural brain changes in patients with CIS who are at high risk of developing MS. Patients with CIS at high risk for MS on interferon-beta (n = 51) and age-, gender-, and education-matched controls (n = 44) underwent comprehensive neuropsychological testing and MRI brain scan with voxel-based morphometry. The CIS group had lower cognitive performance in verbal and nonverbal memory, information processing speed/attention/working memory, and executive and visuo-spatial functions compared to controls (p ≤ 0.040). Lower cognitive performance was present in 18-37 and 14-26% of patients with CIS at high risk for MS depending on the criteria used. Brain volume was reduced predominantly in fronto-temporal regions and the thalamus in the CIS group (p ≤ 0.019). Cognitive performance was not associated with structural brain changes except for the association between worse visuo-spatial performance and lower white matter volume in the CIS group (β = 0.29; p = 0.042). Our results indicated that patients with CIS at high risk for MS may have a pattern of lower cognitive performance and regional brain atrophy similar to that found in patients with MS. Lower cognitive performance may be present in up to one-third of patients with CIS at high risk for MS, but, unlike patients with MS, variability in their cognitive performance may lead to a lack of consistent associations with structural brain changes.

Cognitive clinico‐radiological paradox in early stages of multiple sclerosis

“…Four of these studies also examined the relationships between global or regional brain atrophy and cognitive measures but found no associations. 2,[24][25][26] Other studies did not find associations between MRI and cognitive measures presumably due to the small sample size and heterogeneity of studied cohorts. 17,[19][20][21] This study has several limitations.…”

“…For example, in five cross‐sectional18, 23, 24, 25, 26 and two longitudinal studies,2, 38 which included between 43 and 81 patients in very early stages of MS, no significant associations between MRI lesion burden and cognitive measures were reported. Four of these studies also examined the relationships between global or regional brain atrophy and cognitive measures but found no associations 2, 24, 25, 26. Other studies did not find associations between MRI and cognitive measures presumably due to the small sample size and heterogeneity of studied cohorts 17, 19, 20, 21…”

“…Findings from this study could help elucidate the reason for the lack of associations found in the literature between brain MRI and cognitive metrics in MS cohorts with a low disease burden. For example, in five crosssectional 18,[23][24][25][26] and two longitudinal studies, 2,38 which included between 43 and 81 patients in very early stages of MS, no significant associations between MRI lesion burden and cognitive measures were reported. Four of these studies also examined the relationships between global or regional brain atrophy and cognitive measures but found no associations.…”

“…Even though most previous studies have shown a relationship between lesion burden or brain atrophy on MRI and cognitive impairment, there are still a number of studies that did not report such associations. 2,[17][18][19][20][21][22][23][24][25][26] In addition, the magnitude of reported associations varies wildly between studies. 1,3,27 By further examining these inconsistencies, the interpretation of associations between structural and cognitive metrics can possibly be improved by identifying contextual determinants of the strength of these associations.…”

Clinical trials for multiple sclerosis: Outcome measures and impact on cognitive function

“…16 Several early studies showed an inverse association between cognitive ability and lesion volume or number on conventional MRI. [18][19][20] In addition, the magnitude of the association was highly variable among studies. [18][19][20] In addition, the magnitude of the association was highly variable among studies.…”