Abstract
Background: Cognitive reserve (CR) could attenuate the impact of the brain burden on the cognition in people with multiple sclerosis (PwMS).Objective: To explore the relationship between CR and structural brain connectivity and investigate their role on cognition in PwMS cognitively impaired (PwMS-CI) and cognitively preserved (PwMS-CP).Methods: In this study, 181 PwMS (71% female; 42.9 ± 10.0 years) were evaluated using the Cognitive Reserve Questionnaire (CRQ), Brief Repeatable Battery of Neuropsychological tests, and MRI. Brain lesion and gray matter volumes were quantified, as was the structural network connectivity. Patients were classified as PwMS-CI (z scores = −1.5 SD in at least two tests) or PwMS-CP. Linear and multiple regression analyses were run to evaluate the association of CRQ and structural connectivity with cognition in each group. Hedges's effect size was used to compute the strength of associations.Results: We found a very low association between CRQ scores and connectivity metrics in PwMS-CP, while in PwMS-CI, this relation was low to moderate. The multiple regression model, adjusted for age, gender, mood, lesion volume, and graph metrics (local and global efficiency, and transitivity), indicated that the CRQ (β = 0.26, 95% CI: 0.17–0.35) was associated with cognition (adj R2 = 0.34) in PwMS-CP (55%). In PwMS-CI, CRQ (β = 0.18, 95% CI: 0.07–0.29), age, and network global efficiency were independently associated with cognition (adj R2 = 0.55). The age- and gender-adjusted association between CRQ score and global efficiency on having an impaired cognitive status was −0.338 (OR: 0.71, p = 0.036) and −0.531 (OR: 0.59, p = 0.002), respectively.Conclusions: CR seems to have a marginally significant effect on brain structural connectivity, observed in patients with more severe clinical impairment. It protects PwMS from cognitive decline regardless of their cognitive status, yet once cognitive impairment has set in, brain damage and aging are also influencing cognitive performance.
Highlights
Cognitive impairment (CI) has been reported in 40–70% of people with multiple sclerosis (PwMS) [1] and it has a negative impact on their quality of life [2]
The group of PwMS-confidence intervals (CI) more frequently presented with a secondary progressive phenotype of the disease, with lower Cognitive Reserve Questionnaire (CRQ) scores and with higher Expanded Disability Status Scale (EDSS) scores
We found significant associations between CRQ and zBRB scores in the entire cohort (β = 0.324, 95% confidence interval, CI: 0.24–0.41, p < 0.001), in PwMS-CP (β = 0.253, 95% CI: 0.17– 0.34, p < 0.001; Hedges’ g: 0.521, 95% CI: 0.22–0.82), and in PwMS-CI (β = 0.300, 95% CI: 0.19–0.41, p < 0.001; Hedges’ g: 0.626, 95% CI: 0.33–0.93)
Summary
Cognitive impairment (CI) has been reported in 40–70% of people with multiple sclerosis (PwMS) [1] and it has a negative impact on their quality of life [2] It is associated with the combined effect of both white matter (WM) and gray matter (GM) damage [3]. Some individuals better maintain their cognitive performance despite the presence of substantial brain damage This clinicopathological dissociation [7] indicates that certain factors protect against cognitive decline, such as the cognitive reserve (CR), understood to be lifelong intellectual enrichment that attenuates the negative effect of MS disease burden on neuropsychological activity [8, 9]. CR seems to preserve brain network functional connectivity counterbalancing the impact of the disruption of WM tracts due to lesions in MS on cognition [12]. Cognitive reserve (CR) could attenuate the impact of the brain burden on the cognition in people with multiple sclerosis (PwMS)
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