Cognitive reserve and symptom experience in multiple sclerosis: A buffer to disability progression over time?

Objective: To investigate the possible buffering effect of cognitive reserve on symptom experience for multiple sclerosis (MS) disease course. Design: Secondary analysis of longitudinal data from the North American Research Committee on MS Registry. Setting: Registry study and web-based supplemental survey. Participants: People with MS (N=859). Interventions: Not applicable. Main Outcome Measures: Two health outcome measures, the Symptom Inventory and the Performance Scales, were collected biannually over 1 and 6 years, respectively. Active and passive cognitive reserve was measured using the Stern Leisure Activities and the Sole-Padulles Childhood Enrichment tools, respectively. Linear regression, chi-square, multilevel random-effects modeling, and classification and regression tree modeling were used to compare cross-sectional means, disease course by cognitive reserve, longitudinal trajectories, and active cognitive reserve item endorsement by disability groups, respectively. Results: Patients with high-active reserve had a lesser symptom burden than those with low-active reserve independent of passive reserve (P<.01). Cognitive reserve was associated with course of disease, such that high-active patients were overrepresented among relapsing-remitting patients, and underrepresented among patients with progressive disease (χ²=14.7, P<.03). Longitudinal modeling revealed a significant interaction of active reserve and time in mobility, fatigue, and overall disability in the whole sample (P<.05 in all comparisons). Among patients whose disability trajectories changed over time, active cognitive reserve was associated with less deterioration (P<.001). Passive cognitive reserve evidenced no effect in the longitudinal analyses. Active cognitive reserve scores across disability groups had a similar range but comprised different items, indicating that patients maintain active cognitive reserve with different activities as the disease progresses. Conclusions: Our findings suggest that active cognitive reserve is a buffer for functional limitation across disability groupings. Cognitive reserve may provide an alternative lens for thinking about the disease course of MS, providing a longer "runway" until disability accrual through cortical remodeling. Loss of cognitive reserve may explain the onset of progressive disease in MS.