Abstract
The cognitive abilities of older persons vary greatly, even among those with similar amounts of Alzheimer disease (AD) pathology, suggesting differences in neural reserve. Although its neurobiologic basis is not well understood, reserve may reflect differences in the ability to compensate for the deleterious effects of pathology by recruiting alternative or additional brain networks to perform a specific task. If this is an effective compensatory strategy, then involvement of additional cognitive systems may help maintain function in other cognitive systems despite the accumulation of pathology. OBJECTIVE: We tested the hypothesis that processing resources, specifically perceptual speed and working memory, modify the associations of AD pathology with other cognitive systems. METHOD: A total of 103 older participants of the Rush Memory and Aging Project underwent detailed annual clinical evaluations and brain autopsy. Five cognitive systems including perceptual speed, working memory, semantic memory, visuospatial abilities, and episodic memory were assessed proximate to death, and AD pathology including tau tangles and amyloid load were quantified postmortem. RESULTS: In multiple regression models adjusted for age, sex, and education, processing resources reduced the associations of tangles with other cognitive systems, such that persons with higher levels of perceptual speed and working memory performed better on semantic memory and visuospatial abilities despite the burden of tangles. Perceptual speed also reduced the associations of amyloid with semantic memory, visuospatial abilities, and episodic memory. CONCLUSION: These findings suggest that processing resources may help compensate for the deleterious effects of Alzheimer disease pathology on other cognitive systems in older persons.