Cognitive Reserve Proxies, Alzheimer Pathologies, and Cognition

Abstract BackgroundLimited information is available regarding which of the commonly used cognitive reserve (CR) proxies are more appropriate to precisely reflect moderation effect for the relationship between a specific Alzheimer’s disease (AD) pathology and cognitive decline. We examined the moderating effects of the frequently used four CR proxies [i.e., education, premorbid intelligence quotient (pIQ), occupational complexity (OC), and lifetime cognitive activity (LCA)] on the relationships between various in vivo AD pathologies and cognitive decline. MethodsThis study included 361 older adults (268 cognitively unimpaired, 52 mild cognitive impairment with beta-amyloid (Aβ) deposition, 41 AD dementia with Aβ deposition). All participants underwent multi-modal brain imaging including [11C] Pittsburgh Compound B positron emission tomography (PET), [18F] Fluorodeoxyglucose-PET, and magnetic resonance imaging to measure AD pathologies as well as comprehensive clinical and neuropsychological assessments. Information on education, pIQ estimated with an adult reading test, OC, and LCA was obtained. The Consortium to Establish a Registry for Alzheimer's Disease neuropsychological battery total score (CERAD-TS) was used as the cognitive measure. We used linear regression model predicting cognition to examine the interactions of each CR proxy and each AD pathology.ResultsAmong the CR proxies, only education significantly moderated the relationship between Aβ deposition and CERAD-TS. Education, pIQ, and LCA, but not OC, showed moderating effect on the relationship between AD-signature cerebral hypometabolism and CERAD-TS. In contrast, only OC had a significant moderating effect on the relationship between cortical atrophy of the AD-signature regions and CERAD-TS. ConclusionsThe present findings suggest that the proposed CR proxies have different moderating effects on the relationships between specific AD pathologies and cognitive decline. To investigate CR or related issues, it is necessary to select a proper CR proxy considering the target brain pathology.