Aging, Executive Function, Fronto-Parietal Network Cortical Thickness: Insights from Cognitive Reserv

Cognitive reserve (CR) indexes the nonlinear relationship between neurological insult and behavioral change. CR is manifested in both static factors (e.g., childhood environment, education) and modifiable lifestyle factors, (e.g., leisure activities). Detailed investigation of the influence of CR on cortical thickness, which indexes neuropathology, and cognitive functioning could be particularly important in understanding the heterogeneity of Alzheimer's disease (AD). While memory decline is the hallmark of AD, executive functioning (EF) decline often predates memory changes, making EF an important target for investigating CR influences.;The current study examines the relationship of CR and genetic risk for AD (epsilon4) on EF as it relates to fronto-parietal neural network cortical thickness, and memory performance as it relates to medial temporal lobe thickness and hippocampal volume. This study addresses the heterogeneity of CR measurement by examining three different CR factors (CR1=IQ; CR2=IQ, Activities, CR3=IQ, Activities, Health) in 35 healthy elders age 51-84 (19 epsilon4+/16 epsilon4-).;High CR was associated with better cognition. CR2 was associated with memory and CR3 was predictive of EF. High CR was also associated with greater cortical thickness: CR1 with cingulate; CR2 with inferior and superior parietal; and CR3 with insula, inferior and superior parietal.;Across all CR measures, the interaction of epsilon4 and CR was associated with insula, inferior and superior parietal thickness. CR2 and CR3 further revealed interactions within frontal regions: CR1 and CR2 were associated with right parahippocampal gyrus (PHG), CR2 with left hippocampus, and CR3 with left PHG. Some regions showed an 'Additive Benefit', where high CR was particularly beneficial to ?4 carriers, while others showed an 'Additive Detriment', where low CR was particularly detrimental to epsilon4 carriers.;This study also demonstrated that different CR measures yield disparate results. Nevertheless, CR was beneficial to both cognitive functioning and cortical thickness, particularly in epsilon4 carriers. Results are clinically translatable to identify mechanisms to delay the onset of AD.