Differential effects of brain maintenance and cognitive reserve on age-related cognitive decline

Age-related cognitive changes can be influenced by both brain maintenance (BM), which refers to the relative absence over time of changes in neural resources or neuropathologic changes, and cognitive reserve (CR), which encompasses brain processes that allow for better-than-expected behavioral performance given the degree of life-course related brain changes. This study evaluated the effects of age, BM, and CR on longitudinal changes over two visits, 5 years apart, in four reference cognitive abilities that capture most of age-related variability. Participants included 254 healthy adults aged 20–80 years at recruitment. Potential BM was estimated using whole brain cortical thickness and white matter mean diffusivity at both visits. Education and IQ (estimated with AMNART) were tested as moderating factors for cognitive changes in the four reference abilities. Consistent with BM, after accounting for age, sex, and baseline performance, individual differences in the preservation of mean diffusivity were associated with relative preservation in the four abilities; differential preservation of cortical thickness was associated with preservation of reasoning, processing speed, and memory. Consistent with CR, after accounting for structural brain changes, higher IQ, but not education, was associated with reduced 5-year decline in reasoning. A similar marginal association was seen for memory but not for processing speed. These results demonstrate that both CR and BM can moderate cognitive changes in healthy aging and that the two mechanisms can make differential contributions to preserved cognition. Significance The theoretical constructs of brain maintenance (BM) and cognitive reserve (CR) are postulated to account for individual differences in age-related cognitive decline. To further understand BM and CR mechanisms, this study used a lifespan sample to examine 5-year changes in four cognitive abilities that comprehensively capture cognitive aging. Education has been the most used life exposure when studying CR, but recent studies suggest that education does not moderate age-related changes in brain and cognition in healthy aging so IQ was also considered. The results demonstrated that BM and CR can both exert unique influences on the same cognitive ability and that the two mechanisms differentially moderate change in the four reference abilities. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This work was supported by the National Institute of Aging (grant numbers K01AG051777, R01AG026158, R01AG038465, and R01AG062578-01A1). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: This study was approved by the Columbia University Institutional Review Board. Participants were only tested after they had a complete understanding of the risks and benefits involved in this research and had provided written consent for participation and use of their data. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data examined in the manuscript are available upon request in deidentified format.