Aging-related loss of cognitive and brain function are major contributors to ill health. We will investigate determinants and predictors individual differences in neurocognitive aging, from neurodegenerative disorders to successful neurocognitive aging with minimal loss of function. We will consider blood-based biomarkers such as proteomics, metabolomics, transcriptomics, and telomere length; genetic risk scores; structural and functional neuroimaging measures; health- and lifestyle variables such as hypertension, smoking, and physical activity; as well as psychological traits such as personality. Proxies of biological aging will be computed from omics and clinical markers (e.g., frailty scores). We will account for the heterogenous and multifactorial nature of neurocognitive aging and expect to find subgroups of individuals aging through different mechanisms. Main outcome variables will be neurodegenerative disease status, level and change over time in cognitive function, and MRI-assessed brain characteristics. We will leverage the statistical power of UK Biobank in combination with our local longitudinal datasets for improved characterization of aging trajectories. A large focus will be comparing cross-sectional and longitudinal aging estimates. Another will be to identify early predictors of adverse neurocognitive outcomes. Some analyses will employ the full UK Biobank cohort with available cognitive data to establish normative aging trajectories. Other analyses will be limited to subsets with available data on e.g., neuroimaging and/or omics. The proposed research has the potential to increase knowledge on factors that influence the degree and severity of aging-related cognitive decline in the population, as well as protective factors that can contribute to cognitive resilience. Such factors may also serve as predictive biomarkers that can enable early and individualized interventions. Results will be published in peer-reviewed open-access scientific journals.
