Alzheimer?s disease and related dementias (ADRD) represent a growing health concern as the global population ages. While many promising treatments for ADRD have been developed and tested, they have largely failed to prevent disease onset or slow disease progression in older adults. However, research has found that subtle signs of ADRD pathology are detectable decades before disease onset. To develop treatments that can slow the progression of ADRD before intractable deterioration of the brain has taken place, we will need to better understand the lifespan trajectory of cognitive, biological and brain aging and develop biomarkers that can connect subtle signs of individual differences in midlife aging to ADRD in late life. In the F99 phase of the proposed research, the candidate will characterize signatures of midlife brain aging and investigate potential surrogate biomarkers using a multi-faceted approach in the Dunedin Study, a population representative birth cohort now in midlife. Specifically, the candidate will investigate the ability of widely used measures of risk for ADRD in older adults, including white matter hyperintensities and brain age, to measure accelerated cognitive and biological aging in midlife. The candidate will then develop a longitudinal measure from 20 years of biological aging across 19 biomarkers to investigate the consequences of accelerated pace of biological aging on individual differences in the structural integrity of the brain in midlife. Then the candidate will use childhood exposure to the neurotoxin lead, a known risk factor for ADRD, to further examine the utility of these candidate surrogate biomarkers to capture risk-related features of midlife brain aging. In the K00 phase of the proposed research, the candidate will utilize statistical techniques, developed when creating the pace of biological aging in midlife, to measure correlated decline in brain biomarkers in healthy aging and ADRD in older adults. The proposed research will yield techniques to measure accelerated biological aging in midlife and in older adults, as well as insights into ADRD through application of these measures. Critically, the proposed project will provide a deeper understanding of connections between midlife and late life accelerated aging that will contribute to growing efforts to target ADRD intervention earlier in life.
Findings from the proposed line of research will link accelerated brain and biological aging in midlife to brain aging in older adults with cognitive impairment as well as Alzheimer?s disease and related dementias (ADRD). These findings may help uncover the origins and risk factors for individual differences in brain aging that could help identify those most in need of intervention in midlife as well as help develop novel preventions to target ADRD before disease onset. The long-term goal of this line of research is to lower the global burden of ADRD by advancing our understanding of individual differences in brain aging.
