Favorable cardiovascular health, connectome integrity, and ADRD clinical outcomes and pathologic underpinnings in a diverse cohort.

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PROJECT SUMMARY/ABSTRACT As age-specific incidence rates of Alzheimer’s disease and related dementias (ADRD) decline in the US, due, in part, to improvements in cardiovascular health, it is imperative that we study how favorable cardiovascular health promotes successful brain aging. Favorable cardiovascular health quantified using The American Heart Association’s Life’s Simple 7 (LS7) is cited as an ideal metric to study successful brain aging given its role in preserving and promoting late-life cognitive and motor functioning. The limited data that exists on LS7 and brain health focuses on isolated grey matter atrophy or white matter abnormalities, i.e., white matter hyperintensities (WMHs) and infarcts; no study, to date, has employed a multi-modal assessment of brain health as related to cardiovascular health, or taken advantage of advances in the field of connectomics to study brain network integrity via comprehensive maps of neural connections based on neuroimaging data. Considering the contribution of multiple brain structural alterations is critical given that brain changes suffered at one level, e.g., grey matter atrophy or white matter damage in the form of WMHs and infarcts, negatively impact brain structure at another level, e.g., connectivity between brain regions. Applying previously published methods, we will create multi-modal structural connectome integrity matrices of subtle brain alterations and frank damage to address gaps in the literature and determine how LS7 preserves brain health and promotes cognitive and motor functioning in older non-Latino White, Black, and Latino adults. To achieve the overall goal of this study – to determine cardiovascular-connectome relationships that promote brain health in older adults – we will combine biennial neuroimaging data, annual cardiovascular lifestyle and biological LS7 data, and annual cognitive and motor testing on 535 participants of the Rush Memory and Aging Project with up to 12 years of data collection; a subset of whom also have ADRD neuropathological data. Ante-mortem, cross-sectional data will be available from 450 non-Latino Black and 150 Latino participants from two other harmonized Rush cohort studies. Together, this will ensure our success investigating change in connectome integrity and the role of LS7 (Aim 1), the relationship of connectome integrity with cognitive and motor decline, and how it varies by LS7 (Aim 2), whether LS7 modifies associations between neuropathology and connectome integrity (Aim 3), and cross-sectional associates of LS7 and connectome integrity within non-Latino Black and Latino adults, separately (Aim 4). This study’s cross-cutting themes of cardiovascular health, state-of-the-art neuroimaging analytics, comprehensive behavioral assessment, and gold-standard neuropathology will provide a wealth of information never before documented and exert a sustained influence on the field. Specifically, this R01 will identify neuropathological underpinnings of late-life brain network integrity and the role of favorable cardiovascular health and may provide refined MRI targets and specific behavioral outcomes for use in lifestyle interventions with less healthy older adults.