Blood-based ADRD biomarkers show tremendous promise as a non-invasive method to predict and diagnose ADRD. We will measure changes in these biomarkers to determine whether their ability to predict ADRD differs by sex or by other characteristics, and develop a sex-specific ADRD risk score for personalized medicine and clinical trials.

Late-life Alzheimer's disease and related dementias (ADRD) are devastating multifactorial conditions and the major contributors to loss of independence in older age. There is a critical unmet need to identify which individuals are at the great risk of these conditions, thus permitting accurate prognosis and timely preventative interventions to reduce the burden. Yet, while a number of risk factors have been identified for these conditions, sex differences in these associations have rarely been considered. Furthermore, exciting recent advances in blood amyloid, tau and neurodegeneration (AT(N)) biomarkers for ADRD means that they could soon be used as powerful clinical diagnostic and prognostic tools in a personalized medicine approach. However, a number of critical knowledge gaps remain. Importantly, 1) these biomarkers have not been sufficiently examined in longitudinal studies of older community- based populations without diagnosed dementia; 2) it is unclear how participant characteristics such as comorbidities affect the clinical interpretation of these biomarkers; and 3) how their interpretation may differ between men and women. Together, these large knowledge gaps highlight a crucial need to develop the first sex-specific risk score for ADRD that incorporates blood AT(N) biomarkers and ADRD risk factors.

Inclusion Criteria:

We will use de-identified data and biospecimens originally collected for a large binational NIA-funded ASPirin in Reducing Events in the Elderly (ASPREE) randomized clinical trial and ongoing observational follow-up (U19 AG062682) for analysis.

Exclusion Criteria:

None

The data and biospecimens collected for a large-scale study of initially healthy individuals aged 65-98 years from the US and Australia (12,716 whites, 412 blacks, 339 other minorities) with comprehensive annual in-person cognitive assessments, adjudicated clinical outcomes, detailed data on socio-economic status, lifestyle and health factors collected over a median 9+ years, and existing genetic data (APOE4, dementia polygenic risk scores).