Sex-specific Risk Factors and Trajectories of Blood Biomarkers for Alzheimer's Disease and Related Dementias

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.