Alzheimer Disease, Cognitive Dysfunction, Dementia
Conditions
Brief summary
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.
Detailed description
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.
Interventions
None listed
Sponsors
Anne Murray
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
65 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To prospectively measure plasma AT(N) biomarkers and to identify participant characteristics that are associated with these levels separately in women and men. | In a community population of 21,000 older persons without dementia, we will measure changes in these biomarkers over 7 to 10 years | We hypothesize that: 1a. There will be sex differences in the cross-sectional biomarker levels, and in their trajectories over time. 1b. Chronic comorbidities and genetic risk factors (APOE ε4, polygenic risk score) will be associated with 'worse' AT(N) biomarker levels (reflecting worse ADRD pathology) at baseline and with a greater increase over time over time, and that these associations will differ between men and women. |
Countries
Australia, United States
Outcome results
None listed