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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Cognitive Dysfunction; Dementia; Alzheimer Disease

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.

• Study Type: Observational
• Enrollment (Actual): 13435

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3800
      • Monash University
• United States
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Foundation for Atlanta Veterans Education and Research, Inc.
  • Minnesota
    • Minneapolis, Minnesota, United States, 55415
      • Hennepin Healthcare Research Institute
    • Minneapolis, Minnesota, United States, 55455
      • Regents of the University of Minnesota - Advanced Research & Diagnostic
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27109
      • Wake Forest University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

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).

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To prospectively measure plasma AT(N) biomarkers and to identify participant characteristics that are associated with these levels separately in women and men.	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.	In a community population of 21,000 older persons without dementia, we will measure changes in these biomarkers over 7 to 10 years

Collaborators and Investigators

• Sponsor: Anne Murray
• Investigators: Principal Investigator: Anne Murray, MD, MSc, Hennepin Healthcare Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2022
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027

Study Registration Dates

• First Submitted: October 31, 2025
• First Submitted That Met QC Criteria: October 31, 2025
• First Posted (Estimated): November 4, 2025

Study Record Updates

• Last Update Posted (Estimated): November 4, 2025
• Last Update Submitted That Met QC Criteria: October 31, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Tauopathies; Neurodegenerative Diseases; Cognitive Dysfunction; Alzheimer Disease; Dementia
• Other Study ID Numbers: 1RF1AG079397 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No