Modeling MRI Brain Aging in Autosomal Dominant Alzheimer's Disease

Principal Investigator
Peter Millar, PhD
Washington University School of Medicine in St. Louis
St. Louis, MO, USA
About the Research Project
Program
Award Type
Postdoctoral Fellowship
Award Amount
$200,000
Active Dates
July 01, 2022 - June 30, 2025
Grant ID
A2022014F
Goals
We will measure how “old” a person’s brain appears, and test whether these age predictions are older than expected in participants with a rare genetic mutation that causes Alzheimer disease.
Summary
Recent machine learning tools can measure how “old” a person’s brain appears, compared to other healthy brains. In symptomatic Alzheimer’s disease (AD), brains appear older than expected, e.g., a 75-year-old AD brain might resemble a healthy 84-year-old’s brain. We will study people with a rare genetic mutation for early-onset Alzheimer’s disease, to test if their brains begin to appear older as they approach their expected dementia onset. These analyses will evaluate whether clinicians can use this brain-age approach to identify people with very early AD pathology and predict AD risk.
Unique and Innovative
Brain-age gap (BAG) models may yield novel MRI biomarkers of AD progression, but most BAG studies have focused on sporadic Alzheimer disease (AD). Thus, applying BAG to preclinical autosomal dominant AD (ADAD) is a relatively novel approach. We will extend upon recent work in this area by using more comprehensive, multimodal MRI features, which capture more variance in healthy age differences. This approach also allows us to compare functional and structural age predictions to established MRI markers of AD progression.
Foreseeable Benefits
Brain age gap (BAG) estimates may reflect comprehensive, easily-interpretable, non-invasive biomarkers of brain health and may improve sensitivity to Alzheimer disease (AD) over established MRI measures (e.g., hippocampal volume). Thus, they may offer clinical utility as an AD screening or staging tool or as a clinical trial endpoint. This proposal aims to validate BAG by testing whether BAG patterns previously demonstrated in sporadic AD are consistently observed in autosomal dominant AD participants, who are younger and lack most confounding age-related pathologies.
Grants
Related Grants
Alzheimer's Disease Research
Neurostimulation to Improve Depression and Memory in Dementia
Active Dates
July 01, 2024 - June 30, 2027
Principal Investigator
Davide Cappon, PhD
Neurostimulation to Improve Depression and Memory in Dementia
Active Dates
July 01, 2024 - June 30, 2027

Principal Investigator
Davide Cappon, PhD
Alzheimer's Disease Research
Unfolding Alzheimer's Tau Therapies: Near- and Long-Term Approaches
Active Dates
July 01, 2023 - June 30, 2026
Principal Investigator
Paul Seidler, PhD
Unfolding Alzheimer's Tau Therapies: Near- and Long-Term Approaches
Active Dates
July 01, 2023 - June 30, 2026

Principal Investigator
Paul Seidler, PhD
Alzheimer's Disease Research
What is the Best Way to Give tDCS to People with Alzheimer's Disease?
Active Dates
July 01, 2022 - June 30, 2025
Principal Investigator
Carlos Roncero, PhD
What is the Best Way to Give tDCS to People with Alzheimer's Disease?
Active Dates
July 01, 2022 - June 30, 2025

Principal Investigator
Carlos Roncero, PhD