In people around 78 years old, the worse their Alzheimer’s gets, the less blood flows to their brain and major arteries in their neck and leg — and this isn’t just because they’re older, less active, or have less muscle.

Measure cortical cerebral blood flow, internal carotid artery flow, and femoral artery flow in a cohort of 78-year-olds stratified by Alzheimer’s disease severity (e.g., MMSE or CDR scores), while controlling for age, physical activity (via accelerometry), and muscle volume (via DEXA or MRI), to test for linear trends across severity levels.

Track the same 78-year-old individuals over time as their Alzheimer’s progresses, measuring blood flow changes in the brain and arteries at multiple time points to determine if reductions in flow correlate with worsening disease severity, while controlling for changes in activity and muscle mass.

Compare blood flow in 78-year-olds with severe Alzheimer’s to matched controls without Alzheimer’s, ensuring identical age, physical activity levels, and muscle volume, to isolate whether disease severity alone predicts reduced flow.

Analyze blood flow differences across Alzheimer’s severity subgroups (e.g., preclinical, mild, moderate, severe) in a single cohort of 78-year-olds, using regression models to test for dose-response relationships while adjusting for confounders.

Use existing medical records to compare historical blood flow estimates (e.g., from prior imaging or Doppler studies) in 78-year-olds with documented Alzheimer’s progression, against controls, while extracting proxy data for physical activity and muscle volume.