In people with Alzheimer’s, blood flow problems in the brain, head, and body get worse as the disease gets worse, and this seems to be tied to a chemical in the blood called nitric oxide—meaning the whole body’s blood vessels might be failing together, not just the brain.

Measure cerebral, extracranial, and peripheral circulation (e.g., via Doppler, MRI, plethysmography) and systemic nitric oxide bioavailability (e.g., plasma nitrite/nitrate, endothelial function) in a cohort of Alzheimer’s patients stratified by standardized disease severity (e.g., MMSE, CDR) to test for parallel progression and correlation.

Track changes in circulatory impairments and nitric oxide levels over time in Alzheimer’s patients to determine if worsening vascular metrics consistently parallel disease progression.

Compare circulatory and nitric oxide profiles between Alzheimer’s patients and age-matched non-demented controls to determine if vascular impairments are uniquely linked to disease presence and severity.

Test whether vascular dysfunction and nitric oxide depletion co-evolve with amyloid/tau pathology progression in a controlled model.

Determine if Alzheimer’s-associated molecules (e.g., Aβ oligomers) directly reduce nitric oxide production or bioavailability in vascular cells.