SUMMARY
# Migraine Cortical Hyperexcitability and Alzheimer's Disease Risk: Longitudinal Mechanism Study
## Background and Rationale
This longitudinal clinical study investigates the mechanistic relationship between migraine-associated cortical hyperexcitability and Alzheimer's disease (AD) risk through cortical spreading depression (CSD) pathways. Growing epidemiological evidence suggests migraineurs have altered AD risk profiles, but underlying neurobiological mechanisms remain unclear. CSD, the patho
METHODOLOGY NOTES
Phase 1 (Months 1-6): Recruit 400 participants: 200 migraine patients (≥2 attacks/month, aura present in ≥50%) and 200 age-matched controls. Conduct comprehensive baseline assessments including medical history, Montreal Cognitive Assessment (MoCA), and establish informed consent. Phase 2 (Months 7-12): Perform baseline multimodal neuroimaging using 3T MRI with diffusion tensor imaging, arterial spin labeling, and glymphatic function assessment via gadolinium-based contrast studies. Collect CSF via lumbar puncture and blood samples for amyloid-β42/40 ratio, phosphorylated tau-181, neurofilament light chain, and inflammatory markers (IL-1β, TNF-α, CGRP). Phase 3 (Years 1-10): Conduct annual follow-up visits including cognitive testing battery (neuropsychological assessment, episodic memory tasks), repeat neuroimaging every 2 years, and biomarker collection annually. Implement continuous ambulatory EEG monitoring (72-hour periods quarterly) using high-density electrode arrays to detect CS