🧫 Experiment Protocol
Clinicalproposed
SUMMARY
# Sleep and Circadian Dysfunction as Driver of Neurodegeneration
## Background and Rationale
This clinical study investigates whether sleep and circadian rhythm disruption actively drives neurodegeneration rather than being merely a symptom. The study employs a longitudinal design with cognitively normal adults at genetic risk for AD (APOE4 carriers).
**Protocol**: 500 participants (ages 50-65, APOE4+, cognitively normal) undergo: (1) 2-week actigraphy + sleep diary at baseline, 12mo, 24mo, 36m
METHODOLOGY NOTES
**Phase 1: Participant Recruitment and Baseline Assessment (Weeks 1-4)**
• Recruit 300 cognitively healthy adults aged 50-75 years through community outreach and medical centers
• Screen participants using Mini-Mental State Examination (MMSE ≥26) and exclude those with existing neurological conditions
• Obtain comprehensive medical history, medication review, and informed consent
• Conduct baseline cognitive assessment using Montreal Cognitive Assessment (MoCA) and neuropsychological battery
• Collect baseline blood samples for biomarker analysis (Aβ40, Aβ42, p-tau181, NfL)
• Perform baseline brain MRI with structural and DTI sequences
**Phase 2: Sleep and Circadian Monitoring (Weeks 5-8)**
• Deploy 14-day actigraphy monitoring using wrist-worn ActiGraph GT9X devices
• Conduct overnight polysomnography (PSG) at sleep laboratory for 2 consecutive nights
• Measure circadian markers: salivary melatonin profiles (6 samples over 24h), core body temperature
• Administer Pittsburgh Sleep Q