Sleep and Circadian Dysfunction as Driver of Neurodegeneration

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