SUMMARY
# Sleep Disruption and Alzheimer's Disease — mechanism and intervention
## Background and Rationale
Sleep disturbances represent one of the earliest detectable biomarkers in Alzheimer's Disease (AD), often manifesting years before cognitive symptoms emerge. This longitudinal clinical study investigates the bidirectional relationship between sleep disruption and AD pathogenesis, examining how altered sleep architecture accelerates amyloid-beta accumulation and tau pathology while simultaneously b
METHODOLOGY NOTES
Phase 1 (Months 1-6): Recruit 300 cognitively normal adults aged 60-75 with family history of AD or APOE4 carrier status. Conduct comprehensive baseline assessments including 3-night polysomnography, actigraphy for 2 weeks, amyloid-PET and tau-PET imaging, lumbar puncture for CSF biomarkers (Aβ42/40, p-tau181, p-tau217), and neuropsychological battery. Phase 2 (Months 7-12): Stratify participants by sleep disruption severity using sleep efficiency <85% and slow-wave sleep <15% as cutoffs. Randomize 150 participants with significant sleep disruption to intervention arms: CBT-I (n=50), CPAP therapy for those with AHI>15 (n=50), or low-dose trazodone 50mg (n=50). Control group (n=150) receives sleep hygiene education. Phase 3 (Months 13-24): Implement interventions with monthly compliance monitoring. Repeat polysomnography at 6 and 12 months post-intervention. Conduct interim CSF sampling at 12 months. Phase 4 (Months 25-36): Final comprehensive assessment battery identical to baseline. P