Circadian-Vascular-Metabolic Syndrome (CVMS) Intervention Trial

SUMMARY

# Circadian-Vascular-Metabolic Syndrome (CVMS) Intervention Trial: Detailed Experiment Description ## Background and Rationale Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and frontotemporal dementia, represent a growing public health burden affecting millions globally. Emerging evidence suggests that disruptions in circadian rhythm regulation, vascular homeostasis, and metabolic function converge to accelerate neurodegeneration through common pathogenic mech

METHODOLOGY NOTES

**Phase 1: Screening and Baseline Assessment (Weeks -4 to 0)** • Screen 240 participants aged 50-75 with mild cognitive impairment and metabolic dysfunction • Inclusion: MMSE 24-28, HbA1c 6.0-8.5%, resting BP 130-160/80-100 mmHg, BMI 25-35 • Exclusion: diabetes medication changes <3 months, sleep disorders, shift work • Baseline assessments: 7-day actigraphy, vascular ultrasound (carotid IMT, FMD), metabolic panel (glucose, insulin, lipids), neuropsychological battery (MoCA, TMT-A/B, verbal fluency) • Circadian biomarkers: salivary melatonin and cortisol (6 timepoints over 24h) • Brain MRI with DTI and resting-state fMRI **Phase 2: Randomization and Intervention Initiation (Week 1)** • Randomize 180 eligible participants (1:1:1) to three arms using block randomization (n=60 each) • Arm 1: Circadian optimization (light therapy 10,000 lux 30min morning + melatonin 3mg evening) • Arm 2: Vascular-metabolic intervention (structured exercise 150min/week + Mediterranean diet) • Arm 3: Combin