Noradrenergic Dysregulation, Sleep and Cognition in Older Adults with Insomnia
This study investigates the relationship between the noradrenergic (NA) system, sleep quality, and cognitive function in older adults with insomnia - a population at elevated risk for Alzheimer's disease-related dementias (ADRD) - compared to age and sex matched controls with normal sleep. The study characterizes NA function through multiple approaches: measuring 24-hour plasma levels of norepinephrine (NE) and its brain metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG); evaluating central NA system response using the clonidine suppression test (a presynaptic α2 adrenoreceptor agonist that reduces locus coeruleus NA activity; and employing pupillometry as a non-invasive marker of autonomic function. To explore NA function's mechanistic role in insomnia, the study uses an intervention with bright light exposure to enhance daytime NA activity, with the goal of improving both sleep quality and cognitive performance.
• Age ≥ 55 years;
• Independent in activities of daily living and without clinically significant cognitive impairment as determined by a mini-mental status examination (MMSE) score ≥ 26;
• Due to the effect of reproductive hormones on autonomic regulation, sleep and cognition, women will be postmenopausal;
• time spent in bed not greater than 8.5 hours;
• Sedentary, defined as participation in exercise of moderate intensity for less than 30 minutes per day and less than two times per week on a regular basis.
• average daily light exposure indicative of indoor environments (from questionnaire).
• Meet criteria for chronic insomnia disorder according to the International Classification of Sleep Disorders (3rd Ed.);
• Subjective sleep efficiency less than 80% and/or awakening earlier than desired if before 6 AM for ≥3 nights/week in the previous 4 weeks;
• Subjective WASO (sWASO) ≥ 60 minutes for ≥3 nights/week in previous 4 weeks. sWASO will include time spent awake after sleep onset before final awakening + time spent awake in bed attempting to sleep after the final awakening;
• global PSQI score greater than 5;
• average daily light exposure indicative of indoor environments (from questionnaire).
• No history of chronic or short-term insomnia disorder according to the International Classification of Sleep Disorders (3rd Ed.);
• Subjective sleep efficiency greater than 80%;
• Subjective mean total sleep time of 6.5 hours to 8 hours;
• Habitual bedtime of 9PM-midnight;
• PSQI score ≤ 5. Participants in the control group will be matched with the insomnia group on sex and age (±3 years).