Noradrenergic Dysregulation, Sleep and Cognition in Older Adults With Insomnia

Inclusion Criteria:

1. Age ≥ 55 years;
2. Independent in activities of daily living and without clinically significant cognitive impairment as determined by a mini-mental status examination (MMSE) score ≥ 26;
3. Due to the effect of reproductive hormones on autonomic regulation, sleep and cognition, women will be postmenopausal;
4. time spent in bed not greater than 8.5 hours;
5. 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.
6. average daily light exposure indicative of indoor environments (from questionnaire).

Inclusion criteria for the insomnia group:

1. Meet criteria for chronic insomnia disorder according to the International Classification of Sleep Disorders (3rd Ed.);
2. Subjective sleep efficiency less than 85% and/or awakening earlier than desired if before 6 AM for ≥3 nights/week in the previous 4 weeks;
3. 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;
4. global PSQI score greater than 5;
5. average daily light exposure indicative of indoor environments (from questionnaire).

Inclusion criteria for the control group:

1. No history of chronic or short-term insomnia disorder according to the International Classification of Sleep Disorders (3rd Ed.);
2. Subjective sleep efficiency greater than 85%;
3. Subjective mean total sleep time of 6.5 hours to 8 hours;
4. Habitual bedtime of 9PM-midnight;
5. PSQI score ≤ 5. Participants in the control group will be matched with the insomnia group on sex and age (±3 years).

Exclusion Criteria:

1. Sleep disorders other than insomnia (restless legs syndrome, parasomnias, REM behavior disorder, circadian rhythm sleep-wake disorder, sleep apnea by STOP questionnaire and apnea hypopnea index (AHI) ≥ 15 by home sleep apnea test;
2. habitual bedtime before 9pm or morning awakening before 5am;
3. History of neurological disorders;
4. History of psychiatric disorders;
5. A Beck depression inventory ((BDI-II) score greater than 19);
6. Unstable or serious medical conditions;
7. Prediabetes and diabetes (HbA1C ≥ 5.7)
8. Current, or use within the past month, of psychoactive, hypnotic, stimulant or analgesic medications (except occasionally);
9. Use of medications that interfere with NA system activity including B-blockers, selective serotonin and norepinephrine reuptake inhibitors (SNRIs) and selective norepinephrine-dopamine reuptake inhibitors (NDRIs);
10. Hormone replacement therapy;
11. Use of medications that affects pupil diameter and responses to light (i.e. antihistamines, anticholinergics, benzodiazepines, narcotics for pain;
12. History of visual abnormalities that may interfere with pupillary responses to light exposure such as significant cataracts, narrow-angle glaucoma or blindness;
13. History of heart conditions (i.e. arrhythmia, coronary artery disease, angina, heart failure);
14. Shift work or other types of self-imposed irregular sleep schedules;
15. BMI \> 35 kg/m2;
16. History of habitual smoking (6 or more cigarettes/week) or caffeine consumption \> 400 mg/day.

17.Use of weight-loss medications