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 significantcognitive impairment as determined by a mini-mental status examination (MMSE) score ≥ 26;

3. Due to the effect of reproductive hormones on autonomic regulation, sleep andcognition, 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 InternationalClassification of Sleep Disorders (3rd Ed.);

2. Subjective sleep efficiency less than 80% and/or awakening earlier than desired ifbefore 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. sWASOwill include time spent awake after sleep onset before final awakening + time spentawake 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 InternationalClassification of Sleep Disorders (3rd Ed.);

2. Subjective sleep efficiency greater than 80%;

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 insomniagroup on sex and age (±3 years).

Exclusion Criteria:

1. Sleep disorders other than insomnia (restless legs syndrome, parasomnias, REMbehavior disorder, circadian rhythm sleep-wake disorder, sleep apnea by STOPquestionnaire 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 16);

6. Unstable or serious medical conditions;

7. Diabetes;

8. Current, or use within the past month, of psychoactive, hypnotic, stimulant oranalgesic medications (except occasionally);

9. Use of medications that interfere with NA system activity including B-blockers,selective serotonin and norepinephrine reuptake inhibitors (SNRIs) and selectivenorepinephrine-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 lightexposure such as significant cataracts, narrow-angle glaucoma or blindness;

13. History of heart conditions (i.e. arrhythmia, coronary artery disease, angina, heartfailure);

14. Shift work or other types of self-imposed irregular sleep schedules;

15. BMI > 30 kg/m2;

16. History of habitual smoking (6 or more cigarettes/week) or caffeine consumption > 400 mg/day.