Noradrenergic Dysregulation, Sleep and Cognition in Older Adults with Insomnia

Description

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.

Conditions

Insomnia

Study Overview

Study Details

Study overview

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.

Noradrenergic Dysregulation, Sleep and Cognition in Older Adults with Insomnia

Noradrenergic Dysregulation, Sleep and Cognition in Older Adults with Insomnia

Condition
Insomnia
Intervention / Treatment

-

Contacts and Locations

Chicago

Northwestern University Feinberg School of Medicine, Center for Circadian and Sleep Medicine, Chicago, Illinois, United States, 60611

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

For general information about clinical research, read Learn About Studies.

Eligibility 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).
  • 1. Meet criteria for chronic insomnia disorder according to the International Classification of Sleep Disorders (3rd Ed.);
  • 2. 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;
  • 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).
  • 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 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 insomnia group on sex and age (±3 years).
  • 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 16);
  • 6. Unstable or serious medical conditions;
  • 7. Diabetes;
  • 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 \> 30 kg/m2;
  • 16. History of habitual smoking (6 or more cigarettes/week) or caffeine consumption \> 400 mg/day.

Ages Eligible for Study

55 Years to

Sexes Eligible for Study

ALL

Accepts Healthy Volunteers

Yes

Collaborators and Investigators

Northwestern University,

Daniela Grimaldi, MD, PhD, PRINCIPAL_INVESTIGATOR, Northwestern University

Phyllis C Zee, MD, PhD, PRINCIPAL_INVESTIGATOR, Northwestern University

Study Record Dates

2029-08-31