Active — Not RecruitingNot Applicable

Sleep Disturbance and Emotion Regulation Brain Dysfunction as Mechanisms of Neuropsychiatric Symptoms in Alzheimer's Dementia

United States150 participantsStarted 2021-08-31

Plain-language summary

Recent findings suggest that sleep disruption may contribute to the generation and maintenance of neuropsychiatric symptoms including anxiety, depression, agitation, irritation, and apathy while treating sleep disruption reduces these symptoms. Impairments in the neural systems that support emotion regulation may represent one causal mechanism mediating the relationship between sleep and emotional distress. However, this model has not yet been formally tested within a sample of individuals with or at risk for developing Alzheimer's Disease (AD) This proposal aims to test a mechanistic model in which sleep disturbance contributes to neuropsychiatric symptoms through impairments in fronto-limbic emotion regulation function in a sample of individuals at risk for developing, or at an early stage of AD. This study seeks to delineate the causal association between sleep disruption, fronto-limbic emotion regulation brain function, and neuropsychiatric symptoms. These aims will be achieved through a mechanistic, randomized 2-arm controlled trial design. 150 adults experiencing sleep disturbances and who also have cognitive impairment with the presence of at least mild neuropsychiatric symptoms will be randomized to receive either a sleep manipulation (Cognitive Behavioral Therapy for Insomnia CBT-I; n=75) or an active control (n=75). CBT-I improves sleep patterns through a combination of sleep restriction, stimulus control, mindfulness training, cognitive therapy targeting dysfunctional beliefs about sleep, and sleep hygiene education. Neuropsychiatric symptoms, fronto-limbic functioning, and sleep disruption will be assessed at baseline and at the end of the sleep manipulation through functional Magnetic Resonance Imaging (fMRI), clinical interviews, PSG recordings, and self-report questionnaires. Neuropsychiatric symptoms (anxiety and depression) and sleep disturbance (actigraphy, Insomnia Severity Index, and sleep diaries) will be assayed at baseline and each week throughout the sleep manipulation to assess week-to-week changes following an increasing number of CBT-I sessions. Wristwatch actigraphy will be acquired from baseline to the end of the sleep manipulation at week 11. Neuropsychiatric symptoms and sleep will be assessed again at six months post-manipulation.

Who can participate

Age range

50 Years – 90 Years

Sex

ALL

See this in plain English?

AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Exclusion criteria

. A score of 4 or more for the past month on the C-SSRS
. ) A positive endorsement, relative to the past 90 days, in the "Suicide Behavior" section of item #6 (Have you ever done anything, started to do anything, or prepared to do anything to end your life?)

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1This study is focused on understanding the connection between sleep problems, emotion regulation in the brain, and neuropsychiatric symptoms in Alzheimer's and mild cognitive impairment — does my loved one's specific symptom profile, like agitation or sleep disturbances, match what this study is actually looking at?
2Since the trial is listed as 'active not recruiting,' does that mean there's no longer any way to participate, and if so, are there similar follow-on studies or related research programs we should be watching for?
3This appears to be an observational or mechanistic study rather than a treatment trial — so would participating involve any direct benefit to my loved one, or is it primarily contributing to research that might help future patients?
4The study is measuring brain function in the frontal and limbic regions alongside sleep and neuropsychiatric symptoms — what kinds of tests or brain imaging would my loved one need to undergo, and how demanding would that be given their current cognitive state?
5If sleep disturbance turns out to be a key driver of neuropsychiatric symptoms like the researchers suspect, are there existing treatments for insomnia in Alzheimer's patients that my loved one could try now, rather than waiting for findings from a study like this?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Fronto-limbic function

Timeframe: change between baseline and 6 weeks

Neuropsychiatric Symptoms

Timeframe: 6 weeks

Insomnia symptoms

Timeframe: 6 weeks

Trial details

NCT IDNCT04100057

SponsorStanford University

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2026-04-30

View on ClinicalTrials.gov More Alzheimer Disease trials