RecruitingNot ApplicableNCT04100057

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


Sponsor

Stanford University

Enrollment

150 participants

Start Date

Aug 31, 2021

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 50 YearsMax Age: 90 Years

Plain Language Summary

Simplified for easier understanding

This study investigates how sleep problems and difficulty regulating emotions are connected to behavioral and psychiatric symptoms in people with early-to-moderate Alzheimer's disease. It combines brain imaging, sleep assessments, and questionnaires to better understand what drives these symptoms — with the aim of developing better treatments. **You may be eligible if...** - You are between 50 and 90 years old - You have early-stage memory impairment (Clinical Dementia Rating 0.5 or 1.0) or a diagnosis from an Alzheimer's research center - You have been struggling with sleep problems for at least 3 months that cause daytime problems (Insomnia Severity Index score of 10 or higher) - You have behavioral or mood-related symptoms (neuropsychiatric symptoms) - You have a caregiver or study partner willing to assist with the study - You live within about 60 miles of Stanford University - You are fully vaccinated for COVID-19 **You may NOT be eligible if...** - Your dementia is severe (Mini-Mental State Exam score below 20) - You have bipolar disorder, psychosis, or a history of alcohol/substance abuse - You have untreated severe sleep apnea - You are currently receiving psychotherapy for sleep or depression Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

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Interventions

BEHAVIORALCognitive Behavioral Therapy for Insomnia (CBT-I)

CBT-I improves sleep through a combination of behavioral interventions (stimulus control (SC), sleep restriction (SR)), cognitive therapy (CT) as well as additional components such as mindfulness training and sleep hygiene education. SC is an intervention that re-establishes the connection between the bed/bedroom with sleep to help develop a more consistent sleep/wake pattern. SR leads to higher quality sleep by reducing excessive time spent in bed to the actual amount of sleep, thereby creating mild sleep deprivation and increasing the homeostatic sleep drive. Like CT for other disorders, CT for insomnia targets maladaptive thoughts and cognitions that may interfere with sleep.

BEHAVIORALDesensitization Therapy for insomnia (DT-I)

DT-I is a quasidesensitization treatment presented as a means of eliminating the "conditioned arousal," which prolongs nocturnal awakenings. DT-I has been validated as an active-placebo control condition. Therapists help each DT-I recipient develop a chronological 12-item hierarchy of common activities he/she does on awakening at night (e.g., opening eyes, clock watching). Therapists also help them develop 6 imaginal scenes of themselves engaged in neutral activities (e.g., reading the newspaper). Each session, DT-I recipients are taught to pair neutral scenes with items on the 12-item hierarchy so, by the end of the sixth session, all hierarchy items have been practiced with therapist assistance. Each session, the exercise is tape recorded and the patient is given this tape locked in a player. The patients are told to practice their exercises at home once each day, no less than 2 hours before bedtime, but to avoid using the tape or exercise during sleep periods.


Locations(1)

Andrea Goldstein-Piekarski, PhD

Palo Alto, California, United States

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NCT04100057


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