Sleep Schedule Restriction for Alzheimer's Disease
(ALPS Trial)
Recruiting in Palo Alto (17 mi)
Age: 65+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: University of Pittsburgh
Must not be taking: Antidepressants, Antipsychotics, Anticonvulsants, Steroids
Disqualifiers: Severe psychiatric conditions, CNS diseases, others
No Placebo Group
Trial Summary
What is the purpose of this trial?Dementia caused by Alzheimer's disease affects approximately 5.6 million adults over age 65, with costs expected to rise from $307 billion to $1.5 trillion over the next 30 years. Behavioral interventions have shown promise for mitigating neurodegeneration and cognitive impairments. Sleep is a modifiable health behavior that is critical for cognition and deteriorates with advancing age and Alzheimer's disease. Thus, it is a priority to examine whether improving sleep modifies Alzheimer's disease pathophysiology and cognitive function. Extant research suggests that deeper, more consolidated sleep is positively associated with memory and executive functions and networks that underlie these processes. Preliminary studies confirm that time-in-bed restriction interventions increase sleep efficiency and non-rapid eye movement slow-wave activity (SWA) and suggest that increases in SWA are associated with improved cognitive function. SWA reflects synaptic downscaling predominantly among prefrontal connections. Downscaling of prefrontal connections with the hippocampus during sleep may help to preserve the long-range connections that support memory and cognitive function. In pre-clinical Alzheimer's disease, hyperactivation of the hippocampus is thought to be excitotoxic and is shown to leave neurons vulnerable to further amyloid deposition. Synaptic downscaling through SWA may mitigate the progression of Alzheimer's disease through these pathways. The proposed study will behaviorally increase sleep depth (SWA) through four weeks of time-in-bed restriction in older adults characterized on amyloid deposition and multiple factors associated with Alzheimer's disease risk. This study will examine whether behaviorally enhanced SWA reduces hippocampal hyperactivation, leading to improved task-related prefrontal-hippocampal connectivity, plasma amyloid levels, and cognitive function. This research addresses whether a simple, feasible, and scalable behavioral sleep intervention improves functional neuroimaging indices of excitotoxicity, Alzheimer's pathophysiology, and cognitive performance.
Will I have to stop taking my current medications?
Yes, if you are currently using medications that affect sleep, such as antidepressants, antipsychotics, anticonvulsants, steroids, or sedating drugs used at bedtime, you will need to stop taking them to participate in this trial.
What data supports the effectiveness of the treatment Sleep Schedule Restriction for Alzheimer's Disease?
Research suggests that sleep disturbances are linked to Alzheimer's disease, and addressing these disruptions might help manage the disease. Studies have shown that improving sleep patterns, such as through light therapy, can reduce symptoms like agitation and improve rest-activity rhythms in Alzheimer's patients.
12345Is sleep schedule restriction therapy safe for humans?
The research does not provide specific safety data for sleep schedule restriction therapy, but it discusses the importance of addressing sleep disturbances in Alzheimer's disease, suggesting that managing sleep issues is a valid treatment target.
12467How is the Time in Bed Restriction treatment different from other treatments for Alzheimer's disease?
Time in Bed Restriction is unique because it focuses on improving sleep patterns by limiting the time spent in bed, which may help address sleep disturbances linked to Alzheimer's disease. Unlike medications, this treatment aims to modify the sleep-wake cycle, potentially influencing the progression of the disease by reducing sleep fragmentation and improving overall sleep quality.
12689Eligibility Criteria
This trial is for older adults aged 65-85 with sleep difficulties but without severe psychiatric conditions, heavy alcohol or caffeine consumption, CNS diseases like Alzheimer's, or certain medications that affect sleep. Participants should have normal vision and hearing (with aids if necessary), a tendency to wake up often at night, and not be involved in shift work.Inclusion Criteria
You can see and hear normally or with corrective lenses or aids.
You have trouble sleeping, as shown by your sleep diary and activity tracker, with a low sleep efficiency and long periods of being awake after falling asleep.
I am between 65 and 85 years old.
Exclusion Criteria
You have a score higher than 10 on the Epworth sleepiness test.
You drink more than 14 alcoholic drinks per week or more than 6 drinks at one time.
You have a serious mental health condition like severe depression, panic disorder, substance abuse, or bipolar disorder.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants undergo a time-in-bed restriction intervention to increase sleep efficiency and slow-wave activity
4 weeks
Weekly visits (in-person or virtual)
Follow-up
Participants are monitored for changes in cognitive function and sleep patterns after the intervention
4 weeks
Participant Groups
The study tests whether restricting the time spent in bed can improve deep sleep and cognitive function in older adults. It aims to see if this intervention can reduce brain overactivity related to Alzheimer's disease risk by enhancing slow-wave activity during sleep.
2Treatment groups
Experimental Treatment
Active Control
Group I: Time in Bed RestrictionExperimental Treatment2 Interventions
Time in Bed (TIB) restriction of 85% of habitual TIB.
Group II: ControlActive Control1 Intervention
Participants will follow their typical sleep schedule consistent with measured average sleep and wake times.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
UPMC Western Psychiatric HospitalPittsburgh, PA
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Who Is Running the Clinical Trial?
University of PittsburghLead Sponsor
National Institute on Aging (NIA)Collaborator
References
Sleep and its regulation: An emerging pathogenic and treatment frontier in Alzheimer's disease. [2022]A majority of patients with Alzheimer's disease (AD) experience some form of sleep disruption, including nocturnal sleep fragmentation, increased daytime napping, decreased slow-wave sleep (SWS, stage N3), and decreased rapid-eye-movement sleep (REM). Clinical studies are investigating whether such sleep disturbances are a consequence of the underlying disease, and whether they also contribute to the clinical and pathological manifestations of AD. Emerging research has provided a direct link between several of these sleep disruptions and AD pathophysiology, suggesting that treating sleep disorders in this population may target basic mechanisms of the disease. Here, we provide a comprehensive review of sleep disturbances associated with the spectrum of AD, ranging from the preclinical stages through dementia. We discuss how sleep interacts with AD pathophysiology and, critically, whether sleep impairments can be targeted to modify the disease course in a subgroup of affected AD patients. Ultimately, larger studies that fully utilize new diagnostic and experimental tools will be required to better define the most relevant sleep disturbance to target in AD, the interventions that best modulate this target symptom, and whether successful early intervention can modify AD risk and prevent dementia.
Effect of morning bright light treatment for rest-activity disruption in institutionalized patients with severe Alzheimer's disease. [2019]Disturbances in rest-activity rhythm are prominent and disabling symptoms in Alzheimer's disease (AD). Nighttime sleep is severely fragmented and daytime activity is disrupted by multiple napping episodes. In most institutional environments, light levels are very low and may not be sufficient to enable the circadian clock to entrain to the 24-hour day. The purpose of this randomized, placebo-controlled, clinical trial was to test the effectiveness of morning bright light therapy in reducing rest-activity (circadian) disruption in institutionalized patients with severe AD.
Bright light treatment of behavioral and sleep disturbances in patients with Alzheimer's disease. [2015]The authors tested the hypothesis that evening bright light pulses would improve sleep-wake patterns and reduce agitation in patients with Alzheimer's disease who have severe sundowning (a syndrome of recurring confusion and increased agitation in the late afternoon or early evening) and sleep disorders.
Sleep and Alzheimer disease pathology--a bidirectional relationship. [2022]Factors other than age and genetics may increase the risk of developing Alzheimer disease (AD). Accumulation of the amyloid-β (Aβ) peptide in the brain seems to initiate a cascade of key events in the pathogenesis of AD. Moreover, evidence is emerging that the sleep-wake cycle directly influences levels of Aβ in the brain. In experimental models, sleep deprivation increases the concentration of soluble Aβ and results in chronic accumulation of Aβ, whereas sleep extension has the opposite effect. Furthermore, once Aβ accumulates, increased wakefulness and altered sleep patterns develop. Individuals with early Aβ deposition who still have normal cognitive function report sleep abnormalities, as do individuals with very mild dementia due to AD. Thus, sleep and neurodegenerative disease may influence each other in many ways that have important implications for the diagnosis and treatment of AD.
Increasing walking and bright light exposure to improve sleep in community-dwelling persons with Alzheimer's disease: results of a randomized, controlled trial. [2022]To test the effects of walking, light exposure, and a combination intervention (walking, light, and sleep education) on the sleep of persons with Alzheimer's disease (AD).
The sleep-wake cycle and Alzheimer's disease: what do we know? [2018]Sleep-wake disturbances are a highly prevalent and often disabling feature of Alzheimer's disease (AD). A cardinal feature of AD includes the formation of amyloid plaques, associated with the extracellular accumulation of the amyloid-β (Aβ) peptide. Evidence from animal and human studies suggests that Aβ pathology may disrupt the sleep-wake cycle, in that as Aβ accumulates, more sleep-wake fragmentation develops. Furthermore, recent research in animal and human studies suggests that the sleep-wake cycle itself may influence Alzheimer's disease onset and progression. Chronic sleep deprivation increases amyloid plaque deposition, and sleep extension results in fewer plaques in experimental models. In this review geared towards the practicing clinician, we discuss possible mechanisms underlying the reciprocal relationship between the sleep-wake cycle and AD pathology and behavior, and present current approaches to therapy for sleep disorders in AD.
Development of diagnostic criteria for defining sleep disturbance in Alzheimer's disease. [2017]This article proposes new standards for identifying, defining, and naming sleep/wake cycle disturbances associated with Alzheimer's disease (AD) to aid in more effective research, including the development and testing of potential treatments. Many AD patients develop sleep/wake cycle disturbances associated with distress, depression, and sleep disturbances in the caregiver, as well as early nursing home placement for the patient. The Food and Drug Administration Psychopharmacological Drugs Advisory Committee has emphasized the need for a comprehensive diagnostic system. A key point made by the committee was that behavioral problems associated with dementia (including sleep and chronobiological disturbances) are scientifically and clinically valid targets of pharmacologic treatment. However, current diagnostic criteria preclude development of FDA-acceptable studies of pharmacological interventions because they do not include the required specific indications for treatment. This article attempts to develop better-defined provisional criteria with the goal of promoting epidemiological, physiological, and, especially, pharmacological research on sleep/wake disturbances.
Orexinergic system dysregulation, sleep impairment, and cognitive decline in Alzheimer disease. [2015]Nocturnal sleep disruption develops in Alzheimer disease (AD) owing to the derangement of the sleep-wake cycle regulation pathways. Orexin contributes to the regulation of the sleep-wake cycle by increasing arousal levels and maintaining wakefulness.
Brain amyloid burden, sleep, and 24-hour rest/activity rhythms: screening findings from the Anti-Amyloid Treatment in Asymptomatic Alzheimer's and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration Studies. [2023]To examine in a subsample at the screening phase of a clinical trial of a β-amyloid (Aβ) antibody whether disturbed sleep and altered 24-hour rest/activity rhythms (RARs) may serve as markers of preclinical Alzheimer's disease (AD).