Time-in-bed Restriction in Older Adults With Sleep Difficulties With and Without Risk for Alzheimer's Disease

NCT05138848 | Recruiting Early Phase 1

• 2 other identifiers: STUDY20110278R01AG068001
• Study Type: interventional
• Target: 116
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Mild Cognitive Impairment; Sleep; Cognitive Change; Amyloid; Alzheimer Disease, Late Onset

Outcome Measures

Primary Outcomes (4)

• Mean change in slow-oscillation activity assessed with electroencephalography

  Slow oscillation electroencephalographic power (0.5-1 Hz) during non-rapid eye movement sleep

  Baseline and 4 weeks

• Mean change in Hippocampal Activation

  Change in mean percent signal change of the hippocampus during memory encoding assessed with functional magnetic resonance imaging

  Baseline and 4 weeks

• Change in mean Plasma amyloid-beta 1-42

  Change in mean amyloid-beta detected in the plasma in the morning

  Baseline and 4 weeks

• Overnight memory retention on the AB paired associate task

  Mean change in percent correct memory

  Baseline and 4 weeks

Secondary Outcomes (13)

• Mean change in delta activity during sleep

  Baseline and 4 weeks

• Amyloid positivity status

  Baseline

• Mean change in Sleep Efficiency

  Baseline and 4 weeks

• Mean percent signal change in medial prefrontal activation

  Baseline and 4 weeks

• Medial prefrontal-Hippocampal Connectivity

  Baseline and 4 weeks

Study Arms (2)

Time in Bed Restriction

EXPERIMENTAL

Time in Bed (TIB) restriction of 85% of habitual TIB.

Behavioral: Time in Bed Restriction; Behavioral: Sleep Schedule

Control

ACTIVE COMPARATOR

Participants will follow their typical sleep schedule consistent with measured average sleep and wake times.

Behavioral: Sleep Schedule

Interventions

Time in Bed Restriction BEHAVIORAL

Participants will undergo a 4-week sleep intervention that includes specified in- and out-of-bed times as well as a restriction to their habitual time in bed (average sleep opportunity including naps). This will be truncated equally at the beginning and end of the night.

Time in Bed Restriction

Sleep Schedule BEHAVIORAL

Participants will maintain their typical sleep schedule for 4-weeks.

Control; Time in Bed Restriction

Eligibility Criteria

• Age: 65 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Age 65-85.
• Self-report mean sleep efficiency (the time in bed spent asleep within the time of lights out to final awakening) \< 90% based on diary and actigraphy estimates and wake time after sleep onset \> 20 minutes based on diary and actigraphy estimates.
• Self-reported normal or corrected-to-normal visual and auditory acuity.

You may not qualify if:

• Shift work involving night shift or regular work within the hours of 12am and 6am.
• Presence of a chronic condition that significantly affects sleep.
• Severe psychiatric condition including major depressive disorder, panic disorder, substance use disorders, and alcohol abuse/dependence within the past 6 months, or a lifetime history of a psychotic disorder or bipolar I disorder, based on initial online/phone self-report diagnoses, and subsequently based on a structured psychiatric interview.
• Current use of medications affecting sleep such as antidepressants, antipsychotic medications, anticonvulsants, and steroids.
• Current use of sedating drugs used at bedtime.
• Consumption of \> 14 alcohol drinks per week or \> 6 drinks at a single sitting.
• Consumption of \> 3 caffeine drinks per day.
• Prior diagnosis of a Central nervous system (CNS) disease, such as multiple sclerosis, stroke, Parkinson's disease, Alzheimer's disease, seizure disorder, delirium or dementia, a loss of consciousness \> 24 hours, or traumatic brain injury as identified by the Cumulative Illness Rating Scale for Geriatrics (CIRS). Participants who are diagnosed with Alzheimer's disease based on neuropsychological testing will be excluded.
• Apnea/hypopnea index greater than 15 as determined by one night of Apnea Link Plus screening.
• Metal in the body. Rationale: Due to the nature of magnetic resonance imaging (MRI), participants cannot have any metal implants in their bodies, cannot have worked in a metal shop or been exposed to metal fragments during combat. Metal dental work (e.g. fillings crowns) may be allowed if compatible with the fMRI scanner.
• Claustrophobia. Rationale: Could prevent the participant from completing the MRI scans.
• Severe obesity. BMI \> 40. Rationale: Could prevent the participant from completing the MRI scan.
• Near-miss or prior automobile accident "due to sleepiness" within the past 12 months. Rationale: reduces the risk of sleepiness-related accidents.
• Employed as a commercial driver during the study (for example, bus drivers, train engineers, airplane pilots). Rationale: reduces the risk of sleepiness-related accidents.
• A score below 23 on the Telephone Interview for Cognitive Status. Rationale: This cut-off has been demonstrated to differentiate well between individuals with mild cognitive impairment from individuals with dementia who would have decision making impairments (Seo et al. 2011, Archives of Gerontology and Geriatrics). This ensures that decision making abilities are intact.

Sponsors & Collaborators

• University of Pittsburgh: lead
• National Institute on Aging (NIA): collaborator

Study Sites (1)

UPMC Western Psychiatric Hospital

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Related Publications (1)

• Dong YC, Habte RF, Dessa KM, Fletcher ME, Ianni AM, Lopresti BJ, Aizenstein HJ, Cohen AD, Karikari TK, Weinstein AM, Gebara MA, Wallace ML, Buysse DJ, Wilckens KA. The Alzheimer's Pathways Sleep Study (ALPS): an experimental randomized controlled trial to improve cognition and Alzheimer's pathophysiology through slow-wave sleep. Trials. 2026 Feb 19. doi: 10.1186/s13063-026-09505-w. Online ahead of print.

  PMID: 41715219 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction

Interventions

Time

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders; Cognition Disorders

Intervention Hierarchy (Ancestors)

Physical Phenomena

Central Study Contacts

Kristine Wilckens, PhD.

CONTACT

(412) 586-9434; wilckenska@upmc.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Data collection and data reduction will be performed by sleep technicians and staff who are blind to study hypotheses and the randomization assignment.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Participants will be randomized to one of two intervention groups. The active group will limit their time in bed for 4 weeks by following a consistent sleep schedule with 85% time in bed compared to their baseline time in bed. The control group will not limit their time in bed, but will be asked to maintain their typical sleep schedule consistent with their baseline time in bed.

Study Record Dates

• First Submitted: November 7, 2021
• First Posted: December 1, 2021
• Study Start: January 3, 2022
• Primary Completion: May 31, 2026
• Study Completion: May 31, 2026
• Last Updated: December 19, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will be made available upon publication of the primary aims within 2 years of study completion.

Locations

US (1)