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| ID | Type | Description | Link |
|---|---|---|---|
| R01AG068001 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Aging (NIA) | NIH |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Time in Bed Restriction | Experimental | Time in Bed (TIB) restriction of 85% of habitual TIB. |
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| Control | Active Comparator | Participants will follow their typical sleep schedule consistent with measured average sleep and wake times. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Mean change in delta activity during sleep | Mean change in delta electroencephalographic power (1-4 Hz) during non-rapid eye movement sleep | Baseline and 4 weeks |
| Amyloid positivity status | Amyloid positivity above or below established cutoffs assessed with Pittsburgh Compound B positron emission tomography |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UPMC Western Psychiatric Hospital | Pittsburgh | Pennsylvania | 15213 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41715219 | Derived | 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;27(1):237. doi: 10.1186/s13063-026-09505-w. |
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The investigators will prepare de-identified data sets comprising all of the data collected for this project and make those available to other investigators through NIH data repositories
Data will be made available upon publication of the primary aims within 2 years of study completion.
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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.
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Data collection and data reduction will be performed by sleep technicians and staff who are blind to study hypotheses and the randomization assignment.
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| Sleep Schedule | Behavioral | Participants will maintain their typical sleep schedule for 4-weeks. |
|
| Baseline |
| Mean change in Sleep Efficiency | Mean change in the proportion of time in bed spent sleeping | Baseline and 4 weeks |
| Mean percent signal change in medial prefrontal activation | Mean percent signal change in medial prefrontal cortex activation during a memory encoding task | Baseline and 4 weeks |
| Medial prefrontal-Hippocampal Connectivity | Change in the correlation between medial prefrontal activity and hippocampal activity during memory encoding assessed with functional magnetic resonance imaging during awake rest | Baseline and 4 weeks |
| Mean change in medial temporal-Hippocampal Connectivity | Mean change in | Baseline and 4 weeks |
| mean change in plasma amyloid-beta composite score | mean change in amyloid-beta levels in plasma | Baseline and 4 weeks |
| Mean change in response time on executive function tasks | Computerized executive function task mean response time in milliseconds | Baseline and 4 weeks |
| Mean change in accuracy on executive function tasks | Computerized executive function task mean percent accuracy | Baseline and 4 weeks |
| Apolipoprotein (ApoE) e4 allele carrier status | presence of the e4 apolipoprotein based on genetic testing | Baseline |
| Cognitive status based on neuropsychological adjudication | Cognitive status of healthy control or mild cognitive impairment | Baseline |
| Clinical insomnia status | Diagnosis of insomnia based on clinical cutoffs with self-reported sleep questionnaires | Baseline |
| Preclinical Alzheimer's cognitive composite score | Mean Change in Performance on the Preclinical Alzheimer's Cognitive Composite | 4 weeks |
| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D060825 | Cognitive Dysfunction |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D003072 | Cognition Disorders |
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| ID | Term |
|---|---|
| D013995 | Time |
| ID | Term |
|---|---|
| D055585 | Physical Phenomena |
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