UPMC Western Psychiatric Hospital
Pittsburgh, Pennsylvania, 15213, United States
NCT Number: NCT05138848
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.
Looking for future studies?
Notify Me65 year–85 year
All sexes
Interventional
Early Phase 1
Pittsburgh, Pennsylvania, 15213, United States
Healthy volunteers accepted: Yes
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
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.
Participants will maintain their typical sleep schedule for 4-weeks.
Time frame: Baseline and 4 weeks
Slow oscillation electroencephalographic power (0.5-1 Hz) during non-rapid eye movement sleep
Time frame: Baseline and 4 weeks
Change in mean percent signal change of the hippocampus during memory encoding assessed with functional magnetic resonance imaging
Time frame: Baseline and 4 weeks
Change in mean amyloid-beta detected in the plasma in the morning
Time frame: Baseline and 4 weeks
Mean change in percent correct memory
Time frame: Baseline and 4 weeks
Mean change in delta electroencephalographic power (1-4 Hz) during non-rapid eye movement sleep
Time frame: Baseline
Amyloid positivity above or below established cutoffs assessed with Pittsburgh Compound B positron emission tomography
Time frame: Baseline and 4 weeks
Mean change in the proportion of time in bed spent sleeping
Time frame: Baseline and 4 weeks
Mean percent signal change in medial prefrontal cortex activation during a memory encoding task
Time frame: Baseline and 4 weeks
Change in the correlation between medial prefrontal activity and hippocampal activity during memory encoding assessed with functional magnetic resonance imaging during awake rest
Time frame: Baseline and 4 weeks
Mean change in
Time frame: Baseline and 4 weeks
mean change in amyloid-beta levels in plasma
Time frame: Baseline and 4 weeks
Computerized executive function task mean response time in milliseconds
Time frame: Baseline and 4 weeks
Computerized executive function task mean percent accuracy
Time frame: Baseline
presence of the e4 apolipoprotein based on genetic testing
Time frame: Baseline
Cognitive status of healthy control or mild cognitive impairment
Time frame: Baseline
Diagnosis of insomnia based on clinical cutoffs with self-reported sleep questionnaires
Time frame: 4 weeks
Mean Change in Performance on the Preclinical Alzheimer's Cognitive Composite
University of Pittsburgh
Other
Slow-wave Sleep Enhancement in Those at Risk for Alzheimer's Disease: Links With Memory, Excitotoxicity, and Plasma A-beta
Acronym: ALPS
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View the official ClinicalTrials.gov record (opens in a new tab)This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.
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