Slow-wave Sleep Enhancement in Those at Risk for Alzheimer's Disease: Links With Memory, Excitotoxicity, and Plasma A-beta
University of Pittsburgh
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.
Eligibility
- Age range
- 65–85 years
- Sex
- All
- Healthy volunteers
- Yes
Inclusion Criteria: 1. Age 65-85. 2. 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. 3. Self-reported normal or corrected-to-normal visual and auditory acuity. Exclusion Criteria: 1. Shift work involving night shift or regular work within the hours of 12am and 6am. 2. Presence of a chronic condition that significantly affects sleep. 3. Severe psychiatric condition including major depressive dis…
Interventions
- BehavioralTime in Bed Restriction
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.
- BehavioralSleep Schedule
Participants will maintain their typical sleep schedule for 4-weeks.
Location
- UPMC Western Psychiatric HospitalPittsburgh, Pennsylvania