Preserving slow-wave brain activity during nonrapid eye movement (NREM) sleep could help protect learning and memory in older adults with Alzheimer disease (AD) pathology, according to study findings published in the journal BMC Medicine.
Previous literature has established an association between severe beta-amyloid-related AD pathology and worse cognitive decline. However, among patients with high beta-amyloid burden, some exhibit better cognitive function than others, possibly due to cognitive reserve factors.
Furthermore, prior research has demonstrated close interactions between slow-wave sleep disruption, cognitive performance, and beta-amyloid burden. For the study, researchers hypothesized that sufficient slow-wave brain activity during NREM sleep is a previously unrecognized source of cognitive reserve mitigating the effects of AD pathology.
The researchers conducted an observational trial in 62 cognitively healthy adults, recruited from the Berkeley Aging Cohort Study, with a mean age of approximately 75 years. They quantified beta-amyloid burden for each participant using Pittsburgh compound B (11C-PiB) positron emission tomography (PET). Half of the participants, whose beta-amyloid burden exceeded a numerical cutoff, were classified as beta-amyloid-positive.
[O]f therapeutic importance, and unlike many other cognitive reserve factors identified to date, sleep may represent a novel modifiable reserve factor and thus a promising treatment target.
Within 2 years post-PET imaging, both groups participated in the sleep observation, during which the researchers conducted polysomnography measurements of brain wave activity, particularly the slower delta waves; eye movements; and chin muscle activity.
Afterward, structural MRI studies were obtained to measure medial prefrontal cortical atrophy. Participants also completed memory tasks to evaluate both sleep-dependent learning and stable (trait-like) recall.
The researchers found that relative power over the full delta-wave spectrum (NREM slow-wave activity) was higher in participants who were beta-amyloid-positive than in those with low beta-amyloid burden (0.73±0.07 vs 0.68±0.08, P =.01). Participants across groups performed similarly on memory tests; but multiple linear regression analysis predicting test scores confirmed a strong interaction effect between pronounced slow-wave activity during NREM sleep and beta-amyloid-positive status (standardized coefficient = 0.64, P =.042).
When controlling for age, sex, body mass index (BMI), physical activity, education, prefrontal gray-matter atrophy, and time lag between PET imaging and the sleep observation, this interaction remained an independent predictor of cognitive reserve, as measured by the memory tests. However, the interaction effect was not present in participants with low beta-amyloid burden, or for REM sleep or nondelta wave activity. It also did not predict trait-like memory task performance, but rather was specific for next-day state-like function.
How slow-wave NREM sleep may protect cognition in adults with high beta-amyloid burden is unclear. Potentially beneficial slow-wave-sleep-dependent processes include normalization of hippocampal synaptic activity, restoration of memory consolidation through hippocampal-neocortical coactivation, and improved glymphatic clearance.
The study included only healthy participants; it is unclear whether these findings are generalizable to adults with AD. The researchers also cautioned that, in this observational study, they could not demonstrate that sleep characteristics caused differences in memory-task performance — only that the association existed.
However, they noted, if sleep quality proves to be causal, “of therapeutic importance, and unlike many other cognitive reserve factors identified to date, sleep may represent a novel modifiable reserve factor and thus a promising treatment target.”
Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.