Sleep and longitudinal cognitive performance in preclinical and early symptomatic Alzheimer’s disease

Abstract

Sleep monitoring may provide markers for future Alzheimer’s disease; however, the relationship between sleep and cognitive function in preclinical and early symptomatic Alzheimer’s disease is not well understood. Multiple studies have associated short and long sleep times with future cognitive impairment. Since sleep and the risk of Alzheimer’s disease change with age, a greater understanding of how the relationship between sleep and cognition changes over time is needed. In this study, we hypothesized that longitudinal changes in cognitive function will have a non-linear relationship with total sleep time, time spent in non-REM and REM sleep, sleep efficiency and non-REM slow wave activity. To test this hypothesis, we monitored sleep-wake activity over 4–6 nights in 100 participants who underwent standardized cognitive testing longitudinally, APOE genotyping, and measurement of Alzheimer’s disease biomarkers, total tau and amyloid-β42 in the CSF. To assess cognitive function, individuals completed a neuropsychological testing battery at each clinical visit that included the Free and Cued Selective Reminding test, the Logical Memory Delayed Recall assessment, the Digit Symbol Substitution test and the Mini-Mental State Examination. Performance on each of these four tests was Z-scored within the cohort and averaged to calculate a preclinical Alzheimer cognitive composite score. We estimated the effect of cross-sectional sleep parameters on longitudinal cognitive performance using generalized additive mixed effects models. Generalized additive models allow for non-parametric and non-linear model fitting and are simply generalized linear mixed effects models; however, the linear predictors are not constant values but rather a sum of spline fits. We found that longitudinal changes in cognitive function measured by the cognitive composite decreased at low and high values of total sleep time (P < 0.001), time in non-REM (P < 0.001) and REM sleep (P < 0.001), sleep efficiency (P < 0.01) and <1 Hz and 1–4.5 Hz non-REM slow wave activity (P < 0.001) even after adjusting for age, CSF total tau/amyloid-β42 ratio, APOE ε4 carrier status, years of education and sex. Cognitive function was stable over time within a middle range of total sleep time, time in non-REM and REM sleep and <1 Hz slow wave activity, suggesting that certain levels of sleep are important for maintaining cognitive function. Although longitudinal and interventional studies are needed, diagnosing and treating sleep disturbances to optimize sleep time and slow wave activity may have a stabilizing effect on cognition in preclinical or early symptomatic Alzheimer’s disease.

Prospective association between sleep duration and cognitive impairment: Findings from the China Health and Retirement Longitudinal Study (CHARLS)

“…A recent study with sleep duration measured by polysomnography also supported our results (37). Lucey et al investigated the relationship between cognitive performance and sleep duration measured by the single-channel EEG device, and showed that individuals with sleeping less than 4.5 or more than 6.5 h at night had declined cognitive scores (37). Because the sleep time is about one hour shorter measured by EEG than by self-reported, the results corresponded to 5.5-7.5 h per night of self-reported sleep time to have the lowest risk (34,37).…”

“…Moreover, we recommended 7–8 h for total sleep or 6–7 h for nocturnal sleep per day, because such sleep durations had the lowest risk of cognitive impairment. A recent study with sleep duration measured by polysomnography also supported our results ( 37 ). Lucey et al investigated the relationship between cognitive performance and sleep duration measured by the single-channel EEG device, and showed that individuals with sleeping less than 4.5 or more than 6.5 h at night had declined cognitive scores ( 37 ).…”

“…Lucey et al investigated the relationship between cognitive performance and sleep duration measured by the single-channel EEG device, and showed that individuals with sleeping less than 4.5 or more than 6.5 h at night had declined cognitive scores (37). Because the sleep time is about one hour shorter measured by EEG than by self-reported, the results corresponded to 5.5-7.5 h per night of self-reported sleep time to have the lowest risk (34,37). Although the biological mechanisms of extreme sleep durations on cognition is still unclear, putative pathways included circadian dysfunction (38), increased accumulation of amyloid-β in the brain (39), and elevate levels of systemic inflammatory markers (e.g., C-reactive protein, interleukin-6) (40)(41)(42).…”

Multi-Night at-Home Evaluation of Improved Sleep Detection and Classification with a Memory-Enhanced Consumer Sleep Tracker

“…Treating NREM sleep as a continuum instead of discrete stages has been advocated 46 and tested out in a recent clinical trial. 50 This approach has also been used in studies involving acoustic stimulation to boost slow oscillations. 51 Recent observations concerning heart rate changes in response to slow oscillations and sigma activity (in the frequency of sleep spindles) also motivate removal of the artificial boundary in NREM sleep classification.…”

Possible Neuropathology of Sleep Disturbance Linking to Alzheimer’s Disease: Astrocytic and Microglial Roles

“…Loss of sleep accelerates AD progression not only by emotionally affecting the mental states of patients but also through the pathological changes of AD ( Irwin and Vitiello, 2019 ; Van Egroo et al, 2019 ; Wang and Holtzman, 2020 ). Sleep disorders and AD partially share pathological mechanisms and induce similar cognitive deficits ( Uddin et al, 2020 ; Lucey et al, 2021 ). Therefore, it is important to further characterize the possible neuropathological changes of sleep disturbance linked to AD.…”