Sleep and Alzheimer disease pathology—a bidirectional relationship

Abstract

Factors other than age and genetics may increase the risk of developing Alzheimer disease (AD). Accumulation of the amyloid-β (Aβ) peptide in the brain seems to initiate a cascade of key events in the pathogenesis of AD. Moreover, evidence is emerging that the sleep–wake cycle directly influences levels of Aβ in the brain. In experimental models, sleep deprivation increases the concentration of soluble Aβ and results in chronic accumulation of Aβ, whereas sleep extension has the opposite effect. Furthermore, once Aβ accumulates, increased wakefulness and altered sleep patterns develop. Individuals with early Aβ deposition who still have normal cognitive function report sleep abnormalities, as do individuals with very mild dementia due to AD. Thus, sleep and neurodegenerative disease may influence each other in many ways that have important implications for the diagnosis and treatment of AD.

Evidence of association between sleep quality and APOE ε4 in healthy older adults

“…24,25 Primary findings indicate that individuals with AD have decreased sleep efficiency, increased stage 1 sleep, more nighttime awakenings, and decreased slow wave sleep and REM sleep. 1,[24][25][26][27][28][29] Within our population of healthy adults at genetic risk for AD, we saw a decrease in sleep efficiency, which is similar to changes seen in individuals diagnosed with MCI and AD. We also saw a significant increase in the time and percentage of sleep spent in REM; however, the total difference in REM sleep between the 2 groups is a few minutes.…”

“…This genetic risk may cause some individuals to enter a feed-forward loop where sleep problems cause an increase in Ab deposition in the brain, which then further disrupts sleep circuitry in the brain. 1 This study aimed to investigate the potential relationship between both subjective and objective sleep quality and APOE genotype in a population of healthy, sedentary adults without dementia over the age of 55. We hypothesized that having at least one APOE e4 allele will decrease both subjective and objective sleep quality compared to individuals without an APOE e4 allele.…”

Is Sleep Disruption a Risk Factor for Alzheimer’s Disease?

“…On the other hand, poor-quality sleep causes an enhancement in DMN connectivity and consecutive activity (when compared to high-quality sleep). Thus, Aβ release increases along with the tendency for Aβ plaque formation [47].…”

A Human-Based Integrated Framework forAlzheimer’s Disease Research

“…The primary risk factors for AD include advancing age [27][28][29], nutritional patterns characterized by low intake of plant-derived foods [30], together with metabolic syndrome-related dysfunctions (e.g., cardiovascular disease and diabetes) [8,31], low socioeconomic status and a low level of educational attainment [32][33][34], low level of daily physical activity [35,36], and low cognitive training [37]. Additionally, sleep disorders [38][39][40], known to positively correlate to early A␤ deposition [41,42], exposure to air pollution [43], smoking [44], and the intake of metals (e.g. aluminum [45], dietary copper [46], and manganese [47]) have been described as possible risk factors.…”