Association of Sleep and β-Amyloid Pathology Among Older Cognitively Unimpaired Adults

Abstract

IMPORTANCE Disrupted sleep commonly occurs with progressing neurodegenerative disease. Large, well-characterized neuroimaging studies of cognitively unimpaired adults are warranted to clarify the magnitude and onset of the association between sleep and emerging β-amyloid (Aβ) pathology. OBJECTIVE To evaluate the associations between daytime and nighttime sleep duration with regional Aβ pathology in older cognitively unimpaired adults. DESIGN, SETTING, AND PARTICIPANTS In this cross-sectional study, screening data were collected between April 1, 2014, and December 31, 2017, from healthy, cognitively unimpaired adults 65 to 85 years of age who underwent florbetapir F 18 positron emission tomography (PET), had APOE genotype information, scored between 25 and 30 on the Mini-Mental State Examination, and had a Clinical Dementia Rating of 0 for the Anti-Amyloid Treatment in Asymptomatic Alzheimer Disease (A4) Study. Data analysis was performed from December 1, 2019, to May 10, 2021. EXPOSURES Self-reported daytime and nighttime sleep duration. MAIN OUTCOMES AND MEASURES Regional Aβ pathology, measured by florbetapir PET standardized uptake value ratio. RESULTS Amyloid PET and sleep duration information was acquired on 4425 cognitively unimpaired participants (mean [SD] age, 71.3 [4.7] years; 2628 [59.4%] female; 1509 [34.1%] tested Aβ positive).Each additional hour of nighttime sleep was associated with a 0.005 reduction of global Aβ standardized uptake value ratio (F 1, 4419 = 5.0; P = .03), a 0.009 reduction of medial orbitofrontal Aβ (F 1, 4419 = 17.4; P < .001), and a 0.011 reduction of anterior cingulate Aβ (F 1, 4419 = 15.9; P < .001). When restricting analyses to participants who tested Aβ negative, nighttime sleep was associated with a 0.006 reduction of medial orbitofrontal Aβ (F 1,2910 = 16.9; P < .001) and a 0.005 reduction of anterior cingulate Aβ (F 1,2910 = 7.6; P = .03). Daytime sleep was associated with a 0.013 increase of precuneus Aβ (F 1,2910 = 7.3; P = .03) and a 0.024 increase of posterior cingulate Aβ (F 1,2910 = 14.2; P = .001) in participants who tested Aβ negative. CONCLUSIONS AND RELEVANCEIn this cross-sectional study, the increased risk of Aβ deposition with reduced nighttime sleep duration occurred early, before cognitive impairment or significant Aβ deposition. Daytime sleep may be associated with an increase in risk for early Aβ accumulation and did not appear to be corrective for loss of nighttime sleep, demonstrating a circadian rhythm dependence of sleep in preventing Aβ accumulation. Treatments that improve sleep may reduce early Aβ accumulation and aid in delaying the onset of cognitive dysfunction associated with early Alzheimer disease.

The glymphatic system: Current understanding and modeling

“…The same group also showed that disruption of slow wave activity increases CSF amyloid beta levels acutely, and poorer sleep quality over several days increases tau levels (Ju et al, 2017). Recent large scale studies similarly report that shorter habitual sleep duration is associated with increased tau and amyloid beta levels (Insel et al, 2021;Winer et al, 2021). The glymphatic system contributes to the clearance of soluble amyloid beta as well as tau (Iliff et al, 2012(Iliff et al, , 2014Patel et al, 2019) and therefore constitutes a promising and alternative therapeutic target for curbing buildup of toxic waste protein and preventing cognitive impairment.…”

Sleep disturbance is associated with mild cognitive impairment: a community population-based cross-sectional study

“…Although the exact mechanism of sleep disturbance involved in cognitive impairment has not been fully determined. A growing number of studies have found that sleep disorders may lead to cognitive impairment and accelerate AD pathology, including increased Aβ deposition in the brain [42][43][44][45][46][47][48]. Our recent studies also showed that sleep deprivation induced peripheral Aβ transport dysfunction in young adults, and Aβ accumulation in the brain in rats [49,50].…”

Elementary Pathophysiology, Treatment, Risk Factor of Alzheimer’s Disease

“…NFT pathology was identified in 8 of 27 post-mortem TBI brains [179]. Indeed, extensive NFTs are found in up to one-third of individuals who survive a year or longer from a single TB [180]. Tau levels in TBI patients' CSF were about 1,000-fold higher than in other neurologically afflicted and non-diseased individuals [181].…”

“…Sleeping time and (rapid eye movement) REM sleep decrease as people age. Sleep-wake cycle disruptions, such as more daytime sleep, less nocturnal sleep, and sleep fragmentation, are common in Alzheimer's disease patients[179][180]. During sleep, the interstitial space expands, facilitating Aβ clearance by increasing the exchange between CSF and ISF.…”