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

 Something for your doctors to consider when creating your sleep protocol. Does use of sleeping pills count?

Reading in these 11 posts seems to consider napping very beneficial until you get longer than an hour.

• napping (11 posts to August 2014)

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

Philip S. Insel, PhD^1,2; Brian S. Mohlenhoff, MD^1,3; Thomas C. Neylan, MD^1,3; et al Andrew D. Krystal, MD, MS¹; R. Scott Mackin, PhD^1,3

Author Affiliations Article Information

JAMA Netw Open. 2021;4(7):e2117573. doi:10.1001/jamanetworkopen.2021.17573

Key Points

Question  What is the magnitude and time of onset of the association between daytime and nighttime sleep with β-amyloid (Aβ) pathology in cognitively unimpaired older adults?

Findings  In this cross-sectional study of 4425 cognitively unimpaired participants, each additional hour of nighttime sleep was associated with a statistically significant reduction of Aβ positron emission tomographic standardized uptake value ratio, whereas daytime sleep(Definition of sleep vs. napping?) was associated with increased regional accumulation of Aβ. The association occurs early, before significant Aβ accumulation or cognitive impairment, and in specific regions of the brain.

Meaning  If longer sleep duration leads to reduced amyloid levels, treatments increasing sleep duration may reduce Aβ accumulation and aid in delaying the onset of cognitive dysfunction associated with Aβ deposition.

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 Relevance  In 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.

Introduction

Sleep disruption has been proposed to play a role in increasing amyloid β (Aβ) deposition,^1-3 the defining characteristic of the preclinical phase of Alzheimer disease, thought to begin decades before symptom onset.⁴ Increasing age and the ε4 allele of the APOE gene are principal risk factors for Aβ deposition. Cognitively unimpaired older adults with elevated levels of Aβ are at increased risk for cognitive decline during 3 to 6 years.⁵ Extracellular Aβ aggregation in mice increased with wakefulness, and humans exhibited waking-related increased levels of Aβ in cerebrospinal fluid (CSF).⁶ Chronic partial sleep restriction in rodents has also been experimentally found to increase Aβ deposition.⁷ Sleep deprivation is thought to reduce interstitial fluid volume to levels insufficient to clear Aβ.^8,9 In humans, acute experimental sleep deprivation increased overnight CSF Aβ levels by 25% to 30% compared with levels in sleeping controls.¹⁰ A study¹¹ of partial sleep deprivation revealed loss of slow wave sleep (SWS) associated with an acute increase in next-morning CSF Aβ. Positron emission tomography (PET)–determined Aβ burden in healthy older individuals was strongly associated with SWS.¹ The primary role of SWS in Aβ turnover is thought to be related to higher flow in the brain glymphatic system during SWS.^8,12,13

Such results suggest that less sleep over time may be associated with increased levels of Aβ deposition, but reports^14-20 are mixed and have been limited by small sample sizes. An experiment that involved chronic partial sleep deprivation in humans found no correlation with CSF Aβ.¹⁴ Several studies with fewer than 100 older adult participants found correlations between self-reported total sleep time^15,16 and nocturnal awakenings¹⁷ with PET Aβ deposition, but this finding has been inconsistent.^18-20

We analyzed a sample of 4425 healthy, cognitively unimpaired, older adults with self-reported nighttime and daytime sleep duration, health information, and florbetapir F 18 PET imaging. The aims of these analyses were to evaluate whether self-reported sleep durations were associated with increased Aβ deposition, whether there was a specific regional pattern of deposition associated with sleep, and how early the association developed during Aβ accumulation. Additional factors affecting sleep, including caffeine and alcohol consumption, exercise, and symptoms of depression, were also assessed.^21-23