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

Publication ,  Journal Article
Insel, PS; Mohlenhoff, BS; Neylan, TC; Krystal, AD; Mackin, RS
Published in: JAMA Netw Open
July 1, 2021

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 (F1, 4419 = 5.0; P = .03), a 0.009 reduction of medial orbitofrontal Aβ (F1, 4419 = 17.4; P < .001), and a 0.011 reduction of anterior cingulate Aβ (F1, 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 (F1,2910 = 16.9; P < .001) and a 0.005 reduction of anterior cingulate Aβ (F1,2910 = 7.6; P = .03). Daytime sleep was associated with a 0.013 increase of precuneus Aβ (F1,2910 = 7.3; P = .03) and a 0.024 increase of posterior cingulate Aβ (F1,2910 = 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.

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Published In

JAMA Netw Open

DOI

EISSN

2574-3805

Publication Date

July 1, 2021

Volume

4

Issue

7

Start / End Page

e2117573

Location

United States

Related Subject Headings

  • Sleep Initiation and Maintenance Disorders
  • Sleep
  • Positron-Emission Tomography
  • Plaque, Amyloid
  • Mental Status and Dementia Tests
  • Male
  • Humans
  • Geriatric Assessment
  • Female
  • Ethylene Glycols
 

Citation

APA
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ICMJE
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Insel, P. S., Mohlenhoff, B. S., Neylan, T. C., Krystal, A. D., & Mackin, R. S. (2021). Association of Sleep and β-Amyloid Pathology Among Older Cognitively Unimpaired Adults. JAMA Netw Open, 4(7), e2117573. https://doi.org/10.1001/jamanetworkopen.2021.17573
Insel, Philip S., Brian S. Mohlenhoff, Thomas C. Neylan, Andrew D. Krystal, and R Scott Mackin. “Association of Sleep and β-Amyloid Pathology Among Older Cognitively Unimpaired Adults.JAMA Netw Open 4, no. 7 (July 1, 2021): e2117573. https://doi.org/10.1001/jamanetworkopen.2021.17573.
Insel PS, Mohlenhoff BS, Neylan TC, Krystal AD, Mackin RS. Association of Sleep and β-Amyloid Pathology Among Older Cognitively Unimpaired Adults. JAMA Netw Open. 2021 Jul 1;4(7):e2117573.
Insel, Philip S., et al. “Association of Sleep and β-Amyloid Pathology Among Older Cognitively Unimpaired Adults.JAMA Netw Open, vol. 4, no. 7, July 2021, p. e2117573. Pubmed, doi:10.1001/jamanetworkopen.2021.17573.
Insel PS, Mohlenhoff BS, Neylan TC, Krystal AD, Mackin RS. Association of Sleep and β-Amyloid Pathology Among Older Cognitively Unimpaired Adults. JAMA Netw Open. 2021 Jul 1;4(7):e2117573.

Published In

JAMA Netw Open

DOI

EISSN

2574-3805

Publication Date

July 1, 2021

Volume

4

Issue

7

Start / End Page

e2117573

Location

United States

Related Subject Headings

  • Sleep Initiation and Maintenance Disorders
  • Sleep
  • Positron-Emission Tomography
  • Plaque, Amyloid
  • Mental Status and Dementia Tests
  • Male
  • Humans
  • Geriatric Assessment
  • Female
  • Ethylene Glycols