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Modification of the relationship of the apolipoprotein E ε4 allele to the risk of Alzheimer disease and neurofibrillary tangle density by sleep.

Abstract

IMPORTANCE

The apolipoprotein E (APOE [GenBank, 348; OMIM, 107741]) ε4 allele is a common and well-established genetic risk factor for Alzheimer disease (AD). Sleep consolidation is also associated with AD risk, and previous work suggests that APOE genotype and sleep may interact to influence cognitive function.

OBJECTIVE

To determine whether better sleep consolidation attenuates the relationship of the APOE genotype to the risk of incident AD and the burden of AD pathology.

DESIGN, SETTING, AND PARTICIPANTS

A prospective longitudinal cohort study with up to 6 years of follow-up was conducted. Participants included 698 community-dwelling older adults without dementia (mean age, 81.7 years; 77% women) in the Rush Memory and Aging Project.

EXPOSURES

We used up to 10 days of actigraphic recording to quantify the degree of sleep consolidation and ascertained APOE genotype.

MAIN OUTCOMES AND MEASURES

Participants underwent annual evaluation for AD during a follow-up period of up to 6 years. Autopsies were performed on 201 participants who died, and β-amyloid (Aβ) and neurofibrillary tangles were identified by immunohistochemistry and quantified.

RESULTS

During the follow-up period, 98 individuals developed AD. In a series of Cox proportional hazards regression models, better sleep consolidation attenuated the effect of the ε4 allele on the risk of incident AD (hazard ratio, 0.67; 95% CI, 0.46-0.97; P = .04 per allele per 1-SD increase in sleep consolidation). In a series of linear mixed-effect models, better sleep consolidation also attenuated the effect of the ε4 allele on the annual rate of cognitive decline. In individuals who died, better sleep consolidation attenuated the effect of the ε4 allele on neurofibrillary tangle density (interaction estimate, -0.42; SE = 0.17; P = .02), which accounted for the effect of sleep consolidation on the association between APOE genotype and cognition proximate to death.

CONCLUSIONS AND RELEVANCE

Better sleep consolidation attenuates the effect of APOE genotype on incident AD and development of neurofibrillary tangle pathology. Assessment of sleep consolidation may identify APOE+ individuals at high risk for incident AD, and interventions to enhance sleep consolidation should be studied as potentially useful means to reduce the risk of AD and development of neurofibrillary tangles in APOE ε4+ individuals.

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  • Authors+Show Affiliations

    ,

    Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.

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    Source

    JAMA neurology 70:12 2013 Dec pg 1544-51

    MeSH

    Actigraphy
    Aged
    Aged, 80 and over
    Alzheimer Disease
    Amyloid beta-Peptides
    Apolipoprotein E4
    Cognition Disorders
    Cohort Studies
    Dementia
    Female
    Genotype
    Humans
    Male
    Neurofibrillary Tangles
    Neuropsychological Tests
    Sleep

    Pub Type(s)

    Journal Article
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    24145819

    Citation

    Lim, Andrew S P., et al. "Modification of the Relationship of the Apolipoprotein E Ε4 Allele to the Risk of Alzheimer Disease and Neurofibrillary Tangle Density By Sleep." JAMA Neurology, vol. 70, no. 12, 2013, pp. 1544-51.
    Lim AS, Yu L, Kowgier M, et al. Modification of the relationship of the apolipoprotein E ε4 allele to the risk of Alzheimer disease and neurofibrillary tangle density by sleep. JAMA Neurol. 2013;70(12):1544-51.
    Lim, A. S., Yu, L., Kowgier, M., Schneider, J. A., Buchman, A. S., & Bennett, D. A. (2013). Modification of the relationship of the apolipoprotein E ε4 allele to the risk of Alzheimer disease and neurofibrillary tangle density by sleep. JAMA Neurology, 70(12), pp. 1544-51. doi:10.1001/jamaneurol.2013.4215.
    Lim AS, et al. Modification of the Relationship of the Apolipoprotein E Ε4 Allele to the Risk of Alzheimer Disease and Neurofibrillary Tangle Density By Sleep. JAMA Neurol. 2013;70(12):1544-51. PubMed PMID: 24145819.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Modification of the relationship of the apolipoprotein E ε4 allele to the risk of Alzheimer disease and neurofibrillary tangle density by sleep. AU - Lim,Andrew S P, AU - Yu,Lei, AU - Kowgier,Matthew, AU - Schneider,Julie A, AU - Buchman,Aron S, AU - Bennett,David A, PY - 2013/10/23/entrez PY - 2013/10/23/pubmed PY - 2014/2/22/medline SP - 1544 EP - 51 JF - JAMA neurology JO - JAMA Neurol VL - 70 IS - 12 N2 - IMPORTANCE: The apolipoprotein E (APOE [GenBank, 348; OMIM, 107741]) ε4 allele is a common and well-established genetic risk factor for Alzheimer disease (AD). Sleep consolidation is also associated with AD risk, and previous work suggests that APOE genotype and sleep may interact to influence cognitive function. OBJECTIVE: To determine whether better sleep consolidation attenuates the relationship of the APOE genotype to the risk of incident AD and the burden of AD pathology. DESIGN, SETTING, AND PARTICIPANTS: A prospective longitudinal cohort study with up to 6 years of follow-up was conducted. Participants included 698 community-dwelling older adults without dementia (mean age, 81.7 years; 77% women) in the Rush Memory and Aging Project. EXPOSURES: We used up to 10 days of actigraphic recording to quantify the degree of sleep consolidation and ascertained APOE genotype. MAIN OUTCOMES AND MEASURES: Participants underwent annual evaluation for AD during a follow-up period of up to 6 years. Autopsies were performed on 201 participants who died, and β-amyloid (Aβ) and neurofibrillary tangles were identified by immunohistochemistry and quantified. RESULTS: During the follow-up period, 98 individuals developed AD. In a series of Cox proportional hazards regression models, better sleep consolidation attenuated the effect of the ε4 allele on the risk of incident AD (hazard ratio, 0.67; 95% CI, 0.46-0.97; P = .04 per allele per 1-SD increase in sleep consolidation). In a series of linear mixed-effect models, better sleep consolidation also attenuated the effect of the ε4 allele on the annual rate of cognitive decline. In individuals who died, better sleep consolidation attenuated the effect of the ε4 allele on neurofibrillary tangle density (interaction estimate, -0.42; SE = 0.17; P = .02), which accounted for the effect of sleep consolidation on the association between APOE genotype and cognition proximate to death. CONCLUSIONS AND RELEVANCE: Better sleep consolidation attenuates the effect of APOE genotype on incident AD and development of neurofibrillary tangle pathology. Assessment of sleep consolidation may identify APOE+ individuals at high risk for incident AD, and interventions to enhance sleep consolidation should be studied as potentially useful means to reduce the risk of AD and development of neurofibrillary tangles in APOE ε4+ individuals. SN - 2168-6157 UR - https://www.unboundmedicine.com/medline/citation/24145819/Modification_of_the_relationship_of_the_apolipoprotein_E_ε4_allele_to_the_risk_of_Alzheimer_disease_and_neurofibrillary_tangle_density_by_sleep_ L2 - https://jamanetwork.com/journals/jamaneurology/fullarticle/10.1001/jamaneurol.2013.4215 DB - PRIME DP - Unbound Medicine ER -