ParkinsonCanadaV1, Main, Exploration, bibRecord, 000C74

Sleep Modifies the Relation of APOE to the Risk of Alzheimer Disease and Neurofibrillary Tangle Pathology

Identifieur interne : 000C74 ( Main/Exploration ); précédent : 000C73; suivant : 000C75

Sleep Modifies the Relation of APOE to the Risk of Alzheimer Disease and Neurofibrillary Tangle Pathology

Auteurs : Andrew S. P. Lim [Canada] ; Lei Yu [États-Unis] ; Matthew Kowgier [Canada] ; Julie A. Schneider [États-Unis] ; Aron S. Buchman [États-Unis] ; David A. Bennett [États-Unis]

Source :

JAMA neurology [ 2168-6149 ] ; 2013.

RBID : PMC:3859706

Abstract

IMPORTANCE

The Apolipoprotein E (APOE) 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 relation of the APOE genotype to the risk of incident AD and the burden of AD pathology.

DESIGN

Prospective longitudinal cohort study with up to 6 years of follow-up.

SETTING

Community-based.

PARTICIPANTS

We studied a volunteer sample of 698 community dwelling older adults without dementia (average age 81.7 years; 77% female) in the Rush Memory and Aging Project followed for up to 6 years.

EXPOSURES

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

MAIN OUTCOME MEASURES

Subjects underwent annual evaluation for AD over a follow-up period of up to 6 years. Autopsies were performed on 201 deceased participants, and Aβ and neurofibrillary tangle (NFT) pathology were identified by immunohistochemistry and quantified.

RESULTS

Over a follow-up period, 98 individuals developed AD. In a series of Cox proportional hazards models, better sleep consolidation attenuated the effect of the ε4 allele on the risk of incident AD (HR 0.67 95%CI 0.46–0.97 p=0.036 per allele per 1SD 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 (interaction estimate +0.048 SE=0.012 p<0.001). In deceased individuals, better sleep consolidation attenuated the effect of the ε4 allele on NFT density (interaction estimate −0.42 SE=0.17 p=0.016), 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 NFT pathology. Assessment of sleep consolidation may identify APOE positive 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 NFT pathology in APOE ε4⁺ individuals.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3859706

DOI: 10.1001/jamaneurol.2013.4215
PubMed: 24145819
PubMed Central: 3859706

Affiliations:

Le document en format XML

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<front><div type="abstract" xml:lang="en"><sec id="S1"><title>IMPORTANCE</title>
<p id="P1">The Apolipoprotein E (<italic>APOE</italic>
) 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 <italic>APOE</italic>
 genotype and sleep may interact to influence cognitive function.</p>
</sec>
<sec id="S2"><title>OBJECTIVE</title>
<p id="P2">To determine whether better sleep consolidation attenuates the relation of the <italic>APOE</italic>
 genotype to the risk of incident AD and the burden of AD pathology.</p>
</sec>
<sec id="S3"><title>DESIGN</title>
<p id="P3">Prospective longitudinal cohort study with up to 6 years of follow-up.</p>
</sec>
<sec id="S4"><title>SETTING</title>
<p id="P4">Community-based.</p>
</sec>
<sec id="S5"><title>PARTICIPANTS</title>
<p id="P5">We studied a volunteer sample of 698 community dwelling older adults without dementia (average age 81.7 years; 77% female) in the Rush Memory and Aging Project followed for up to 6 years.</p>
</sec>
<sec id="S6"><title>EXPOSURES</title>
<p id="P6">We used up to 10 days of actigraphic recording to quantify the degree of sleep consolidation, and ascertained <italic>APOE</italic>
 genotype.</p>
</sec>
<sec id="S7"><title>MAIN OUTCOME MEASURES</title>
<p id="P7">Subjects underwent annual evaluation for AD over a follow-up period of up to 6 years. Autopsies were performed on 201 deceased participants, and Aβ and neurofibrillary tangle (NFT) pathology were identified by immunohistochemistry and quantified.</p>
</sec>
<sec id="S8"><title>RESULTS</title>
<p id="P8">Over a follow-up period, 98 individuals developed AD. In a series of Cox proportional hazards models, better sleep consolidation attenuated the effect of the ε4 allele on the risk of incident AD (HR 0.67 95%CI 0.46–0.97 p=0.036 per allele per 1SD 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 (interaction estimate +0.048 SE=0.012 p<0.001). In deceased individuals, better sleep consolidation attenuated the effect of the ε4 allele on NFT density (interaction estimate −0.42 SE=0.17 p=0.016), which accounted for the effect of sleep consolidation on the association between <italic>APOE</italic>
 genotype and cognition proximate to death.</p>
</sec>
<sec id="S9"><title>CONCLUSIONS AND RELEVANCE</title>
<p id="P9">Better sleep consolidation attenuates the effect of <italic>APOE</italic>
 genotype on incident AD and NFT pathology. Assessment of sleep consolidation may identify <italic>APOE</italic>
 positive 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 NFT pathology in <italic>APOE</italic>
 ε4<sup>+</sup>
 individuals.</p>
</sec>
</div>
</front>
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La maladie de Parkinson au Canada (serveur d'exploration)

Sleep Modifies the Relation of APOE to the Risk of Alzheimer Disease and Neurofibrillary Tangle Pathology

Sleep Modifies the Relation of APOE to the Risk of Alzheimer Disease and Neurofibrillary Tangle Pathology

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Abstract

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