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. 2024 Jun 13;47(6):zsae081.
doi: 10.1093/sleep/zsae081.

Longer sleep duration and neuroinflammation in at-risk elderly with a parental history of Alzheimer's disease

Andrée-Ann Baril  1   2 , Cynthia Picard  3 , Anne Labonté  3 , Erlan Sanchez  4 , Catherine Duclos  1   5 , Béry Mohammediyan  3 , John C S Breitner  3 , Sylvia Villeneuve  3 , Judes Poirier  3 ; PREVENT-AD Research Group
Collaborators, Affiliations

Longer sleep duration and neuroinflammation in at-risk elderly with a parental history of Alzheimer's disease

Andrée-Ann Baril et al. Sleep. .

Abstract

Study objectives: Although short sleep could promote neurodegeneration, long sleep may be a marker of ongoing neurodegeneration, potentially as a result of neuroinflammation. The objective was to evaluate sleep patterns with age of expected Alzheimer's disease (AD) onset and neuroinflammation.

Methods: We tested 203 dementia-free participants (68.5 ± 5.4 years old, 78M). The PREVENT-AD cohort includes older persons with a parental history of AD whose age was nearing their expected AD onset. We estimated expected years to AD onset by subtracting the participants' age from their parent's at AD dementia onset. We extracted actigraphy sleep variables of interest (times of sleep onset and morning awakening, time in bed, sleep efficiency, and sleep duration) and general profiles (sleep fragmentation, phase delay, and hypersomnia). Cerebrospinal fluid (CSF) inflammatory biomarkers were assessed with OLINK multiplex technology.

Results: Proximity to, or exceeding, expected age of onset was associated with a sleep profile suggestive of hypersomnia (longer sleep and later morning awakening time). This hypersomnia sleep profile was associated with higher CSF neuroinflammatory biomarkers (IL-6, MCP-1, and global score). Interaction analyses revealed that some of these sleep-neuroinflammation associations were present mostly in those closer/exceeding the age of expected AD onset, APOE4 carriers, and those with better memory performance.

Conclusions: Proximity to, or exceeding, parental AD dementia onset was associated with a longer sleep pattern, which was related to elevated proinflammatory CSF biomarkers. We speculate that longer sleep may serve a compensatory purpose potentially triggered by neuroinflammation as individuals are approaching AD onset. Further studies should investigate whether neuroinflammatory-triggered long sleep duration could mitigate cognitive deficits.

Keywords: Dementia; MCI; apolipoprotein; cerebrospinal fluid; circadian; cytokines; inflammation; mild cognitive impairment; total sleep time.

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Figures

Graphical Abstract
Graphical Abstract
Figure 1.
Figure 1.
(A) Significant associations between lower EYO scores with later time of last morning awakening, longer sleep duration, and higher PC3-Hypersomnia score, adjusted for age and sex. (B) Lower EYO was observed in those with longer sleep duration (>8h) as compared to other sleep duration categories. Note that a lower EYO score includes negative values, representing dementia-free people older than their parent’s age at symptom onset. Betas are standardized. EYO, estimated years remaining to expected onset; PC3-Hypersomnia, third principal component of sleep characteristics representing a sleep pattern suggestive of hypersomnia.
Figure 2.
Figure 2.
(A) Significant associations between higher CSF IL-6 with longer sleep duration, longer time in bed, and higher PC3-Hypersomnia score. (B) Significant associations between higher CSF MCP-1 with longer sleep duration, later time of last morning awakening, and higher PC3-Hypersomnia score. (C) Significant associations between higher CSF PC-OLINK of inflammatory biomarkers with longer sleep duration and higher PC3-Hypersomnia score. All analyses are adjusted for age, sex and time interval between CSF collection and actigraphy. Betas are standardized. CSF, cerebrospinal fluid; PC3-Hypersomnia, third principal component of sleep characteristics representing a hypersomnia sleep pattern; PC-OLINK, single solution principal component of OLINK inflammatory biomarkers in the CSF.
Figure 3.
Figure 3.
Significant associations between higher CSF IL-6 with higher PC3-Hypersomnia were observed only in those with better delayed recall memory performance (RBANS delayed recall memory, median split). All analyses are adjusted for age, sex and time interval between CSF collection and actigraphy. Betas are standardized. CSF, cerebrospinal fluid; PC3-Hypersomnia, the third principal component of sleep characteristics representing a sleep pattern suggestive of hypersomnia.
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