APOE ε4, Alzheimer’s disease neuropathology and sleep disturbance, in individuals with and without dementia

Blackman, Jonathan; Love, Seth; Sinclair, Lindsey I; Cain, Richard E.; Coulthard, Elizabeth

doi:10.1186/s13195-022-00992-y

Cited by 20 publications

(10 citation statements)

References 91 publications

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“…Previous findings have been mixed in linking the APOE polymorphism to sleep disturbances at a single time point . Here, we demonstrate that the APOE ε4 allele (vs ε3/ε3) was associated with greater SWS loss.…”

Section: Discussionmentioning

confidence: 47%

Association Between Slow-Wave Sleep Loss and Incident Dementia

Himali,

Baril,

Cavuoto

et al. 2023

JAMA Neurol

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ImportanceSlow-wave sleep (SWS) supports the aging brain in many ways, including facilitating the glymphatic clearance of proteins that aggregate in Alzheimer disease. However, the role of SWS in the development of dementia remains equivocal.ObjectiveTo determine whether SWS loss with aging is associated with the risk of incident dementia and examine whether Alzheimer disease genetic risk or hippocampal volumes suggestive of early neurodegeneration were associated with SWS loss.Design, Setting, and ParticipantsThis prospective cohort study included participants in the Framingham Heart Study who completed 2 overnight polysomnography (PSG) studies in the time periods 1995 to 1998 and 1998 to 2001. Additional criteria for individuals in this study sample were an age of 60 years or older and no dementia at the time of the second overnight PSG. Data analysis was performed from January 2020 to August 2023.ExposureChanges in SWS percentage measured across repeated overnight sleep studies over a mean of 5.2 years apart (range, 4.8-7.1 years).Main OutcomeRisk of incident all-cause dementia adjudicated over 17 years of follow-up from the second PSG.ResultsFrom the 868 Framingham Heart Study participants who returned for a second PSG, this cohort included 346 participants with a mean age of 69 years (range, 60-87 years); 179 (52%) were female. Aging was associated with SWS loss across repeated overnight sleep studies (mean [SD] change, −0.6 [1.5%] per year; P &lt; .001). Over the next 17 years of follow-up, there were 52 cases of incident dementia. In Cox regression models adjusted for age, sex, cohort, positivity for at least 1 APOE ε4 allele, smoking status, sleeping medication use, antidepressant use, and anxiolytic use, each percentage decrease in SWS per year was associated with a 27% increase in the risk of dementia (hazard ratio, 1.27; 95% CI, 1.06-1.54; P = .01). SWS loss with aging was accelerated in the presence of Alzheimer disease genetic risk (ie, APOE ε4 allele) but not hippocampal volumes measured proximal to the first PSG.Conclusions and RelevanceThis cohort study found that slow-wave sleep percentage declined with aging and Alzheimer disease genetic risk, with greater reductions associated with the risk of incident dementia. These findings suggest that SWS loss may be a modifiable dementia risk factor.

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Section: Discussionmentioning

confidence: 47%

Association Between Slow-Wave Sleep Loss and Incident Dementia

Himali,

Baril,

Cavuoto

et al. 2023

JAMA Neurol

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“…CPAP treatment may delay the progression of cognitive impairment, and the duration of CPAP is critical for improving the therapeutic effect of cognitive impairment in OSA patients [35, 36]. The apolipoprotein epsilon 4 ( APOEε4 ) allele is the strongest genetic risk factor for late-onset AD, and the effect of APOEε4 on sleep quality may contribute to sleep disturbances in individuals at increased risk for dementia [37]. In addition, a study showed that mutations in natural short sleep genes can reduce the AD pathology in animals, which opens a new path for the treatment of neurodegenerative diseases such as sleep deprivation-induced AD [38].…”

Section: Discussionmentioning

confidence: 99%

Association between Sleep and Alzheimer’s Disease: A Bibliometric Analysis from 2003 to 2022

Tang,

Wu,

Shen

et al. 2023

Neuroepidemiology

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Introduction: Alzheimer’s disease (AD) often presents with sleep disorders, which are also an important risk factor for AD, affecting cognitive function to a certain extent. This study aimed to reveal the current global status, present hotspots, and discuss emerging trends of sleep and AD using a bibliometric approach. Methods: Research and review articles related to sleep and AD from 2003 to 2022 were extracted from the Web of Science Core Collection. VOSviewer 1.6.18.0, Scimago Graphica, and CiteSpace 6.2.R2 were used to map the productive and highly cited countries, institutions, journals, authors, references, and keywords in the field. Results: Overall, 4,008 publications were included in this bibliometric analysis. The number of publications and citations showed an increasing trend over the past two decades. The USA and China had the largest and second largest, respectively, number of publications and citations and cooperated with other countries more closely. Ancoli-Israel Sonia published the most papers, and Holtzman David M was co-cited most frequently. The most productive journal was Journal of Alzheimer’s Disease, and Neurology was the most frequently cited journal. The risk factors, β-amyloid (Aβ), tau, neuroinflammation, astrocytes, glymphatic system, orexin, functional connectivity, and management have been the main research directions of researchers over the past few years and may be the future trend of valuable research. Conclusion: We identified hotspots and emerging trends including risk factors, Aβ, tau, neuroinflammation, the glymphatic system, orexin, and management, which may help identify new therapeutic targets and improve clinical efficacy of sleep and AD.

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“…Likewise, APOEε4 may affect sleep by mechanisms that are both dependent and independent of AD pathological change. 97…”

Section: Molecular Mechanisms Of Admentioning

confidence: 99%

Impact of Sleep Disorders and Disturbed Sleep on Brain Health: A Scientific Statement From the American Heart Association

Gottesman,

Lutsey,

Benveniste

et al. 2024

Stroke

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Accumulating evidence supports a link between sleep disorders, disturbed sleep, and adverse brain health, ranging from stroke to subclinical cerebrovascular disease to cognitive outcomes, including the development of Alzheimer disease and Alzheimer disease–related dementias. Sleep disorders such as sleep-disordered breathing (eg, obstructive sleep apnea), and other sleep disturbances, as well, some of which are also considered sleep disorders (eg, insomnia, sleep fragmentation, circadian rhythm disorders, and extreme sleep duration), have been associated with adverse brain health. Understanding the causal role of sleep disorders and disturbances in the development of adverse brain health is complicated by the common development of sleep disorders among individuals with neurodegenerative disease. In addition to the role of sleep disorders in stroke and cerebrovascular injury, mechanistic hypotheses linking sleep with brain health and biomarker data (blood-based, cerebrospinal fluid-based, and imaging) suggest direct links to Alzheimer disease–specific pathology. These potential mechanisms and the increasing understanding of the “glymphatic system,” and the recognition of the importance of sleep in poststroke recovery, as well, support a biological basis for the indirect (through the worsening of vascular disease) and direct (through specific effects on neuropathology) connections between sleep disorders and brain health. Given promising evidence for the benefits of treatment and prevention, sleep disorders and disturbances represent potential targets for early treatment that may improve brain health more broadly. In this scientific statement, we discuss the evidence supporting an association between sleep disorders and disturbances and poor brain health ranging from stroke to dementia and opportunities for prevention and early treatment.

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APOE ε4, Alzheimer’s disease neuropathology and sleep disturbance, in individuals with and without dementia

Cited by 20 publications

References 91 publications

Association Between Slow-Wave Sleep Loss and Incident Dementia

Association Between Slow-Wave Sleep Loss and Incident Dementia

Association between Sleep and Alzheimer’s Disease: A Bibliometric Analysis from 2003 to 2022

Impact of Sleep Disorders and Disturbed Sleep on Brain Health: A Scientific Statement From the American Heart Association

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