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September 19, 2017; 89 (12) Article

Sleep architecture and the risk of incident dementia in the community

Matthew P. Pase, Jayandra J. Himali, Natalie A. Grima, Alexa S. Beiser, Claudia L. Satizabal, Hugo J. Aparicio, Robert J. Thomas, Daniel J. Gottlieb, Sandford H. Auerbach, Sudha Seshadri
First published August 23, 2017, DOI: https://doi.org/10.1212/WNL.0000000000004373
Matthew P. Pase
From the Department of Neurology (M.P.P., J.J.H., A.S.B., C.L.S., H.J.A., S.H.A., S.S.), Boston University School of Medicine; Framingham Heart Study (M.P.P., J.J.H., A.S.B., C.L.S., H.J.A., S.H.A., S.S.), MA; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Australia; Department of Biostatistics (J.J.H., A.S.B.), Boston University School of Public Health; Cognitive Neurology Unit (N.A.G.) and Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine (R.J.T.), Beth Israel Deaconess Medical Center; Harvard Medical School (N.A.G., D.J.G.); Division of Sleep and Circadian Disorders (D.J.G.), Brigham & Women's Hospital, Boston; and Medical Service (D.J.G.), VA Boston Healthcare System, MA.
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Jayandra J. Himali
From the Department of Neurology (M.P.P., J.J.H., A.S.B., C.L.S., H.J.A., S.H.A., S.S.), Boston University School of Medicine; Framingham Heart Study (M.P.P., J.J.H., A.S.B., C.L.S., H.J.A., S.H.A., S.S.), MA; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Australia; Department of Biostatistics (J.J.H., A.S.B.), Boston University School of Public Health; Cognitive Neurology Unit (N.A.G.) and Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine (R.J.T.), Beth Israel Deaconess Medical Center; Harvard Medical School (N.A.G., D.J.G.); Division of Sleep and Circadian Disorders (D.J.G.), Brigham & Women's Hospital, Boston; and Medical Service (D.J.G.), VA Boston Healthcare System, MA.
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Natalie A. Grima
From the Department of Neurology (M.P.P., J.J.H., A.S.B., C.L.S., H.J.A., S.H.A., S.S.), Boston University School of Medicine; Framingham Heart Study (M.P.P., J.J.H., A.S.B., C.L.S., H.J.A., S.H.A., S.S.), MA; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Australia; Department of Biostatistics (J.J.H., A.S.B.), Boston University School of Public Health; Cognitive Neurology Unit (N.A.G.) and Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine (R.J.T.), Beth Israel Deaconess Medical Center; Harvard Medical School (N.A.G., D.J.G.); Division of Sleep and Circadian Disorders (D.J.G.), Brigham & Women's Hospital, Boston; and Medical Service (D.J.G.), VA Boston Healthcare System, MA.
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Alexa S. Beiser
From the Department of Neurology (M.P.P., J.J.H., A.S.B., C.L.S., H.J.A., S.H.A., S.S.), Boston University School of Medicine; Framingham Heart Study (M.P.P., J.J.H., A.S.B., C.L.S., H.J.A., S.H.A., S.S.), MA; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Australia; Department of Biostatistics (J.J.H., A.S.B.), Boston University School of Public Health; Cognitive Neurology Unit (N.A.G.) and Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine (R.J.T.), Beth Israel Deaconess Medical Center; Harvard Medical School (N.A.G., D.J.G.); Division of Sleep and Circadian Disorders (D.J.G.), Brigham & Women's Hospital, Boston; and Medical Service (D.J.G.), VA Boston Healthcare System, MA.
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Claudia L. Satizabal
From the Department of Neurology (M.P.P., J.J.H., A.S.B., C.L.S., H.J.A., S.H.A., S.S.), Boston University School of Medicine; Framingham Heart Study (M.P.P., J.J.H., A.S.B., C.L.S., H.J.A., S.H.A., S.S.), MA; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Australia; Department of Biostatistics (J.J.H., A.S.B.), Boston University School of Public Health; Cognitive Neurology Unit (N.A.G.) and Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine (R.J.T.), Beth Israel Deaconess Medical Center; Harvard Medical School (N.A.G., D.J.G.); Division of Sleep and Circadian Disorders (D.J.G.), Brigham & Women's Hospital, Boston; and Medical Service (D.J.G.), VA Boston Healthcare System, MA.
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Hugo J. Aparicio
From the Department of Neurology (M.P.P., J.J.H., A.S.B., C.L.S., H.J.A., S.H.A., S.S.), Boston University School of Medicine; Framingham Heart Study (M.P.P., J.J.H., A.S.B., C.L.S., H.J.A., S.H.A., S.S.), MA; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Australia; Department of Biostatistics (J.J.H., A.S.B.), Boston University School of Public Health; Cognitive Neurology Unit (N.A.G.) and Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine (R.J.T.), Beth Israel Deaconess Medical Center; Harvard Medical School (N.A.G., D.J.G.); Division of Sleep and Circadian Disorders (D.J.G.), Brigham & Women's Hospital, Boston; and Medical Service (D.J.G.), VA Boston Healthcare System, MA.
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Robert J. Thomas
From the Department of Neurology (M.P.P., J.J.H., A.S.B., C.L.S., H.J.A., S.H.A., S.S.), Boston University School of Medicine; Framingham Heart Study (M.P.P., J.J.H., A.S.B., C.L.S., H.J.A., S.H.A., S.S.), MA; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Australia; Department of Biostatistics (J.J.H., A.S.B.), Boston University School of Public Health; Cognitive Neurology Unit (N.A.G.) and Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine (R.J.T.), Beth Israel Deaconess Medical Center; Harvard Medical School (N.A.G., D.J.G.); Division of Sleep and Circadian Disorders (D.J.G.), Brigham & Women's Hospital, Boston; and Medical Service (D.J.G.), VA Boston Healthcare System, MA.
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Daniel J. Gottlieb
From the Department of Neurology (M.P.P., J.J.H., A.S.B., C.L.S., H.J.A., S.H.A., S.S.), Boston University School of Medicine; Framingham Heart Study (M.P.P., J.J.H., A.S.B., C.L.S., H.J.A., S.H.A., S.S.), MA; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Australia; Department of Biostatistics (J.J.H., A.S.B.), Boston University School of Public Health; Cognitive Neurology Unit (N.A.G.) and Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine (R.J.T.), Beth Israel Deaconess Medical Center; Harvard Medical School (N.A.G., D.J.G.); Division of Sleep and Circadian Disorders (D.J.G.), Brigham & Women's Hospital, Boston; and Medical Service (D.J.G.), VA Boston Healthcare System, MA.
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Sandford H. Auerbach
From the Department of Neurology (M.P.P., J.J.H., A.S.B., C.L.S., H.J.A., S.H.A., S.S.), Boston University School of Medicine; Framingham Heart Study (M.P.P., J.J.H., A.S.B., C.L.S., H.J.A., S.H.A., S.S.), MA; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Australia; Department of Biostatistics (J.J.H., A.S.B.), Boston University School of Public Health; Cognitive Neurology Unit (N.A.G.) and Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine (R.J.T.), Beth Israel Deaconess Medical Center; Harvard Medical School (N.A.G., D.J.G.); Division of Sleep and Circadian Disorders (D.J.G.), Brigham & Women's Hospital, Boston; and Medical Service (D.J.G.), VA Boston Healthcare System, MA.
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Sudha Seshadri
From the Department of Neurology (M.P.P., J.J.H., A.S.B., C.L.S., H.J.A., S.H.A., S.S.), Boston University School of Medicine; Framingham Heart Study (M.P.P., J.J.H., A.S.B., C.L.S., H.J.A., S.H.A., S.S.), MA; Centre for Human Psychopharmacology (M.P.P.), Swinburne University of Technology, Australia; Department of Biostatistics (J.J.H., A.S.B.), Boston University School of Public Health; Cognitive Neurology Unit (N.A.G.) and Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine (R.J.T.), Beth Israel Deaconess Medical Center; Harvard Medical School (N.A.G., D.J.G.); Division of Sleep and Circadian Disorders (D.J.G.), Brigham & Women's Hospital, Boston; and Medical Service (D.J.G.), VA Boston Healthcare System, MA.
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Citation
Sleep architecture and the risk of incident dementia in the community
Matthew P. Pase, Jayandra J. Himali, Natalie A. Grima, Alexa S. Beiser, Claudia L. Satizabal, Hugo J. Aparicio, Robert J. Thomas, Daniel J. Gottlieb, Sandford H. Auerbach, Sudha Seshadri
Neurology Sep 2017, 89 (12) 1244-1250; DOI: 10.1212/WNL.0000000000004373

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Abstract

Objective: Sleep disturbance is common in dementia, although it is unclear whether differences in sleep architecture precede dementia onset. We examined the associations between sleep architecture and the prospective risk of incident dementia in the community-based Framingham Heart Study (FHS).

Methods: Our sample comprised a subset of 321 FHS Offspring participants who participated in the Sleep Heart Health Study between 1995 and 1998 and who were aged over 60 years at the time of sleep assessment (mean age 67 ± 5 years, 50% male). Stages of sleep were quantified using home-based polysomnography. Participants were followed for a maximum of 19 years for incident dementia (mean follow-up 12 ± 5 years).

Results: We observed 32 cases of incident dementia; 24 were consistent with Alzheimer disease dementia. After adjustments for age and sex, lower REM sleep percentage and longer REM sleep latency were both associated with a higher risk of incident dementia. Each percentage reduction in REM sleep was associated with approximately a 9% increase in the risk of incident dementia (hazard ratio 0.91; 95% confidence interval 0.86, 0.97). The magnitude of association between REM sleep percentage and dementia was similar following adjustments for multiple covariates including vascular risk factors, depressive symptoms, and medication use, following exclusions for persons with mild cognitive impairment at baseline and following exclusions for early converters to dementia. Stages of non-REM sleep were not associated with dementia risk.

Conclusions: Despite contemporary interest in slow-wave sleep and dementia pathology, our findings implicate REM sleep mechanisms as predictors of clinical dementia.

GLOSSARY

Aβ=
β-amyloid;
AD=
Alzheimer disease;
AHI=
apnea-hypopnea index;
CI=
confidence interval;
DSM-IV=
Diagnostic and Statistical Manual of Mental Disorders, 4th edition;
FHS=
Framingham Heart Study;
HR=
hazard ratio;
MAOI=
monoamine oxidase inhibitor;
MCI=
mild cognitive impairment;
MMSE=
Mini-Mental State Examination;
PSG=
polysomnography;
SWS=
slow-wave sleep

Footnotes

  • ↵* These authors contributed equally to this work.

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at Neurology.org

  • Received February 14, 2017.
  • Accepted in final form July 3, 2017.
  • © 2017 American Academy of Neurology
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Disputes & Debates: Rapid online correspondence

  • Author response to Dr. Kim
    • Matthew P. Pase, Senior Research Fellow, Swinburne University of Technologymatthewpase@gmail.com
    • Jayandra J. Himali, Natalie A. Grima, Alexa S. Beiser, Claudia L. Satizabal, Hugo J. Aparicio, Robert J. Thomas, Daniel J. Gottlieb, Sanford H. Auerbach, Sudha Seshadri, Boston, MA
    Submitted October 31, 2017
  • Possible future study and other confounding factors in sleep architecture and link to dementia
    • David D. Kim, MD, Western Universitydavid.kim@medportal.ca
    Submitted October 11, 2017
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