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March 09, 2021; 96 (10) Article

Slow-Wave Sleep and MRI Markers of Brain Aging in a Community-Based Sample

Andrée-Ann Baril, Alexa S. Beiser, View ORCID ProfileVincent Mysliwiec, Erlan Sanchez, Charles S. DeCarli, Susan Redline, Daniel J. Gottlieb, Pauline Maillard, Jose Rafael Romero, View ORCID ProfileClaudia L. Satizabal, Jared M. Zucker, Sudha Seshadri, Matthew P. Pase, Jayandra J. Himali
First published December 22, 2020, DOI: https://doi.org/10.1212/WNL.0000000000011377
Andrée-Ann Baril
From the Framingham Heart Study (A.-A.B., A.S.B., J.R.R., C.L.S., J.M.Z., S.S., M.P.P. J.J.H.); Department of Neurology (A.-A.B., A.S.B., C.L.S., S.S., J.J.H.), Boston University School of Medicine; Department of Biostatistics (A.S.B., J.J.H. ), Boston University School of Public Health, MA; Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases (V.M., C.L.S., S.S., J.J.H.), and Department of Population Health Sciences (J.J.H.), University of Texas Health Sciences Center, San Antonio; Centre for Advanced Research in Sleep Medicine (E.S.), Hôpital du Sacré-Coeur de Montréal, CIUSSS-NIM; Department of Neuroscience (E.S.), Université de Montréal, Quebec, Canada; Department of Neurology (C.D., P.M.), and School of Medicine and Imaging of Dementia and Aging Laboratory, Center for Neuroscience (P.M.), University of California, Davis, Sacramento; Division of Sleep and Circadian Disorders (S.R., D.J.G.), Brigham & Women’s Hospital; Beth Israel Deaconess Medical Center (S.R., D.J.G.); Division of Sleep Medicine Harvard Medical School, Boston, MA; VA Boston Healthcare System (D.J.G.), Boston, MA; Turner Institute for Brain and Mental Health (M.P.P.), School of Psychological Sciences, Monash University, Melbourne, VIC, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
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Alexa S. Beiser
From the Framingham Heart Study (A.-A.B., A.S.B., J.R.R., C.L.S., J.M.Z., S.S., M.P.P. J.J.H.); Department of Neurology (A.-A.B., A.S.B., C.L.S., S.S., J.J.H.), Boston University School of Medicine; Department of Biostatistics (A.S.B., J.J.H. ), Boston University School of Public Health, MA; Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases (V.M., C.L.S., S.S., J.J.H.), and Department of Population Health Sciences (J.J.H.), University of Texas Health Sciences Center, San Antonio; Centre for Advanced Research in Sleep Medicine (E.S.), Hôpital du Sacré-Coeur de Montréal, CIUSSS-NIM; Department of Neuroscience (E.S.), Université de Montréal, Quebec, Canada; Department of Neurology (C.D., P.M.), and School of Medicine and Imaging of Dementia and Aging Laboratory, Center for Neuroscience (P.M.), University of California, Davis, Sacramento; Division of Sleep and Circadian Disorders (S.R., D.J.G.), Brigham & Women’s Hospital; Beth Israel Deaconess Medical Center (S.R., D.J.G.); Division of Sleep Medicine Harvard Medical School, Boston, MA; VA Boston Healthcare System (D.J.G.), Boston, MA; Turner Institute for Brain and Mental Health (M.P.P.), School of Psychological Sciences, Monash University, Melbourne, VIC, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
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Vincent Mysliwiec
From the Framingham Heart Study (A.-A.B., A.S.B., J.R.R., C.L.S., J.M.Z., S.S., M.P.P. J.J.H.); Department of Neurology (A.-A.B., A.S.B., C.L.S., S.S., J.J.H.), Boston University School of Medicine; Department of Biostatistics (A.S.B., J.J.H. ), Boston University School of Public Health, MA; Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases (V.M., C.L.S., S.S., J.J.H.), and Department of Population Health Sciences (J.J.H.), University of Texas Health Sciences Center, San Antonio; Centre for Advanced Research in Sleep Medicine (E.S.), Hôpital du Sacré-Coeur de Montréal, CIUSSS-NIM; Department of Neuroscience (E.S.), Université de Montréal, Quebec, Canada; Department of Neurology (C.D., P.M.), and School of Medicine and Imaging of Dementia and Aging Laboratory, Center for Neuroscience (P.M.), University of California, Davis, Sacramento; Division of Sleep and Circadian Disorders (S.R., D.J.G.), Brigham & Women’s Hospital; Beth Israel Deaconess Medical Center (S.R., D.J.G.); Division of Sleep Medicine Harvard Medical School, Boston, MA; VA Boston Healthcare System (D.J.G.), Boston, MA; Turner Institute for Brain and Mental Health (M.P.P.), School of Psychological Sciences, Monash University, Melbourne, VIC, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
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Erlan Sanchez
From the Framingham Heart Study (A.-A.B., A.S.B., J.R.R., C.L.S., J.M.Z., S.S., M.P.P. J.J.H.); Department of Neurology (A.-A.B., A.S.B., C.L.S., S.S., J.J.H.), Boston University School of Medicine; Department of Biostatistics (A.S.B., J.J.H. ), Boston University School of Public Health, MA; Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases (V.M., C.L.S., S.S., J.J.H.), and Department of Population Health Sciences (J.J.H.), University of Texas Health Sciences Center, San Antonio; Centre for Advanced Research in Sleep Medicine (E.S.), Hôpital du Sacré-Coeur de Montréal, CIUSSS-NIM; Department of Neuroscience (E.S.), Université de Montréal, Quebec, Canada; Department of Neurology (C.D., P.M.), and School of Medicine and Imaging of Dementia and Aging Laboratory, Center for Neuroscience (P.M.), University of California, Davis, Sacramento; Division of Sleep and Circadian Disorders (S.R., D.J.G.), Brigham & Women’s Hospital; Beth Israel Deaconess Medical Center (S.R., D.J.G.); Division of Sleep Medicine Harvard Medical School, Boston, MA; VA Boston Healthcare System (D.J.G.), Boston, MA; Turner Institute for Brain and Mental Health (M.P.P.), School of Psychological Sciences, Monash University, Melbourne, VIC, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
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Charles S. DeCarli
From the Framingham Heart Study (A.-A.B., A.S.B., J.R.R., C.L.S., J.M.Z., S.S., M.P.P. J.J.H.); Department of Neurology (A.-A.B., A.S.B., C.L.S., S.S., J.J.H.), Boston University School of Medicine; Department of Biostatistics (A.S.B., J.J.H. ), Boston University School of Public Health, MA; Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases (V.M., C.L.S., S.S., J.J.H.), and Department of Population Health Sciences (J.J.H.), University of Texas Health Sciences Center, San Antonio; Centre for Advanced Research in Sleep Medicine (E.S.), Hôpital du Sacré-Coeur de Montréal, CIUSSS-NIM; Department of Neuroscience (E.S.), Université de Montréal, Quebec, Canada; Department of Neurology (C.D., P.M.), and School of Medicine and Imaging of Dementia and Aging Laboratory, Center for Neuroscience (P.M.), University of California, Davis, Sacramento; Division of Sleep and Circadian Disorders (S.R., D.J.G.), Brigham & Women’s Hospital; Beth Israel Deaconess Medical Center (S.R., D.J.G.); Division of Sleep Medicine Harvard Medical School, Boston, MA; VA Boston Healthcare System (D.J.G.), Boston, MA; Turner Institute for Brain and Mental Health (M.P.P.), School of Psychological Sciences, Monash University, Melbourne, VIC, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
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Susan Redline
From the Framingham Heart Study (A.-A.B., A.S.B., J.R.R., C.L.S., J.M.Z., S.S., M.P.P. J.J.H.); Department of Neurology (A.-A.B., A.S.B., C.L.S., S.S., J.J.H.), Boston University School of Medicine; Department of Biostatistics (A.S.B., J.J.H. ), Boston University School of Public Health, MA; Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases (V.M., C.L.S., S.S., J.J.H.), and Department of Population Health Sciences (J.J.H.), University of Texas Health Sciences Center, San Antonio; Centre for Advanced Research in Sleep Medicine (E.S.), Hôpital du Sacré-Coeur de Montréal, CIUSSS-NIM; Department of Neuroscience (E.S.), Université de Montréal, Quebec, Canada; Department of Neurology (C.D., P.M.), and School of Medicine and Imaging of Dementia and Aging Laboratory, Center for Neuroscience (P.M.), University of California, Davis, Sacramento; Division of Sleep and Circadian Disorders (S.R., D.J.G.), Brigham & Women’s Hospital; Beth Israel Deaconess Medical Center (S.R., D.J.G.); Division of Sleep Medicine Harvard Medical School, Boston, MA; VA Boston Healthcare System (D.J.G.), Boston, MA; Turner Institute for Brain and Mental Health (M.P.P.), School of Psychological Sciences, Monash University, Melbourne, VIC, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
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Daniel J. Gottlieb
From the Framingham Heart Study (A.-A.B., A.S.B., J.R.R., C.L.S., J.M.Z., S.S., M.P.P. J.J.H.); Department of Neurology (A.-A.B., A.S.B., C.L.S., S.S., J.J.H.), Boston University School of Medicine; Department of Biostatistics (A.S.B., J.J.H. ), Boston University School of Public Health, MA; Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases (V.M., C.L.S., S.S., J.J.H.), and Department of Population Health Sciences (J.J.H.), University of Texas Health Sciences Center, San Antonio; Centre for Advanced Research in Sleep Medicine (E.S.), Hôpital du Sacré-Coeur de Montréal, CIUSSS-NIM; Department of Neuroscience (E.S.), Université de Montréal, Quebec, Canada; Department of Neurology (C.D., P.M.), and School of Medicine and Imaging of Dementia and Aging Laboratory, Center for Neuroscience (P.M.), University of California, Davis, Sacramento; Division of Sleep and Circadian Disorders (S.R., D.J.G.), Brigham & Women’s Hospital; Beth Israel Deaconess Medical Center (S.R., D.J.G.); Division of Sleep Medicine Harvard Medical School, Boston, MA; VA Boston Healthcare System (D.J.G.), Boston, MA; Turner Institute for Brain and Mental Health (M.P.P.), School of Psychological Sciences, Monash University, Melbourne, VIC, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
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Pauline Maillard
From the Framingham Heart Study (A.-A.B., A.S.B., J.R.R., C.L.S., J.M.Z., S.S., M.P.P. J.J.H.); Department of Neurology (A.-A.B., A.S.B., C.L.S., S.S., J.J.H.), Boston University School of Medicine; Department of Biostatistics (A.S.B., J.J.H. ), Boston University School of Public Health, MA; Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases (V.M., C.L.S., S.S., J.J.H.), and Department of Population Health Sciences (J.J.H.), University of Texas Health Sciences Center, San Antonio; Centre for Advanced Research in Sleep Medicine (E.S.), Hôpital du Sacré-Coeur de Montréal, CIUSSS-NIM; Department of Neuroscience (E.S.), Université de Montréal, Quebec, Canada; Department of Neurology (C.D., P.M.), and School of Medicine and Imaging of Dementia and Aging Laboratory, Center for Neuroscience (P.M.), University of California, Davis, Sacramento; Division of Sleep and Circadian Disorders (S.R., D.J.G.), Brigham & Women’s Hospital; Beth Israel Deaconess Medical Center (S.R., D.J.G.); Division of Sleep Medicine Harvard Medical School, Boston, MA; VA Boston Healthcare System (D.J.G.), Boston, MA; Turner Institute for Brain and Mental Health (M.P.P.), School of Psychological Sciences, Monash University, Melbourne, VIC, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
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Jose Rafael Romero
From the Framingham Heart Study (A.-A.B., A.S.B., J.R.R., C.L.S., J.M.Z., S.S., M.P.P. J.J.H.); Department of Neurology (A.-A.B., A.S.B., C.L.S., S.S., J.J.H.), Boston University School of Medicine; Department of Biostatistics (A.S.B., J.J.H. ), Boston University School of Public Health, MA; Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases (V.M., C.L.S., S.S., J.J.H.), and Department of Population Health Sciences (J.J.H.), University of Texas Health Sciences Center, San Antonio; Centre for Advanced Research in Sleep Medicine (E.S.), Hôpital du Sacré-Coeur de Montréal, CIUSSS-NIM; Department of Neuroscience (E.S.), Université de Montréal, Quebec, Canada; Department of Neurology (C.D., P.M.), and School of Medicine and Imaging of Dementia and Aging Laboratory, Center for Neuroscience (P.M.), University of California, Davis, Sacramento; Division of Sleep and Circadian Disorders (S.R., D.J.G.), Brigham & Women’s Hospital; Beth Israel Deaconess Medical Center (S.R., D.J.G.); Division of Sleep Medicine Harvard Medical School, Boston, MA; VA Boston Healthcare System (D.J.G.), Boston, MA; Turner Institute for Brain and Mental Health (M.P.P.), School of Psychological Sciences, Monash University, Melbourne, VIC, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
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Claudia L. Satizabal
From the Framingham Heart Study (A.-A.B., A.S.B., J.R.R., C.L.S., J.M.Z., S.S., M.P.P. J.J.H.); Department of Neurology (A.-A.B., A.S.B., C.L.S., S.S., J.J.H.), Boston University School of Medicine; Department of Biostatistics (A.S.B., J.J.H. ), Boston University School of Public Health, MA; Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases (V.M., C.L.S., S.S., J.J.H.), and Department of Population Health Sciences (J.J.H.), University of Texas Health Sciences Center, San Antonio; Centre for Advanced Research in Sleep Medicine (E.S.), Hôpital du Sacré-Coeur de Montréal, CIUSSS-NIM; Department of Neuroscience (E.S.), Université de Montréal, Quebec, Canada; Department of Neurology (C.D., P.M.), and School of Medicine and Imaging of Dementia and Aging Laboratory, Center for Neuroscience (P.M.), University of California, Davis, Sacramento; Division of Sleep and Circadian Disorders (S.R., D.J.G.), Brigham & Women’s Hospital; Beth Israel Deaconess Medical Center (S.R., D.J.G.); Division of Sleep Medicine Harvard Medical School, Boston, MA; VA Boston Healthcare System (D.J.G.), Boston, MA; Turner Institute for Brain and Mental Health (M.P.P.), School of Psychological Sciences, Monash University, Melbourne, VIC, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
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Jared M. Zucker
From the Framingham Heart Study (A.-A.B., A.S.B., J.R.R., C.L.S., J.M.Z., S.S., M.P.P. J.J.H.); Department of Neurology (A.-A.B., A.S.B., C.L.S., S.S., J.J.H.), Boston University School of Medicine; Department of Biostatistics (A.S.B., J.J.H. ), Boston University School of Public Health, MA; Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases (V.M., C.L.S., S.S., J.J.H.), and Department of Population Health Sciences (J.J.H.), University of Texas Health Sciences Center, San Antonio; Centre for Advanced Research in Sleep Medicine (E.S.), Hôpital du Sacré-Coeur de Montréal, CIUSSS-NIM; Department of Neuroscience (E.S.), Université de Montréal, Quebec, Canada; Department of Neurology (C.D., P.M.), and School of Medicine and Imaging of Dementia and Aging Laboratory, Center for Neuroscience (P.M.), University of California, Davis, Sacramento; Division of Sleep and Circadian Disorders (S.R., D.J.G.), Brigham & Women’s Hospital; Beth Israel Deaconess Medical Center (S.R., D.J.G.); Division of Sleep Medicine Harvard Medical School, Boston, MA; VA Boston Healthcare System (D.J.G.), Boston, MA; Turner Institute for Brain and Mental Health (M.P.P.), School of Psychological Sciences, Monash University, Melbourne, VIC, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
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Sudha Seshadri
From the Framingham Heart Study (A.-A.B., A.S.B., J.R.R., C.L.S., J.M.Z., S.S., M.P.P. J.J.H.); Department of Neurology (A.-A.B., A.S.B., C.L.S., S.S., J.J.H.), Boston University School of Medicine; Department of Biostatistics (A.S.B., J.J.H. ), Boston University School of Public Health, MA; Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases (V.M., C.L.S., S.S., J.J.H.), and Department of Population Health Sciences (J.J.H.), University of Texas Health Sciences Center, San Antonio; Centre for Advanced Research in Sleep Medicine (E.S.), Hôpital du Sacré-Coeur de Montréal, CIUSSS-NIM; Department of Neuroscience (E.S.), Université de Montréal, Quebec, Canada; Department of Neurology (C.D., P.M.), and School of Medicine and Imaging of Dementia and Aging Laboratory, Center for Neuroscience (P.M.), University of California, Davis, Sacramento; Division of Sleep and Circadian Disorders (S.R., D.J.G.), Brigham & Women’s Hospital; Beth Israel Deaconess Medical Center (S.R., D.J.G.); Division of Sleep Medicine Harvard Medical School, Boston, MA; VA Boston Healthcare System (D.J.G.), Boston, MA; Turner Institute for Brain and Mental Health (M.P.P.), School of Psychological Sciences, Monash University, Melbourne, VIC, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
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Matthew P. Pase
From the Framingham Heart Study (A.-A.B., A.S.B., J.R.R., C.L.S., J.M.Z., S.S., M.P.P. J.J.H.); Department of Neurology (A.-A.B., A.S.B., C.L.S., S.S., J.J.H.), Boston University School of Medicine; Department of Biostatistics (A.S.B., J.J.H. ), Boston University School of Public Health, MA; Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases (V.M., C.L.S., S.S., J.J.H.), and Department of Population Health Sciences (J.J.H.), University of Texas Health Sciences Center, San Antonio; Centre for Advanced Research in Sleep Medicine (E.S.), Hôpital du Sacré-Coeur de Montréal, CIUSSS-NIM; Department of Neuroscience (E.S.), Université de Montréal, Quebec, Canada; Department of Neurology (C.D., P.M.), and School of Medicine and Imaging of Dementia and Aging Laboratory, Center for Neuroscience (P.M.), University of California, Davis, Sacramento; Division of Sleep and Circadian Disorders (S.R., D.J.G.), Brigham & Women’s Hospital; Beth Israel Deaconess Medical Center (S.R., D.J.G.); Division of Sleep Medicine Harvard Medical School, Boston, MA; VA Boston Healthcare System (D.J.G.), Boston, MA; Turner Institute for Brain and Mental Health (M.P.P.), School of Psychological Sciences, Monash University, Melbourne, VIC, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
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Jayandra J. Himali
From the Framingham Heart Study (A.-A.B., A.S.B., J.R.R., C.L.S., J.M.Z., S.S., M.P.P. J.J.H.); Department of Neurology (A.-A.B., A.S.B., C.L.S., S.S., J.J.H.), Boston University School of Medicine; Department of Biostatistics (A.S.B., J.J.H. ), Boston University School of Public Health, MA; Glenn Biggs Institute for Alzheimer’s & Neurodegenerative Diseases (V.M., C.L.S., S.S., J.J.H.), and Department of Population Health Sciences (J.J.H.), University of Texas Health Sciences Center, San Antonio; Centre for Advanced Research in Sleep Medicine (E.S.), Hôpital du Sacré-Coeur de Montréal, CIUSSS-NIM; Department of Neuroscience (E.S.), Université de Montréal, Quebec, Canada; Department of Neurology (C.D., P.M.), and School of Medicine and Imaging of Dementia and Aging Laboratory, Center for Neuroscience (P.M.), University of California, Davis, Sacramento; Division of Sleep and Circadian Disorders (S.R., D.J.G.), Brigham & Women’s Hospital; Beth Israel Deaconess Medical Center (S.R., D.J.G.); Division of Sleep Medicine Harvard Medical School, Boston, MA; VA Boston Healthcare System (D.J.G.), Boston, MA; Turner Institute for Brain and Mental Health (M.P.P.), School of Psychological Sciences, Monash University, Melbourne, VIC, Australia; and Harvard T.H. Chan School of Public Health (M.P.P.), Boston, MA.
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Citation
Slow-Wave Sleep and MRI Markers of Brain Aging in a Community-Based Sample
Andrée-Ann Baril, Alexa S. Beiser, Vincent Mysliwiec, Erlan Sanchez, Charles S. DeCarli, Susan Redline, Daniel J. Gottlieb, Pauline Maillard, Jose Rafael Romero, Claudia L. Satizabal, Jared M. Zucker, Sudha Seshadri, Matthew P. Pase, Jayandra J. Himali
Neurology Mar 2021, 96 (10) e1462-e1469; DOI: 10.1212/WNL.0000000000011377

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Abstract

Objective To test the hypothesis that reduced slow-wave sleep, or N3 sleep, which is thought to underlie the restorative functions of sleep, is associated with MRI markers of brain aging, we evaluated this relationship in the community-based Framingham Heart Study Offspring cohort using polysomnography and brain MRI.

Methods We studied 492 participants (age 58.8 ± 8.8 years, 49.4% male) free of neurological diseases who completed a brain MRI scan and in-home overnight polysomnography to assess slow-wave sleep (absolute duration and percentage of total sleep). Volumes of total brain, total cortical, frontal cortical, subcortical gray matter, hippocampus, and white matter hyperintensities were investigated as a percentage of intracranial volume, and the presence of covert brain infarcts was evaluated. Linear and logistic regression models were adjusted for age, age squared, sex, time interval between polysomnography and MRI (3.3 ± 1.0 years), APOE ε4 carrier status, stroke risk factors, sleeping pill use, body mass index, and depression.

Results Less slow-wave sleep was associated with lower cortical brain volume (absolute duration, β [standard error] = 0.20 [0.08], p = 0.015; percentage, 0.16 [0.08], p = 0.044), lower subcortical brain volume (percentage, 0.03 [0.02], p = 0.034), and higher white matter hyperintensities volume (absolute duration, −0.12 [0.05], p = 0.010; percentage, −0.10 [0.04], p = 0.033). Slow-wave sleep duration was not associated with hippocampal volume or the presence of covert brain infarcts.

Conclusion Loss of slow-wave sleep might facilitate accelerated brain aging, as evidence by its association with MRI markers suggestive of brain atrophy and injury. Alternatively, subtle injuries and accelerated aging might reduce the ability of the brain to produce slow-wave sleep.

Glossary

Aβ=
β-amyloid;
PSG=
polysomnography;
SWS=
slow-wave sleep

Footnotes

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

  • ↵* These authors contributed equally to this work as senior authors.

  • Received July 24, 2020.
  • Accepted in final form December 2, 2020.
  • © 2020 American Academy of Neurology
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