title: Associations of brain lesions at autopsy with polysomnography features before death.
abstract: OBJECTIVE
  To determine how sleep-disordered breathing, nocturnal hypoxia, and changes in sleep architecture in the elderly may be related to the development of the neuropathologic correlates of dementia.
  
  
  METHODS
  The Honolulu-Asia Aging Study is a prospective cohort study of Japanese American men in Honolulu, HI. We examined brain lesions at autopsy (Braak stage, neurofibrillary tangle and neuritic plaque counts, microinfarcts, generalized brain atrophy, lacunar infarcts, Lewy bodies [LBs], neuronal loss and gliosis in the locus ceruleus) in 167 participants who underwent polysomnography in 1999-2000 (mean age, 84 years) and died through 2010 (mean 6.4 years to death). Polysomnography measures included the apnea-hypopnea index, duration of apnea or hypopnea, duration of hypoxemia, minimum oxygen saturation (SpO₂), duration of slow-wave sleep (SWS, non-REM stage N3), and arousals.
  
  
  RESULTS
  Sleep duration with SpO₂ <95% was associated with higher levels of microinfarcts (adjusted odds ratio [OR] 3.88, 95% confidence interval [CI] 1.10-13.76, comparing the highest to lowest quartiles of %sleep with SpO₂ <95%). Greater SWS duration was associated with less generalized atrophy (adjusted OR 0.32, 95% CI 0.10-1.03, comparing highest to lowest quartiles of %sleep in SWS). LBs were less common with greater %sleep with SpO₂ <95% (adjusted OR 0.17, 95% CI 0.04-0.78, comparing highest to lowest quartiles). Higher minimum SpO₂ during REM sleep was associated with less gliosis and neuronal loss in the locus ceruleus. Cognitive scores declined less among men with greater SWS duration.
  
  
  CONCLUSIONS
  The findings support a role for lower nocturnal oxygenation and SWS in the development of microinfarcts and brain atrophy, but not Alzheimer lesions or LBs.
authors.affiliation: From the VA Pacific Islands Health Care System (R.P.G., G.W.R., H.P.), Pacific Health Research and Education Institute (R.P.G., G.W.R., H.P., J.H.U.-L., L.R.W.), Departments of Medicine (G.W.R., H.P.), Geriatric Medicine (G.W.R., H.P., K.H.M., L.R.W.), and Pathology (J.H.U.-L.), University of Hawaii John A. Burns School of Medicine, and Kuakini Medical Center (K.H.M.), Honolulu, HI; Department of Pathology (J.A.S.), University of Utah, Salt Lake City; Department of Neurology (C.Z.), Keck School of Medicine, University of Southern California, Los Angeles; Departments of Medicine and Neurology, Brigham and Women's Hospital (S.R.), Department of Medicine, Beth Israel Deaconess Medical Center (S.R.), and Harvard Medical School (S.R.), Boston, MA; and the Laboratory of Epidemiology and Population Sciences (L.J.L., L.R.W.), Intramural Research Program, National Institute on Aging, NIH, Bethesda, MD. rebecca.gelber@va.gov.
authors.forename: Rebecca P
authors.initials: RP
authors.lastname: Gelber
authors.affiliation: From the VA Pacific Islands Health Care System (R.P.G., G.W.R., H.P.), Pacific Health Research and Education Institute (R.P.G., G.W.R., H.P., J.H.U.-L., L.R.W.), Departments of Medicine (G.W.R., H.P.), Geriatric Medicine (G.W.R., H.P., K.H.M., L.R.W.), and Pathology (J.H.U.-L.), University of Hawaii John A. Burns School of Medicine, and Kuakini Medical Center (K.H.M.), Honolulu, HI; Department of Pathology (J.A.S.), University of Utah, Salt Lake City; Department of Neurology (C.Z.), Keck School of Medicine, University of Southern California, Los Angeles; Departments of Medicine and Neurology, Brigham and Women's Hospital (S.R.), Department of Medicine, Beth Israel Deaconess Medical Center (S.R.), and Harvard Medical School (S.R.), Boston, MA; and the Laboratory of Epidemiology and Population Sciences (L.J.L., L.R.W.), Intramural Research Program, National Institute on Aging, NIH, Bethesda, MD.
authors.forename: Susan
authors.initials: S
authors.lastname: Redline
authors.affiliation: From the VA Pacific Islands Health Care System (R.P.G., G.W.R., H.P.), Pacific Health Research and Education Institute (R.P.G., G.W.R., H.P., J.H.U.-L., L.R.W.), Departments of Medicine (G.W.R., H.P.), Geriatric Medicine (G.W.R., H.P., K.H.M., L.R.W.), and Pathology (J.H.U.-L.), University of Hawaii John A. Burns School of Medicine, and Kuakini Medical Center (K.H.M.), Honolulu, HI; Department of Pathology (J.A.S.), University of Utah, Salt Lake City; Department of Neurology (C.Z.), Keck School of Medicine, University of Southern California, Los Angeles; Departments of Medicine and Neurology, Brigham and Women's Hospital (S.R.), Department of Medicine, Beth Israel Deaconess Medical Center (S.R.), and Harvard Medical School (S.R.), Boston, MA; and the Laboratory of Epidemiology and Population Sciences (L.J.L., L.R.W.), Intramural Research Program, National Institute on Aging, NIH, Bethesda, MD.
authors.forename: G Webster
authors.initials: GW
authors.lastname: Ross
authors.affiliation: From the VA Pacific Islands Health Care System (R.P.G., G.W.R., H.P.), Pacific Health Research and Education Institute (R.P.G., G.W.R., H.P., J.H.U.-L., L.R.W.), Departments of Medicine (G.W.R., H.P.), Geriatric Medicine (G.W.R., H.P., K.H.M., L.R.W.), and Pathology (J.H.U.-L.), University of Hawaii John A. Burns School of Medicine, and Kuakini Medical Center (K.H.M.), Honolulu, HI; Department of Pathology (J.A.S.), University of Utah, Salt Lake City; Department of Neurology (C.Z.), Keck School of Medicine, University of Southern California, Los Angeles; Departments of Medicine and Neurology, Brigham and Women's Hospital (S.R.), Department of Medicine, Beth Israel Deaconess Medical Center (S.R.), and Harvard Medical School (S.R.), Boston, MA; and the Laboratory of Epidemiology and Population Sciences (L.J.L., L.R.W.), Intramural Research Program, National Institute on Aging, NIH, Bethesda, MD.
authors.forename: Helen
authors.initials: H
authors.lastname: Petrovitch
authors.affiliation: From the VA Pacific Islands Health Care System (R.P.G., G.W.R., H.P.), Pacific Health Research and Education Institute (R.P.G., G.W.R., H.P., J.H.U.-L., L.R.W.), Departments of Medicine (G.W.R., H.P.), Geriatric Medicine (G.W.R., H.P., K.H.M., L.R.W.), and Pathology (J.H.U.-L.), University of Hawaii John A. Burns School of Medicine, and Kuakini Medical Center (K.H.M.), Honolulu, HI; Department of Pathology (J.A.S.), University of Utah, Salt Lake City; Department of Neurology (C.Z.), Keck School of Medicine, University of Southern California, Los Angeles; Departments of Medicine and Neurology, Brigham and Women's Hospital (S.R.), Department of Medicine, Beth Israel Deaconess Medical Center (S.R.), and Harvard Medical School (S.R.), Boston, MA; and the Laboratory of Epidemiology and Population Sciences (L.J.L., L.R.W.), Intramural Research Program, National Institute on Aging, NIH, Bethesda, MD.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Sonnen
authors.affiliation: From the VA Pacific Islands Health Care System (R.P.G., G.W.R., H.P.), Pacific Health Research and Education Institute (R.P.G., G.W.R., H.P., J.H.U.-L., L.R.W.), Departments of Medicine (G.W.R., H.P.), Geriatric Medicine (G.W.R., H.P., K.H.M., L.R.W.), and Pathology (J.H.U.-L.), University of Hawaii John A. Burns School of Medicine, and Kuakini Medical Center (K.H.M.), Honolulu, HI; Department of Pathology (J.A.S.), University of Utah, Salt Lake City; Department of Neurology (C.Z.), Keck School of Medicine, University of Southern California, Los Angeles; Departments of Medicine and Neurology, Brigham and Women's Hospital (S.R.), Department of Medicine, Beth Israel Deaconess Medical Center (S.R.), and Harvard Medical School (S.R.), Boston, MA; and the Laboratory of Epidemiology and Population Sciences (L.J.L., L.R.W.), Intramural Research Program, National Institute on Aging, NIH, Bethesda, MD.
authors.forename: Chris
authors.initials: C
authors.lastname: Zarow
authors.affiliation: From the VA Pacific Islands Health Care System (R.P.G., G.W.R., H.P.), Pacific Health Research and Education Institute (R.P.G., G.W.R., H.P., J.H.U.-L., L.R.W.), Departments of Medicine (G.W.R., H.P.), Geriatric Medicine (G.W.R., H.P., K.H.M., L.R.W.), and Pathology (J.H.U.-L.), University of Hawaii John A. Burns School of Medicine, and Kuakini Medical Center (K.H.M.), Honolulu, HI; Department of Pathology (J.A.S.), University of Utah, Salt Lake City; Department of Neurology (C.Z.), Keck School of Medicine, University of Southern California, Los Angeles; Departments of Medicine and Neurology, Brigham and Women's Hospital (S.R.), Department of Medicine, Beth Israel Deaconess Medical Center (S.R.), and Harvard Medical School (S.R.), Boston, MA; and the Laboratory of Epidemiology and Population Sciences (L.J.L., L.R.W.), Intramural Research Program, National Institute on Aging, NIH, Bethesda, MD.
authors.forename: Jane H
authors.initials: JH
authors.lastname: Uyehara-Lock
authors.affiliation: From the VA Pacific Islands Health Care System (R.P.G., G.W.R., H.P.), Pacific Health Research and Education Institute (R.P.G., G.W.R., H.P., J.H.U.-L., L.R.W.), Departments of Medicine (G.W.R., H.P.), Geriatric Medicine (G.W.R., H.P., K.H.M., L.R.W.), and Pathology (J.H.U.-L.), University of Hawaii John A. Burns School of Medicine, and Kuakini Medical Center (K.H.M.), Honolulu, HI; Department of Pathology (J.A.S.), University of Utah, Salt Lake City; Department of Neurology (C.Z.), Keck School of Medicine, University of Southern California, Los Angeles; Departments of Medicine and Neurology, Brigham and Women's Hospital (S.R.), Department of Medicine, Beth Israel Deaconess Medical Center (S.R.), and Harvard Medical School (S.R.), Boston, MA; and the Laboratory of Epidemiology and Population Sciences (L.J.L., L.R.W.), Intramural Research Program, National Institute on Aging, NIH, Bethesda, MD.
authors.forename: Kamal H
authors.initials: KH
authors.lastname: Masaki
authors.affiliation: From the VA Pacific Islands Health Care System (R.P.G., G.W.R., H.P.), Pacific Health Research and Education Institute (R.P.G., G.W.R., H.P., J.H.U.-L., L.R.W.), Departments of Medicine (G.W.R., H.P.), Geriatric Medicine (G.W.R., H.P., K.H.M., L.R.W.), and Pathology (J.H.U.-L.), University of Hawaii John A. Burns School of Medicine, and Kuakini Medical Center (K.H.M.), Honolulu, HI; Department of Pathology (J.A.S.), University of Utah, Salt Lake City; Department of Neurology (C.Z.), Keck School of Medicine, University of Southern California, Los Angeles; Departments of Medicine and Neurology, Brigham and Women's Hospital (S.R.), Department of Medicine, Beth Israel Deaconess Medical Center (S.R.), and Harvard Medical School (S.R.), Boston, MA; and the Laboratory of Epidemiology and Population Sciences (L.J.L., L.R.W.), Intramural Research Program, National Institute on Aging, NIH, Bethesda, MD.
authors.forename: Lenore J
authors.initials: LJ
authors.lastname: Launer
authors.affiliation: From the VA Pacific Islands Health Care System (R.P.G., G.W.R., H.P.), Pacific Health Research and Education Institute (R.P.G., G.W.R., H.P., J.H.U.-L., L.R.W.), Departments of Medicine (G.W.R., H.P.), Geriatric Medicine (G.W.R., H.P., K.H.M., L.R.W.), and Pathology (J.H.U.-L.), University of Hawaii John A. Burns School of Medicine, and Kuakini Medical Center (K.H.M.), Honolulu, HI; Department of Pathology (J.A.S.), University of Utah, Salt Lake City; Department of Neurology (C.Z.), Keck School of Medicine, University of Southern California, Los Angeles; Departments of Medicine and Neurology, Brigham and Women's Hospital (S.R.), Department of Medicine, Beth Israel Deaconess Medical Center (S.R.), and Harvard Medical School (S.R.), Boston, MA; and the Laboratory of Epidemiology and Population Sciences (L.J.L., L.R.W.), Intramural Research Program, National Institute on Aging, NIH, Bethesda, MD.
authors.forename: Lon R
authors.initials: LR
authors.lastname: White
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001213:Asian; D001344:Autopsy; D001921:Brain / Q000473:pathology*; D020520:Brain Infarction / Q000209:etiology / Q000473:pathology; D016009:Chi-Square Distribution; D015331:Cohort Studies; D003643:Death; D003704:Dementia / Q000150:complications* / Q000473:pathology; D006801:Humans; D008297:Male; D016874:Neurofibrillary Tangles / Q000473:pathology; D009483:Neuropsychological Tests; D058225:Plaque, Amyloid / Q000473:pathology; D017286:Polysomnography / Q000379:methods*; D012891:Sleep Apnea Syndromes / Q000150:complications* / Q000175:diagnosis*