Obstructive sleep apnea severity affects amyloid burden in cognitively normal elderly: A longitudinal study

Ram A. Sharma, Andrew W. Varga, Omonigho M. Bubu, Elizabeth Pirraglia, Korey Kam, Ankit Parekh, Margaret Wohlleber, Margo D. Miller, Andreia Andrade, Clifton Lewis, Samuel Tweardy, Maja Buj, Po L. Yau, Reem Sadda, Lisa Mosconi, Yi Li, Tracy Butler, Lidia Glodzik, Els Fieremans, James S. BabbKaj Blennow, Henrik Zetterberg, Shou E. Lu, Sandra G. Badia, Sergio Romero, Ivana Rosenzweig, Nadia Gosselin, Girardin Jean-Louis, David M. Rapoport, Mony J. De Leon, Indu Ayappa, Ricardo S. Osorio

Research output: Contribution to journalArticlepeer-review

154 Scopus citations


Rationale: Recent evidence suggests that obstructive sleep apnea (OSA) may be a risk factor for developing mild cognitive impairment and Alzheimer's disease. However, how sleep apnea affects longitudinal risk for Alzheimer's disease is less well understood. Objectives: To test the hypothesis that there is an association between severity ofOSAand longitudinal increase in amyloid burden in cognitively normal elderly. Methods: Data were derived from a 2-year prospective longitudinal study that sampled community-dwelling healthy cognitively normal elderly. Subjects were healthy volunteers between the ages of 55 and 90, were nondepressed, and had a consensus clinical diagnosis of cognitively normal. Cerebrospinal fluid amyloid b was measured using ELISA. Subjects received Pittsburgh compound B positron emission tomography scans following standardized procedures. Monitoring of OSA was completed using a home sleep recording device. Measurements and Main Results: We found that severity of OSA indices (AHIall [F1,88 = 4.26; P<0.05] andAHI4%[F1,87 = 4.36; P < 0.05]) were associated with annual rate of change of cerebrospinal fluid amyloid β42 using linear regression after adjusting for age, sex, body mass index, and apolipoprotein E4 status. AHIall and AHI4% were not associated with increases in ADPiB-mask (Alzheimer's disease vulnerable regions of interest Pittsburg compound B positron emission tomography mask) most likely because of the small sample size, although there was a trend for AHIall (F1,28 = 2.96, P = 0.09; and F1,28 = 2.32, not significant, respectively). Conclusions: In a sample of cognitively normal elderly, OSA was associated with markers of increased amyloid burden over the 2-year follow-up. Sleep fragmentation and/or intermittent hypoxia fromOSA are likely candidate mechanisms. If confirmed, clinical interventions for OSA maybeuseful inpreventing amyloidbuild-up incognitivelynormal elderly.

Original languageEnglish
Pages (from-to)933-943
Number of pages11
JournalAmerican Journal of Respiratory and Critical Care Medicine
Issue number7
StatePublished - 1 Apr 2018


  • Amyloid burden
  • Cognitive impairment
  • Obstructive sleep apnea
  • Pittsburgh compound B positron emission tomography scan cerebrospinal fluid amyloid β


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