Title | Obstructive Sleep Apnea Severity Affects Amyloid Burden in Cognitively Normal Elderly. A Longitudinal Study. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Sharma RA, Varga AW, Bubu OM, Pirraglia E, Kam K, Parekh A, Wohlleber M, Miller MD, Andrade A, Lewis C, Tweardy S, Buj M, Yau PL, Sadda R, Mosconi L, Li Y, Butler T, Glodzik L, Fieremans E, Babb JS, Blennow K, Zetterberg H, Lu SE, Badia SG, Romero S, Rosenzweig I, Gosselin N, Jean-Louis G, Rapoport DM, de Leon MJ, Ayappa I, Osorio RS |
Journal | Am J Respir Crit Care Med |
Volume | 197 |
Issue | 7 |
Pagination | 933-943 |
Date Published | 2018 04 01 |
ISSN | 1535-4970 |
Keywords | Aged, Aged, 80 and over, Amyloid beta-Peptides, Brain, Enzyme-Linked Immunosorbent Assay, Female, Follow-Up Studies, Humans, Longitudinal Studies, Male, Middle Aged, Positron-Emission Tomography, Prospective Studies, Severity of Illness Index, Sleep Apnea, Obstructive |
Abstract | 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 of OSA and 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 β 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 [F = 4.26; P < 0.05] and AHI4% [F = 4.36; P < 0.05]) were associated with annual rate of change of cerebrospinal fluid amyloid β using linear regression after adjusting for age, sex, body mass index, and apolipoprotein E4 status. AHIall and AHI4% were not associated with increases in AD-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 (F = 2.96, P = 0.09; and F = 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 from OSA are likely candidate mechanisms. If confirmed, clinical interventions for OSA may be useful in preventing amyloid build-up in cognitively normal elderly. |
DOI | 10.1164/rccm.201704-0704OC |
Alternate Journal | Am J Respir Crit Care Med |
PubMed ID | 29125327 |
PubMed Central ID | PMC6020410 |
Grant List | R01 AG022374 / AG / NIA NIH HHS / United States R01 HL111724 / HL / NHLBI NIH HHS / United States R01 AG035137 / AG / NIA NIH HHS / United States R01 AG013616 / AG / NIA NIH HHS / United States R01 AG012101 / AG / NIA NIH HHS / United States K24 HL109156 / HL / NHLBI NIH HHS / United States R01 AG056031 / AG / NIA NIH HHS / United States R21 AG049348 / AG / NIA NIH HHS / United States / WT_ / Wellcome Trust / United Kingdom R01 HL118624 / HL / NHLBI NIH HHS / United States P30 AG008051 / AG / NIA NIH HHS / United States R01 AG056531 / AG / NIA NIH HHS / United States 103952/Z/14/Z / WT_ / Wellcome Trust / United Kingdom |
Related Institute:
Brain Health Imaging Institute (BHII)