OBJECTIVE: To assess whether informant-reported apneas during sleep (witnessed apneas) in cognitively unimpaired (CU) elderly persons are associated with higher levels of brain tau. METHODS: From the population-based Mayo Clinic Study of Aging, we identified 292 CU elderly ≥65 years of age with both AV-1451 tau-PET and Pittsburgh compound B (PiB)-PET scans and whose bed partners and close relatives had completed a questionnaire that assessed whether participants had witnessed apneas during sleep. For this cross-sectional analysis, we selected the entorhinal and inferior temporal cortices as our regions of interest (ROIs) because they are highly susceptible to tau accumulation. PET signal was scaled to the cerebellum crus to calculate standardized uptake value ratio (SUVR). We fit linear models to assess the association between regional tau and witnessed apneas while controlling for age, sex, years of education, body mass index, hypertension, hyperlipidemia, diabetes, reduced sleep, excessive daytime sleepiness, and global PiB. RESULTS: Forty-three participants (14.7%) were found to have witnessed apneas during sleep. The report of witnessed apneas was associated with higher tau-PET SUVR elevation in our ROIs: 0.049 SUVR (95% confidence interval [CI] 0.010-0.087, p = 0.015) in the entorhinal cortex and 0.037 SUVR (95% CI 0.006-0.067, p = 0.019) in the inferior temporal cortex after controlling for confounders. CONCLUSION: We identified a significant association between witnessed apneas in CU elderly and elevated tau-PET signal in tau-susceptible brain regions. These results suggest a plausible mechanism that could contribute to cognitive impairment and the development of Alzheimer disease. Longitudinal observations are necessary to determine direction of causality.
OBJECTIVE: To assess whether informant-reported apneas during sleep (witnessed apneas) in cognitively unimpaired (CU) elderly persons are associated with higher levels of brain tau. METHODS: From the population-based Mayo Clinic Study of Aging, we identified 292 CU elderly ≥65 years of age with both AV-1451 tau-PET and Pittsburgh compound B (PiB)-PET scans and whose bed partners and close relatives had completed a questionnaire that assessed whether participants had witnessed apneas during sleep. For this cross-sectional analysis, we selected the entorhinal and inferior temporal cortices as our regions of interest (ROIs) because they are highly susceptible to tau accumulation. PET signal was scaled to the cerebellum crus to calculate standardized uptake value ratio (SUVR). We fit linear models to assess the association between regional tau and witnessed apneas while controlling for age, sex, years of education, body mass index, hypertension, hyperlipidemia, diabetes, reduced sleep, excessive daytime sleepiness, and global PiB. RESULTS: Forty-three participants (14.7%) were found to have witnessed apneas during sleep. The report of witnessed apneas was associated with higher tau-PET SUVR elevation in our ROIs: 0.049 SUVR (95% confidence interval [CI] 0.010-0.087, p = 0.015) in the entorhinal cortex and 0.037 SUVR (95% CI 0.006-0.067, p = 0.019) in the inferior temporal cortex after controlling for confounders. CONCLUSION: We identified a significant association between witnessed apneas in CU elderly and elevated tau-PET signal in tau-susceptible brain regions. These results suggest a plausible mechanism that could contribute to cognitive impairment and the development of Alzheimer disease. Longitudinal observations are necessary to determine direction of causality.
Authors: Brendan P Lucey; Austin McCullough; Eric C Landsness; Cristina D Toedebusch; Jennifer S McLeland; Aiad M Zaza; Anne M Fagan; Lena McCue; Chengjie Xiong; John C Morris; Tammie L S Benzinger; David M Holtzman Journal: Sci Transl Med Date: 2019-01-09 Impact factor: 17.956
Authors: Adam J Schwarz; Peng Yu; Bradley B Miller; Sergey Shcherbinin; James Dickson; Michael Navitsky; Abhinay D Joshi; Michael D Devous; Mark S Mintun Journal: Brain Date: 2016-03-02 Impact factor: 13.501
Authors: Clifford R Jack; Heather J Wiste; Stephen D Weigand; Terry M Therneau; Val J Lowe; David S Knopman; Jeffrey L Gunter; Matthew L Senjem; David T Jones; Kejal Kantarci; Mary M Machulda; Michelle M Mielke; Rosebud O Roberts; Prashanthi Vemuri; Denise A Reyes; Ronald C Petersen Journal: Alzheimers Dement Date: 2016-09-30 Impact factor: 21.566
Authors: Jae-Eun Kang; Miranda M Lim; Randall J Bateman; James J Lee; Liam P Smyth; John R Cirrito; Nobuhiro Fujiki; Seiji Nishino; David M Holtzman Journal: Science Date: 2009-09-24 Impact factor: 47.728
Authors: Prashanthi Vemuri; Val J Lowe; David S Knopman; Matthew L Senjem; Bradley J Kemp; Christopher G Schwarz; Scott A Przybelski; Mary M Machulda; Ronald C Petersen; Clifford R Jack Journal: Alzheimers Dement (Amst) Date: 2016-12-21
Authors: Jonathan Cedernaes; Ricardo S Osorio; Andrew W Varga; Korey Kam; Helgi B Schiöth; Christian Benedict Journal: Sleep Med Rev Date: 2016-02-11 Impact factor: 11.609
Authors: Alexandria B Marciante; John Howard; Mia N Kelly; Juan Santiago Moreno; Latoya L Allen; Elisa J Gonzalez-Rothi; Gordon S Mitchell Journal: J Appl Physiol (1985) Date: 2022-07-21
Authors: Patrick Lao; Molly E Zimmerman; Sigan L Hartley; José Gutierrez; David Keator; Kay C Igwe; Krystal K Laing; Dejania Cotton-Samuel; Mithra Sathishkumar; Fahmida Moni; Howard Andrews; Sharon Krinsky-McHale; Elizabeth Head; Joseph H Lee; Florence Lai; Michael A Yassa; H Diana Rosas; Wayne Silverman; Ira T Lott; Nicole Schupf; Adam M Brickman Journal: Sleep Adv Date: 2022-05-05
Authors: Anna E Mullins; Korey Kam; Ankit Parekh; Omonigho M Bubu; Ricardo S Osorio; Andrew W Varga Journal: Neurobiol Dis Date: 2020-08-27 Impact factor: 5.996
Authors: Diego Z Carvalho; Erik K St Louis; Scott A Przybelski; Timothy I Morgenthaler; Mary M Machulda; Bradley F Boeve; Ronald C Petersen; Clifford R Jack; Jonathan Graff-Radford; Prashanthi Vemuri; Michelle M Mielke Journal: Front Aging Neurosci Date: 2022-07-11 Impact factor: 5.702
Authors: Joseph R Winer; Allison Morehouse; Laura Fenton; Theresa M Harrison; Lylian Ayangma; Mark Reed; Samika Kumar; Suzanne L Baker; William J Jagust; Matthew P Walker Journal: J Neurosci Date: 2021-07-21 Impact factor: 6.167
Authors: Omonigho M Bubu; Ogie Q Umasabor-Bubu; Arlener D Turner; Ankit Parekh; Anna E Mullins; Korey Kam; Madeline K Birckbichler; Fahad Mukhtar; Alfred K Mbah; Natasha J Williams; David M Rapoport; Mony de Leon; Girardin Jean-Louis; Indu Ayappa; Andrew W Varga; Ricardo S Osorio Journal: Alzheimers Dement Date: 2020-10-08 Impact factor: 21.566
Authors: Helena U Zacharias; Antoine Weihs; Mohamad Habes; Katharina Wittfeld; Stefan Frenzel; Tanweer Rashid; Beate Stubbe; Anne Obst; András Szentkirályi; Robin Bülow; Klaus Berger; Ingo Fietze; Thomas Penzel; Norbert Hosten; Ralf Ewert; Henry Völzke; Hans J Grabe Journal: JAMA Netw Open Date: 2021-10-01