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April 28, 2020; 94 (17) Article

Witnessed apneas are associated with elevated tau-PET levels in cognitively unimpaired elderly

Diego Z. Carvalho, Erik K. St. Louis, Christopher G. Schwarz, Val J. Lowe, Bradley F. Boeve, Scott A. Przybelski, Ashritha Reddy, Michelle M. Mielke, David S. Knopman, Ronald C. Petersen, Clifford R. Jack, Prashanthi Vemuri
First published March 26, 2020, DOI: https://doi.org/10.1212/WNL.0000000000009315
Diego Z. Carvalho
From the Departments of Neurology (D.Z.C., E.K.S.L., B.F.B., M.M.M., D.S.K., R.C.P.), Radiology (C.G.S., V.J.L., A.R., C.R.J., P.V.), and Health Sciences Research (S.A.P., M.M.M.), Mayo Clinic, Rochester, MN.
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Erik K. St. Louis
From the Departments of Neurology (D.Z.C., E.K.S.L., B.F.B., M.M.M., D.S.K., R.C.P.), Radiology (C.G.S., V.J.L., A.R., C.R.J., P.V.), and Health Sciences Research (S.A.P., M.M.M.), Mayo Clinic, Rochester, MN.
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Christopher G. Schwarz
From the Departments of Neurology (D.Z.C., E.K.S.L., B.F.B., M.M.M., D.S.K., R.C.P.), Radiology (C.G.S., V.J.L., A.R., C.R.J., P.V.), and Health Sciences Research (S.A.P., M.M.M.), Mayo Clinic, Rochester, MN.
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Val J. Lowe
From the Departments of Neurology (D.Z.C., E.K.S.L., B.F.B., M.M.M., D.S.K., R.C.P.), Radiology (C.G.S., V.J.L., A.R., C.R.J., P.V.), and Health Sciences Research (S.A.P., M.M.M.), Mayo Clinic, Rochester, MN.
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Bradley F. Boeve
From the Departments of Neurology (D.Z.C., E.K.S.L., B.F.B., M.M.M., D.S.K., R.C.P.), Radiology (C.G.S., V.J.L., A.R., C.R.J., P.V.), and Health Sciences Research (S.A.P., M.M.M.), Mayo Clinic, Rochester, MN.
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Scott A. Przybelski
From the Departments of Neurology (D.Z.C., E.K.S.L., B.F.B., M.M.M., D.S.K., R.C.P.), Radiology (C.G.S., V.J.L., A.R., C.R.J., P.V.), and Health Sciences Research (S.A.P., M.M.M.), Mayo Clinic, Rochester, MN.
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Ashritha Reddy
From the Departments of Neurology (D.Z.C., E.K.S.L., B.F.B., M.M.M., D.S.K., R.C.P.), Radiology (C.G.S., V.J.L., A.R., C.R.J., P.V.), and Health Sciences Research (S.A.P., M.M.M.), Mayo Clinic, Rochester, MN.
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Michelle M. Mielke
From the Departments of Neurology (D.Z.C., E.K.S.L., B.F.B., M.M.M., D.S.K., R.C.P.), Radiology (C.G.S., V.J.L., A.R., C.R.J., P.V.), and Health Sciences Research (S.A.P., M.M.M.), Mayo Clinic, Rochester, MN.
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David S. Knopman
From the Departments of Neurology (D.Z.C., E.K.S.L., B.F.B., M.M.M., D.S.K., R.C.P.), Radiology (C.G.S., V.J.L., A.R., C.R.J., P.V.), and Health Sciences Research (S.A.P., M.M.M.), Mayo Clinic, Rochester, MN.
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Ronald C. Petersen
From the Departments of Neurology (D.Z.C., E.K.S.L., B.F.B., M.M.M., D.S.K., R.C.P.), Radiology (C.G.S., V.J.L., A.R., C.R.J., P.V.), and Health Sciences Research (S.A.P., M.M.M.), Mayo Clinic, Rochester, MN.
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Clifford R. Jack Jr
From the Departments of Neurology (D.Z.C., E.K.S.L., B.F.B., M.M.M., D.S.K., R.C.P.), Radiology (C.G.S., V.J.L., A.R., C.R.J., P.V.), and Health Sciences Research (S.A.P., M.M.M.), Mayo Clinic, Rochester, MN.
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Prashanthi Vemuri
From the Departments of Neurology (D.Z.C., E.K.S.L., B.F.B., M.M.M., D.S.K., R.C.P.), Radiology (C.G.S., V.J.L., A.R., C.R.J., P.V.), and Health Sciences Research (S.A.P., M.M.M.), Mayo Clinic, Rochester, MN.
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Citation
Witnessed apneas are associated with elevated tau-PET levels in cognitively unimpaired elderly
Diego Z. Carvalho, Erik K. St. Louis, Christopher G. Schwarz, Val J. Lowe, Bradley F. Boeve, Scott A. Przybelski, Ashritha Reddy, Michelle M. Mielke, David S. Knopman, Ronald C. Petersen, Clifford R. Jack, Prashanthi Vemuri
Neurology Apr 2020, 94 (17) e1793-e1802; DOI: 10.1212/WNL.0000000000009315

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Abstract

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.

Glossary

Aβ=
β-amyloid;
AD=
Alzheimer disease;
AHI=
apnea-hypopnea index;
BMI=
body mass index;
CU=
cognitively unimpaired;
EDS=
excessive daytime sleepiness;
MCI=
mild cognitive impairment;
MCSA=
Mayo Clinic Study of Aging;
OSA=
obstructive sleep apnea;
p-tau=
hyperphosphorylated tau;
PiB=
Pittsburgh compound B;
ROI=
region of interest;
SUVR=
standardized uptake value ratio;
SWA=
slow-wave activity

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.

  • Received July 15, 2019.
  • Accepted in final form November 13, 2019.
  • © 2020 American Academy of Neurology
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