@article{61191d7b695746b4a27024c0bd2946c6,
title = "The association of multimorbidity with preclinical AD stages and SNAP in cognitively unimpaired persons",
abstract = "Background: Multimorbidity (defined as ≥2 chronic conditions) has been associated with increased risk of mild cognitive impairment and cross-sectionally with imaging biomarkers of neurodegeneration in cognitively unimpaired persons aged ≥70 years. Its association with preclinical Alzheimer{\textquoteright}s disease stages has not been studied in detail yet. The objective of the study was to assess the cross-sectional association of multimorbidity with preclinical Alzheimer{\textquoteright}s disease stages and suspected non-amyloid pathophysiology in cognitively unimpaired participants of the Mayo Clinic Study of Aging (≥50 years of age). Methods: The study included 1,535 cognitively unimpaired participants with multimorbidity, 11C-PiB positron emission topography and magnetic resonance imaging data available. Abnormal (elevated) 11C-PiB-positron emission topography retention ratio (A+; standardized uptake value ratio >1.42) and abnormal (reduced) Alzheimer{\textquoteright}s disease signature cortical thickness (N+; <2.67 mm) were used to define biomarker combinations (A−N−, A+N−, A−N+, A+N+). Chronic medical conditions were ascertained by using the Rochester Epidemiology Project medical records linkage system and International Classification of Diseases criteria. Cross-sectional associations were examined using multinomial logistic regression models adjusting for age, sex, education, and apolipoprotein E ℇ4 allele status. Results: Frequency of A+, N+, A+N+, and A−N+ biomarker groups increased significantly with increasing number of chronic conditions. Multimorbidity was significantly associated with A+N+ (vs A−N−; odds ratio, 1.76, 95% confidence interval 1.02, 2.90) and A−N+ (vs A− N−; odds ratio, 2.16, 95% confidence interval 1.47, 3.18). There was a dose–response relationship between increasing number of chronic conditions (eg, 0–1, 2–3, and 4+) and the odds of A+N+ and A−N+ (vs A−N−). Conclusions: Multimorbidity was associated with biomarker combinations that included neurodegeneration with or without elevated amyloid deposition (ie, A−N+, A+N+). The associations should be validated in longitudinal studies.",
keywords = "Amyloid, Multimorbidity, Neurodegeneration, Preclinical AD, SNAP",
author = "Maria Vassilaki and Aakre, {Jeremiah A.} and Kremers, {Walter K.} and Mielke, {Michelle M.} and Geda, {Yonas E.} and Alhurani, {Rabe E.} and Taru Dutt and Machulda, {Mary M.} and Knopman, {David S.} and Prashanthi Vemuri and Coloma, {Preciosa M.} and Barbara Schauble and Lowe, {Val J.} and Jack, {Clifford R.} and Petersen, {Ronald C.} and Roberts, {Rosebud O.}",
note = "Funding Information: The study was supported by the National Institutes of Health (U01 AG006786, P50 AG016574, R01 AG011378, R01 AG041851, R01 NS097495), F. Hoffman-La Roche, the GHR Foundation, the Elsie and Marvin Dekelboum Family Foundation, the Alexander Family Alzheimer?s Disease Research Professorship of the Mayo Clinic, the Alice Weiner Postdoctoral Research Fellowship in Alzheimer?s Disease Research, Mayo Foundation for Medical Education and Research, the Liston Award, and the Schuler Foundation, and was made possible by the Rochester Epidemiology Project (R01 AG034676). M.V. receives research funding from Roche and Biogen. W.K.K. receives research funding from Department of Defense, NIH, Astra Zeneca, Biogen, and Roche. M.M.Mi. is a consultant for Eli Lilly and Lysosomal Therapeutics and receives unrestricted research grants from Biogen, Lundbeck and Roche, and research funding from the NIH/NIA and Department of Defense. Y.E.G. receives funding from NIH and Roche, and serves on Lundbeck Advisory Board. M.M.Ma. and P.V. receive NIH funding. D.S.K. serves on a Data Safety Monitoring Board for the DIAN study. He is an investigator in clinical trials sponsored by Lilly Pharmaceuticals, Biogen, and the Alzheimer?s Treatment and Research Institute at USC, and receives research support from the NIH. P.M.C. and B.S. are full-time employees of, and own shares at, F. Hoffmann-La Roche Ltd. V.J.L. serves on scientific advisory boards for Bayer Schering Pharma, Piramal Life Sciences, and Merck Research, and receives research support from GE Healthcare, Siemens Molecular Imaging, AVID Radiopharmaceuticals, and the NIH (NIA, NCI). C.R.J. serves on scientific advisory board for Eli Lilly, receives research support from the NIH/NIA and the Alexander Family Alzheimer?s Disease Research Professorship of the Mayo Foundation, and holds stock in Johnson & Johnson. R.C.P. is a consultant for Roche, Biogen, Merck, Eli Lilly, and Genentech. He receives publishing royalties from Mild Cognitive Impairment (Oxford University Press, 2003) and research support from the NIH. R.O.R. receives research funding from the NIH/NIA, Biogen, and Roche. J.A.A., R.E.A., and T.D. declare nothing to disclose. Funding Information: The study was supported by the National Institutes of Health (U01 AG006786, P50 AG016574, R01 AG011378, R01 AG041851, R01 NS097495), F. Hoffman-La Roche, the GHR Foundation, the Elsie and Marvin Dekelboum Family Foundation, the Alexander Family Alzheimer{\textquoteright}s Disease Research Professorship of the Mayo Clinic, the Alice Weiner Postdoctoral Research Fellowship in Alzheimer{\textquoteright}s Disease Research, Mayo Foundation for Medical Education and Research, the Liston Award, and the Schuler Foundation, and was made possible by the Rochester Epidemiology Project (R01 AG034676). Publisher Copyright: {\textcopyright} The Author(s) 2018. Published by Oxford University Press on behalf of The Gerontological Society of America.",
year = "2019",
month = may,
day = "16",
doi = "10.1093/gerona/gly149",
language = "English (US)",
volume = "74",
pages = "877--883",
journal = "Journals of Gerontology - Series A Biological Sciences and Medical Sciences",
issn = "1079-5006",
publisher = "Oxford University Press",
number = "6",
}