@article{7e1258d8c4404cf4a4578e67ec66df3d,
title = "Association Between Functional Performance and Alzheimer's Disease Biomarkers in Individuals Without Dementia",
abstract = "Objectives: To examine the cross-sectional association between functional performance and Alzheimer's disease (AD) neuroimaging biomarkers in individuals without dementia (cognitively unimpaired (CU), and those with mild cognitive impairment (MCI)). Design: Cross-sectional. Setting: Olmsted County, Minnesota. Participants: Population-based Mayo Clinic Study of Aging (MCSA) participants (aged ≥ 50, mean age 71.3 ± 10.2; 53.4% male; 28.3% apolipoprotein (APO)E ε4 allele carriers, 1,578 CU, 204 MCI) who underwent 11C-Pittsburgh compound B (11C-PiB) positron emission tomography (PET) (N=1,782). Measurements: We defined an abnormal (high) 11C-PiB-PET retention ratio as a standardized uptake value ratio greater than 1.42 (high amyloid; A+), abnormal (reduced) AD signature cortical thickness (neurodegeneration; N+) as less than 2.67 mm (MRI measurement), and biomarker groups according to the combination of abnormality (or not) for amyloid accumulation (A+/A–) and neurodegeneration (N+/N–). Functional performance was assessed using the Clinical Dementia Rating (CDR) Sum of Boxes (SOB) for functional domains and the Functional Activities Questionnaire (FAQ). Results: Participants with a CDR-SOB (functional) score greater than 0 were almost 4 times as likely to have N + (odds ratio (OR)=3.92, 95% confidence interval (CI)=1.77–8.67, adjusting for age, sex, education, global cognitive z-score, and APOE ε4 allele status; p<.001) and those with a FAQ score greater than 0 were 1.5 times as likely to have A + (OR=1.48, 95% CI=1.04–2.11, p=.03). Higher FAQ scores were associated with greater odds of A+N + and A–N + in CU participants. Conclusion: The findings of this cross-sectional study supplement limited available information that supports an association between functional performance and AD neuroimaging biomarkers very early in the dementia pathophysiology. The associations should be validated in longitudinal studies. J Am Geriatr Soc 66:2274–2281, 2018.",
keywords = "CDR, FAQ, amyloid, functional performance, neurodegeneration",
author = "Maria Vassilaki and Aakre, {Jeremiah A.} and Kremers, {Walter K.} and Mielke, {Michelle M.} and Geda, {Yonas E.} and Machulda, {Mary M.} and Knopman, {David S.} and Coloma, {Preciosa M.} and Barbara Schauble and Prashanthi Vemuri and Lowe, {Val J.} and Jack, {Clifford R.} and Petersen, {Ronald C.} and Roberts, {Rosebud O.}",
note = "Funding Information: The study was supported by National Institutes of Health (NIH) Grants 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; the 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). Funding Information: The study was supported by National Institutes of Health (NIH) Grants 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; the 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). Funding Information: Conflict of Interest: Maria Vassilaki receives research funding from NIH, Roche, and Biogen. Walter Kremers receives research funding from the Department of Defense, NIH, Astra Zeneca, Biogen, and Roche. Michelle Mielke consults for Eli Lilly and Lysosomal Therapeutics, Inc. and receives unrestricted research grants from Biogen, Lund-beck, and Roche and research funding from the National Institute on Aging, NIH and the Department of Defense. Yonas Geda receives funding from the NIH and Roche and serves on the Lundbeck Advisory Board. Mary Machulda receives NIH funding. David Knopman serves on a Data Safety Monitoring Board for the DIAN study; is an investigator in clinical trials sponsored by Lilly Pharmaceuticals, Biogen, and the Alzheimer{\textquoteright}s Treatment and Research Institute at USC; and receives research support from the NIH. Prashanthi Vemuri receives NIH Funding. Preciosa M. Coloma and Barbara Schauble are full-time employees of and own shares in F. Hoffmann-La Roche Ltd. Val Lowe 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, National Cancer Institute). Clifford Jack receives research support from the NIH/NIA and the Alexander Family Alzheimer{\textquoteright}s Disease Research Professorship of the Mayo Foundation. Ronald Petersen is a consultant for Roche, Inc., Biogen, Inc., Merck, Inc., Eli Lilly and Company, and Genentech, Inc. and receives publishing royalties from Mild Cognitive Impairment (Oxford University Press, 2003) and research support from the NIH. Rosebud Roberts receives research funding from the NIH/NIA, Biogen, and Roche. Publisher Copyright: {\textcopyright} 2018, Copyright the Authors Journal compilation {\textcopyright} 2018, The American Geriatrics Society Copyright: Copyright 2019 Elsevier B.V., All rights reserved.",
year = "2018",
month = dec,
doi = "10.1111/jgs.15577",
language = "English (US)",
volume = "66",
pages = "2274--2281",
journal = "Journal of the American Geriatrics Society",
issn = "0002-8614",
publisher = "Wiley-Blackwell",
number = "12",
}