Association Between Functional Performance and Alzheimer's Disease Biomarkers in Individuals Without Dementia

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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.

Original languageEnglish (US)
Pages (from-to)2274-2281
Number of pages8
JournalJournal of the American Geriatrics Society
Volume66
Issue number12
DOIs
StatePublished - Dec 1 2018

Fingerprint

Dementia
Alzheimer Disease
Biomarkers
Amyloid
Neuroimaging
Positron-Emission Tomography
Alleles
Odds Ratio
Confidence Intervals
Apolipoprotein E4
Sex Education
Longitudinal Studies
Cross-Sectional Studies
Population
Surveys and Questionnaires
2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
Cognitive Dysfunction

Keywords

  • amyloid
  • CDR
  • FAQ
  • functional performance
  • neurodegeneration

ASJC Scopus subject areas

  • Geriatrics and Gerontology

Cite this

@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 = "amyloid, CDR, FAQ, functional performance, neurodegeneration",
author = "Maria Vassilaki and Aakre, {Jeremiah A.} and Kremers, {Walter K} and Mielke, {Michelle M} and Geda, {Yonas Endale} and Machulda, {Mary Margaret} and Knopman, {David S} and Coloma, {Preciosa M.} and Barbara Schauble and Vemuri, {Prashanthi D} and Val Lowe and Jack, {Clifford R Jr.} and Petersen, {Ronald Carl} and Roberts, {Rosebud O}",
year = "2018",
month = "12",
day = "1",
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",

}

TY - JOUR

T1 - Association Between Functional Performance and Alzheimer's Disease Biomarkers in Individuals Without Dementia

AU - Vassilaki, Maria

AU - Aakre, Jeremiah A.

AU - Kremers, Walter K

AU - Mielke, Michelle M

AU - Geda, Yonas Endale

AU - Machulda, Mary Margaret

AU - Knopman, David S

AU - Coloma, Preciosa M.

AU - Schauble, Barbara

AU - Vemuri, Prashanthi D

AU - Lowe, Val

AU - Jack, Clifford R Jr.

AU - Petersen, Ronald Carl

AU - Roberts, Rosebud O

PY - 2018/12/1

Y1 - 2018/12/1

N2 - 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.

AB - 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.

KW - amyloid

KW - CDR

KW - FAQ

KW - functional performance

KW - neurodegeneration

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U2 - 10.1111/jgs.15577

DO - 10.1111/jgs.15577

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JO - Journal of the American Geriatrics Society

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