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

Maria Vassilaki; Jeremiah A. Aakre; Walter K. Kremers; Michelle M. Mielke; Yonas E. Geda; Mary M. Machulda; David S. Knopman; Preciosa M. Coloma; Barbara Schauble; Prashanthi Vemuri; Val J. Lowe; Clifford R. Jack; Ronald C. Petersen; Rosebud O. Roberts

doi:10.1111/jgs.15577

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

Maria Vassilaki, Jeremiah A. Aakre, Walter K. Kremers, Michelle M. Mielke, Yonas E. Geda, Mary M. Machulda, David S. Knopman, Preciosa M. Coloma, Barbara Schauble, Prashanthi Vemuri, Val J. Lowe, Clifford R. Jack, Ronald C. Petersen, Rosebud O. Roberts

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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 language	English (US)
Pages (from-to)	2274-2281
Number of pages	8
Journal	Journal of the American Geriatrics Society
Volume	66
Issue number	12
DOIs	https://doi.org/10.1111/jgs.15577
State	Published - Dec 2018

Keywords

CDR
FAQ
amyloid
functional performance
neurodegeneration

ASJC Scopus subject areas

Geriatrics and Gerontology

Access to Document

10.1111/jgs.15577

Cite this

Vassilaki, M., Aakre, J. A., Kremers, W. K., Mielke, M. M., Geda, Y. E., Machulda, M. M., Knopman, D. S., Coloma, P. M., Schauble, B., Vemuri, P., Lowe, V. J., Jack, C. R., Petersen, R. C., & Roberts, R. O. (2018). Association Between Functional Performance and Alzheimer's Disease Biomarkers in Individuals Without Dementia. Journal of the American Geriatrics Society, 66(12), 2274-2281. https://doi.org/10.1111/jgs.15577

Vassilaki, M, Aakre, JA, Kremers, WK, Mielke, MM, Geda, YE, Machulda, MM , Knopman, DS, Coloma, PM, Schauble, B, Vemuri, P , Lowe, VJ , Jack, CR , Petersen, RC & Roberts, RO 2018, 'Association Between Functional Performance and Alzheimer's Disease Biomarkers in Individuals Without Dementia', Journal of the American Geriatrics Society, vol. 66, no. 12, pp. 2274-2281. https://doi.org/10.1111/jgs.15577

@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). Publisher Copyright: {\textcopyright} 2018, Copyright the Authors Journal compilation {\textcopyright} 2018, The American Geriatrics Society",

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",

}

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 E.

AU - Machulda, Mary M.

AU - Knopman, David S.

AU - Coloma, Preciosa M.

AU - Schauble, Barbara

AU - Vemuri, Prashanthi

AU - Lowe, Val J.

AU - Jack, Clifford R.

AU - Petersen, Ronald C.

AU - Roberts, Rosebud O.

N1 - 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: 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). Publisher Copyright: © 2018, Copyright the Authors Journal compilation © 2018, The American Geriatrics Society

PY - 2018/12

Y1 - 2018/12

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 - CDR

KW - FAQ

KW - amyloid

KW - functional performance

KW - neurodegeneration

UR - http://www.scopus.com/inward/record.url?scp=85056840117&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85056840117&partnerID=8YFLogxK

U2 - 10.1111/jgs.15577

DO - 10.1111/jgs.15577

M3 - Article

C2 - 30462843

AN - SCOPUS:85056840117

SN - 0002-8614

VL - 66

SP - 2274

EP - 2281

JO - Journal of the American Geriatrics Society

JF - Journal of the American Geriatrics Society

IS - 12

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this