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 ¹¹ C-Pittsburgh compound B (¹¹ C-PiB) positron emission tomography (PET) (N=1,782).

Measurements: We defined an abnormal (high) ¹¹ C-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.

Figure 1.

Percentage of participants (50+ years of age) with CDR-SOB (functional) and FAQ-total score higher than zero by neuroimaging biomarkers’ combinations in cognitively unimpaired (A) and participants with MCI (B). In cognitively unimpaired participants, there were overall 21 (out of 1532) participants with CDR-SOB (functional)>0 and 130 (out of 1518) with FAQ score>0. In MCI participants, there were overall 53 (out of 198) participants with CDR-SOB (functional)>0 and 95 (out of 192) with FAQ score>0.