SELF- AND INFORMANT-RATED DAILY FUNCTION IS ASSOCIATED WITH AMYLOID AND NEURODEGENERATIVE IMAGING IN COGNITIVELY NORMAL INDIVIDUALS

Abstract

Early identification of individuals with significant brain amyloid and neurodegeneration is critical to prevent or delay cognitive impairment and dementia. We examined associations of self- and informant-report of functional ability, using the Everyday Cognition (ECog) questionnaire, with neuroimaging measures of amyloid and neurodegeneration in cognitively normal (CN) individuals. We included 301 participants from the Mayo Clinic Study on Aging, aged 70 and older, with both self- and informant-reported ECog data and neuroimaging (MRI, FDG-PET, PiB-PET). The ECog measures cognitively-relevant functional abilities across six domains. We used a global composite score from 39 questions covering all domains. Each question was rated 1-4 (1=better or no change compared to 10 years earlier, 2=questionable/occasionally worse, 3=consistently a little worse, 4=consistently much worse). Participants were pathologically classified into 4 groups based on imaging biomarkers of amyloid (PiB-PET SUVR≥1.5 [A+ or A-]) and neurodegeneration (abnormal hippocampal volume or FDG hypometabolism in “Alzheimer signature” regions [N+ or N-]). There were 132 participants who were A-N-, 54 A+N-, 41 A+N+, and 74 A-N+. We used logistic regression models to examine the relationships of self- and informant rating with odds of amyloid and neurodegeneration, adjusting for age, sex, education, depression, and APOE genotype. Self-report of everyday function was worse than informant-report (mean (SD): 1.4 (0.4) vs. 1.2 (0.3), p<0.0001). Compared to A-N- participants, each 1-point increase in self-reported ECog was associated with higher odds of being A+N+ (OR 3.32, 95% CI: 1.11-9.88) and A-N+ (OR 2.63, 95% CI: 1.04, 6.65), but not A+N- (OR 2.44, 95% CI: 0.88, 6.78). The ORs between informant ratings and imaging biomarkers of amyloid and neurodegenerative pathology, compared to A-N-, were 3-5-fold stronger than for self-report: A+N+ (OR 12.55, 95% CI: 3.16, 49.79), A-N+ (OR 5.96, 95% CI: 1.74, 20.40), and A+N- (OR 8.33, 95% CI: 2.28, 30.48). Among CN individuals, self- and informant-reports of functional activities are associated with neuroimaging measures of amyloid and neurodegeneration. While CN individuals self-report greater functional difficulties than informants, the identification of worse functioning by informants is a stronger indicator of neuroimaging measures of amyloid and neurodegenerative pathology.