DOES BRAIN AMYLOID DEPOSITION IMPACT EVERYDAY FUNCTIONING IN SUBJECTS WITH COGNITIVE COMPLAINTS? RESULTS FROM THE INSIGHT COHORT

Abstract

Subjective cognitive decline (SCD) is increasingly identified as a potential at-risk stage for Alzheimer's disease (AD). A key issue in SCD is to identify the earliest clinical symptoms indicative of preclincal AD, when these subjects are considered to be predominantly asymptomatic. Experiencing difficulties with performing instrumental activities of daily living (IADL) is potentially such an early symptom. Because amyloid is one of the earliest pathological changes in AD, the objective of the current study is to investigate the relationship between amyloid deposition and IADL in SCD. Subjects were included from the prospective INSIGHT pre-AD cohort, which is conducted at the University Salpêtrière Hospital, Paris, France. We used baseline cross-sectional data, and included subjects with SCD who had amyloid Florbetapir PET and IADL assessments available. β-Amyloid deposition was measured by the standard uptake value ratio (SUVr) in cortical regions; frontal, temporal, parietal, anterior cingulate, posterior cingulate and precuneus, using whole cerebellum and pons as reference regions. Subjects' partners completed the French version of the Amsterdam IADL Questionnaire. IADL and SUVr data data were log transformed to obtain normal distributions. The relationship between amyloid (global and local effects) and IADL was investigated using linear regression analyses, with correction for age, sex and education if necessary. A total of 304 participants were included (Mean age=76, SD=3.45, 64% female). Global amyloid SUVr was related to IADL scores (β=.246, 95% CI .052 -.441, p=.013), which remained significant after correction for confounding. When looking at amyloid deposition in specific brain regions, IADL was associated with SUVr in frontal, parietal and temporal regions. Subsequently, a total of 82 (27%) participants was defined by cut-off as amyloid positive, and we found a trend for amyloid positive subjects to have more IADL difficulties (β=.090, 95% CI -.001-.181, p=.053). Specific activities that differed between both groups were primarily related to everyday technology use. Our findings suggest that in subjects with SCD a greater amyloid burden impacts IADL functioning. This indicates that IADL is an early clinical symptom, and potentially a useful clinical marker of preclinical AD. As a next step, we aim to study longitudinal trajectories of IADL functioning.