A novel approach to measure dyadic patterns of subjective cognitive changes: its association to Alzheimer’s disease biomarkers and ability to predict clinical progression in cognitively normal older adults

Abstract

AbstractBackgroundDiscrepancy in the dyadic relationship of subjective cognitive change has revealed both increased/heightened awareness and decreased awareness/unawareness in the predementia stages of Alzheimer’s Disease (AD). The dyadic relationship is often calculated using the mean discrepancy between an individual and their study partner’s scores on a memory complaints questionnaire. However, participants may display heightened awareness on some questions and unawareness on others, canceling out each other’s effect and masking subtle changes in either direction. Here, we present a new item‐level methodological approach allowing us to examine individual subtle changes in these two awareness dimensions separately. Moreover, we compared them to AD pathology and investigated their ability to predict clinical progression.MethodA total of 503 ADNI participants (Table.1) with baseline clinical dementia rating (CDR) = 0 and baseline CSF (Aβ1‐42 and t‐tau) were included. A subset (N = 329) had at least two follow‐up CDR time points to compute clinical progression. A traditional score was calculated as the average discrepancy between the partner and participant’s responses on the Everyday Cognition questionnaire, with positive scores indicating heightened awareness and negative scores indicating unawareness. An unawareness (resp., heightened awareness) sub‐score was computed by applying a ceiling (resp., floor) at zero to item‐level differences before averaging. Each measure was compared by AD pathology, adjusted for age and sex. Survival analyses examined the relationship of the new scores with clinical progression.ResultCSF t‐tau, but not Aβ1‐42, was a significant independent predictor of the traditional and unawareness scores in models adjusting for each other. There was no significant interaction between the two (Table.2). Survival analyses showed a one‐point improvement on the unawareness sub‐score associated with an 84% reduction in progression hazard (HR = 0.16, p<0.001), or equivalently. A one‐point decline and 525% increase in progression hazard, with no significant effect for the heightened awareness score.ConclusionDecomposing the traditional awareness score into two sub‐scores, allowed the investigation of the relationship between AD and awareness with more specific, sensitive measures. Of these, the unawareness sub‐score was associated with t‐tau and a strong predictor of clinical progression, providing further support that discordant self‐ and informant‐reported cognitive decline may provide important clinical information.