TAU AND AMYLOID PATHOLOGY IN ASSOCIATION WITH SUBJECTIVE COGNITIVE PERFORMANCE IN NORMAL ELDERLY AND EARLY MILD COGNITIVE IMPAIRMENT

Abstract

Introduction Subjective cognitive decline (SCD) is increasingly recognized as the initial outward sign of preclinical Alzheimer s disease. The ability to explore associations between individual domains (memory, language, executive function, and visuospatial processing) within SCD and pathological biomarkers of early Alzheimer s disease (AD) would provide an important tool to understand the pathological basis of SCD and the risk of developing AD. This study utilizes multiple data analysis strategies to characterize the severity of tau and amyloid burden in clinically normal elderly adults (CN) and early mild cognitive impairment (EMCI) subjects in association with their subjective cognitive decline. Methods All subject data were downloaded from the Alzheimer s Disease Neuroimaging Initiative (ADNI) database. These included [18F]flortaucipir tau and [18F]florbetapir amyloid positron emission tomography (PET) images as well as the subjects’ SCD scores. For SCD, we used the self- and informant-reported individual items of Everyday Cognition questionnaire, including Everyday Memory, Everyday Language, Everyday Visuospatial abilities, Everyday Planning, Everyday Organization, and Everyday Divided Attention. The severity of the amyloid burden was calculated as the global PET standardized uptake value ratio (SUVR). The severity of the tau burden was assessed with both standard uptake-based approaches (tau SUVR in entorhinal, limbic, and isocortical Braak regions) and with a novel texture analysis tool, the weighted two-point correlation (wS2) analysis, which characterizes the spatial clustering of the tau-PET image as a sensitive early biomarker of abnormal tau accumulation and spread. Using a series of backward-elimination regression models, we identified the combination of predictors (from tau PET, global amyloid-PET, sex, APOE, and age) that constructed the best model to predict each Everyday Cognition item. Results Across the different cognitive tests, the wS2-based tau measures explained more variability, as indicated by p-values and elevated R-squared values, than standardized uptake value ratios from different anatomical regions, including the entorhinal cortex which is believed to be among the first regions to show signs of tau pathology. Our backward-elimination regression analyses (figure 1) suggested that the strongest models for predicting some of the subjective cognitive items (Everyday Memory, Everyday Language, Everyday Organization) were more likely amyloid-related whereas other items (Everyday Visuospatial, Everyday Planning) were more tau-related (together with age and sex). Conclusions Different pathological pathways may influence the manifestation of different subjective cognitive items. In vivo texture analysis techniques may be used as sensitive tools to explore these pathological pathways in association with the earliest signs of cognitive changes.