TAU BURDEN IS ASSOCIATED WITH SUBJECTIVE COGNITIVE CONCERNS IN THE CONTEXT OF β-AMYLOID BURDEN IN PRECLINICAL AD

Abstract

Alzheimer’s disease (AD) is characterized by the deposition of β-amyloid (Aβ) and paired helical filament tau. The relationship of these deposits to the preclinical manifestations of the AD phenotype can now be evaluated in vivo with positron emission tomography (PET). Endorsement of subjective cognitive concerns (SCC) is associated with Aβ in this early phase of the disease trajectory, but until now, a relationship between SCC and regional tau deposition has not been interrogated. We aimed to elucidate the relationship between entorhinal cortical (EC) and inferior temporal (IT) tau, neocortical Aβ and SCC in clinically-normal (CN) older adults. Seventy-three CN (CDR = 0) participants (77yrs (SD=6.2), 58% female, 28% Aβ+, 28% APOEε4 carriers) participating in the Harvard Aging Brain Study underwent T807 (aka AV1451) and PiB PET imaging within 6 months of responding to three SCC questionnaires. An SCC composite was created using z-transformed memory subscales from the Memory Functioning Questionnaire, the Everyday Cognition Scale, and the adapted Structured Telephone Inventory for Dementia Assessment. Greater EC tau was associated with greater SCC (β=0.39, p<.001) after taking into account age, depressive symptoms, sex and education. IT tau was marginally associated (β=0.18, p=.16). After interactions between tau and Aβ were included, no interactive effect of EC tau and Aβ was found on SCC (p=.93), but an IT and Aβ interaction was now marginally associated with greater SCC (p=.07). This is the first study to demonstrate regionally-specific patterns of association between tau burden and SCC. Specifically, EC tau was strongly associated with greater SCC, but the effect was independent of Aβ burden. Increasing IT tau deposition, on the other hand, was related to greater SCC only within the context of increasing Ab burden. As such, both tau and Aβ are associated with SCC and appear to become multiplicative under certain circumstances. It is possible that IT tau-driven SCC reflects individuals likely on the AD trajectory, whereas EC-related SCC captures a range of phenomena including normal aging, in which EC tauopathy is very common. It remains to be seen whether regional tau underlies qualitatively different SCC phenotypes.