Optimizing semantic memory measures to detect tau- and amyloid- related cognitive change

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PROJECT SUMMARY / ABSTRACT The overall goal of the proposed K23 research project is to better characterize semantic memory in relation to Alzheimer's disease (AD) biomarkers in order to maximize the predictive utility of cognitive markers to AD- related cognitive change. Episodic memory impairment, the earliest and most prominently disabling cognitive change in AD, is linked to AD pathology and remains the central focus of outcome measures used in clinical trials. However, there is growing evidence that semantic memory (i.e., memory for meaning, general knowledge, and factual information) also declines relatively early in the AD process which compels us to explore whether semantic memory measures are sensitive and specific for identifying AD risk, are associated with in vivo measures of AD pathology, and are potentially useful as clinical trial outcome measures. Based on our preliminary data, we hypothesize that semantic memory will be related to both amyloid (PiB) and tau (T807/AV1451) deposition on PET neuroimaging. Furthermore, we expect novel measures of semantic memory to add sensitivity and specificity to traditional episodic memory measures and thus provide a useful composite outcome measure in secondary prevention trials. The proposed research will leverage the rich imaging and clinical dataset available from the NIA funded Harvard Aging Brain Study cohort and related studies, but will provide a unique avenue of investigation for the candidate. The candidate is a clinical neuropsychologist who seeks training in cognitive test development and validation, multi-modal neuroimaging, and advanced analytic methods, in order to position her to become an independent researcher. The candidate's career development will benefit from the close mentorship and scientific guidance of well- established investigators with expertise spanning multiple disciplines. The findings from this study will inform future secondary prevention trials, in which sensitive cognitive indicators of early AD will be necessary to better identify high-risk subjects and track early clinical decline and response to treatment.