Novel Neurocognitive Markers of Risk for and Resilience to Cognitive Decline in Preclinical Alzheimer's Disease

点击翻译按钮获取中文摘要

PROJECT ABSTRACT There is a strong public health need to detect Alzheimer’s disease (AD) in its earliest stages and predict who is most vulnerable to clinical progression. The goal of this K23 proposal is to provide the candidate with the experience, knowledge, and technical expertise to independently investigate novel early predictors of risk for and resilience to AD-associated cognitive decline. The career development plan comprises a complementary set of training and research activities to support the candidate’s transition to independence. Specific training goals include: 1) to develop expertise in using electroencephalography (EEG) to assess brain network dynamics in aging populations; 2) to increase depth of knowledge of functional neuroanatomy, with a focus on frontal networks compromised early in the course of AD; 3) to gain specialized training in clinical research design and statistics, with an emphasis on dimension reduction and analysis of complex data; and 4) to receive formal mentorship in professional development. The training plan draws on an exemplary interdisciplinary team with expertise in the electroencephalography (S. Jones), cognitive neuroscience and functional neuroanatomy (Heindel), statistical methods and the cognitive reserve hypothesis (R. Jones), and clinical neuropsychology (Tremont). Training activities will take place through formal mentorship, experiential laboratory training, didactics, and the completion of a rigorous research project. The scientific objective of the research project is to investigate behavioral and electrophysiological markers of frontal control network integrity that may serve as novel markers of risk for and resilience to AD-associated cognitive decline. Each research aim corresponds to a complementary area of training. Specific aims include 1) to examine behavioral and electrophysiological markers of frontal network dynamics in older adults at risk for AD; 2) to validate the behavioral and electrophysiological markers using independent measures of frontal network integrity (i.e., magnetic resonance imaging); and 3) to validate the markers as indices of cognitive resilience. The research project will leverage the infrastructure of the Rhode Island Alzheimer’s Disease Prevention Registry, a large cohort of older adults whose cognition is monitored annually. Successful completion of these interrelated training and research activities will foster the candidate’s development into an independent clinical researcher with expertise in the early prediction of risk for and resilience to AD-associated cognitive decline.