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

临床前阿尔茨海默氏病认知下降风险和恢复能力的新型神经认知标志物

• 批准号: 10630092
• 负责人: Laura Korthauer
• 金额: $ 15.65万
• 依托单位: RHODE ISLAND HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-15 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10630092
• 关键词: Affect; Age; Aging; Alzheimer disease detection; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease risk; Alzheimer’s disease biomarker; American; Amyloid; Apolipoprotein E; Area; Atrophic; Behavior; Behavioral; Brain; Caregivers; Clinical; Clinical Research; Cognition; Cognitive; Compensation; Data; Development; Development Plans; Diffusion Magnetic Resonance Imaging; Dimensions; Dorsal; Early Diagnosis; Early treatment; Economic Burden; Elderly; Electroencephalography; Electrophysiology (science); Family; First Degree Relative; Fostering; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Impaired cognition; Individual; Infrastructure; Investigation; Knowledge; Magnetic Resonance Imaging; Measures; Medial; Mediating; Memory; Mentorship; Monitor; Neuroanatomy; Neurocognitive; Neurons; Neuropsychology; Participant; Pathway interactions; Patients; Performance; Persons; Phase; Population; Proxy; Public Health; Quality of life; Recording of previous events; Registries; Research; Research Activity; Research Design; Research Personnel; Research Project Grants; Resources; Rest; Retrieval; Rhode Island; Risk; Risk Marker; Semantics; Signal Transduction; Statistical Methods; Synapses; Technical Expertise; Temporal Lobe; Training; Training Activity; biomarker performance; biomarker validation; blood oxygen level dependent; career development; cognitive control; cognitive neuroscience; cognitive reserve; cohort; complex data; diagnostic accuracy; executive function; experience; high risk; improved; indexing; laboratory experience; mild cognitive impairment; network dysfunction; neural; novel; novel marker; pre-clinical; resilience; risk prediction; statistics; tau Proteins; temporal measurement; treatment strategy; validation studies; white matter

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.

项目摘要