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Investigating age-related neural dedifferentiation longitudinally and in Alzheimer’s pathology

纵向研究阿尔茨海默病病理学中与年龄相关的神经去分化

基本信息

批准号：
10645120
负责人：
Thad A Polk
金额：
$ 69.72万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-05-15 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10645120
关键词：
Age Aging Alzheimer&apos s Disease Alzheimer&apos s disease pathology Amyloid beta-Protein Animals Autopsy Behavior Behavioral Brain Childhood Cognition Cognitive Cohort Effect Cross-Sectional Studies Data Education Elderly Exhibits Functional Magnetic Resonance Imaging Funding Grant Growth Individual Individual Differences Intervention Longitudinal Studies Magnetic Resonance Spectroscopy Measures Mediating Michigan Modeling Motor Neurofibrillary Tangles Neurotransmitters Participant Patients Persons Positron-Emission Tomography Research Research Personnel Sample Size Senile Plaques Sensory Stimulus Testing Time Work abeta accumulation age difference age group age related behavior prediction behavior test behavioral impairment experience gamma-Aminobutyric Acid healthy aging imaging study insight interest mild cognitive impairment neural neuropathology new therapeutic target normal aging novel nutrition pathological aging recruit response tau Proteins young adult β-amyloid burden

项目摘要

Project Summary/Abstract A growing body of research has found that neural representations are less distinctive in older relative to younger adults, a phenomenon known as age-related neural dedifferentiation. Neural dedifferentiation has been associated with many of the behavioral impairments typically observed in healthy aging, and evidence collected by our group during the original funding period has found a strong relationship between neural dedifferentiation and gamma-aminobutyric acid (GABA), the brain’s major inhibitory neurotransmitter. Specifically, we found that GABA levels are lower in older vs. younger adults and that older adults with less GABA exhibit greater dedifferentiation. We propose to take this line of research in two new directions. (1) We will conduct a longitudinal study and explore age-related trajectories of change in GABA, neural distinctiveness, and behavior, as well as directional relationships among these measures (e.g., Do GABA levels at age 65 predict subsequent declines in neural distinctiveness? Does neural distinctiveness at age 65 predict behavioral declines over the next decade). (2) We will also examine how dedifferentiation is related to Alzheimer’s pathology by collecting the same measures in patients with Mild Cognitive Impairment in whom amyloid beta and tau burden has already been measured. The proposed studies will provide novel insights into how the brain changes with age and with neuropathology, whether those changes can explain the observed behavioral deficits, and whether changes in GABA levels are a contributing cause. Such insights could lead to novel interventions to alleviate the behavioral impairments associated with healthy and pathological aging.

项目总结/摘要越来越多的研究发现，神经表征在老年人相对于年轻人，这种现象被称为与年龄相关的神经去分化神经去分化与许多行为学上的在健康老龄化中通常观察到的损伤，以及我们小组收集的证据在最初的资助期间，发现了神经元之间的强烈关系，去分化和γ-氨基丁酸（GABA），大脑的主要抑制神经传递素具体来说，我们发现老年人的GABA水平低于年轻人，成年人和老年人较少的GABA表现出更大的去分化。我们提出把这条研究线引向两个新方向。(1)我们将进行纵向研究并探索与年龄相关的GABA变化轨迹，神经特异性，行为以及这些度量之间的方向关系（例如，做GABA 65岁时的水平可以预测随后神经独特性的下降？神经 65岁时的独特性预测未来十年的行为衰退）。(2)我们将还研究如何去分化与阿尔茨海默病的病理学有关，通过收集在患有轻度认知障碍的患者中进行相同的测量，负担已经得到了衡量。拟议的研究将提供新的见解，大脑如何随着年龄和神经病理学的变化，这些变化是否可以解释所观察到的行为缺陷，以及GABA水平的变化是否是一个贡献事业这些见解可能会导致新的干预措施，以减轻与健康和病理性衰老相关的行为障碍。

项目成果

期刊论文数量（8）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

GABA levels in ventral visual cortex decline with age and are associated with neural distinctiveness.

DOI：
10.1016/j.neurobiolaging.2021.02.013
发表时间：
2021-06
期刊：
Neurobiology of aging
影响因子：
4.2
作者：
Chamberlain JD;Gagnon H;Lalwani P;Cassady KE;Simmonite M;Seidler RD;Taylor SF;Weissman DH;Park DC;Polk TA
通讯作者：
Polk TA

DOI：
10.1080/13825585.2021.1999383
发表时间：
2022-05
期刊：
Neuropsychology, development, and cognition. Section B, Aging, neuropsychology and cognition
影响因子：
0
作者：
Simmonite M;Polk TA
通讯作者：
Polk TA

Network segregation varies with neural distinctiveness in sensorimotor cortex.

DOI：
10.1016/j.neuroimage.2020.116663
发表时间：
2020-05-15
期刊：
NeuroImage
影响因子：
5.7
作者：
Cassady K;Gagnon H;Freiburger E;Lalwani P;Simmonite M;Park DC;Peltier SJ;Taylor SF;Weissman DH;Seidler RD;Polk TA
通讯作者：
Polk TA