Biological Underpinnings and Cognitive Expression of Brain Aging

大脑衰老的生物学基础和认知表达

• 批准号: 7847750
• 负责人: Po Lu
• 金额: $ 1.29万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-15 至 2010-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7847750
• 关键词: Action Potentials; Address; Adult; Affect; Age; Age of Onset; Age-associated memory impairment; Aging; Alleles; Alzheimer' s Disease; Animal Experiments; Apolipoprotein E; Attenuated; Autopsy; Biological; Biological Markers; Body of uterus; Bone callus; Brain; Clinical; Cognition; Cognitive; Cognitive deficits; Cross-Sectional Studies; Data; Dementia; Deterioration; Diagnosis; Diffuse; Digit structure; Elderly; Endowment; Epidemiologic Studies; Evaluation; Exhibits; Failure; Future; Genetic; Genetic Markers; Genetic Status; Genotype; Healthcare Systems; Image; Impaired cognition; Incidence; Individual; Intervention; Investigation; Knowledge; Language; Learning; Literature; Longevity; Magnetic Resonance Imaging; Measures; Mediating; Memory; Mental Processes; Methodology; Methods; Modeling; Monitor; Myelin; Nature; Neurobehavioral Manifestations; Neuropsychological Tests; Participant; Patients; Performance; Preventive; Process; Prospective Studies; Protocols documentation; Reaction Time; Relaxation; Reporting; Research; Risk Factors; Sampling; Scanning; Short-Term Memory; Source; Specificity; Speed; Staging; Structure of genu of corpus callosum; Testing; Time; Tissues; Translating; Verbal Learning; age related; aging brain; apolipoprotein E-4; base; career development; clinically significant; cognitive change; cognitive function; cohort; cost; design; experience; follow-up; frontal lobe; improved; in vivo; information processing; insight; instrument; middle age; mild neurocognitive impairment; myelination; neuroimaging; neuromechanism; neuropsychological; normal aging; pathological aging; processing speed; prospective; prospective memory; research study; transmission process; white matter

DESCRIPTION (provided by applicant): There is an urgent need to understand the biological and functional changes associated with brain aging, particularly when considering that age is the most potent risk factor for developing Alzheimer's disease (AD). Myelination and speed of mental processing both improve up to the mid-30's then breakdown or deteriorate progressively with advancing age. The similarity in trajectory between these two processes leads to the hypothesis that myelin breakdown may underlie the age-related slowing in cognitive speed. Apolipoprotein E4 (ApoE4) genotype increases the likelihood of developing AD and decreases age of onset. In healthy adults, presence of ApoE4 allele is associated with more rapid age-related cognitive deterioration while ApoE2 allele mitigates against cognitive decline. Cross-sectional data has demonstrated differential myelin breakdown in association with ApoE genotype with ApoE4 carriers manifesting more severe myelin breakdown. This proposal aims to investigate 1) the prospective change in myelin breakdown with age, 2) the relationship between prospective changes in myelin breakdown and processing speed, and 3) the effects of genetic markers on the prospective changes in biological and cognitive processes. We hypothesize that myelin will breakdown significantly with age; that myelin breakdown will be related to a decline in cognitive speed, and genetic status will modulate this structural-functional relationship. A cohort of 152 healthy elderly subjects underwent MRI and neuropsychological testing, producing some of the results summarized above. We plan to re-contact these subjects to repeat the imaging and cognitive testing using the same imaging protocol and test battery as the baseline evaluation. The inter-assessment interval will be about 6 years. This project will provide a rich source of longitudinal data that can be used to address questions beyond its major focus, such as predicting progression into clinically significant cognitive deficits (i.e., mild cognitive impairment; MCI). LAY LANGUAGE SUMMARY: By the time that a patient is diagnosed with MCI, they already have significant cognitive deficits and a substantial portion of such patients will develop Alzheimer's disease, which affects millions of people in the US and costs the healthcare system over $100 billion annually. This project has the potential to identify the interaction of imaging and genetic factors in predicting age-related cognitive decline leading to earlier implementation of clinical intervention or preventive efforts.

描述（由申请人提供）：迫切需要了解与大脑衰老相关的生物学和功能变化，特别是考虑到年龄是发生阿尔茨海默氏病（AD）的最有力的危险因素时。髓鞘形成和心理处理速度在 30 多岁之前都会得到改善，然后随着年龄的增长而逐渐崩溃或恶化。这两个过程之间轨迹的相似性导致了这样的假设：髓磷脂分解可能是与年龄相关的认知速度减慢的原因。载脂蛋白 E4 (ApoE4) 基因型会增加患 AD 的可能性并降低发病年龄。在健康成年人中，ApoE4 等位基因的存在与年龄相关的认知衰退更快相关，而 ApoE2 等位基因则可以缓解认知衰退。横断面数据表明，不同的髓磷脂破坏与 ApoE 基因型相关，ApoE4 携带者表现出更严重的髓磷脂破坏。该提案旨在研究 1) 髓磷脂分解随年龄的预期变化，2) 髓磷脂分解的预期变化与处理速度之间的关系，以及 3) 遗传标记对生物和认知过程的预期变化的影响。我们假设髓磷脂会随着年龄的增长而显着分解；髓磷脂分解与认知速度下降有关，而遗传状态将调节这种结构功能关系。由 152 名健康老年受试者组成的队列接受了 MRI 和神经心理学测试，得出了上面总结的一些结果。我们计划重新联系这些受试者，使用相同的成像协议和测试电池作为基线评估重复成像和认知测试。评估间隔约为6年。该项目将提供丰富的纵向数据源，可用于解决其主要重点之外的问题，例如预测临床显着认知缺陷（即轻度认知障碍；MCI）的进展。通俗语言总结：当患者被诊断患有 MCI 时，他们已经出现了严重的认知缺陷，其中很大一部分患者将患上阿尔茨海默病，这种病影响着美国数百万人，每年给医疗保健系统造成的损失超过 1000 亿美元。该项目有可能确定影像学和遗传因素的相互作用，预测与年龄相关的认知能力下降，从而更早实施临床干预或预防工作。