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，尤其是在考虑年龄是发展阿尔茨海默氏病（AD）的最有效危险因素时。髓鞘和心理处理的速度都可以改善直至30年代中期，然后随着年龄的增长而逐渐恶化。这两个过程之间的轨迹相似性导致了以下假设：髓磷脂分解可能是认知速度与年龄相关的放缓的基础。载脂蛋白E4（APOE4）基因型增加了开发AD并降低发作年龄的可能性。在健康的成年人中，APOE4等位基因的存在与更快的年龄相关认知恶化有关，而APOE2等位基因会缓解认知能力下降。横截面数据表明，与APOE基因型与APOE4载体相关的差异髓磷脂分解，表现出更严重的髓磷脂分解。该建议旨在调查1）髓鞘分解随年龄的预期变化，2）髓磷脂分解和加工速度的前瞻性变化之间的关系，以及3）遗传标记对生物学和认知过程的前瞻性变化的影响。我们假设髓鞘会随着年龄的增长而大幅度分解。髓磷脂分解将与认知速度下降有关，遗传状况将调节这种结构性功能关系。 152名健康的老年受试者组成的队列进行了MRI和神经心理学测试，从而产生了以上总结的一些结果。我们计划重新连接这些受试者，以使用相同的成像协议重复成像和认知测试，并测试电池与基线评估。评估间隔大约为6年。该项目将提供丰富的纵向数据来源，该数据可用于解决超出其主要重点的问题，例如预测发展为临床上重要的认知缺陷（即轻度认知障碍； MCI）。外行语言摘要：当患者被诊断出患有MCI时，他们已经患有严重的认知缺陷，大部分此类患者将发展阿尔茨海默氏病，这会影响美国数百万的人，并每年造成超过1000亿美元的医疗保健系统。该项目有可能在预测与年龄相关的认知下降中确定成像和遗传因素的相互作用，从而较早实施临床干预或预防措施。