The impact of non-amyloid processes on cognitive aging

非淀粉样蛋白过程对认知衰老的影响

• 批准号: 8732992
• 负责人: Charles DeCarli
• 金额: $ 63.7万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-15 至 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8732992
• 关键词: Accounting; Affect; African American; Age; Age-Years; Age-associated memory impairment; Aging; Alzheimer' s Disease; Amyloid; Amyloidosis; Area; Atrophic; Attention; Blood Vessels; Brain; Brain Infarction; Brain Injuries; Brain Pathology; Brain-Derived Neurotrophic Factor; CCL2 gene; Cerebrovascular Disorders; Cerebrovascular Trauma; Cerebrum; Cognition; Cognitive; Cognitive aging; Communities; Corpus callosum splenium; Data; Dementia; Elderly; Epidemiologic Studies; Etiology; Fibrinogen; Future; Goals; Health; Hippocampus (Brain); Hispanics; Impaired cognition; Individual; Infarction; Interleukin-6; Magnetic Resonance Imaging; Measures; Mediating; Memory; Metabolic; Pathology; Performance; Population; Positron-Emission Tomography; Predisposition; Prevention; Prevention strategy; Primary Prevention; Process; Risk; Risk Factors; Secondary Prevention; Structure; Tumor Necrosis Factor-alpha; White Matter Hyperintensity; age related cognitive change; aged; amyloid imaging; base; brain volume; cerebral atrophy; clinically relevant; cognitive change; cohort; executive function; gray matter; human TNF protein; improved; in vivo; inflammatory marker; insight; mild cognitive impairment; public health relevance; vascular factor; white matter

DESCRIPTION (provided by applicant): Advancing age is associated with changes in brain structure and widely varying trajectories of cognitive performance. At least some of these differences are attributable to Alzheimer's disease (AD) and a major effort is underway to delineate the effects of brain amyloid on age related cognitive change and incident dementia. However, approximately 75 percent of cognitively normal individuals aged 70-79 do not have significant brain amyloid retention. These data suggest that factors other than amyloidosis are associated with declining cognitive performance amongst older individuals. Epidemiological studies repeatedly show that cerebrovascular disease (CVD) is extremely common and associated with decreased cognitive performance as well as incident MCI and dementia, independent of AD pathology. This is particularly true for African American and Hispanic communities where CVD is more prevalent. Evidence for CVD-related cognitive change has led to the hypothesis that the population burden of age-related cognitive decline may be considerably lessened through prevention and treatment of vascular risk factors. However, this hypothesis has been difficult to assess. Both Alzheimer's and CVD pathologies commonly co-occur in the brains of demented individuals making the independent effects of each pathology on cognitive decline difficult to discern. Amyloid imaging, however, allows for the measure of at least one component of AD pathology thereby creating the opportunity to assess cognitive trajectories, brain differences and risk factors for cognitive decline amongst individuals free of extensive amyloidosis. The premise of this study is that structural brain changes, ranging from infarction to WMH, loss of white matter integrity and brain atrophy are extremely common with aging. Further, these changes are associated with cognitive decline and increased risk for dementia. Therefore, it is critically important to identify the extent and consequences of brain injury in the absence of extensive amyloid. To accomplish this goal, we will characterize non-amyloid related changes in brain structure and cognitive trajectories in a diverse group of older individuals. In so doing, we will advance understanding of the impact of vascular factors on brain structure and cognition that will provide new insights into the course of cognitive aging and susceptibility to future cognitive impairment in a community based, ethnically and racially diverse cohort.

描述（由申请人提供）：年龄的增长与大脑结构的变化和认知表现的广泛变化轨迹有关。至少其中一些差异可归因于阿尔茨海默病（AD），目前正在进行一项重大努力，以描述脑淀粉样蛋白对与年龄相关的认知变化和痴呆的影响。然而，在70-79岁的认知正常人群中，大约75%的人没有明显的脑淀粉样蛋白保留。这些数据表明，淀粉样变以外的因素与老年人认知能力下降有关。流行病学研究反复表明，脑血管病（CVD）极为常见，与认知能力下降以及MCI和痴呆的发生率相关，与AD病理无关。对于心血管疾病更为普遍的非裔美国人和西班牙裔社区尤其如此。心血管疾病相关认知改变的证据导致了一种假设，即通过预防和治疗血管危险因素，可以大大减轻与年龄相关的认知能力下降的人口负担。然而，这一假设一直难以评估。阿尔茨海默病和心血管疾病通常同时发生在痴呆个体的大脑中，这使得每种病理对认知衰退的独立影响难以辨别。然而，淀粉样蛋白成像允许测量AD病理的至少一个组成部分，从而创造了评估认知轨迹、大脑差异和无广泛淀粉样变性个体认知能力下降的危险因素的机会。本研究的前提是，随着年龄的增长，从梗死到WMH、白质完整性丧失和脑萎缩等脑结构变化极为常见。此外，这些变化与认知能力下降和痴呆风险增加有关。因此，在没有广泛淀粉样蛋白的情况下，确定脑损伤的程度和后果是至关重要的。为了实现这一目标，我们将在一组不同的老年人中描述大脑结构和认知轨迹的非淀粉样蛋白相关变化。在此过程中，我们将进一步了解血管因子对大脑结构和认知的影响，这将为认知衰老和认知过程提供新的见解