The impact of non-amyloid processes on cognitive aging

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。这些差异中至少有一些可归因于阿尔茨海默病（AD），并且正在进行一项重大努力来描绘脑淀粉样蛋白对与年龄相关的认知变化和痴呆事件的影响。然而，大约75%的70-79岁的认知正常个体没有明显的大脑淀粉样蛋白保留。这些数据表明，淀粉样变性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，脑血管疾病（CVD）非常常见，与认知能力下降以及MCI和痴呆事件相关，与AD病理无关。这对于CVD更普遍的非洲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，年龄相关认知下降的人群负担可能会大大减轻。然而，这一假设一直难以评估。阿尔茨海默病和CVD病理通常共同发生在痴呆个体的大脑中，使得每种病理对认知下降的独立影响难以辨别。然而，淀粉样蛋白成像允许测量AD病理学的至少一种组分，从而创造了评估无广泛淀粉样变性的个体中认知轨迹、脑差异和认知下降的风险因素的机会。这项研究的前提是，脑结构的变化，从梗死到WMH，白色物质完整性的丧失和脑萎缩是非常常见的老龄化。此外，这些变化与认知能力下降和痴呆症风险增加有关。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至关重要。为了实现这一目标，我们将在一组不同的老年人中描述脑结构和认知轨迹的非淀粉样蛋白相关变化。通过这样做，我们将进一步了解血管因素对大脑结构和认知的影响，这将为认知老化的过程提供新的见解， 在一个基于社区的、种族和人种多样化的队列中，对未来认知障碍的易感性。

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.