Cognitive Aging Trajectories: Cardiovascular Risk, White Matter, and Medication Predictors

项目摘要/摘要 拟议的培训奖学金侧重于认知老化的风险和保护因素。增加了 老年人口导致心血管疾病(CVD)患病率随之增加， 是认知功能减退和相关脑血管功能障碍的已知危险因素。虽然药理学上 治疗在减少心血管疾病相关事件(如心脏病发作、中风、 降低胆固醇)，但该领域关于影响的集体知识仍然存在相当大的差距 药物治疗对认知结果的影响。拟议的培训计划提供了候选人 除了博士课程之外，还有额外的培训。奖学金所提供的重点， 如果获奖，包括(1)老龄化的医学和药理学方面的课程(流行病学、老年病学、 和神经科学)，(2)FLAIR和T1 MRI图像处理的教学和实践培训(用于 白质疾病的量化)，以及(3)纵向数据分析的高级实践。这个 候选人得到强大、高效的指导团队的支持，该团队在建议的领域具有特定的专业知识 学习。培训是由一项研究计划推动的，该计划将对20,368名60岁和60岁以上的成年人进行调查 年龄较大的，来自国家阿尔茨海默氏症协调中心(NACC)。NACC沿线参与者 将包括认知连续体(例如，痴呆症期间的认知正常)和2-10年的随访。 NACC数据库提供了异常丰富的数据来源，用于研究这些问题，因为 样本量、纵向场合、个体的广泛抽样、子集上的并发成像 个人，所有参与者的详细药物清单，以及使用统一的数据集 神经心理学数据收集。拟议的工作将调查心血管疾病之间的联系 (包括高血压等危险因素和心肌梗死等合并症)、血管 神经病理学(感兴趣区白质高信号)，以及4例患者的变化轨迹 认知域(记忆、注意力、执行功能/处理速度和语言)。这项研究将 进一步研究药物治疗(心血管药物)是否能缓解认知衰退。 因此，拟议的研究有两个具体目标：(1)确认参与者的水平和纵向 心血管疾病的变化率与四个认知领域的水平和变化率有关 并进一步研究心血管疾病的药物治疗是否会减缓这种影响 关联性，以及(2)在基线收集其结构MRI数据的参与者子集中， 确定血管神经病理的基线指标是否在 基线脑血管密度对认知水平和随时间变化的速度的影响。

PROJECT SUMMARY/ABSTRACT The proposed training fellowship focuses on risks and protective factors in cognitive aging. Increases in the older adult population have resulted concomitant increases in cardiovascular disease (CVD) prevalence, which is a known risk factor for cognitive decline and related cerebrovascular dysfunction. While pharmacological treatment has made substantial advances in reductions of CVD-related events (e.g. heart attack, stroke, lowering cholesterol), there remain considerable gaps in the field’s collective knowledge regarding the impacts of pharmacological treatment on cognitive outcomes. The proposed training plan provides the candidate with additional training beyond that afforded by her Ph.D. program. Emphases afforded by the fellowship, if awarded include (1) coursework in medical and pharmacological aspects of aging (epidemiology, geriatrics, and neuroscience), (2) didactic and hands-on training in the processing of FLAIR and T1 MRI images (for the quantification of white matter disease), and (3) advanced practice with longitudinal data analyses. The candidate is supported by a strong, productive mentoring team with specific expertise in the proposed areas of study. Training is motivated by a research plan that will investigate, in a sample of 20,368 adults aged 60 and older, drawn from the National Alzheimer’s Coordinating Center (NACC). NACC participants along the cognitive continuum (e.g. cognitively normal through dementia) with 2-10 years of follow-up will be included. The NACC database offers an unusually rich source of data in which to investigate these questions because of sample size, longitudinal occasions, broad sampling of individuals, concurrent imaging on a subset of individuals, detailed medication inventories on all participants, and the use of a uniform data set for neuropsychological data collection. The proposed work will investigate the associations between CVD (including both risk factors like hypertension and comorbidities like myocardial infarction), vascular neuropathology (white matter hyperintensities in regions of interest), and trajectories of change in four cognitive domains (Memory, Attention, Executive Function/Processing Speed, and Language). The study will further investigate whether pharmacological treatment (cardiovascular medication) mitigates cognitive decline. Thus, the proposed study has two specific aims: (1) To confirm that participants’ level and longitudinal rate of change in CVD is associated with level and rate of change in the four cognitive domains over the subsequent decade; and to further investigate whether pharmacological treatment of CVD moderates that association, and (2) In a subset of participants for whom structural MRI data were collected at baseline, to determine whether baseline indicators of vascular neuropathology mediate the relationship between baseline CVD on level and rate of change in cognition over time.