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

项目总结/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 老年人导致心血管疾病（CVD）患病率的同时增加， 是认知能力下降和相关脑血管功能障碍的已知危险因素。虽然药理学 治疗在减少CVD相关事件（例如心脏病发作，中风， 降低胆固醇），在该领域的集体知识方面仍然存在相当大的差距， 药物治疗对认知结果的影响。拟议的培训计划为候选人提供了 除了她的博士学位之外，程序.研究金给予的重点， 如果授予包括（1）课程在医学和药理学方面的老龄化（流行病学，老年医学， 和神经科学），（2）FLAIR和T1 MRI图像处理的教学和实践培训（针对 白色疾病的量化），和（3）具有纵向数据分析的高级实践。的 候选人得到一个强大的、富有成效的指导团队的支持，该团队在以下领域具有特定的专业知识： study.培训的动机是一项研究计划，该计划将调查20，368名60岁以上的成年人， 老年人，来自国家阿尔茨海默氏症协调中心（NACC）。NACC参与者沿着 将纳入随访2-10年的认知连续体（例如，认知正常至痴呆）。 NACC数据库为研究这些问题提供了异常丰富的数据来源， 样本量，纵向情况，广泛的个人抽样，同时成像的子集 个人，所有参与者的详细药物库存，以及使用统一的数据集， 神经心理学数据收集。这项工作将探讨心血管疾病之间的关联 （包括高血压等风险因素和心肌梗死等合并症），血管 神经病理学（感兴趣区域中的白色高信号），以及四个区域中的变化轨迹。 认知领域（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）是否能减轻认知能力下降。 因此，本研究有两个具体的目的：（1）确认参与者的水平和纵向 CVD的变化率与四个认知领域的水平和变化率相关。 并进一步研究CVD药物治疗是否能缓解 （2）在基线时收集结构MRI数据的参与者子集中， 确定血管神经病理学的基线指标是否介导了 基线CVD水平和认知随时间的变化率。

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.