Multisystem risk profile of older adults to predict cognitive function and impairment

项目摘要/摘要 AD和ADRD的发病机制和病理生理是多方面的、复杂的。不同的个体 各种因素使疾病的发生、发展和结果进一步复杂化。例如，尽管有很大的 认知功能减退与心血管疾病(CV)关系的研究进展 在很大程度上，目前还不清楚还有哪些其他因素与心血管疾病共存，如 (神经)炎症、代谢紊乱和身体功能下降，起作用和程度有多大。使用 这些通常是同时发生的情况，要理清这些风险的独立或相对影响是具有挑战性的。 个体差异进一步混淆了这些因素。这份报告陈述了一个重要的主题，即“… 心血管、代谢和其他危险因素；神经炎症；神经成像和其他生物标记物…， 意味着需要对风险因素和标记物识别进行更全面的调查，以推动 外地前锋和雇用“新”劳动力。此外，最重要的是要更加重视 通过同时研究多个因素来确定认知下降的复合风险和独立风险 系统风险因素(“MRF”)，特别是在高危个体中，如那些有认知功能的人 下降或轻度认知障碍(MCI)，甚至是那些目前无症状、有可识别风险的人 因素，以动员预防AD/ADRD的努力。因此，我们建议仔细审查多系统风险 预测认知功能和损害状态的因素分为以下五个领域： 神经炎症、代谢、血流动力学、心理社会和身体功能。利用 正在进行的R01研究对老年人(65-89岁)和招募人员进行行为干预 其他参与者(包括更多使用神经心理学方法正式诊断为MCI的人 测试)，来自德拉诺-伍兹博士的诊所(UCSD记忆、衰老和弹性中心，MARC)，我们将 能够利用现有的和新获得的关于五个领域和认知领域的拟议风险因素的数据 结果。认知功能和损害的评估和定义将使用蒙特利尔认知 评估(MoCA)和神经心理学(NP)组合，对于该组合， 将在中期审查框架的可预测性范围内审查两项衡量标准。横断面和前瞻性 将调查MRF的可预测性，并测试性别和性别与年龄的交互影响。

PROJECT SUMMARY/ABSTRACT Pathogenesis and pathophysiology of AD and ADRD are multifaceted and complex. Varying individual factors further complicate the onset, progression and outcomes of the disease. For example, in spite of great interests and progress made in uncovering the association between cognitive decline and cardiovascular (CV) conditions, it largely remains unclear what other factors that are comorbid with CV conditions such as (neuro)inflammation, metabolic disorders and declined physical function, play a role and to what extent. With these often concurring conditions, it is challenging to disentangle independent or relative effects of those risk factors further confounded by individual differences. This RFA states one of the important topics as “… cardiovascular, metabolic and other risk factors; neuroinflammation; neuroimaging and other biomarkers…”, signifying the need for more comprehensive investigations on risk factor and marker identification to move the field forward and by engaging “new” workforce. Furthermore, it is paramount to pay more attention to identifying composite as well as independent risk for a cognitive decline by simultaneously investigating multi- system risk factors (“MRFs”) especially, among the high-risk individuals such as those with a cognitive function decline or mild cognitive impairment (MCI) or even those who are currently asymptomatic with identifiable risk factors in order to mobilize efforts in prevention of AD/ADRD. Thus, we propose to scrutinize multisystem risk factors categorized into following five domains in predicting cognitive function and impairment status: neuroinflammatory, metabolic, hemodynamic, psychosocial and physical functioning. Leveraging an ongoing R01 study of a behavioral intervention among elderly individuals (65 – 89 years of age) and recruiting additional participants (to include more individuals with a formal diagnosis of MCI using neuropsychological test) from Co-I, Dr. Delano-Woods’ clinic (UCSD Memory, Aging and Resilience Center, MARC), we will be able to utilize the existing and newly acquired data of proposed risk factors in five domains as well as cognitive outcomes. The cognitive function and impairment will be assessed and defined by using Montreal Cognitive Assessment (MoCA) and a neuropsychological (NP) battery for which the levels of ‘agreement’ between the two measures will be examined in the context of predictability of MRFs. The cross-sectional and prospective predictability of MRFs will be investigated and the sex and sex by age interaction effects will be tested.