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

项目总结/摘要 AD和ADRD的发病机制和病理生理学是多方面的、复杂的。不同个体 这些因素进一步使疾病的发作、进展和结果复杂化。例如，尽管 在揭示认知能力下降与心血管（CV）之间的关联方面的兴趣和进展 但在很大程度上仍不清楚与CV条件共病的其他因素，如 （神经）炎症、代谢紊乱和身体功能下降，在多大程度上起作用。与 由于这些风险往往同时存在，因此很难区分这些风险的独立或相对影响 这些因素进一步被个体差异所混淆。该RFA指出了重要的主题之一，如“… 心血管、代谢和其他风险因素;神经炎症;神经成像和其他生物标志物."， 这表明需要对风险因素和标识进行更全面的调查， 通过“新”的劳动力，“新”的劳动力。此外，最重要的是要更多地关注 通过同时调查多个因素，确定认知能力下降的复合风险和独立风险， 系统风险因素（“MRF”），特别是在高风险个体中，例如具有认知功能的那些 衰退或轻度认知障碍（MCI），甚至是目前无症状但有可识别风险的患者 这些因素，以动员预防AD/ADRD的努力。因此，我们建议审查多系统风险 在预测认知功能和损伤状态方面，分为以下五个领域的因素： 神经炎症、代谢、血液动力学、心理社会和身体功能。利用 正在进行的R 01研究，在老年人（65 - 89岁）中进行行为干预并招募 额外的参与者（包括更多使用神经心理学方法正式诊断为MCI的个体） Delano-Woods博士的诊所（UCSD记忆，衰老和恢复力中心，MARC），我们将 能够利用现有和新获得的五个领域的拟议风险因素的数据，以及认知 结果。认知功能和损害将通过使用蒙特利尔认知评估和定义。 评估（莫卡）和神经心理学（NP）电池之间的“一致性”水平 将在衡量报告框架的可预测性方面审查两项措施。横截面和前瞻性 将调查MRF的可预测性，并检验性别和性别与年龄的相互作用效应。

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.