Visual impairment and cognitive decline: understanding the longitudinal relationships and mechanisms

视觉障碍和认知能力下降：理解纵向关系和机制

• 批准号: 10572333
• 负责人: Dandan Diane Zheng
• 金额: $ 13.26万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-01 至 2027-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10572333
• 关键词: Acceleration; Address; Adult; Affect; Aging; Alzheimer associated neurodegeneration; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Area; Blood Vessels; Brain; Cerebrovascular Disorders; Characteristics; Chronic; Clinical; Clinical assessments; Cognition; Cognitive; Communities; Complement; Complex; Contrast Sensitivity; Data; Data Sources; Dementia; Development; Disease; Elderly; Epidemiology; Equation; Etiology; Eye diseases; Fostering; Future; Genetic; Genotype; Goals; Health; Impaired cognition; K-Series Research Career Programs; Life; Link; Measures; Mediating; Mental Depression; Mentorship; Microvascular Dysfunction; Modeling; Nerve Degeneration; Outcome; Pathway interactions; Pattern; Play; Process; Psychological Factors; Quality of life; Research; Research Personnel; Risk; Risk Factors; Role; Scientist; Social isolation; Statistical Methods; Statistical Models; Structure; Techniques; Thick; Training; Training Activity; Vision; Vision Disorders; Visual Acuity; Visual impairment; White Matter Hyperintensity; biobank; brain magnetic resonance imaging; cardiovascular disorder risk; cognitive function; cognitive neuroscience; cognitive reserve; cohort; epidemiology study; experience; improved; middle age; modifiable risk; neuroimaging; normal aging; novel; preservation; prevent; programs; psychologic; sex; skills; social; social engagement; statistics

PROJECT SUMMARY/ABSTRACT Visual impairment (VI) and cognitive impairment are chronic conditions that disproportionately affect older adults. Research has revealed a consistent relationship between VI and cognitive impairment and dementia in older adults. VI is a risk factor for Alzheimer disease (AD) and is associated with future cognitive decline. However, the extent to which VI is associated with the characteristics of the longitudinal cognitive trajectory of aging adult remains unclear, particularly how VI status in midlife affects the cognitive trajectory in older life. Additionally, the mechanisms through which VI affects cognitive functioning have not been well elucidated. VI and cognitive decline could both be the result of a common underlying cause such as brain neurodegeneration. Alternatively, VI may reduce older adults’ ability to participate in activities and engage socially, which become risk factors for cognitive decline. Cardiovascular diseases (CVD) risk factors influence the risk of both VI and cognitive outcomes which may serve as important etiologic pathways underlying cognitive impairment. Important genetic factors such as APOE ε4 which is positively associated with AD has been demonstrated to be related to certain cerebrovascular diseases and visual disorders. These important and complex associations among VI, CVD risk factors, brain neurodegeneration, APOE ε4 genotype and cognitive decline have not been studied in a systematic and comprehensive manner. The current proposal leverages two large epidemiological cohort (The Health ABC Study and UK Biobank) and presents an unprecedented opportunity to employ sophisticated and novel application of Structure Equation Modeling techniques to investigate the complex associations between VI, brain neurodegeneration, CVD risk factors, APOE ε4 genotype, and sociopsychological factors as they relate to the longitudinal trajectories of cognitive decline and the linking mechanisms between VI and cognitive decline. The research in this career development award is complemented by training activities that build on the candidate’s strong background in statistics and provides new trainings on 1) cognitive neurosciences and clinical assessment of normal aging, cognitive impairment and AD; 2) cerebrovascular disease and risk factors and their relevant disease mechanisms and consequences; 3) neuroimaging and markers of brain neurodegeneration; 4) clinical aspects of VI and conducting ocular epidemiological study. This sophisticated research and training plan combined with a highly experienced and committed mentorship team will facilitate acquisition of meaningful skills and foster the applicant’s development into an independent investigator. This research will answer the important question of whether VI is associated with accelerated downward trajectories of cognitive decline and will elucidate critical underlying mechanisms linking VI with cognitive decline. The treatment for AD and ADRD is currently very limited. VI is a prevalent condition that is highly treatable and represents an important modifiable risk factor that can be prevented and treated as an effective means to preserve cognitive function and improve quality of life.

项目摘要/摘要 视觉障碍（VI）和认知障碍是慢性病，对较老的影响不成比例 成年人。研究揭示了VI与认知障碍与痴呆之间的一致关系 老年人。 VI是阿尔茨海默氏病（AD）的危险因素，与未来的认知下降有关。 但是，VI与纵向认知轨迹的特征相关的程度 衰老的成年人仍然不清楚，尤其是中年中的VI状况如何影响较旧生活的认知轨迹。 另外，VI影响认知功能的机制尚未得到很好的阐明。 vi 认知能力下降都可能是诸如脑神经退行性的常见根本原因的结果。 另外，VI可能会降低老年人参加活动和社交参与的能力，这成为 认知能力下降的风险因素。心血管疾病（CVD）风险因素影响VI和 认知结果可能是认知障碍的重要病因学途径。 与AD相关的重要遗传因素，例如APOEε4 与某些脑血管疾病和视觉疾病有关。这些重要而复杂的 VI，CVD危险因素，脑神经退行性的关联，APOEε4基因型和认知能力下降 尚未以系统而全面的方式进行研究。当前的提议利用两个大型 流行病学队列（健康ABC研究和英国生物库），并提供了前所未有的机会 采用结构方程建模技术的复杂和新颖的应用来研究 VI，大脑神经退行性变化，CVD风险因素，APOEε4基因型和 社会心理学因素与认知下降的纵向轨迹和联系有关 VI和认知能力下降之间的机制。该职业发展奖的研究是 通过培训活动完成，这些活动以候选人的统计背景为基础，并提供 对1）认知神经科学和正常衰老，认知障碍和临床评估的新培训 广告; 2）脑血管疾病和危险因素及其相关疾病机制和后果； 3） 脑神经变性的神经影像和标记； 4）VI的临床方面和进行眼 流行病学研究。这个复杂的研究和培训计划结合了经验丰富且经验丰富的 坚定的Mentalship团队将促进获得有意义的技能并促进申请人的发展 进入独立研究者。这项研究将回答VI是否相关的重要问题 随着认知下降的加速轨迹，将阐明关键的潜在机制 将VI与认知能力下降联系起来。目前对AD和ADRD的治疗非常有限。 vi是普遍的 高度治疗，代表可预防的重要修改风险因素的状况，并且 被视为保留认知功能并改善生活质量的有效手段。