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.

项目概要/摘要 视觉障碍 (VI) 和认知障碍是对老年人影响尤为严重的慢性疾病 成年人。研究表明，VI 与认知障碍和痴呆症之间存在一致的关系 老年人。 VI 是阿尔茨海默病 (AD) 的危险因素，与未来认知能力下降有关。 然而，VI 与纵向认知轨迹特征的关联程度 老年人仍不清楚，特别是中年的 VI 状态如何影响老年生活的认知轨迹。 此外，VI 影响认知功能的机制尚未得到很好的阐明。六、 认知能力下降都可能是大脑神经退行性变等共同根本原因的结果。 另外，VI 可能会降低老年人参与活动和社交的能力，这会成为 认知能力下降的危险因素。心血管疾病 (CVD) 危险因素影响 VI 和 认知结果可能是认知障碍的重要病因途径。 重要的遗传因素如与 AD 呈正相关的 APOE ε4 已被证明 与某些脑血管疾病和视力障碍有关。这些重要而复杂的 VI、CVD 危险因素、脑神经变性、APOE ε4 基因型和认知能力下降之间的关联 尚未得到系统、全面的研究。当前的提案利用了两个大的 流行病学队列（健康 ABC 研究和英国生物银行）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、脑神经变性、CVD 危险因素、APOE ε4 基因型和 社会心理因素，因为它们与认知衰退的纵向轨迹和联系有关 VI 与认知衰退之间的机制。该职业发展奖的研究是 辅之以基于候选人强大的统计背景的培训活动，并提供 新培训涉及 1) 认知神经科学和正常衰老、认知障碍和 广告; 2）脑血管疾病及其危险因素及其相关疾病机制和后果； 3） 神经影像学和脑神经变性的标志物； 4) VI 的临床方面和进行眼科 流行病学研究。这项复杂的研究和培训计划与经验丰富的专家相结合 忠诚的导师团队将促进申请人获得有意义的技能并促进其发展 成为一名独立调查员。这项研究将回答 VI 是否相关的重要问题 认知能力下降加速下降，并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 AD 和 ADRD 的治疗非常有限。 VI是一种流行的 病情高度可治疗，是一个重要的可改变的风险因素，可以预防和预防 被视为保持认知功能和提高生活质量的有效手段。