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

项目摘要/摘要 视力损害(VI)和认知损害是对老年人影响不成比例的慢性疾病 成年人。研究表明，VI与认知障碍和痴呆之间存在一致的关系 上了年纪的人。VI是阿尔茨海默病(AD)的危险因素，与未来的认知能力下降有关。 然而，VI在多大程度上与被试的纵向认知轨迹特征有关 老年人仍不清楚，特别是中年VI状态如何影响老年人的认知轨迹。 此外，VI影响认知功能的机制还没有得到很好的阐明。六、 认知能力下降都可能是共同的潜在原因造成的，比如脑神经退化。 或者，VI可能会降低老年人参与活动和参与社交的能力，这将成为 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，这可能是认知损害的重要病因。 重要的遗传因素，如与AD呈正相关的载脂蛋白Eε4，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、心血管危险因素、脑神经退行性变、载脂蛋白Eε4基因与认知功能减退的关系 还没有得到系统和全面的研究。目前的提案利用了两个大的 流行病学队列(Health ABC Study和UK Biobank)，提供了一个前所未有的机会 运用复杂而新颖的结构方程建模技术来研究 VI、脑神经退行性变、心血管疾病危险因素、载脂蛋白Eε4基因和 社会心理因素与认知衰退的纵向轨迹及其联系 VI与认知功能衰退之间的机制。这项职业发展奖的研究是 辅以培训活动，以候选人在统计方面的强大背景为基础，并提供 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 脑血管疾病和危险因素及其相关的发病机制和后果；3) 脑神经退行性变的神经影像和标志物；4)VI和导眼的临床特点 流行病学研究。这一复杂的研究和培训计划与经验丰富的 尽职尽责的导师团队将促进获得有意义的技能并促进申请者的发展 成为一名独立的调查员。这项研究将回答VI是否关联的重要问题 认知衰退的加速下行轨迹，并将阐明关键的潜在机制 将VI与认知能力下降联系起来。目前对AD和ADRD的治疗非常有限。VI是一种流行的 高度可治疗的疾病，是一个重要的可改变的风险因素，可以预防和 被视为保护认知功能、提高生活质量的有效手段。

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.