Vitamin K and D and Cognitive Impairment in Older Adults

项目摘要 确定延迟认知功能下降的饮食因素对减少认知功能下降具有重要意义。 阿尔茨海默氏痴呆症（AD）的负担，并随着人口老龄化而减少医疗保健费用。不足 维生素K和维生素D的摄入在老年人中很常见，越来越多的证据表明， 营养素在阿尔茨海默病（AD）的发病机理和相关病理中具有生物学作用， 阿尔茨海默氏症的风险。我们在拉什记忆和衰老项目（MAP）的研究中证明， 死后大脑中较高的维生素K和维生素D水平与较好的认知功能有关， 至死对神经病理学定义结果的进一步研究表明， 浓度与较低的总体AD病理学相关，特别是较少的神经元缠结， 与较小的路易体（必要条件帕金森氏病和路易体痴呆症）。现在有一个 迫切需要更多的研究来阐明这些认知保护的生物学机制。 方面的影响.基于我们集体先前的研究和令人兴奋的新的研究成果，在目前的 项目期间，我们提出了一个总体目标，以阐明维生素K和维生素D之间的关联， 脑结构（神经病理学和神经影像学结果）和脑功能（认知和运动）， 老年人从两个特点鲜明的社区为基础的研究，MAP和拉什少数民族老龄化 研究（MARS）。在强有力的初步数据的指导下，这一目标将通过以下方式实现： 两个目标：具体目标1：确定维生素K和维生素D与MRI衍生指数的相关性， 白色和灰质组织完整性和脑神经病理学的测量：（a）死后脑样品; 和（B）死前血液样品;和具体目标2：确定脑维生素K和 维生素D与运动功能和帕金森症状的关系。该方法具有创新性，因为它 多学科团队将：（1）扩大我们的大脑结构成果，包括神经影像学 利用新的深度学习方法，除了神经病理学结果， 两种维生素参与AD和相关病理中发生的脑组织完整性变化;（2） 扩展脑功能结局，以包括运动功能和帕金森病体征的现有结局， 除了认知结果，对于年龄相关认知的常见机制的新见解， 和身体功能下降;和（3）增加非裔美国人死者与尸检从火星，以提高 调查结果的普遍性。这项拟议中的研究意义重大，因为摄入这两种营养素， 通常低于老年人的推荐量，是可改变的，低成本的，安全的 当消耗量更大时。成功完成拟议的研究将为 未来的研究，修改维生素K和/或维生素D对AD风险的影响。

PROJECT SUMMARY Identification of dietary factors that delay decline in cognitive function has important implications for reducing the burden of Alzheimer’s dementia (AD) and reducing health care costs as the population ages. Inadequate intakes of vitamin K and vitamin D are common among the elderly, and there is growing evidence that both nutrients have biological roles in the pathogenesis of Alzheimer’s disease (AD) and related pathologies, and the risk of Alzheimer’s dementia. We demonstrated in the Rush Memory and Aging Project (MAP) study that higher postmortem brain levels of vitamin K and vitamin D were associated with better cognitive function prior to death. Further investigation of neuropathologically-defined outcomes revealed that higher brain vitamin K concentrations were associated with lower global AD pathology, specifically fewer neurofibrillary tangles, and with lesser Lewy bodies (sine qua non of Parkinson’s disease and Lewy Body Dementia). There is now an urgent need for additional research to clarify the biologic mechanism(s) underlying these cognitive protective effects. Based on our collective prior research and exciting new research findings generated during the current project period, we propose an overall goal to elucidate associations between Vitamin K and Vitamin D with brain structure (neuropathology and neuroimaging outcomes) and brain function (cognitive and motor) in older persons from two well-characterized community-based studies, MAP and the Rush Minority Aging Research Study (MARS). Guided by strong preliminary data, this objective will be accomplished by pursuing two aims: Specific Aim 1: Determine associations of Vitamin K and Vitamin D with MRI-derived indices of white and gray matter tissue integrity and measures of brain neuropathology in: (a) postmortem brain samples; and (b) antemortem blood samples; and Specific Aim 2: Determine the associations of brain vitamin K and vitamin D with motor function and parkinsonian signs. The proposed approach is innovative because this highly productive and multidisciplinary team will: (1) expand our brain structure outcomes to include neuroimaging that leverage novel deep-learning approaches, in addition to neuropathologic outcomes, to determine if these two vitamins are involved in changes in brain tissue integrity that occur in AD and related pathologies; (2) expand brain function outcomes to include existing outcomes of motor function and parkinsonian signs, in addition to cognitive outcomes, for novel insight into common mechanisms underlying age-related cognitive and physical function declines; and (3) add African-American decedents with autopsies from MARS to enhance generalizability of the findings. The proposed research is significant because intakes of these two nutrients, which are generally below the recommended amounts in older persons, are modifiable, low-cost, and safe when consumed in higher amounts. Successful completion of the proposed study will provide the foundation for future studies on the impact of modifying vitamin K and/or vitamin D on AD risk.