Vitamin K and D and Cognitive Impairment in Older Adults

项目总结 确定延缓认知功能下降的饮食因素对减少 阿尔茨海默氏症(AD)的负担和随着人口老龄化而降低的医疗费用。不足之处 维生素K和维生素D的摄入量在老年人中很常见，而且越来越多的证据表明，这两种物质 营养素在阿尔茨海默病(AD)的发病机制和相关病理中具有生物学作用，以及 阿尔茨海默氏症的风险。我们在Rush Memory and Aging Project(MAP)研究中证明 死后大脑中维生素K和维生素D水平较高与先前较好的认知功能有关 直到死亡。对神经病理学结果的进一步研究表明，较高的大脑维生素K 浓度与较低的全球AD病理相关，特别是较少的神经原纤维缠绕，以及 有较轻的路易体(帕金森氏病和路易体痴呆的必要条件)。现在有一个 迫切需要更多的研究来阐明这些认知保护背后的生物学机制(S) 效果。基于我们先前的集体研究和在当前 在项目期间，我们提出了一个总体目标，以阐明维生素K和维生素D之间的联系 脑结构(神经病理和神经成像结果)和脑功能(认知和运动) 来自两项以社区为基础的研究的老年人，MAP和Rush少数民族老龄化 研究性研究(火星)。在强劲的初步数据的指引下，这一目标将通过追求 两个目标：具体目标1：确定维生素K和维生素D与核磁共振成像指标的相关性 脑白质和灰质组织的完整性和脑神经病理测量：(A)死后脑标本； 和(B)死前血液样本；以及具体目标2：确定大脑维生素K和 维生素D具有运动功能和帕金森症状。建议的方法是创新的，因为这是高度 富有成效的多学科团队将：(1)扩展我们的大脑结构成果，将神经成像包括在内 利用新的深度学习方法，以及神经病理结果，来确定这些 两种维生素参与阿尔茨海默病及相关病理的脑组织完整性改变； 扩展脑功能结果以包括运动功能和帕金森症状的现有结果，在 除了认知结果之外，还提供了对年龄相关认知基础的共同机制的新见解 身体机能下降；以及(3)增加来自火星的非裔美国人的身体，以增强 研究结果的概括性。这项拟议的研究意义重大，因为摄入这两种营养物质， 通常低于老年人的推荐量，是可修改的、低成本和安全的 当消耗更多的量时。成功完成拟议的研究将提供基础 关于修改维生素K和/或维生素D对AD风险的影响的未来研究。

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.