Vitamin K and D and Cognitive Impairment in Older Adults

维生素 K 和 D 与老年人的认知障碍

• 批准号: 10651784
• 负责人: SARAH Louise BOOTH
• 金额: $ 68.69万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10651784
• 关键词: 25-hydroxyvitamin D; African American; African American population; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Anterior; Autopsy; Biological; Blood Vessels; Blood specimen; Brain; Brain region; Cerebellar vermis structure; Cessation of life; Cognitive; Communities; Consumption; Data; Dementia; Deposition; Development; Dietary Factors; Elderly; Foundations; Future; Gait speed; Goals; Health Care Costs; Hemorrhage; Hippocampus; Impaired cognition; Impairment; Inferior; Intake; Investigation; Lewy Bodies; Lewy Body Dementia; Link; Magnetic Resonance Imaging; Measures; Memory; Microvascular Dysfunction; Minority; Mission; Motor; Neocortex; Nerve Degeneration; Neurofibrillary Tangles; Neurosciences; Nutrient; Outcome; Parkinson Disease; Parkinsonian Disorders; Participant; Pathogenesis; Pathology; Physical Function; Population; Population Intervention; Productivity; Public Health; Recommendation; Research; Research Personnel; Resources; Role; Sampling; Solid; Structure; Supplementation; Temporal Lobe; Testing; Tissues; Vitamin D; Vitamin K; Vitamin K 1; Vitamin K 2; Vitamins; White Matter Hyperintensity; age related; brain tissue; circulating biomarkers; cognitive function; cohort; cost; deep learning; dementia risk; disorder risk; gray matter; high risk; indexing; innovation; insight; intervention cost; motor symptom; multidisciplinary; neocortical; neuroimaging; neuropathology; novel; older men; older women; protective effect; research study; white matter

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.

项目摘要 识别延迟认知功能下降的饮食因素对减少的重要意义 随着人口年龄的增长，阿尔茨海默氏症痴呆症（AD）的伯恩（AD）降低了医疗保健费用。不足 维生素K和维生素D的摄入量很常见，并且有越来越多的证据表明 营养在阿尔茨海默氏病（AD）和相关病理的发病机理中具有生物学作用，并且 阿尔茨海默氏症的痴呆症风险。我们在Rush记忆和衰老项目（MAP）研究中证明了 维生素K和维生素D的较高验尸大脑水平与先验的认知功能更好 致死。对神经病理学定义的结果的进一步研究表明，脑维生素K较高 浓度与较低的全球AD病理学相关，特别是较少的神经原纤维缠结和 有较小的路易尸体（帕金森氏病和路易人的痴呆症的正弦）。现在有一个 迫切需要进行其他研究以阐明这些认知保护性的生物学机制 效果。基于我们的集体研究和当前产生的令人兴奋的新研究结果 项目期，我们提出了一个总体目标，以阐明维生素K和维生素D与维生素D之间的关联 大脑结构（神经病理学和神经影像学结果）和大脑功能（认知和运动） 来自两个良好特征社区研究的老年人，MAP和RUSH少数族裔老化 研究（火星）。在强大的初步数据的指导下，该目标将通过追求来实现 两个目的：特定目的1：确定维生素K和维生素D与MRI衍生指数的关联 白物和灰质组织完整性和脑神经病理学的度量：（a）死后脑样本； （b）Anthertem血液样本；和特定目标2：确定脑维生素K和 维生素D具有运动功能和帕金森氏症标志。提出的方法是创新的，因为这很高 生产性和多学科团队将：（1）扩大我们的大脑结构结果，包括神经影像学 除了神经病理学的结果外，还利用新颖的深度学习方法来确定这些是否是否 两种维生素参与AD和相关病理中发生的脑组织完整性的变化。 （2） 扩展大脑功能结果，包括运动功能和帕金森氏症标志的现有结果， 除了认知结果外，还可以深入了解与年龄相关的认知基础的常见机制 身体功能下降； （3）加上有火星尸检的非裔美国人死者以增强 调查结果的普遍性。拟议的研究很重要，因为这两种营养素的摄入量， 通常低于老年人建议的金额，可修改，低成本且安全 当消费量更高时。拟议研究的成功完成将为基础提供 对于未来的研究，修改维生素K和/或维生素D对AD风险的影响。