Vitamin B12 status, cognitive decline and incident dementia

维生素 B12 状况、认知能力下降和痴呆症

• 批准号: 10369056
• 负责人: PAUL F JACQUES
• 金额: $ 73.24万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10369056
• 关键词: Address; Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Alzheimer' s disease brain; American; Blood specimen; Brain; Caregivers; Chronic; Clinical; Clinical Research; Cognition; Cognitive; Data; Dementia; Disease; Economic Burden; Elderly; Ethics; Failure; Family member; Folic Acid; Framingham Heart Study; Functional disorder; Goals; Healthcare; Heterogeneity; High Prevalence; Hippocampus (Brain); Homocysteine; Impaired cognition; Incidence; Individual; Lead; Long-Term Care; Magnetic Resonance Imaging; Measurement; Measures; Medicare/Medicaid; Memory; Metabolic; Methodology; Methods; Methylmalonic Acid; Nervous System Physiology; Neurocognitive; Neurocognitive Deficit; Neurologic; Neuropsychological Tests; Neuropsychology; Observational Study; Persons; Prevalence; Prevention; Public Health; Randomized Controlled Trials; Sampling; Services; Structure; Thick; Time; Uncertainty; Verbal Learning; Vitamin B 12; Vitamin B 12 Deficiency; age related; aged; base; beneficiary; brain volume; care costs; cerebral atrophy; circulating biomarkers; clinical effect; cognitive function; cohort; cost estimate; design; follow-up; hospice environment; human old age (65+); neuroimaging; nutrition; offspring; payment; prevent; prospective; public health relevance; randomized trial; visual memory

PROJECT SUMMARY The serious neurologic consequences of clinical vitamin B12 deficiency results is well-established, but it is generally believed that undiagnosed B12 deficiency is uncommon, present in approximately 5% of those aged ≥60 y. There is also limited evidence that long-term, subclinical B12 deficiency, which is believed to be present in up to 40% of older individuals, leads to neurocognitive dysfunction. However, this relationship remains uncertain because of serious limitations in the existing evidence. Given its high prevalence, it is critical to understand the potential neurocognitive consequences of subclinical B12 deficiency. Many observational and clinical studies have suggested that subclinical B12 insufficiency is associated with reduced neurocognitive function in the elderly, but other studies have not. A major reason for these observed inconstancies is the difficulty in determining B12 status. Combining multiple measurements of B12 status, such as circulating B12, total homocysteine and methylmalonic acid, will provide a more reliable assessment of B12 status. Another key, but often overlooked, factor in the discrepancies between studies of B12 status and neurocognitive function is the failure to account for the worsening effect of excess folate on clinical effects of B12 insufficiency. Other limitations of existing studies of B12 and neurocognitive function that may be, in part, responsible for the inconsistent evidence are the lack of repeated assessment of B12 status during follow-up, insufficient numbers of subjects and follow-up duration, and heterogeneity and weaknesses in cognition-assessment methodology. Undertaking randomized trials to examine the relationship between subclinical B12 deficiency and cognitive decline is fraught with ethical considerations because it would require that individuals with low B12 levels go untreated for long periods of follow-up. Therefore, gaining a better understanding of inadequate vitamin B12 status in neurologic function of aging individuals will require well-designed observational studies. The goal of the proposed project is to address the critical gap in our understanding of B12 status and neurocognitive function using existing blood samples to assess folate status and B12 status using a combined marker based on the 3 aforementioned markers of B12 status, and existing data on cognitive decline, dementia including Alzheimer's disease, and brain atrophy in up to 3500 individuals followed for 20+ years. Existing samples and data from the Framingham Heart Study present a unique opportunity to assess the relationship between subclinical B12 deficiency and age-related neurocognitive changes with few limitations of earlier studies. Findings from the proposed study will provide a scientific basis for treatment of subclinical B12 deficiency and could have a substantial public health impact as subclinical deficiency of B12 is common and undiagnosed subclinical B12 deficiency may be an important missed opportunity for prevention of age-related neurocognitive decline and dementia. Subclinical B12 deficiency can be easily identified and treated with B12 supplements.

项目总结 临床维生素B12缺乏导致的严重神经系统后果是公认的，但事实并非如此。 普遍认为，未诊断的B12缺乏症并不常见，约5%的老年人存在这种缺乏症 ≥60岁。也有有限的证据表明，据信存在长期亚临床B12缺乏症 在高达40%的老年人中，会导致神经认知功能障碍。然而，这种关系仍然存在 由于现有证据的严重限制，这是不确定的。鉴于其高流行率，至关重要的是 了解亚临床B12缺乏症的潜在神经认知后果。许多观察性的和 临床研究表明，亚临床B12缺乏与神经认知功能减退有关 对老年人的作用，但其他研究还没有。这些观察到的不一致的一个主要原因是 很难确定B12的状态。组合B12状态的多个测量，例如循环B12， 总同型半胱氨酸和甲基丙二酸，将提供更可靠的B12状态评估。另一个 B12状态和神经认知研究之间差异的关键因素，但往往被忽视 功能是未能解释过量叶酸对B12缺乏的临床效果的恶化影响。 对B12和神经认知功能的现有研究的其他局限性可能在一定程度上导致 不一致的证据是在随访期间缺乏对B12状态的重复评估，数量不足 受试者和随访持续时间的差异，以及认知评估方法的异质性和弱点。 开展随机试验研究亚临床B12缺乏症与认知功能的关系 下降充满了伦理方面的考虑，因为这将要求B12水平较低的人 长期未接受治疗的随访。因此，更好地了解维生素B12不足 老年人的神经功能状况将需要精心设计的观察性研究。的目标是 拟议的项目是为了解决我们对B12状态和神经认知的理解上的关键差距 使用现有血液样本评估叶酸状态和B12状态的功能，使用基于 关于上述B12状态的3个标志，以及现有的认知能力下降的数据，痴呆症包括 对多达3500人的阿尔茨海默氏症和脑萎缩进行了20多年的跟踪调查。现有样本和 来自弗雷明翰心脏研究的数据提供了一个独特的机会来评估 亚临床B12缺乏症和年龄相关的神经认知改变，几乎没有早期研究的局限性。 研究结果将为亚临床B12缺乏症的治疗提供科学依据。 可能会对公共卫生造成重大影响，因为B12的亚临床缺陷很常见，而且没有诊断出来 亚临床B12缺乏症可能是预防年龄相关神经认知障碍的一个重要机会 衰老和痴呆症。亚临床B12缺乏症可以很容易地被识别出来，并通过补充B12来治疗。