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: 10090549
• 负责人: PAUL F JACQUES
• 金额: $ 75.85万
• 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/10090549
• 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.

项目摘要 临床维生素B12缺乏的严重神经系统后果是公认的，但它是 一般认为，未确诊的B12缺乏症是罕见的，目前在约5%的老年人 ≥60岁也有有限的证据表明长期、亚临床B12缺乏，据信这种缺乏是存在的 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局限性，鉴于其高流行率， 了解亚临床B12缺乏的潜在神经认知后果。许多观察和 临床研究表明，亚临床B12不足与神经认知功能降低有关， 在老年人中起作用，但其他研究没有。这些观察到的不稳定性的主要原因是 难以确定B12状态。结合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，将提供更可靠的评估B12状态。另一 一个关键的，但经常被忽视的因素，在B12状态和神经认知研究之间的差异 功能是未能解释过量叶酸对B12不足的临床效果的恶化作用。 现有的B12和神经认知功能研究的其他局限性可能部分导致 不一致的证据是在随访期间缺乏对B12状态的重复评估， 受试者和随访持续时间，以及认知评估方法的异质性和弱点。 进行随机试验，以检查亚临床B12缺乏症与认知功能之间的关系。 下降充满了伦理考虑，因为它需要B12水平低的人去 长期未接受治疗。因此，更好地了解维生素B12不足 老年人的神经功能状态需要精心设计的观察性研究。的目标 拟议的项目是解决我们对B12状态和神经认知的理解的关键差距， 功能使用现有的血液样本来评估叶酸状态和B12状态，使用基于 关于上述3种B12状态标志物，以及关于认知能力下降、痴呆症（包括 阿尔茨海默氏病和脑萎缩，在多达3500人随访了20年以上。现有的样品和 来自心脏研究的数据提供了一个独特的机会来评估 亚临床B12缺乏和年龄相关的神经认知变化，早期研究的局限性很少。 这项研究的结果将为亚临床B12缺乏症的治疗提供科学依据， 可能会对公共卫生产生重大影响，因为亚临床B12缺乏症很常见且未确诊 亚临床B12缺乏可能是预防与年龄相关的神经认知功能障碍的重要机会。 衰退和痴呆。亚临床B12缺乏症可以很容易地识别和治疗B12补充剂。