Vitamin B12 status, cognitive decline and incident dementia

维生素 B12 状况、认知能力下降和痴呆症

基本信息

批准号：
10574499
负责人：
PAUL F JACQUES
金额：
$ 50.72万
依托单位：
TUFTS UNIVERSITY BOSTON
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2025-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10574499
关键词：
Acceleration Address Age Age-associated memory impairment Aging Alzheimer&apos s Disease 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 Homocysteine Impaired cognition Incidence Individual 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 Uncertainty Verbal Learning Vitamin B 12 Vitamin B 12 Deficiency age related aged 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 verbal visual memory

项目摘要

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.

项目概要维生素 B12 缺乏的临床结果已明确会导致严重的神经系统后果，但人们普遍认为，未确诊的 B12 缺乏症并不常见，大约 5% 的老年人存在这种情况也有有限的证据表明存在长期、亚临床 B12 缺乏症。高达 40% 的老年人会导致神经认知功能障碍，但这种关系仍然存在。由于现有证据存在严重局限性，因此尚不确定。鉴于其患病率很高，因此至关重要。了解亚临床 B12 缺乏症的潜在神经认知后果许多观察和结果。临床研究表明，亚临床维生素 B12 缺乏与神经认知能力下降有关老年人的功能，但其他研究没有发现这些观察到的不一致的主要原因是难以结合多种 B12 状态测量值（例如循环 B12），总同型半胱氨酸和甲基丙二酸，将为 B12 状态提供更可靠的评估。 B12 状态和神经认知研究之间存在差异的关键但经常被忽视的因素功能是未能解释过量叶酸对 B12 不足的临床效果的恶化影响。现有 B12 和神经认知功能研究的其他局限性可能在一定程度上导致了证据不一致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，以及认知评估方法的异质性和弱点。进行随机试验来检查亚临床维生素 B12 缺乏症与认知能力之间的关系维生素 B12 水平下降充满了道德考虑，因为这需要维生素 B12 水平低的个体去长期未治疗的随访因此，更好地了解维生素 B12 不足的情况。老年人的神经功能状况需要精心设计的观察性研究的目标。拟议的项目旨在解决我们对 B12 状态和神经认知的理解中的关键差距使用基于组合标记的血液样本评估叶酸状态和 B12 状态的现有功能关于 B12 状态的 3 个提到的标志物，以及认知能力下降、痴呆症的现有数据，包括对多达 3500 名个体的阿尔茨海默病和脑萎缩进行了 20 多年的跟踪研究。弗雷明汉心脏研究的数据提供了一个独特的机会来评估之间的关系亚临床 B12 缺乏症和与年龄相关的神经认知变化，早期研究几乎没有局限性。拟议研究的结果将为治疗亚临床 B12 缺乏症和可能会对公共健康产生重大影响，因为亚临床维生素 B12 缺乏症很常见且未经诊断亚临床 B12 缺乏可能是预防与年龄相关的神经认知障碍的一个重要机会亚临床维生素 B12 缺乏症可以轻松识别并通过维生素 B12 补充剂进行治疗。