VITAL-DEP (VITamin D and OmegA 3 TriaL-Depression Endpoint Prevention)

VITAL-DEP（维生素 D 和 OmegA 3 试验抑郁症终点预防）

基本信息

批准号：
10512847
负责人：
Olivia Ifeoma Okereke
金额：
$ 129.74万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-29 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10512847
关键词：
Address Adult Affect African American Age Age-associated memory impairment Anxiety Behavioral Biological Black race Blood Blood Vessels Brain Brain region Center for Translational Science Activities Cholecalciferol Clinical Clinical Sciences Cognition Cognitive Collaborations Collection Data Dementia Diagnostic Dimensions Eicosanoids Elderly Enrollment Functional Magnetic Resonance Imaging Funding Genetic Markers Genotype Health Hormones Impaired cognition Impairment Inflammation Inflammatory Interview Investigation Lipids Liquid substance Literature Long-Term Effects Magnetic Resonance Imaging Measures Mediation Mediator of activation protein Mental Depression Mental Health Moods Morbidity - disease rate N-terminal Neuropsychological Tests Neuropsychology Omega-3 Fatty Acids Outcome Participant Patient Self-Report Phase Phenotype Placebos Plasma Positron-Emission Tomography Prevention Prevention strategy Public Health Quality of life Race Randomized Randomized Controlled Trials Research Resources Risk Risk Factors Risk Marker Sampling Sex Differences Source Specific qualifier value Structure Testing Vitamin D Woman aged anxious apolipoprotein E-4 base biological sex brain volume cancer prevention cardiovascular disorder prevention cerebral atrophy cognitive benefits cognitive change cognitive function cohort daily functioning depressive symptoms design emotion regulation ethnic diversity ethnic minority executive function follow-up geriatric depression imaging biomarker inflammatory marker lifestyle factors men mood symptom neuroimaging marker neuropsychiatric symptom neuropsychiatry novel novel strategies older women pre-clinical primary outcome prospective racial and ethnic racial difference relating to nervous system response retention rate secondary outcome sex social systemic inflammatory response tau Proteins treatment effect white matter

项目摘要

VITAL-DEP (VITamin D and OmegA-3 TriaL-Depression Endpoint Prevention; NCT01696435) began as a first- of-its-kind factorial randomized controlled trial of two plausible agents – vitamin D3 (cholecalciferol 2000 IU/d) and omega-3 fatty acids (EPA and DHA in 1:1 ratio, 1000 mg/d) – for the prevention of late-life depression (LLD) and promotion of long-term healthier mood among older adults. VITAL-DEP, an ancillary of the VITAL trial of cardiovascular disease and cancer prevention, enrolled over 18,000 men and women, aged 50+ years (mean age=67 years) and at risk for depression, who were followed for a median of 5.3 years of randomized treatment. Detailed phenotypic assessments were completed at baseline and follow-up in a subset of over 1,000 participants in the local Clinical and Translational Science Center for: psychiatric diagnostic interviews; neuropsychological testing; self-reports on dimensional measures of depression, anxiety, daily functioning, and social, health and behavioral risk factors. VITAL-DEP achieved substantial racial/ethnic diversity: 20% of participants are Black/African American adults and 30% are racial/ethnic minorities. This competing renewal leverages the rich resources of the assembled cohort and builds on the findings regarding randomized treatment effects in the prior funding period. We observed: 1) evidence that vitamin D3 significantly reduces decline in global cognition and executive function among Black adults; 2) modest differences in effects of omega-3 on LLD risk and sex differences in effects. Inflammatory, structural and functional MRI, and plasma and PET tau markers selected for this proposal show evidence in the literature and preliminary data for relevance to LLD and cognition. Also, given evidence of higher burden of LLD and cognitive decline for women, Black adults, APOE4 carriers and those with higher systemic inflammation, we will determine moderation in outcomes by these risk groups. Specific Aims: 1) We will test causal effects of long-term vitamin D3 on serial measures of plasma tau (NT1), which is associated with neuropsychiatric symptoms in preclinical dementia and has high long-term predictive validity for cognitive decline, independent of other preclinical cognitive markers. 2) We will measure associations of baseline plasma tau with long-term cognitive change, mood symptoms and differences in MRI and PET-tau markers at follow-up. Secondarily, we will examine biological mechanisms for observed sex differences for omega-3 and LLD risk and race differences for vitamin D3 and cognitive decline. In exploratory aims, we hypothesize: study associations will be moderated by baseline inflammation, vascular risk, age, hormone status (in women), and APOE4. Findings from prior funding periods already have implications for public health regarding use of both supplements for prevention in late-life mental health. This renewal proposal will similarly impact the field by clarifying mechanisms for treatment effects on LLD and cognition in key clinical groups and the direct effects of the agents on the brain and preclinical risk markers.

VITAL-DEP（维生素 D 和 OmegA-3 TriaL-抑郁症终点预防；NCT01696435）最初是作为第一个两种可能的药物 – 维生素 D3（胆钙化醇 2000 IU/天）的同类析因随机对照试验和 omega-3 脂肪酸（EPA 和 DHA 比例为 1:1，1000 毫克/天）——用于预防晚年抑郁症 (LLD) VITAL-DEP 是 VITAL 试验的一个辅助项目，可促进老年人长期保持更健康的情绪。心血管疾病和癌症预防，招募了超过 18,000 名男性和女性，年龄 50 岁以上（平均年龄 = 67 岁）且有抑郁症风险，对他们进行中位随机治疗 5.3 年的随访。在超过 1,000 名受试者的基线和随访阶段完成了详细的表型评估当地临床和转化科学中心的参与者：精神病学诊断访谈；神经心理学测试；关于抑郁、焦虑、日常功能的维度测量的自我报告； VITAL-DEP 实现了显着的种族/民族多样性：20% 的社会、健康和行为风险因素。参与者是黑人/非裔美国成年人，30% 是少数族裔/族裔。利用集合队列的丰富资源，并以随机治疗的研究结果为基础我们观察到：1）有证据表明维生素 D3 显着减少了下降。黑人成年人的整体认知和执行功能；2) omega-3 对 LLD 的影响略有差异炎症、结构和功能 MRI、血浆和 PET tau 标记物的风险和性别差异。本提案所选的内容显示了与 LLD 和认知相关的文献证据和初步数据。此外，有证据表明女性、黑人成年人、APOE4 携带者的 LLD 负担较高，认知能力下降以及那些全身炎症较高的患者，我们将根据这些风险人群确定结果的适度调整。具体目标：1) 我们将测试长期维生素 D3 对血浆 tau (NT1) 一系列测量值的因果影响，与临床前痴呆症的神经精神症状相关，并且具有较高的长期预测性认知能力下降的有效性，独立于其他临床前认知标志物 2) 我们将测量关联性。基线血浆 tau 蛋白与长期认知变化、情绪症状以及 MRI 和 PET-tau 蛋白的差异其次，我们将检查观察到的性别差异的生物学机制。 omega-3 和 LLD 风险以及维生素 D3 和认知能力下降的种族差异在探索性目标中，我们。维持：研究关联将受到基线炎症、血管风险、年龄、激素状态的调节（在女性中），以及 APOE4 之前资助期间的研究结果已经对公共卫生产生了影响。关于使用这两种补充剂来预防晚年心理健康，该更新提案也将类似地进行。通过阐明关键临床群体 LLD 和认知治疗效果的机制来影响该领域，药物对大脑和临床前风险标记的直接影响。