Depression and Alzheimer's Disease: CaTAUstrophy?

抑郁症和阿尔茨海默病：CaTAU 营养不良？

• 批准号: 10688098
• 负责人: Jennifer Rose Gatchel
• 金额: $ 82.65万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10688098
• 关键词: Address; Affective Symptoms; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; Amyloid; Amyloid beta-42; Biological Markers; Blood Tests; Brain region; Brain scan; Clinical; Clinical Trials; Cognition; Cognitive; Data; Elderly; Enrollment; Equation; Evaluation; Exclusion; Funding; Goals; Impaired cognition; Knowledge; Major Depressive Disorder; Measurement; Measures; Medial; Memory; Mental Depression; Modeling; N-terminal; Neurobehavioral Manifestations; PET positivity; Participant; Pathologic; Performance; Pittsburgh Compound-B; Plasma; Positioning Attribute; Positron-Emission Tomography; Prevention; Public Health; Readiness; Research; Resolution; Risk; Severities; Site; Temporal Lobe; Testing; Thinking; Time; behavioral and social science; clinical translation; clinically significant; cohort; dementia risk; depressive symptoms; design; follow-up; geriatric depression; innovation; neglect; neuropsychiatric symptom; novel; participant enrollment; pre-clinical; prevent; social science research; spatiotemporal; tau Proteins; therapy development

ABSTRACT Better understanding the interface of depression and Alzheimer’s Disease (AD) pathology could lead to new strategies to prevent or slow cognitive decline, with significant public health impact. Depression has historically been neglected and/or excluded in observational cohort and clinical trial research on AD– so we have limited knowledge about its relationship with pathological hallmarks of AD and cognitive decline. Our data suggest an association between tau and depression that may potentiate cognitive decline in preclinical stages of AD—when amyloid are below PET positivity thresholds--and confer dementia risk. Currently, the model of tau- associated depressive symptoms needs to be validated across the full spectrum of depressive symptom severity, including major depressive disorder (MDD). The current study was designed to address this critical gap. Our overarching goal is to investigate the relationships between tau and depressive symptoms over time in cognitively unimpaired older adults using both longitudinal tau PET (with spatiotemporal resolution) and novel plasma tau measures (with greater potential for clinical translation than PET or CSF) that are gaining rapid readiness for clinical translation). Achieving this goal will help characterize risk of cognitive decline for older adults with clinically significant depressive symptoms, optimize approaches to depression evaluation, and provide potential opportunities for early recognition and prevention of AD. Our primary hypothesis is that tau in temporal brain regions will predict more severe depressive symptoms, and that greater depressive symptoms will potentiate tau-associated cognitive decline. We will test these hypotheses in 150 cognitively unimpaired older adults across the spectrum of depression (subclinical to Major Depressive Disorder [MDD]) integrating longitudinal affective and cognitive symptom characterization, tau PET, and tau plasma biomarker assessments.This is the first study to our knowledge to investigate longitudinal tau PET and plasma measures in a cohort of older adults across the full range of depressive symptom severity. Better understanding of the mechanisms underlying depressive symptoms in preclinical AD could inform prevention efforts, including tau measurement as a means of identifying risk in older adults with late life depression. Thus, we will address the FOA goal “to encourage biomedical, behavioral and social sciences research that will enhance knowledge of mechanisms underlying neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) or Alzheimer's disease-related dementias (ADRD) so as to enable novel treatment development.”

摘要 更好地了解抑郁症和阿尔茨海默病（AD）病理学的界面可以 导致新的战略，以防止或减缓认知能力下降，具有重大的公共卫生影响。 抑郁症历来被忽视和/或排除在观察性队列和临床 因此，我们对其与病理学的关系了解有限。 AD和认知能力下降的标志。我们的数据表明tau蛋白和 抑郁症可能在AD的临床前阶段增强认知能力下降--当淀粉样蛋白 低于PET阳性阈值-并赋予痴呆风险。目前，Tau的模型- 相关的抑郁症状需要在整个抑郁症谱中得到验证。 症状严重程度，包括重度抑郁症（MDD）。本研究旨在 来填补这一关键空白。我们的首要目标是研究tau蛋白与 和抑郁症状随着时间的推移在认知未受损的老年人使用这两种 纵向tau PET（具有时空分辨率）和新的血浆tau测量（具有 比PET或CSF更大的临床翻译潜力）， 临床翻译）。实现这一目标将有助于描述老年人认知能力下降的风险。 有临床显著抑郁症状的成年人，优化抑郁症的治疗方法 评估，并提供早期识别和预防AD的潜在机会。我们 主要假设是颞叶脑区的tau蛋白将预测更严重的抑郁症， 更严重的抑郁症状会增强tau相关的认知功能， 下降我们将在全国150名认知未受损的老年人中测试这些假设。 抑郁症谱（亚临床至重度抑郁症[MDD]）整合 纵向情感和认知症状表征、tau PET和tau血浆 生物标志物评估。这是我们所知的第一个研究纵向tau蛋白的研究。 一个老年人队列中的PET和血浆测量， 症状严重程度。更好地理解抑郁症的潜在机制， 临床前AD可以为预防工作提供信息，包括tau测量作为一种手段， 确定老年人晚年抑郁症的风险。因此，我们将致力于FOA目标“， 鼓励生物医学，行为和社会科学研究，这将提高知识， 阿尔茨海默病（AD）中神经精神症状（NMPs）的潜在机制， 阿尔茨海默病相关痴呆症（ADRD），以便能够开发新的治疗方法。