Neurobiological Basis of Emotion Regulation Trajectories in Early Alzheimer's Disease

早期阿尔茨海默病情绪调节轨迹的神经生物学基础

基本信息

批准号：
10177830
负责人：
Virginia Emily Sturm
金额：
$ 75.98万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-15 至 2023-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10177830
关键词：
Address Adult Affect Affective Affective Symptoms Alzheimer&apos s Disease Alzheimer&apos s disease pathology Alzheimer&apos s disease risk Alzheimer’s disease biomarker Amyloid Amyloid beta-Protein Anatomic Models Anatomy Anxiety Arousal Atrophic Autonomic nervous system Behavior Biological Biological Markers Brain Clinical Clinical Trials Cognition Cognitive Cognitive deficits Data Detection Deterioration Disease Disease Progression Early Diagnosis Emotional Emotional Stability Emotions Empathy Episodic memory Facial Expression Family Gene Expression Generations Genetic Genetic Variation Goals Imaging Techniques Impaired cognition Individual Individual Differences Interpersonal Relations Investigation Laboratories Laboratory Study Longitudinal Studies Magnetic Resonance Imaging Measures Medial Memory Loss Modeling Molecular Monitor Nerve Degeneration Neurobehavioral Manifestations Neurobiology Neurologic Neuropsychological Tests Participant Patients Pattern Phase Physiology Positron-Emission Tomography Process Research Rest Risk Risk Factors Sex Differences Signs and Symptoms Single Nucleotide Polymorphism Social Behavior Societies Structure Support System Symptoms System Temporal Lobe Time Visit Woman apolipoprotein E-4 base contagion disease phenotype disorder subtype emotion dysregulation emotion regulation emotional behavior emotional experience experience genetic analysis improved men mild cognitive impairment network dysfunction normal aging novel marker pathological aging pre-clinical preservation relating to nervous system sex support network tau Proteins uptake

项目摘要

ABSTRACT The majority of research on early Alzheimer's disease (AD) has focused on cognition and has overlooked the possibility that changes in emotion may be one of AD's first manifestations. Molecular positron emission tomography (PET) scans detect elevated uptake of beta amyloid and tau, proteins that are neuropathological hallmarks of AD, in living patients with AD and in those with mild cognitive impairment (MCI), the clinical phase that precedes AD. An amyloid positive (amyloid+) PET scan in cognitively normal adults indicates preclinical AD, a phase that may begin years or decades before cognitive symptoms emerge. In addition to cognitive deficits, alterations in emotion are also common in MCI and AD and reflect changes in the neural systems that support emotion generation and emotion regulation. Declining emotion regulation may signify a pathological aging process and the presence of incipient neurodegenerative changes. Laboratory studies of emotion physiology and behavior have the potential to uncover the biological basis of affective change in AD and to determine how and when AD emotion trajectories diverge from those of normal aging. Individual differences in biological variables including sex and genetics (AD risk factor Apolipoprotein Ɛ4 as well as single nucleotide polymorphisms and gene expression profiles) may modify disease progression or relate to variability in emotion functioning over time. The overall goal of the proposed project is to elucidate the neural systems and genetic factors that underlie emotion change in AD. Anatomically-specific markers of emotion could be used to broaden current conceptualizations of early AD phenotypes, identify subtypes at greatest risk for affective symptoms, monitor symptom progression, or track disease-related decline in clinical trials of asymptomatic or mildly symptomatic individuals. We will conduct a longitudinal study of 200 participants: 50 amyloid negative healthy controls, 50 amyloid+ healthy controls, 50 amyloid+ patients with MCI, and 50 amyloid+ patients with AD. Participants will undergo baseline genetic analyses as well as laboratory assessments of emotion (i.e., autonomic nervous system reactivity, facial expression, and subjective experience) and magnetic resonance imaging at three annual research visits. The central hypothesis of this proposal is that emotion dysregulation is an early feature of AD that can be assessed via objective measures of physiology and behavior, direct readouts of emotion systems. We will address three key aims. In Aim 1, we will determine how early AD emotion trajectories diverge from those of normal aging. In Aim 2, we will identify how emotion circuit decline relates to decreasing emotion regulation over time. In Aim 3, we will examine how sex and genetic variation relate to individual differences in emotion across the AD continuum. This project has the potential to advance current models of the neurobiological basis of emotion change in early AD.

抽象的大多数关于早期阿尔茨海默病 (AD) 的研究都集中在认知上，而忽视了情绪变化可能是 AD 的最初表现之一。断层扫描 (PET) 扫描可检测到 β 淀粉样蛋白和 tau 蛋白的摄取升高，这些蛋白是神经病理学蛋白 AD 的特征，在 AD 活体患者和轻度认知障碍 (MCI) 患者中，临床阶段认知正常成人中淀粉样蛋白阳性（淀粉样蛋白+）的 PET 扫描表明存在临床前症状。 AD，除了认知症状之外，可能在认知症状出现前数年或数十年就开始的阶段。缺陷、情绪改变在 MCI 和 AD 中也很常见，反映了神经系统的变化，这些变化支持情绪产生和情绪调节下降可能意味着病态。衰老过程和早期神经退行性变化的实验室研究情绪。生理学和行为学有可能揭示 AD 情感变化的生物学基础，并确定 AD 情绪轨迹如何以及何时偏离正常衰老的个体差异。生物变量，包括性别和遗传学（AD 风险因素载脂蛋白 Ɛ4 以及单核苷酸多态性和基因表达谱）可能改变疾病进展或与变异相关拟议项目的总体目标是阐明神经系统和情绪的功能。 AD 情绪变化背后的遗传因素可用于情绪的解剖学特异性标记。拓宽当前对早期 AD 表型的概念，确定情感风险最大的亚型在无症状或无症状的临床试验中监测症状进展或跟踪与疾病相关的衰退我们将对 200 名参与者进行一项纵向研究：50 名淀粉样蛋白阴性。健康对照、50 名淀粉样蛋白+ 健康对照、50 名淀粉样蛋白+ 患有 MCI 的患者和 50 名淀粉样蛋白+ 患有 MCI 的患者 AD。参与者将接受基线遗传分析以及实验室情绪评估（即，自主神经系统反应、面部表情和主观体验）和磁共振该提案的中心假设是情绪失调是在每年三次的研究访问中进行的成像。 AD 的一个早期特征，可以通过生理学和行为的客观测量来评估，直接在目标 1 中，我们将确定 AD 的早期程度。情绪轨迹与正常衰老时的情绪轨迹不同在目标 2 中，我们将确定情绪回路如何衰退。在目标 3 中，我们将研究性别和遗传变异如何影响情绪调节。与整个 AD 连续体中情绪的个体差异有关，该项目具有推进的潜力。早期 AD 情绪变化的神经生物学基础的当前模型。