Emotion alterations across the Alzheimer's disease spectrum

阿尔茨海默病谱系中的情绪变化

• 批准号: 10622518
• 负责人: Virginia Emily Sturm
• 金额: $ 79.6万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10622518
• 关键词: Affect; Affective Symptoms; Alzheimer' s Disease; Alzheimer' s disease model; Alzheimer' s disease pathology; Amyloid beta-Protein; Anxiety; Atrophic; Autonomic nervous system; Behavior; Behavioral; Biological Markers; Biological Models; Brain; Clinical; Clinical Data; Cognitive deficits; Color; Data; Deposition; Diagnosis; Disease; Disease Progression; Disinhibition; Early Diagnosis; Emotional; Emotions; Empathy; Episodic memory; Face; Facial Expression; Functional disorder; Generations; Impaired cognition; Interoception; Laboratories; Language; Link; Measures; Medial; Memory Loss; Molecular; Moods; Nerve Degeneration; Neuroanatomy; Neurobehavioral Manifestations; Participant; Pathologic Processes; Pathology; Pattern; Persons; Phase; Physiology; Positron-Emission Tomography; Primary Progressive Aphasia; Reaction; Reporting; Research; Severity of illness; Social Behavior; Social Environment; Specificity; Structure; Support System; Syndrome; System; Temporal Lobe; Testing; Tracer; Variant; Visuospatial; Woman; abeta accumulation; abeta deposition; cerebral atrophy; experience; forging; improved; men; network dysfunction; neural circuit; neural network; neuroimaging; neuropathology; pre-clinical; tau Proteins; tau mutation; uptake

ABSTRACT Changes in emotion and social behavior are early yet overlooked features of Alzheimer's disease (AD). In AD, there is progressive accumulation of beta amyloid (Aβ) and tau proteins, a pathological process that leads to neurodegeneration and functional connectivity alterations in distributed brain networks. Episodic memory decline is a hallmark feature of typical amnestic AD presentations, but AD can also cause atypical dysexecutive/amnestic, language (i.e., logopenic variant primary progressive aphasia [lvPPA]), and visuospatial (i.e., posterior cortical atrophy [PCA]) syndromes. In typical AD, default mode network dysfunction is accompanied by elevated functional connectivity in the salience network, a system that supports emotion generation and interoception. Enhanced salience network connectivity in AD is associated with greater affective symptoms such as anxiety. Our previous studies have found that specific types of emotional empathy, a rudimentary form of affect-sharing, are elevated in typical AD and relate to default mode network atrophy. Whether emotion elevations are present in atypical AD syndromes is unknown but are suggested by clinical and neuroimaging data. There is emerging evidence that gains in emotional empathy are evident even in preclinical AD, a prodromal phase in which people have signs of AD pathology on biomarker testing but lack cognitive symptoms. A central hypothesis of this proposal is that early neuropathology and neurodegeneration in AD-vulnerable networks disinhibits the salience network and elevates emotion functioning across AD syndromes. A more detailed understanding of emotion in AD will help to improve diagnosis by broadening current conceptualizations of each syndrome, to identify emotion measures that suggest the presence of early AD, and to uncover new biomarkers that change as neuropathology affects emotion-relevant brain networks. In the proposed studies, we will conduct laboratory-based assessments of emotion (i.e., autonomic nervous system activity, facial behavior, and subjective experience) in 200 people with AD, as indicated by elevated Aβ (Aβ+) and tau deposition on molecular PET scans (110 amnestic/dysexecutive AD, 45 lvPPA, and 45 PCA), and 150 older healthy controls with and without AD pathology (75 Aβ+ and 75 Aβ-) with varying levels of tau pathology. By relating emotion measures to clinical data, structural and functional connectivity, Aβ and tau burden, and affective symptoms, we will address three key aims. In Aim 1, we will quantify emotion, empathy, and social behavior in AD syndromes and Aβ+ healthy controls. In Aim 2, we will delineate the structural and functional neural networks underlying emotion alterations across the AD spectrum. In Aim 3, we will elucidate associations among Aβ and tau pathology, emotion system functioning, and affective symptoms. By forging links among measures of emotion, neural network dysfunction, affective symptoms, and Aβ and tau deposition, the proposed research will help to broaden models of AD's earliest manifestations and to elucidate how specific neuropathological changes alter emotion systems and relate to affective symptoms.

抽象的 情绪和社会行为的变化是阿尔茨海默病 (AD) 的早期但被忽视的特征。 β 淀粉样蛋白 (Aβ) 和 tau 蛋白逐渐积累，这一病理过程导致 分布式大脑网络中的神经退行性变和功能连接改变。 衰退是典型遗忘性 AD 表现的一个标志性特征，但 AD 也可能导致非典型性 AD 表现。 执行障碍/遗忘症、语言（即，语言减少变异型原发性进行性失语症 [lvPPA]），以及 视觉空间（即后皮质萎缩 [PCA]）综合征 在典型的 AD 中，默认模式网络功能障碍。 伴随着显着网络（支持情感的系统）中功能连接的提高 AD 中增强的显着性网络连接与更大的相关性。 我们之前的研究发现，特定类型的情感同理心， 情感分享的一种基本形式，在典型 AD 中升高，并与默认模式网络萎缩有关。 非典型 AD 综合征中是否存在情绪高涨尚不清楚，但临床表明 和神经影像数据显示，即使在情感同理心方面，效果也很明显。 临床前 AD，这是一个前驱阶段，在该阶段，人们在生物标志物测试中出现 AD 病理学迹象，但缺乏 该提案的一个中心假设是早期神经病理学和神经变性。 在 AD 易受影响的网络中抑制显着性网络并提升整个 AD 的情绪功能 更详细地了解 AD 中的情绪将有助于扩大诊断范围，从而改善诊断。 当前每种综合征的概念化，以确定表明存在早期症状的情绪测量 AD，并发现随着神经病理学影响情绪相关大脑网络而变化的新生物标志物。 在拟议的研究中，我们将进行基于实验室的情绪评估（即自主神经 200 名 AD 患者的系统活动、面部行为和主观体验），如 Aβ 升高所示 分子 PET 扫描中的 (Aβ+) 和 tau 沉积（110 次遗忘/执行不良 AD、45 lvPPA 和 45 PCA）， 以及 150 名患有或不患有 AD 病理的老年健康对照（75 名 Aβ+ 和 75 名 Aβ-），具有不同水平的 tau 通过将情绪测量与临床数据、结构和功能连接、Aβ 和 tau 相关联。 在目标 1 中，我们将量化情绪、同理心、 AD 综合征和 Aβ+ 健康对照中的社会行为和社会行为 在目标 2 中，我们将描述结构和行为。 在目标 3 中，我们将阐明 AD 谱系中情绪变化的功能神经网络。 Aβ 和 tau 病理学、情绪系统功能和情感症状之间的关联。 情绪测量、神经网络功能障碍、情感症状以及 Aβ 和 tau 沉积之间的联系， 拟议的研究将有助于扩大 AD 最早表现的模型，并阐明如何 特定的神经病理学变化会改变情绪系统并与情感症状相关。

项目成果

Increasing empathic concern relates to salience network hyperconnectivity in cognitively healthy older adults with elevated amyloid-β burden.

• DOI: 10.1016/j.nicl.2022.103282
• 发表时间: 2023
• 期刊: NEUROIMAGE-CLINICAL
• 影响因子: 4.2
• 作者: Chow, Tiffany E.;Veziris, Christina R.;La Joie, Renaud;Lee, Alex J.;Brown, Jesse A.;Yokoyama, Jennifer S.;Rankin, Katherine P.;Kramer, Joel H.;Miller, Bruce L.;Rabinovici, Gil D.;Seeley, William W.;Sturm, Virginia E.
• 通讯作者: Sturm, Virginia E.

Selective vulnerability of medial temporal regions to short-term blood pressure variability and cerebral hypoperfusion in older adults.

• DOI: 10.1016/j.ynirp.2022.100080
• 发表时间: 2022-03
• 期刊: Neuroimage. Reports
• 作者: I. Sible;Belinda Yew;Shubir Dutt;Yanrong Li;A. Blanken;J. Jang;Jean K. Ho;Anisa J. Marshall;Arunima Kapoor;Aimée Gaubert;K. Bangen;V. Sturm;Xingfeng Shao;Danny J. J. Wang-Danny-J.-J.-Wang-3065062;D. Nation