Neuroanatomical associations with the factor structure underlying neuropsychiatric symptoms in Alzheimer's disease

神经解剖学与阿尔茨海默病神经精神症状因素结构的关联

• 批准号: 10450779
• 负责人: Edward D Huey
• 金额: $ 39.48万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2022-12-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10450779
• 关键词: Address; Adverse effects; Alzheimer' s Disease; Alzheimer' s disease brain; Alzheimer' s disease patient; Alzheimer' s disease related dementia; Amygdaloid structure; Anatomy; Anxiety; Assessment tool; Behavior Disorders; Bilateral; Biological; Brain; Caring; Classification; Clinic; Clinical; Clinical Trials; Communities; DSM-V; Data; Development; Diagnosis; Equipment and supply inventories; Evaluation; Functional Magnetic Resonance Imaging; Funding; Goals; Gold; Interview; Investigation; Joints; Knowledge; MRI Scans; Magnetic Resonance Imaging; Measurement; Measures; Memory Disorders; Molecular; Moods; Nature; Neurobehavioral Manifestations; Neurodegenerative Disorders; Participant; Patient Care; Patients; Pharmacological Treatment; Population; Prefrontal Cortex; Preparation; Property; Psychiatric Diagnosis; Psychiatry; Psychometrics; Psychopathology; Psychoses; Public Health; Research; Resources; Rest; Severities; Standardization; Structure; Sum; Symptoms; Testing; Transcranial magnetic stimulation; Traumatic Brain Injury; United States National Institutes of Health; associated symptom; base; cingulate cortex; cohort; common symptom; community clinic; cost; design; experience; geriatric depression; improved; informant; instrument; member; mortality; motor symptom; neuropsychiatric symptom; neuropsychiatry; novel; programs; psychiatric symptom; recruit; response; sound; symptom treatment; tool; white matter

We propose to utilize a factor-based approach to classify Neuropsychiatric Symptoms (NPS) in a data-driven manner, and to determine the brain networks associated with different NPS factors, in 200 participants with mild Alzheimer’s disease (AD). There is a crucial need to develop improved treatments for NPS in ADRD. Current pharmacological treatments for NPS were developed 50 years ago, are often inefficacious, and can have serious adverse effects including increased mortality. Neuroanatomically-based treatments such as TMS and transcranial direct current stimulation (tDCS) for NPS are promising, but their development has been hampered by our lack of knowledge about the neuroanatomical bases of NPS in ADRD. The proposed project attempts to leverage current NIH-funded research programs and assessment tools developed in psychiatric settings to address this knowledge gap by: 1. Measuring and classifying NPS in a data-driven manner; 2. Determining the associations between empirically-determined NPS factors and specific brain networks; 3. Comparing a novel brief data-driven measure of NPS to two commonly used NPS measures using a neuro- anatomic gold-standard. These investigations have not been previously performed. Our subjects will be recruited from one ongoing NIH-funded study of a community-based cohort, the Predictors of Severity in AD study (AG007370), and the Columbia Memory and Behavioral Disorders Clinic. For the proposed project, we will perform the following measures in a single cross-sectional administration: Structural, DTI, and resting BOLD MRI; The Structured Clinical Interview for DSM-5 Research Version or SCID-5-RV; And the self- and informant-based DSM 5 Cross-Cutting Psychiatric Symptom Measure or “Cross-Cutting Measure”. The SCID- 5-RV is a standardized clinical psychiatric interview developed over decades to assess a very large range of psychiatric symptoms in a reliable, valid, and psychometrically sound manner. The Cross-Cutting Measure is a valid, reliable, brief, adaptive instrument designed to assess all major domains of psychopathology with good psychometric properties. It can be administered on-line. A small number of factors have been found to underlie psychiatric diagnoses detected by the SCID, including Internalizing, Externalizing, and Psychosis factors. Damage to networks involving the ventromedial prefrontal cortex (vmPFC) and amydgala is associated with the Internalizing factor, the ventrolateral PFC (vlPFC) with the Externalizing factor, and the posterior cingulate cortex (PCC) with the Psychosis factor. We will assess the factor structure of NPS on the SCID-5-RV and determine the brain networks associated with these factors on sMRI, DTI, and fMRI. We will compare the Cross-Cutting Measure to the Neuropsychiatric Inventory and Geriatric Depression Scale using a neuroanatomic gold standard. These investigations could improve our measurement and understanding of the neuroanatomical bases of NPS and provide novel data-driven measures of NPS and treatment targets for use in clinical trials of neuroanatomically-based treatments for NPS in ADRD such as TMS and tDCS.

我们建议利用一种基于因子的方法在数据驱动中对神经精神症状（NP）进行分类 方式，并确定与不同NPS因素相关的大脑网络，其中200名参与者 温和的阿尔茨海默氏病（AD）。在ADRD中，需要改善NP的治疗方法至关重要。 NP的当前药物治疗是在50年前开发的，通常是效率低下的，并且可以 具有严重的不利影响，包括死亡率增加。基于神经解剖学的治疗，例如TMS NP的NP和trancranial直流电流刺激（TDC）是有希望的，但它们的发展一直是 由于我们对ADRD中NP的神经解剖基础的知识不足而受到阻碍。拟议的项目 试图利用精神科开发的当前NIH资助的研究计划和评估工具 以数据驱动方式测量和分类NP的设置来解决此知识差距：1。 2。 确定经验确定的NPS因子与特定的大脑网络之间的关联； 3。 比较新型的简短数据驱动的NP与两个常用的NP使用神经 - 解剖金标准。这些调查以前尚未进行。我们的主题将是 从一项正在进行的NIH资助的基于社区的队列的研究中招募，AD的严重程度的预测因素 研究（AG007370）和哥伦比亚记忆和行为障碍诊所。对于拟议的项目，我们 将在单个横截面给药中执行以下措施：结构，DTI和静止 大胆的MRI; DSM-5研究版本或SCID-5-RV的结构化临床访谈；和自我和 基于线人的DSM 5跨切割精神病症状度量或“跨切割措施”。 scid- 5-RV是一种标准化的临床精神病学访谈，数十年来，用于评估非常范围的 以可靠，有效和心理的良好方式出现精神病症状。横切措施是 有效，可靠，简短，自适应工具旨在评估精神病理学的所有主要领域 心理测量特性。它可以在线管理。发现少数因素 SCID检测到的精神病诊断基础，包括互化，外在化和精神病 因素。涉及腹侧前额叶皮层（VMPFC）和杏仁核的网络损害 与间隔因子相关，腹外侧PFC（VLPFC）与外部化因子，以及 具有精神病因子的后扣带回皮质（PCC）。我们将评估NP在 SCID-5-RV并确定与SMRI，DTI和fMRI上这些因素相关的大脑网络。我们将 将跨切割措施与神经精神库存和老年抑郁量表进行比较 神经解剖学金标准。这些调查可以改善我们对 NP的神经解剖基础，并提供了新的数据驱动测量NP和治疗靶标的 在对TMS和TDC等ADRD中NP的基于神经解剖学治疗的临床试验中。