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

我们建议使用基于因素的方法来对神经精神症状(NPS)进行数据驱动的分类 方法，并确定与不同NPS因素相关的脑网络，在200名 轻度阿尔茨海默病(AD)。迫切需要为ADRD的NPS开发改进的治疗方法。 目前对NPS的药物治疗是在50年前开发的，往往无效，而且可以 有严重的不利影响，包括增加死亡率。以神经解剖学为基础的治疗，如TMS 经颅直流电刺激(Tdcs)治疗NPS前景看好，但其发展一直很缓慢。 由于我们对ADRD中NPS的神经解剖学基础缺乏了解而受到阻碍。拟议中的项目 试图利用目前由NIH资助的研究计划和在精神病学领域开发的评估工具 解决这一知识差距的设置：1.以数据驱动的方式衡量和分类核动力源；2. 确定经验性确定的NPS因素与特定脑网络之间的关联； 将一种新的简短的数据驱动的NPS测量方法与两种常用的使用神经网络的NPS测量方法进行比较- 解剖学的黄金标准。这些调查以前从未进行过。我们的主题将是 从NIH资助的一项正在进行的社区队列研究中招募的AD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。就建议的项目而言，我们 将在一次横断面管理中执行以下措施：结构、DTI和休息 BOLD MRI；DSM-5研究版或SCID-5-RV的结构化临床访谈；以及自我和 基于告密者的DSM 5交叉精神症状测量或“交叉测量”。SCID- 5-RV是一种标准化的临床精神病学访谈，经过几十年的发展，评估了非常广泛的 以可靠的、有效的和心理测量学健康的方式出现精神症状。交叉措施是一项 有效、可靠、简单、适应性强的工具，用于评估精神病理学的所有主要领域 心理测量学特性。它可以在网上管理。已发现有少数因素会导致 SCID检测到的精神病学诊断的基础，包括内在化、外在化和精神病 各种因素。涉及腹内侧前额叶皮质(VmPFC)和杏仁核的网络受损 与内化因子相关，与外化因子相关的腹外侧PFC(VLPFC)，以及 后扣带回皮质(PCC)与精神病因素。我们将评估NPS的因素结构 SCID-5-RV，并在sMRI、DTI和fMRI上确定与这些因素相关的脑网络。我们会 将交叉测量与神经精神病学问卷和老年抑郁量表进行比较 神经解剖学的黄金标准。这些调查可以提高我们对 NPS的神经解剖学基础，并为NPS提供新的数据驱动措施和治疗靶点 在基于神经解剖学的治疗ADRD NPS的临床试验中，如TMS和tDCs。

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.