Diagnostic and prognostic certainty in behavioral variant frontotemporal dementia

行为变异型额颞叶痴呆的诊断和预后确定性

• 批准号: 10053090
• 负责人: DAVID C PERRY
• 金额: $ 80.61万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-15 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10053090
• 关键词: Activities of Daily Living; Affective Symptoms; Age of Onset; Alzheimer' s Disease; Atrophic; Autopsy; Behavioral; Behavioral Symptoms; Biological Markers; Caregivers; Caring; Characteristics; Classification; Clinical; Clinical Trials; Cognition; Cognitive; Data; Dementia; Development; Diagnosis; Diagnostic; Disease; Disinhibition; Enrollment; Evaluation; Family; Frontotemporal Dementia; Frontotemporal Lobar Degenerations; Gene Expression; Genetic; Goals; Heterogeneity; Image; Immune; Impaired cognition; Individual; Inflammatory; International; Lead; Light; Medical Genetics; Mental disorders; Microtubules; Molecular Target; Motor; Motor Neuron Disease; Nerve Degeneration; Neurodegenerative Disorders; Neurologic; Neurologic Examination; Neuropsychology; Newly Diagnosed; Observation in research; Observational Study; Parkinsonian Disorders; Pathologic; Patients; Pattern; Personality; Phenocopy; Predictive Factor; Process; Program Research Project Grants; Research; Serum Markers; Services; Severities; Social Functioning; Structure; Symptoms; Syndrome; Time; Tissue-Specific Gene Expression; Uncertainty; Visit; Weight; Work; accurate diagnosis; behavioral variant frontotemporal dementia; classification algorithm; clinical Diagnosis; clinical care; clinical diagnostics; clinical heterogeneity; cognitive testing; cohort; emotional functioning; follow-up; functional decline; genetic testing; improved; individual patient; molecular subtypes; neurofilament; neuroimaging; outcome forecast; predictive tools; preservation; prognostic; psychiatric symptom; tau Proteins; white matter

ABSTRACT Frontotemporal dementia (FTD) is a common neurodegenerative cause of early age-of-onset dementia. The behavioral variant of FTD (bvFTD) results in profound changes in personality, as well as social and emotional functioning. Diagnostic uncertainty remains a common concern in bvFTD in spite of improved diagnostic criteria that focus on particular behavioral and cognitive features accompanied by characteristic neuroimaging patterns. Accurate diagnoses at the first visit are especially challenging, when cognitive impairment can be mild and functional abilities are more preserved. Other dementia syndromes can mimic features of bvFTD and there is partial overlap with the symptoms of psychiatric illnesses. With the clarity provided by longitudinal follow-up clinicians sometimes change bvFTD diagnoses. There are over 15 potential neuropathological diagnoses that underlie bvFTD. Even when a bvFTD diagnosis is clear it is challenging to predict the specific molecular subtype causing an individual patient’s symptoms. There is substantial heterogeneity in the clinical course in bvFTD as well, with some declining rapidly within 2-3 years and others surviving over more than a decade. Motor features may be present or absent, and their severity in the context of bvFTD can impact the level of care a patient requires. There are few reliable indicators to prognosticate a patient’s disease course. The proposed research will study 60 patients with bvFTD longitudinally with neurological examinations, cognitive testing, and structural and functional neuroimaging, and will retrospectively review the clinical features of 284 autopsied patients with bvFTD. The central hypothesis of this proposal is that in spite of the similarities between patients with bvFTD there will be clinical, neuropsychological, neuroimaging, serum marker, genetic, and gene expression differences that permit improved predictive certainty at the first visit. In Aim 1 we will use longitudinal assessment of diagnostic stability in order to determine factors that predict certainty in the bvFTD diagnosis. In Aim 2 we will identify clinical, gene expression, and imaging profiles in a cohort of autopsied patients with bvFTD that allow accurate prediction of a patient’s pathological diagnosis. In Aim 3 we will use longitudinal data on patients with bvFTD to determine factors that allow accurate prognostication of the clinical course. The results of the proposed research will provide guidance to clinicians who are considering a diagnosis of bvFTD and will improve the diagnostic and prognostic information available to patients, families, and clinicians, leading to improved clinical care from the time of the first visit. It will also facilitate enrollment of patients into observational research and molecularly targeted clinical trials.

抽象的 额颞痴呆（FTD）是年龄发作年龄痴呆症的常见神经退行性原因。 FTD（BVFTD）的行为变异会导致人格以及社交和情感的深刻变化 功能。尽管诊断有所改善，但诊断不确定性仍然是BVFTD的普遍关注点 侧重于特定行为和认知特征的标准以及具有特征性神经影像的标准 模式。当认知障碍可能是 轻度和功能能力更加保存。其他痴呆综合症可以模仿BVFTD和 精神病的症状部分重叠。纵向提供的清晰度 后续临床医生有时会更改BVFTD诊断。有15多个潜在的神经病理学 诊断为BVFTD的基础。即使BVFTD诊断很明显，预测特定的挑战也很挑战 分子亚型引起单个患者的症状。临床存在很大的异质性 BVFTD的课程也在2 - 3年内迅速下降 十年。电机功能可能存在或不存在，并且在BVFTD背景下的严重性可能会影响 患者需要的护理水平。几乎没有可靠的指标可以证明患者的疾病病程。 拟议的研究将研究60例BVFTD纵向患者，并通过神经检查， 认知测试以及结构和功能性神经影像学，并将回顾性地检查临床 BVFTD患者的284例尸检功能。该提议的核心假设是 BVFTD患者之间的相似性将有临床，神经心理学，神经影像学，串行 第一次访问时允许改善预测确定性的标记，遗传和基因表达差异。在 目标1我们将使用纵向评估诊断稳定性，以确定预测的因素 BVFTD诊断中的确定性。在AIM 2中，我们将确定A中的临​​床，基因表达和成像曲线 BVFTD的尸检患者队列，可以准确预测患者的病理诊断。在 目标3我们将使用BVFTD患者的纵向数据来确定允许准确的因素 临床过程的预测。拟议研究的结果将为临床医生提供指导 正在考虑诊断BVFTD的人，并将改善可用的诊断和预后信息 对于患者，家庭和临床医生，从第一次访问开始就可以改善临床护理。它也会 促进患者参与观察性研究和分子靶向临床试验。