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: 10260561
• 负责人: DAVID C PERRY
• 金额: $ 79.57万
• 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/10260561
• 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; Prognosis; 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; participant enrollment; 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 额颞叶痴呆（FTD）是早期发病痴呆的常见神经退行性原因。这 FTD 行为变异（bvFTD）会导致人格以及社交和情感的深刻变化 发挥作用。尽管诊断技术有所改进，但诊断不确定性仍然是 bvFTD 中普遍关注的问题 侧重于特定行为和认知特征以及特征性神经影像学的标准 模式。当认知障碍可能会被诊断出来时，首次就诊时的准确诊断尤其具有挑战性。 轻度和功能性能力得到更多保留。其他痴呆症综合征可以模仿 bvFTD 的特征， 与精神疾病的症状有部分重叠。通过纵向提供的清晰度 后续临床医生有时会改变 bvFTD 诊断。有超过 15 种潜在的神经病理学 bvFTD 的基础诊断。即使 bvFTD 诊断明确，预测具体的诊断也具有挑战性。 导致个体患者症状的分子亚型。临床上存在很大的异质性 bvFTD 的过程也是如此，其中一些在 2-3 年内迅速下降，而另一些则在超过 十年。运动特征可能存在或不存在，并且它们在 bvFTD 背景下的严重程度可能会影响 患者需要的护理水平。很少有可靠的指标可以预测患者的病程。 拟议的研究将对 60 名 bvFTD 患者进行纵向研究，并进行神经学检查， 认知测试、结构和功能神经影像学，并将回顾性审查临床 284 名 bvFTD 尸检患者的特征。该提案的中心假设是，尽管 bvFTD 患者之间存在临床、神经心理学、神经影像学、血清学方面的相似之处 标记物、遗传和基因表达差异可以提高首次就诊时的预测确定性。在 目标 1 我们将使用诊断稳定性的纵向评估来确定预测因素 bvFTD 诊断的确定性。在目标 2 中，我们将确定临床、基因表达和成像特征 患有 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 并将改善可用的诊断和预后信息的人 患者、家属和临床医生，从而从第一次就诊时起改善临床护理。它还将 促进患者参加观察性研究和分子靶向临床试验。