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.

摘要