Distinct antemortem profiles in patients with pathologically defined frontotemporal dementia

Background: Clinical-pathologic studies are crucial to understanding brain-behavior relations and improving diagnostic accuracy in neurodegenerative diseases. Objective: To establish clinical, neuropsychological, and imaging features of clinically diagnosed patients with frontotemporal dementia (FTD) that help discriminate between pathologically determined tau-positive FTD, tau-negative FTD, and frontal-variant Alzheimer disease. Design: Retrospective clinical-pathologic survey. Setting: Academic medical center. Patients: Sixty-one participants with the clinical diagnosis of a frontotemporal spectrum disorder who underwent a neuropsychological evaluation and had an autopsy-confirmed disease. Main Outcome Measures: Neuropsychological performance and high-resolution structural magnetic resonance imaging (MRI). Results: Distinguishing features of patients with tau-positive FTD include visual perceptual-spatial difficulty and an extrapyramidal disorder significantly more often than other patients, significant cortical atrophy in the frontal and parietal regions as evidenced on MRI, and the burden of pathology is greatest in the frontal and parietal regions. Patients with tau-negative FTD are distinguished by their greater difficulties with social, language, and verbally mediated executive functions, significant cortical atrophy in the frontal and temporal regions as evidenced on MRI, and significant frontal and temporal pathology. Patients with Alzheimer disease at autopsy have significantly impaired delayed recall during episodic memory testing; atrophy that involves temporal areas, including the hippocampus, as evidenced on MRI; and widely distributed pathology including the medial temporal structures. A discriminant function analysis grouped patients on the basis of clinical and neuropsychological features with 87.5% accuracy. Conclusion: Clinical, neuropsychological, and imaging profiles can contribute to accurate antemortem diagnosis in FTD.