Distinct antemortem profiles in patients with pathologically defined frontotemporal dementia
ABSTRACT Clinical-pathologic studies are crucial to understanding brain-behavior relations and improving diagnostic accuracy in neurodegenerative diseases.
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.
Retrospective clinical-pathologic survey.
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.
Neuropsychological performance and high-resolution structural magnetic resonance imaging (MRI).
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.
Clinical, neuropsychological, and imaging profiles can contribute to accurate antemortem diagnosis in FTD.
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ABSTRACT: In the search for therapeutic modifiers, frontotemporal dementia (FTD) has traditionally been overshadowed by other conditions such as Alzheimer's disease (AD). A clinically and pathologically diverse condition, FTD has been galvanized by a number of recent discoveries such as novel genetic variants in familial and sporadic forms of disease and the identification of TAR DNA binding protein of 43 kDa (TDP-43) as the defining constituent of inclusions in more than half of cases. In combination with an ever-expanding knowledge of the function and dysfunction of tau—a protein which is pathologically aggregated in the majority of the remaining cases—there exists a greater understanding of FTD than ever before. These advances may indicate potential approaches for the development of hypothetical therapeutics, but FTD remains highly complex and the roles of tau and TDP-43 in neurodegeneration are still wholly unclear. Here the challenges facing potential therapeutic strategies are discussed, which include sufficiently accurate disease diagnosis and sophisticated technology to deliver effective therapies.Frontiers in Aging Neuroscience 08/2014; DOI:10.3389/fnagi.2014.00204 · 2.84 Impact Factor
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ABSTRACT: Primary progressive aphasia (PPA) is a progressive disorder of language that is increasingly recognised as an important presentation of a specific spectrum of neurodegenerative conditions. In an era of etiologically specific treatments for neurodegenerative conditions, it is crucial to establish the histopathologic basis for PPA. In this review, I discuss biomarkers for identifying the pathology underlying PPA. Clinical syndromes suggest a probabilistic association between a specific PPA variant and an underlying pathology, but there are also many exceptions. A considerable body of work with biomarkers is now emerging as an important addition to clinical diagnosis. I review genetic, neuroimaging and biofluid studies that can help determine the pathologic basis for PPA. Together with careful clinical examination, there is great promise that supplemental biomarker assessments will lead to accurate diagnosis of the pathology associated with PPA during life and serve as the basis for clinical trials in this spectrum of disease.Aphasiology 09/2014; 28(8-9):922-940. DOI:10.1080/02687038.2014.929631 · 1.73 Impact Factor