Are frontotemporal lobar degeneration, progressive supranuclear palsy and corticobasal degeneration distinct diseases?

Abstract

New findings relating to the clinical, genetic and molecular bases of neurodegenerative disorders have led to a shift away from traditional nomenclatures of clinical syndromes. Historically, frontotemporal lobar degeneration (FTLD), corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) were classified on the basis of distinct clinical and pathological features. In recent years, however, advances in molecular and genetic research have led clinicians to suggest that the similar etiologies of the three disorders warrant their amalgamation into a single disorder with three subtypes. In this Review, we consider the utility and validity of combining FTLD, CBD and PSP. The earliest reports of these disorders demonstrate their distinctiveness, whereas recent findings challenge traditional nomenclatures by showing etiological overlap. For example, tau inclusions have been confirmed in patients with CBD and those with PSP, and in some patients with FTLD, implying that all three disorders are 'tauopathies'. Furthermore, most patients with progressive nonfluent aphasia, a subtype of FTLD, show PSP or CBD post-mortem. Even tau-related cases of FTLD, CBD and PSP are distinguishable on the basis of other criteria, however, and many FTLD cases do not show tau pathology. We argue, therefore, that FTLD, CBD and PSP should be considered as pathologically similar but distinct syndromes. New research criteria for CBD and PSP should note that progressive nonfluent aphasia is often a precursor of these conditions.

Apolipoprotein E ε4 is associated with disease-specific effects on brain atrophy in Alzheimer's disease and frontotemporal dementia

“…Second, a vast majority of our cases are not pathology-confirmed; however, these patients were well characterized by a multidisciplinary team, and the accuracy of the clinical diagnoses was supported in all cases that underwent 11C-labeled Pittsburgh Compound-B (11C-PIB) PET imaging or that came to autopsy. The autopsy results on the available five bvFTD cases highlight the pathological heterogeneity of FTLD with Pick's disease, progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD), all falling within the FTLD spectrum of disease (33), and additional AD features present in one case. Finally, although we performed extensive neuropsychological testing, no quantitative social-behavioral measures are available to fully characterize FTD patients.…”

Ocular motor abnormalities in neurodegenerative disorders

“…31 Although FTLD, CBD, and PSP might present with similar pathology, they do represent distinct syndromes. 32 The results of the ocular motor studies so far suggest that saccadic analysis may be useful in differentiating these groups (saccadic gain and velocity, and antisaccade performance). 19,33 Dementia with lewy bodies (DLB)…”

Phenotypic Variation of Autosomal-Dominant Corticobasal Degeneration

“…CBD is also known to overlap PPA and FTD. Wordfinding difficulties and other cognitive deficits are frequent presenting symptoms in CBD [27,31] . One study investigated patients who presented with PPA or FTD and developed movement disorder/ symptoms of CBD over time.…”

“…Since there were only two informative meioses available in our family, testing for linkage to this locus was not feasible. The diverse clinicopathological phenotypes of hereditary 4R tauopathies might represent different points on a single disease spectrum and additional genetic or epigenetic factors might contribute to the phenotypic diversity [1,[26][27][28] . Variable clinical manifestations in families with hereditary tauopathy with MAPT mutation P301S as either PSP or CBD have previously been described [29,30] .…”