Background: Frontotemporal dementia (FTD) is a new label for clinical Pick’s disease (PiD) because the eponymic term is increasingly restricted to the pathologic finding of Pick bodies. This restriction created the impression that PiD is rare and that it is difficult to diagnose. FTD is also a term most often used for behavioral and personality alterations. Primary progressive aphasia (PPA) and corticobasal degeneration (CBD), formerly the extrapyramidal variety of PiD, are also part of the syndrome. Recently, chromosome 17 localization and tau mutations were discovered in familial forms of the disease.
Review Summary: FTD consists of behavioral and personality changes, often beginning with apathy and disinterest, which may be mistaken for depression. Disinhibition and perseverative, compulsive behavior often appear at the same time. A quantifiable frontal behavioral inventory is useful in the diagnosis beyond a checklist.
The second type of presentation is progressive language loss (PPA). A less common variety is semantic dementia; the meaning of nouns and objects is lost. As the disease progresses, all components tend to overlap. CBD and progressive supranuclear palsy (PSP), although described as distinct entities, show a great deal of clinical, pathologic, genetic, and biochemical overlap. The evidence suggests they also belong to the complex. The association of motor neuron disease (MND) with FTD and other varieties of the complex is also reviewed.
Conclusion: Clinical Pick’s disease or Pick Complex includes the overlapping syndromes of FTD, PPA, CBD, PSP, and FTD-MND. The neuropathological and genetic spectrum should be viewed with emphasis on the commonalities rather than the differences, allowing the recognition of the relatively high frequency of this presenile syndrome.
Frontotemporal dementia (FTD) is becoming increasingly recognized. The original descriptions of Pick included the behavioral presentation of FTD as well as the aphasic variety, but only specified frontotemporal atrophy and not the histology. 1–3 Round argyrophilic inclusions (Pick bodies), ballooned achromatic neurons (Pick cells), gliosis, and superficial cortical spongiform changes were subsequently identified as the underlying histology. 4 Pick bodies were relatively infrequent in clinical PiD with frontotemporal atrophy, however, and the notion that PiD is rare took hold. After reviewing a large series, Constantinidis et al 5 classified PiD as: A) with Pick bodies, B) only with swollen neurons, and C) only gliosis. They felt “in spite of the dissimilarities between these forms, considering the absence of sufficient knowledge about pathogenesis, it seems prudent at present to maintain the uniqueness of Pick’s entity.”
Some pathologists restricted the use of the term PiD to cases where Pick bodies were identified. Those cases without this typical histologic picture were called frontal lobe degeneration (FLD) or dementia of the frontal lobe type (DFT) 6,7 and subsequently frontotemporal degeneration (FTD). 7 These terms were initially applied mainly for the behavioral presentation but later to other components of the disease. 7 FLD was estimated to be 20% of degenerative dementias. 8 FTD had the same prevalence as AD in presenile or early onset dementia in a recent epidemiological survey. 9 A similar clinicopathological picture was described under the label of “Dementia Lacking Distinctive Histology” (DLDH) 10 and other publications appeared using various terminology for sporadic and familial cases (Table 1).
Mesulam 11,12 described a series of cases with progressive nonfluent aphasia later labeled as primary progressive aphasia (PPA). He suggested the underlying pathology was heterogenous but noted the high incidence of PiD. Subsequently, both PPA and FTD were considered part of the same entity and since PiD was reserved for the pathologic phenomena with Pick bodies, the term “Pick Complex” was suggested to include FTD, PPA, and corticobasal degeneration (CBD). 13 Evidence has rapidly accumulated for the substantial clinical and pathologic overlap of these conditions and will be presented in detail. Dominantly inherited familial forms of the disease were also described and linked to chromosome 17, 14 and subsequently a number of missense and splice mutations were found in various isoforms of the microtubular binding protein tau. 15 Subsequently, the relationship of these entities was accepted to a variable degree by various consensus conferences and working groups. 7,16,17 Table 1 lists a sample of the terms used for this group of clinicopathologically related conditions. Table 2 indicates the common pathology in the various clinical presentations. A glossary of terms currently used is available below. Many of them remain dichotomous, used ambiguously. Although FTD is beginning to be used for the whole condition, it is still used mostly to designate the behavioral presentation (see below). Only Pick complex avoids the ambiguity and can be applied to all the clinical and pathologic variations. Not everyone, however, has accepted such an integrative approach.
“The predominantly behavioral changes often begin with apathy and disinterest, which is often diagnosed as depression.”
From the Department of Clinical Neurological Sciences, St. Joseph’s Hospital, University of Western Ontario, London, Ontario, Canada.
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