Elsevier

Neurologic Clinics

Volume 18, Issue 4, 1 November 2000, Pages 979-992
Neurologic Clinics

FRONTOTEMPORAL DEMENTIA

https://doi.org/10.1016/S0733-8619(05)70235-8Get rights and content

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NOMENCLATURE AND HISTORY OF THE DISORDER

The first description of frontotemporal dementia (FTD) was offered by the Czech-German neuropsychiatrist Arnold Pick in 1892. Ironically, most modern investigators consider Pick's disease to be a frontal dementia associated with silver-staining, hematoxylin and eosin–positive neuronal inclusions within frontal neurons; however, Pick's original cases showed left anterior temporal atrophy and spared the frontal lobes. Today these patients would be considered to suffer from semantic dementia

CLINICAL PRESENTATION

Frontotemporal dementia involves progressive dysfunction of the anterior temporal and frontal lobes. Increasingly it is recognized that the location of the most severe degeneration varies from patient to patient.55 Despite the presence of relatively uniform pathology, some patients display diffuse, bilateral frontal and temporal degeneration, whereas others may suffer degeneration primarily in the frontal or temporal lobe. The degeneration can be either symmetric or highly asymmetric, affecting

NEARY AND COLLEAGUES' CONSENSUS CRITERIA

A consensus statement from a conference of international investigators identified three clinical subtypes of FTD: frontotemporal dementia (FTD), progressive nonfluent aphasia (PA), and semantic dementia (SD).54 Common to all three clinical syndromes is the insidious onset with slow progression of a frontotemporal syndrome. Patients with FTD may initially present with one of the different clinical syndromes; however, as the disease progresses, patients are likely to develop features of the other

ANATOMIC SUBTYPES: LEFT VERSUS RIGHT VARIANTS OF FTD

A four-quadrant approach to FTD emphasizes the fact that the dysfunction associated with left or right frontal or temporal lobe degeneration leads to different neuropsychologic and behavioral manifestations of this disorder. Nonfluent aphasia represents a left frontal variant of FTD. The mirror image degeneration in the right frontal lobe leads to loss of insight, disinhibition, diminished respect for interpersonal space, and antisocial behavior.45 A bilateral frontal variant of FTD that

PATHOLOGY

Selective involvement of the frontal and temporal lobes, particularly the anterior portions of the temporal lobes, is reflected both at the macroscopic level, where atrophy is visibly more severe in these regions, and at the microscopic level. The degree of atrophy can vary in severity and can eventually be seen in many parts of the brain; however, it is most prominent in the anterior temporal and frontal lobes.5, 6, 55 In the most careful assessment of the pattern of atrophy, Mann and South43

GENETICS

Early discussions of Pick's disease identified genetic factors as important, 64 and there are descriptions of hereditary Pick's disease in the literature.24 As FTD began to be described, an increased incidence of dementia in families of FTD patients compared with the families of control patients with Alzheimer's disease was noted.25 More recent studies estimate that 38% to 45% of all FTD cases suggest a strong hereditary component.11, 33 In the study by Chow and colleagues11 80% of the familial

NEUROIMAGING

Anatomic abnormalities suggestive of FTD have been demonstrated with magnetic resonance (MR) imaging. Abnormalities of cerebral blood flow, measured with single-photon emission computed tomography (SPECT), and cerebral metabolism, measured with positron emission tomography (PET), have been delineated in FTD as well. MR imaging findings can be quite variable in FTD. As would be expected from the results of pathologic studies, quantitative assessments of atrophy in patients with FTD have shown

DIFFERENTIAL DIAGNOSIS

Not all patients with degenerative dementia and frontal lobe dysfunction have FTD pathology. Patients with progressive supranuclear palsy, 1, 10 corticobasal ganglionic degeneration, 23, 61 Creutzfeldt-Jakob disease, 13, 32 and subcortical ischemic white matter disease2, 35 can present with a dysexecutive syndrome suggestive of frontal lobe pathology or language problems. In addition, one must consider tumors affecting the frontal lobes, particularly orbitofrontal meningiomas.27, 63 Because the

SUMMARY

Frontotemporal dementia is a unique neurodegenerative disease whose manifestations are partly cognitive, but behavioral disturbances are a central component. Unlike Alzheimer' disease, FTD involves neocortical structures early, and affects structures crucial to episodic memory, such as the hippocampus, relatively late. Thus, although memory is relatively spared in the early stages, other cognitive functions are very prominently affected. Because the disease can begin in the left or right

ACKNOWLEDGMENT

We would like to acknowledge Sangeeta Bhojwani for her invaluable administrative assistance.

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      Patients typically present with a frontal syndrome, including behavioral, personality, and cognitive changes occurring over years, followed by dementia (see article by Josephs elsewhere in this issue). Fifteen percent or more of patients who have FTD develop amyotrophic lateral sclerosis and these patients typically die within 1.4 years from the time of diagnosis [30–33]. Corticobasal degeneration (CBD) is a clinically and pathologically heterogeneous atypical parkinsonian dementia often confused clinically with AD, PSP, or FTD (see article by Boeve elsewhere in this issue) [34–38].

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    Address reprint requests to Bruce Miller, MD, University of California, San Francisco, Memory and Aging Center, 350 Parnassus, Suite 800, Box 1207, San Francisco, CA 94143–1207, [email protected]

    This work was supported by The John Douglas French Foundation, The Koret Foundation, and The McBean Foundation.

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    Copyright © 2000 W. B. Saunders Company. Published by Elsevier Inc. All rights reserved.