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From the Neuroepidemiology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health (Dr. Litvan, Mr. Sastrj), Bethesda, MD; the Fédération de Neurologie and INSERM U 289, Hôpital de la Salpêtrière (Drs. Agid and Brandel), Paris, France; the Department of Neurology (Drs. Jankovic and Lai), Baylor College of Medicine, Houston, TX; the University Department of Clinical Neurology (Dr. Wenning), Institute of Neurology, London, UK; the Department of Neurology Rush Medical College (Dr. Goetz), Chicago, IL; the Raymond Escourolle Neuropathology Laboratory, INSERM U 360, Hôpital de la Salpêtrière (Dr. Verny), Paris, France; the Ludwig Boltzmann Institute of Clinical Neurobiology (Dr. Jellinger), Vienna, Austria; the Department of Neurology (Dr. Ray-Chaudhuri), Institute of Psychiatry, London, UK; the Department of Neuropathology(Dr. McKee), Massachusetts General Hospital, Boston, MA; the Parkinson's Disease Society Brain Bank Research Center (Dr. Pearce), London, UK; and the Division of Epidemiology and Research Studies, National Institute of Mental Health (Dr. Bartko), Bethesda, MD.
Address correspondence and reprint requests to Dr. Litvan, Federal Building, Room 714, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-9130.
Several studies have evaluated the reliability and validity of the clinical diagnosis of Alzheimer's disease (AD) using well-defined neuropathologic criteria, but none has attempted to evaluate the diagnostic accuracy of Pick's disease. We determined the accuracy of the clinical diagnosis of Pick's by presenting 105 autopsy-confirmed cases of Pick's (n = 7) and related disorders (non-Pick's, n = 98) as clinical vignettes in randomized order to six neurologists who were unaware of the autopsy findings. The group of raters had moderate to fair agreement for the diagnosis of Pick's as measured by the 
statistics. The sensitivity for the diagnosis of Pick's for the first visit (mean, 53 months after onset) and last visit (mean, 78 months after onset) was low (range, 0 to 71%), but specificity was near-perfect. Median positive predictive values at both visits were 83 to 85%. False-negative misdiagnoses mainly involved AD. False-positive diagnoses were rare and occurred with corticobasal degeneration (first visit) and with dementia with Lewy bodies (last visit). Pick's was also misdiagnosed by primary neurologists. The best clinical predictors for the early diagnosis of Pick's included "frontal" dementia, early "cortical" dementia with severe frontal lobe disturbances, absence of apraxia, and absence of gait disturbance at onset. However, the first neurologic evaluation in some of the Pick's cases took place in advanced stages of the disease. Our findings suggest that this disorder is underdiagnosed in clinical practice. Although the low sensitivity for the clinical diagnosis of Pick's is disappointing, our data suggest that when clinicians suspect Pick's, their diagnosis is almost always correct. Absence of awareness of the main features of this disorder and of specificity of the frontal lobe syndrome may partially explain the low detection of Pick's disease.
Dr. Wenning is currently at the Department of Neurology, University Hospital, Innsbruck, Austria.
Presented in part at the Fifth International Conference on Alzheimer's Disease and Related Disorders, Osaka, Japan, July 24-29, 1996.
Received December 12, 1996. Accepted in final form December 24, 1996.
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