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This Article Figures Only Full Text Full Text (PDF) Take the CME quiz CME: Take the course for this article: Volume 70, Number 22, May 27, 2008 All Versions of this Article: 01.wnl.0000303816.25065.bcv1 70/22/2036    most recent Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Grossman, M. Articles by Trojanowski, J. Q. PubMed PubMed Citation Articles by Grossman, M. Articles by Trojanowski, J. Q. Related Collections Frontotemporal dementia

Longitudinal decline in autopsy-defined frontotemporal lobar degeneration

From the Departments of Neurology (M.G., L.M., P.M., L.V., R.B., A.C., H.B.C., H.I.H.), Biostatistics and Epidemiology (S.X.X., X.W.), and Pathology (M.S.F., V.M.-Y.L., J.Q.T.), and the Center for Neurodegenerative Disease Research (M.S.F., V.M.-Y.L.), University of Pennsylvania School of Medicine, Philadelphia; and University of Medicine and Dentistry of New Jersey–School of Osteopathic Medicine (D.J.L., J.Q.T.).

Address correspondence and reprint requests to Dr. Murray Grossman, Department of Neurology, 2 Gibson, Hospital of the University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104-4283 mgrossma{at}mail.med.upenn.edu

Background: The natural history of patients with pathologically proven frontotemporal lobar degeneration (FTLD) is important from clinical and biologic perspectives, but is not well documented quantitatively.

Methods: We examine longitudinal decline in cognitive functioning in an autopsy-proven cohort of patients with the clinical diagnosis of a FTLD spectrum disorder or FTLD pathology using a panel of neuropsychological measures. Patients are categorized according to findings at autopsy into tau-positive FTLD, tau-negative FTLD, and frontal variant-Alzheimer disease (fvAD) subgroups.

Results: Patients decline significantly over time on all neuropsychological measures. Moreover, several measures differentiate between histopathologically distinct subgroups throughout the course of the disease process. This includes a significant double dissociation involving relative difficulty on a visual constructional measure in tau-positive patients compared to relatively impaired visual confrontation naming in tau-negative patients. Longitudinal measures of FAS naming fluency and animal naming fluency also distinguish tau-positive patients and tau-negative patients with FTLD from patients with fvAD. Other measures show significant decline but do not distinguish between histopathologic groups longitudinally.

Conclusion: Our findings suggest different longitudinal patterns of cognitive decline in pathologically defined subgroups of patients. Measures consistently distinguishing between patient subgroups can be used to bolster diagnostic accuracy throughout the course of these diseases, while measures demonstrating undifferentiated longitudinal decline may serve as useful endpoints in treatment trials.

Abbreviations: AD = Alzheimer disease; CBD = corticobasal degeneration; FTLD = frontotemporal lobar degeneration; FTLD-U = frontotemporal lobar degeneration with tau-negative but ubiquitin/TDP-43 immunoreactive-positive inclusions; fvAD = frontal variant-Alzheimer disease; MMSE = Mini-Mental State Examination; PiD = Pick bodies.

e-Pub ahead of print on April 16, 2008, at www.neurology.org.

Supported by the NIH (AG17586, AG15116, AG44266, AG10124) and the Dana Foundation.

Disclosure: The authors report no disclosures.

Received June 15, 2007. Accepted in final form October 3, 2007.