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Regional Brain Metabolism and Long-term Outcome

Daniel H. S. Silverman, MD,PhD; Gary W. Small, MD; Carol Y. Chang, BSc; Carolyn S. Lu, BSc; Michelle A. Kung de Aburto, BSc; Wei Chen, MD,PhD; Johannes Czernin, MD; Stanley I. Rapoport, MD; Pietro Pietrini, MD,PhD; Gene E. Alexander, PhD; Mark B. Schapiro, MD; William J. Jagust, MD; John M. Hoffman, MD; Kathleen A. Welsh-Bohmer, PhD; Abass Alavi, MD; Christopher M. Clark, MD; Eric Salmon, MD,PhD; Mony J. de Leon, EdD; Ruediger Mielke, MD,PhD; Jeffrey L. Cummings, MD; Arthur P. Kowell, MD,PhD; Sanjiv S. Gambhir, MD,PhD; Carl K. Hoh, MD; Michael E. Phelps, PhD

JAMA. 2001;286:2120-2127.

Context  Deficits in cerebral glucose utilization have been identified in patients with cognitive dysfunction attributed to various disease processes, but their prognostic and diagnostic value remains to be defined.

Objective  To assess the sensitivity and specificity with which cerebral metabolic patterns at a single point in time forecast subsequent documentation of progressive dementia.

Design, Setting, and Patients  Positron emission tomography (PET) studies of [¹⁸F]fluorodeoxyglucose in 146 patients undergoing evaluation for dementia with at least 2 years' follow-up for disease progression at the University of California, Los Angeles, from 1991 to 2000, and PET studies in 138 patients undergoing evaluation for dementia at an international consortium of facilities, with histopathological diagnoses an average of 2.9 years later, conducted from 1984 to 2000.

Main Outcome Measures  Regional distribution of [¹⁸F]fluorodeoxyglucose in each patient, classified by criteria established a priori as positive or negative for presence of a progressive neurodegenerative disease in general and of Alzheimer disease (AD) specifically, compared with results of longitudinal or neuropathologic analyses.

Results  Progressive dementia was detected by PET with a sensitivity of 93% (191/206) and a specificity of 76% (59/78). Among patients with neuropathologically based diagnoses, PET identified patients with AD and patients with any neurodegenerative disease with a sensitivity of 94% and specificities of 73% and 78%, respectively. The negative likelihood ratio of experiencing a progressive vs nonprogressive course over the several years following a single negative brain PET scan was 0.10 (95% confidence interval, 0.06-0.16), and the initial pattern of cerebral metabolism was significantly associated with the subsequent course of progression overall (P<.001).

Conclusion  In patients presenting with cognitive symptoms of dementia, regional brain metabolism was a sensitive indicator of AD and of neurodegenerative disease in general. A negative PET scan indicated that pathologic progression of cognitive impairment during the mean 3-year follow-up was unlikely to occur.

Author Affiliations: Departments of Molecular and Medical Pharmacology (Drs Silverman, Chen, Czernin, Kowell, Gambhir, and Phelps, and Mss Chang, Lu, and Kung de Aburto), Psychiatry and Biobehavioral Sciences (Dr Small), and Neurology (Dr Cummings), University of California, Los Angeles; Department of Internal Medicine, Kaiser Permanente, Los Angeles, Calif (Dr Chen); National Institute on Aging, National Institutes of Health, Bethesda, Md (Drs Rapoport, Pietrini, Alexander, and Schapiro); Department of Clinical Biochemistry, University of Pisa, Pisa, Italy (Dr Pietrini); Department of Neurology, University of California, Davis (Dr Jagust); Departments of Radiology (Dr Hoffman) and Psychiatry (Dr Welsh-Bohmer), Duke University, Durham, NC; Department of Radiology, University of Pennsylvania, Philadelphia (Drs Alavi and Clark); Cyclotron Research Centre, Université de Liège, Liège, Belgium (Dr Salmon); Department of Psychiatry, New York University School of Medicine, New York, NY (Dr de Leon); Department of Neurology, Max Planck Institut für Neurologische Forschung, Köln, Germany (Dr Mielke); and Division of Nuclear Medicine, University of California, San Diego (Dr Hoh). Dr Alexander is now with the Department of Psychology, Arizona Center for Alzheimer's Disease Research and Arizona State University, Tempe, and Dr Hoffman is now with the National Cancer Institute, National Institutes of Health, Bethesda, Md.

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