clinical practice The new england journal of medicine n engl j med 349;11 www.nejm.org september 11, 2003 1056 This Journal feature begins with a case vignette highlighting a common clinical problem. Evidence supporting various strategies is then presented, followed by a review of formal guidelines, when they exist. The article ends with the author’s clinical recommendations. Early Alzheimer’s Disease Claudia H. Kawas, M.D. From the Institute for Brain Aging and De- mentia and the Departments of Neurolo- gy and Neurobiology and Behavior, Univer- sity of California, Irvine. Address reprint requests to Dr. Kawas at the University of California, Irvine, 1121 Gillespie, Irvine, CA 92697-4540, or at ckawas@uci.edu. N Engl J Med 2003;349:1056-63. Copyright © 2003 Massachusetts Medical Society. A 72-year-old, college-educated woman comes in for the evaluation of mild memory loss that has been gradually progressing for the past two years. The patient lives alone, drives her own car, and manages her own finances, although she has recently made some errors in her checkbook. She also forgot the location of her car in a mall parking lot for two hours. Her score on the Mini–Mental State Examination is 26 of a possible 30, but she missed several items pertaining to memory. How should this patient be evaluated and treated? At present, 4 million Americans have Alzheimer’s disease, and the number of cases is expected to quadruple by the middle of this century. 1 Advancing age is the major risk factor for dementia, with a doubling of risk every five years after the age of 65. Alzhei- mer’s disease accounts for 50 to 75 percent of all cases of dementia. Other frequent causes of dementia include vascular dementia, either alone or in combination with Alz- heimer’s disease (in 10 to 20 percent of cases), dementia with Lewy bodies (in 10 to 15 percent), and frontotemporal dementia (in 5 to 15 percent). There are no definitive im- aging or laboratory tests for the diagnosis of dementia or most of the disorders that cause dementia, including Alzheimer’s disease. The evaluation thus depends on careful history taking in interviews with both the patient and a reliable informant, thorough physical and neurologic examinations (including careful testing of mental status), and use of diagnostic criteria for dementia and Alzheimer’s disease that have high reliabil- ity and validity. definitions of dementia, mild cognitive impairment, and normal aging The criteria for dementia as specified in the Diagnostic and Statistical Manual of Mental Dis- orders, third edition (revised) 2 and fourth edition, 3 require that a patient have cognitive loss in two or more domains, such as memory, language, calculations, orientation, and judgment. In addition, the loss must be of sufficient severity to cause social or occu- pational disability (Table 1). The use of neuropsychological tests and screening instru- ments, such as the Mini–Mental State Examination (MMSE) 5 and the Blessed Infor- mation–Memory–Concentration test (IMC), 6 is recommended to detect and follow cognitive decline. 7,8 The interpretation of scores depends on a person’s age and educa- tion level, but patients with cognitive losses in two or more domains typically have an MMSE score of less than 24 (the maximal score is 30 and the minimal score 0, with lower scores indicating poorer performance) or an IMC score of more than 8 (the maximal score [number of errors] is 33 and the minimal score 0, with higher scores indicating poorer performance). Patients with profound memory loss without other cognitive impairments and pa- tients with minor impairments in numerous cognitive domains but no functional im- the clinical problem Copyright © 2003 Massachusetts Medical Society. All rights reserved. Downloaded from www.nejm.org on April 10, 2005 . This article is being provided free of charge for use in Argentina.