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Apolipoprotein E Status as a Predictor of the Development of Alzheimer's Disease in Memory-Impaired Individuals

Ronald C. Petersen, PhD, MD; Glenn E. Smith, PhD; Robert J. Ivnik, PhD; Eric G. Tangalos, MD; Daniel J. Schaid, PhD; Stephen N. Thibodeau, PhD; Emre Kokmen, MD; Stephen C. Waring, DVM, PhD; Leonard T. Kurland, MD, DrPH
JAMA. 1995;273(16):1274-1278. doi:10.1001/jama.1995.03520400044042.
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Objective.  —The outcome of patients with mild cognitive impairment is not known, yet these patients present a difficult dilemma for the clinician. This study was designed to characterize the outcome of a group of patients with mild cognitive impairment and to determine whether the presence of the ε4 allele on the apolipoprotein E gene (APOE) is a predictor of that outcome.

Design.  —A prospective, longitudinal inception cohort.

Setting.  —General community clinic.

Participants.  —A consecutive sample of 66 patients who met criteria for a diagnosis of a mild cognitive impairment and who had at least one clinical reevaluation was identified from the Mayo Clinic Alzheimer's Disease Center/Alzheimer's Disease Patient Registry.

Interventions.  —We evaluated patients initially and at 12- to 18-month intervals up to 54 months using standard neurological and neuropsychological measures such as the Mini-Mental State Examination, the Dementia Rating Scale, the Wechsler Adult Intelligence Scale—Revised, the Wechsler Memory Scale—Revised, and the Free and Cued Selective Reminding Test. The APOE status of study patients was determined.

Main Outcome Measure.  —The development of dementia as determined by the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition and the National Institute of Neurological and Communicative Disorders and Stroke/ Alzheimer's Disease and Related Disorders Association criteria.

Results.  —Sixty-six individuals had been reevaluated once (mean of 18 months), 36 individuals twice (mean of 36 months), and 22 individuals on three occasions (mean of 54 months), with conversion rates to dementia at these intervals of 24%, 44%, and 55%, respectively. A multivariate Cox regression model demonstrated that possession of an APOE ε4 allele was the strongest predictor of clinical outcome.

Conclusions.  —These data suggest the following: (1) patients with mild cognitive impairment can be clinically defined, (2) many members of this group progress to Alzheimer's disease, and (3) APOE ε4 allele status appears to be a strong predictor of clinical progression.(JAMA. 1995;273:1274-1278)


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