Apolipoprotein E Type 4 Allele and Cerebral Glucose Metabolism in Relatives at Risk for Familial Alzheimer Disease

Objective.—Cerebral parietal hypometabolism and left-right asymmetry occur early in the course of Alzheimer disease (AD), and the apolipoprotein E type 4 alal- (APOE ε4) is a risk factor for familial AD. To determine if APOE ε4 is associated with lowered brain function in nondemented relatives at risk for familial AD, we studied 12 relatives with APOE ε4 and 19 relatives without APOE ε4. We also compared them with seven patients with probable AD.Design.—After grouping subjects according to diagnosis and genotype, brain function measures were compared among groups.Setting.—University medical center.Patients.—At-risk subjects had mild memory complaints, normal cognitive performance, and at least two relatives with AD. Subjects with APOE ε4 did not differ from those without APOE ε4 in mean age at examination (56.4 vs 55.5 years) or in neuropsychological performance (mean Mini-Mental State Examination score, 28.8 vs 29.3).Main Outcome Measures.—Cerebral glucose metabolism was measured using positron emission tomography and fludeoxyglucose F 18.Results.—Parietal metabolism was significantly lower and left-right parietal asymmetry was significantly higher in at-risk subjects with APOE ε4 compared with those without APOE ε4. Patients with dementia had significantly lower parietal metabolism than did at-risk subjects with APOE ε4.Conclusions.—These results suggest that the inheritance of APOE ε4 is associated with reduced cerebral parietal metabolism and increased asymmetry in nondemented relatives at risk for probable AD. Longitudinal study will determine if glucose metabolic measures provide a means to monitor experimental treatment responses during the early phases of the disorder.(JAMA. 1995;273:942-947