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 allele (APOE epsilon 4) is a risk factor for familial AD. To determine if APOE epsilon 4 is associated with lowered brain function in nondemented relatives at risk for familiar AD, we studied 12 relatives with APOE epsilon 4 and 19 relatives without APOE epsilon 4. 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 epsilon 4 did not differ from those without APOE epsilon 4 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 epsilon 4 compared with those without APOE epsilon 4, Patients with dementia had significantly lower parietal metabolism than did at-risk subjects with APOE epsilon 4. Conclusions.-These results suggest that the inheritance of APOE epsilon 4 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.