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 o ccur early in the course of Alzheimer disease (AD), and the apolipopro tein 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 func tion in nondemented relatives at risk for familiar AD, we studied 12 r elatives with APOE epsilon 4 and 19 relatives without APOE epsilon 4. We also compared them with seven patients with probable AD. Design.-Af ter grouping subjects according to diagnosis and genotype, brain funct ion measures were compared among groups. Setting.-University medical c enter. Patients.-At-risk subjects had mild memory complaints, normal c ognitive performance, and at least two relatives with AD. Subjects wit h APOE epsilon 4 did not differ from those without APOE epsilon 4 in m ean age at examination (56.4 vs 55.5 years) or in neuropsychological p erformance (mean Mini-Mental State Examination score, 28.8 vs 29.3). M ain Outcome Measures.-Cerebral glucose metabolism was measured using p ositron emission tomography and fludeoxyglucose F 18. Results.-Parieta l metabolism was significantly lower and left-right parietal asymmetry was significantly higher in at-risk subjects with APOE epsilon 4 comp ared with those without APOE epsilon 4, Patients with dementia had sig nificantly lower parietal metabolism than did at-risk subjects with AP OE epsilon 4. Conclusions.-These results suggest that the inheritance of APOE epsilon 4 is associated with reduced cerebral parietal metabol ism and increased asymmetry in nondemented relatives at risk for proba ble AD, Longitudinal study will determine if glucose metabolic measure s provide a means to monitor experimental treatment responses during t he early phases of the disorder.