NO DIFFERENCE IN CEREBRAL GLUCOSE-METABOLISM IN PATIENTS WITH ALZHEIMER-DISEASE AND DIFFERING APOLIPOPROTEIN-E GENOTYPES

Background: Recent findings of a reduced cerebral metabolic rate of gl ucose (CMRGlu) in at-risk relatives of patients with Alzheimer disease (AD) who carry the apolipoprotein E (APOE) E4 allele suggest a causat ive role for the E4 isoform in cognitive changes that lead to AD. It i s not known whether E4 allele-associated deficits exist in patients wi th clinical AD. Objective: To determine whether distinct patterns of c erebral hypometabolism exist in patients who carry the E4 allele. Pati ents and Methods: Information on the CMRGlu and APOE genotype was avai lable for 46 patients at a memory disorders clinic: 31 patients were d iagnosed as having probable AD, 3 demented patients did not meet crite ria for AD, and 12 patients had mild memory complaints. Positron emiss ion tomography with the use of F-18-fludeoxyglucose was used to calcul ate the CMRGlu in the frontal and temporoparietal regions of the corte x. Estimates were standardized to the sensorimotor area of the cortex. Linear regression models were constructed to relate the APOE genotype to the CMRGlu, adjusting for cognitive status (ie, the Mini-Mental St ate Examination score). Results: Distinct patterns of the CMRGlu did n ot emerge for patients with different APOE genotypes. Bilateral defici ts in the CMRGlu were found in the patients with AD. Left-right asymme try was found in 8 of 12 patients with mild memory complaints: 7 of 8 had CMRGlu ratios less than 0.85 in the left side of the temporopariet al region of the cortex. Conclusions: The APOE E4 allele does not appe ar to be associated with specific deficits in brain metabolism in pati ents with AD despite evidence that the E4 allele is associated with pr eclinical alterations. This finding is consistent with previous epidem iologic results that have demonstrated a higher risk for AD in carrier s of the E4 allele, but no change in the rate of progression of AD.