The utility of apolipoprotein E genotyping in the diagnosis of Alzheimer disease in a community-based case series

Context: A recent collaborative study found that apolipoprotein E (APOE) ge notype, in conjunction with the clinical diagnosis of Alzheimer disease (AD ), was useful in improving diagnostic specificity (correctly not diagnosing AD) relative to the clinical diagnosis alone. Since these samples are part icularly enriched with patients with AD and the APOE epsilon 4 allele, resu lts may not be generalizable to patients seen in the general medical commun ity. Objective: To evaluate the diagnostic utility of the APOE genotype in diagn osing AD in a community-based case series from the largest health maintenan ce organization in an urban area. Design: We examined the effect of including APOE genotype on the diagnosis of AD in a community-based case series of patients presenting with memory c omplaints. Patients: Clinical and neuropathologic diagnoses and APOE genotype were obt ained from 132 patients who underwent evaluation for dementia and subsequen t autopsy. Main Outcome Measures: Sensitivity, specificity, and positive and negative predictive values given various combinations of clinical diagnoses and the presence of an APOE epsilon 4 allele. Results: Of the 132 patients, 94 had neuropathologically confirmed AD, yiel ding a prevalence of 71%. The clinical diagnosis alone yielded a sensitivit y of 84%, an estimated specificity of 50%, and positive and negative predic tive values of 81% and 56%, respectively. The presence of an epsilon 4 alle le alone was associated with an estimated sensitivity of 59%, specificity o f 71%, and positive and negative predictive values of 83% and 41%, respecti vely. Using the presence of clinical AD and an epsilon 4 allele decreased t he sensitivity to 49% and increased the specificity to 84%. The positive an d negative predictive values were 88% and 40%, respectively. Alternatively, the clinical diagnosis of AD or the presence of an epsilon 4 allele in ind ividuals not meeting clinical criteria for AD increases the estimated sensi tivity to 94% but decreases the specificity to 37%. The positive and negati ve predictive values were 79% and 70%, respectively. The changes in the sen sitivity and specificity for the combined tests relative to clinical diagno sis alone offset each other. For lower prevalence communities, the positive predictive value will be much lower than those observed herein. Conclusions: Our findings do not support the use of APOE gene typing alone in the diagnosis of AD in the general medical community. Although the prese nce of an epsilon 4 allele in older persons with clinical AD increased the probability of having AD and the absence of an epsilon 4 allele in this gro up decreased the probability of having AD, the association is not strong en ough in the differential diagnosis of non-Alzheimer dementia and AD.