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) genotype, 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 particularly enriched with patients with AD and the APOE ε4 allele, results may not be generalizable to patients seen in the general medical community. Objective: To evaluate the diagnostic utility of the APOE genotype in diagnosing AD in a community-based case series from the largest health maintenance 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 complaints. Patients: clinical and neuropathologic diagnoses and APOE genotype were obtained from 132 patients who underwent evaluation for dementia and sub-sequent autopsy. Main Outcome Measures: Sensitivity, specificity, and positive and negative predictive values given various combinations of clinical diagnoses and the presence of an APOE ε4 allele. Results: Of the 132 patients, 94 had neuropathologically confirmed AD, yielding a prevalence of 71%. The clinical diagnosis alone yielded a sensitivity of 84%, an estimated specificity of 50%, and positive and negative predictive values of 81% and 56%, respectively. The presence of an ε4 allele alone was associated with an estimated sensitivity of 59%, specificity of 71%, and positive and negative predictive values of 83% and 41%, respectively. Using the presence of clinical AD and an ε4 allele decreased the sensitivity to 49% and increased the specificity to 84%. The positive and negative predictive values were 88% and 40%, respectively. Alternatively, the clinical diagnosis of AD or the presence of an ε4 allele in individuals not meeting clinical criteria for AD increases the estimated sensitivity to 94% but decreases the specificity to 37% . The positive and negative predictive values were 79% and 70%, respectively. The changes in the sensitivity and specificity for the combined tests relative to clinical diagnosis 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 genotyping alone in the diagnosis of AD in the general medical community. Although the presence of an ε4 allele in older persons with clinical AD increased the probability of having AD and the absence of an ε4 allele in this group decreased the probability of having AD, the association is not strong enough in the differential diagnosis of non-Alzheimer dementia and AD.