An Analysis of the Relationship Between the APOE4 Allele Count, Age of Onset, and Cognitive Impairment Prevalence in the NACC Database: Evaluating the Nigerian Paradox

Background/Objectives: This study analyzes the database of the National Alzheimer’s Coordinating Center (NACC) to examine the correlation between the age of onset and the prevalence of cognitive impairment with the number of subjects carrying APOE4 alleles. The research also evaluates the interaction of race and gender in the effect of APOE4 on cognition and age of onset to determine whether the findings support or refute the Nigerian paradox. This paradox refers to the observed resistance of Nigerians to the increasing prevalence of cognitive impairment associated with a higher APOE4 count. Methods: The NACC67 dataset consists of 195,196 rows and 1024 columns, yielding data from 40,210 individual subjects, including information on race, gender, APOE alleles, and cognitive impairment. Among these subjects, 24,673 had recorded data on the age when cognitive decline was first observed. Logistic regression, Chi-square tests, and ANOVA analyses were performed to explore these relationships. The hypotheses tested were as follows: (1) that the APOE4 count is associated with both the prevalence and earlier onset of cognitive impairment and (2) whether the Nigerian paradox (a resistance to APOE4-associated cognitive impairment) could be observed in racial groups represented in the NACC dataset. Results: The results showed a significant positive association between cognitive impairment and the APOE4 count. A logistic regression analysis assessed potential interactions between race or gender and the relationship between the APOE4 count, cognitive impairment prevalence, and the age of onset. No significant interactions were observed among White, Black, Asian, and “Other” racial groups. Across all racial groups except for Pacific Islanders, an increase in APOE4 count was associated with an earlier onset of cognitive impairment and a higher prevalence of the condition. A statistically significant correlation between APOE4 count and age of onset was found only in Black and White individuals. The female gender, the White race, and a higher APOE4 count were associated with a greater prevalence of cognitive impairment and an earlier onset. However, gender and race did not significantly modify the effect of the APOE4 count on cognitive impairment. Conclusions: These findings do not support the Nigerian paradox in White, Black, Asian, and “Other” racial groups, comprising a total of 39,660 subjects. The association between APOE4 and the age of cognitive decline remained consistent across gender and racial groups.