Racial Differences in the Effect of APOE-ε4 Genotypes on Trail Making Test Part B in Alzheimer’s disease

Abstract

The trail making test part B (TMT-B) evaluates "executive" functions, memory, and sensorimotor functions. No previous studies were found to examine the longitudinal effect of apolipoprotein E epsilon 4 (APOE-ε4) genotypes on the TMT-B scores in Alzheimer’s disease (AD), and/or mild cognitive impairment (MCI) participants. This study used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI): 482 participants with AD, 503 with cognitive normal (CN), 1,293 with MCI at baseline and follow-up of four years. The multivariable linear mixed model was used to determine the longitudinal changes in the TMT-B scores. The individuals with 1 or 2 APOE-ε4 alleles revealed significantly higher TMT-B scores (poor cognitive function) compared with individuals without APOE-ε4 allele at baseline and four follow-up visits (all p values < 0.0001). Compared with Whites, non-Hispanic African American and Hispanic populations had higher TMT-B scores (p = 0.0007 and 0.0044, respectively). Furthermore, stratified by diagnosis, the African American CN group had the highest TMT-B scores (p < 0.0001) and the Hispanic AD group had higher TMT-B scores (p = 0.0123) compared with Whites, while both African American and Hispanic MCI groups had higher TMT-B scores compared with Whites (p = 0.162 and 0.0274, respectively). In addition, stratified by racial groups, the subjects with APOE-ε4-homozgous and APOE-ε4-heterozgous showed higher TMT-B scores compared with subjects who carry zero APOE-ε4 allele just in Whites (p = 0.0023 and 0.0003, respectively); whereas there was no difference among APOE-ε4 genotypes in AA and Hispanics. In conclusion, the APOE-ε4 allele was associated with increased TMT-B scores but such associations varied by racial groups.