Racial differences in the effect of APOE-4 genotypes on trail making test B in Alzheimer's disease: A longitudinal study

Objectives: The trail making test part B (TMT-B) evaluates executive functions, memory, and sensorimotor functions. No previous study was found to examine the longitudinal effect of APOE-epsilon 4 genotypes on the TMT-B scores in Alzheimer's disease (AD) across racial groups.Methods: This study used the data from Alzheimer's Disease Neuroimaging Initiative (ADNI): 382 participants with AD, 503 with cognitive normal (CN), 1293 with mild cognitive impairment (MCI) at baseline and follow-up of four years. The multivariable linear mixed model was used to investigate the effect of APOE-epsilon 4 genotypes on changes in TMT-B scores.Results: Compared with Whites, African Americans (AA) and Hispanics had higher TMT-B scores (poor cognitive function). Furthermore, Whites subjects with 1 or 2 APOE-epsilon 4 alleles had significantly higher TMT-B scores compared with individuals without APOE-epsilon 4 allele at baseline and four follow-up visits; however, no differences in TMT-B were found between APOE-epsilon 4 alleles in the Hispanic and AA groups. No APOE-epsilon 4 by visit interactions was found for 3 racial groups. Stratified by AD diagnosis, the APOE-epsilon 4 allele was associated with TMT-B scores only in the MCI group, while there were significant interactions for visit by education, APOE-epsilon 4 allele, and the Mini Mental State Examination (MMSE) score in the MCI group. In addition, TMT-B was significantly correlated with the MMSE, AD Assessment Scale-cognitive subscale 13 (ADAS13), tTau, pTau, A beta 42, and hippocampus.Conclusions: APOE-e4 allele is associated with TMT-B scores in Whites subjects, but not in the Hispanic and AA groups. APOE-epsilon 4 showed interaction with visit in the MCI group.