There is a pressing need for sensitive, non-invasive indicators of cognitive impairment in those at risk for Alzheimer’s disease (AD). One group at an increased risk for AD is APOEε4 carriers. One study found that cognitively normal APOEε4 carriers are less likely to produce low frequency (i.e., less common) words on semantic fluency tasks relative to non-carriers, but this finding has not yet been replicated. This study aims to replicate these findings within the Wake Forest ADRC clinical core population, and examine whether these findings extend to additional semantic fluency tasks.

This sample includes 221 APOEε4 non-carriers (165 females, 56 males; 190 White, 28 Black/African American, 3 Asian; Mage = 69.55) and 79 APOEε4 carriers (59 females, 20 males; 58 White, 20 Black/African American, 1 Asian; Mage = 65.52) who had been adjudicated as cognitively normal at baseline. Semantic fluency data for both the animal task and vegetable task was scored for total number of items as well as mean lexical frequency (attained via the SUBTLEXus database). Demographic variables and additional cognitive variables (MMSE, MoCA, AMNART scores) were also included from the participants’ baseline visit.

APOEε4 carriers and non-carriers did not differ on years of education, AMNART scores, or gender (ps > 0.05). APOEε4 carriers were slightly younger and included more Black/African American participants (ps < 0.05). Stepwise linear regression was used to determine the variance in total fluency score and mean lexical frequency accounted for by APOEε4 status after including relevant demographic variables (age, sex, race, years of education, and AMNART score). As expected, demographic variables accounted for significant variance in total fluency score (p < 0.0001). Age accounted for significant variance in total fluency score for both the animal task (ß = -0.32, p <0.0001) and the vegetable task (ß = -0.29, p < 0.0001), but interestingly, not the lexical frequency of words produced. After accounting for demographic variables, APOEε4 status did not account for additional variance in lexical frequency for either fluency task (ps > 0.05). Interestingly, APOEε4 status was a significant predictor of total words for the vegetable semantic fluency task only (ß = 0.13, p = 0.01), resulting in a model that accounted for more variance (R2 = 0.25, F(6, 292) = 16.11, p < 0.0001) in total words than demographic variables alone (R2 = 0.23, F(5, 293) = 17.75, p < 0.0001).

Unsurprisingly, we found that age, AMNART, and education were significant predictors of total word fluency. One unexpected finding was that age did not predict the lexical frequency - that is - regardless of age, participants tended to retrieve words of the same lexical frequency, which stands in contrast to the notion that retrieval efficiency of infrequent words declines with age. With regard to APOEε4, we did not replicate existing work demonstrating differences in lexical frequency and semantic fluency tasks for ε4 carriers and non-carriers; possibly due to differences in the demographic characteristics of the sample.