ApoE Epsilon4 allele and disease duration affect verbal learning in mild temporal lobe epilepsy

Summary: Purpose: To clarify the possible role of other factors including the ApoE ɛ4 allele for memory decline in temporal lobe epilepsy (TLE). Methods: We conducted a neuropsychological and molecular study in 138 consecutive patients (78 female patients; mean age, 50.2 years, SD ± 17.9; range, 14 to 87 years) with mild nonlesional TLE, who rarely or never had seizures at long-term follow-up. The mean age at seizure onset was 33.0 years (SD, ±21.7), and the mean duration of epilepsy was 17.1 years (SD, ±15.7). Results: Thirty-four (25%) of 138 patients had test scores indicating verbal learning deficit (VLD). The presence of an ApoE ɛ4 allele was associated with an increased risk of VLD (OR, 4.18; 95% CI, 1.66–10.55). The effect of the ApoE genotype was independent of both the age at epilepsy onset and disease duration as well as of a low educational level, which were separately associated with VLD (p values = 0.045, 0.001, and 0.001, respectively). A significant linear trend (p = 0.005) was seen in the relation between disease duration and cognitive impairment, with the highest risk being in patients with an epilepsy duration ≥25.5 years (OR, 7.06; 95% CI, 1.67–29.85), especially if they carried the ɛ4 allele (OR, 32.29; 95% CI, 5.23–195.72). Conclusions: These results provide evidence for an alteration in cognitive performance as a function of the presence of the ApoE ɛ4 allele and point to the critical role of disease duration itself for cognitive impairment in TLE.