ApoE epsilon4 allele and disease duration affect verbal learning in mild temporal lobe epilepsy

Purpose: To clarify the possible role of other factors including the ApoE epsilon4 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 epsilon4 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 greater than or equal to 25.5 years (OR, 7.06; 95 % CI, 1.67-29.85), especially if they carried the 64 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 epsilon4 allele and point to the critical role of disease duration itself for cognitive impairment in TLE.