ApoE- 4 is associated with reduced memory in long-standing intractable temporal lobe epilepsy

Objective: To investigate the relationship between the apolipoprotein (ApoE) ε4 allele and memory performance (verbal and nonverbal) in patients with medically intractable temporal lobe epilepsy (TLE) who underwent temporal lobectomy. Methods: Presurgical and postsurgical memory performance was examined in 87 adult patients with TLE (ε4 22; non-ε4 65) to determine whether the expression of ApoE-ε4 may be associated with memory performance in this population and to examine how this relationship may be affected by duration of epilepsy. Results: There was a significant interaction between ApoE-ε4 status and duration of epilepsy such that ε4 carriers with a long duration of epilepsy demonstrated the poorest memory performance on both verbal and nonverbal measures. This relationship was observed both before and after temporal lobectomy, with little change in test performance over time. Conclusions: The ApoE-ε4 allele interacts with longstanding seizures to affect memory performance, both verbal and nonverbal, in patients with medically intractable temporal lobe epilepsy. NEUROLOGY 2007;68:409–414 Memory decline, which is commonly associated with temporal lobe seizures, has been related to age at epilepsy onset,1,2 duration of disorder,1,3 chronological age,3 and etiology,4,5 but little is known about underlying biologic factors that may predispose patients to memory loss. Two studies have examined the relationship between apolipoprotein (ApoE) polymorphisms and cognitive performance in patients with epilepsy. One examined IQ and memory performance in patients with newly diagnosed partial epilepsy and found that ε4 carriers had significantly lower IQ scores than patients without ε4.6 Carriers also performed more poorly on a list-learning measure, although the difference was not significant. Another study, which examined memory of patients with mild, well-controlled nonlesional temporal lobe epilepsy (TLE),7 found that ε4 carriers demonstrated lower performance on a verbal list-learning task than noncarriers, particularly among patients with duration greater than 25.5 years. No published studies have examined the relationship between ApoE-ε4 and memory performance in patients with medically intractable epilepsy or the relationship between ε4 and memory performance after surgical intervention for the treatment of epilepsy. This study was designed to investigate the relationships among the apolipoprotein ε4 allele, duration of epilepsy, and memory performance in a group of patients with medically intractable TLE who underwent temporal lobectomy. Methods. Participants. This study involved an institutional review board–approved review of previously collected and archived data from 89 patients treated at Cleveland Clinic. Participants were older adolescent and adult patients (aged 16 years and older) with medically refractory epilepsy who underwent temporal lobectomies for treatment of their seizure disorders. Patients were included in the study if they completed presurgical and postsurgical neuropsychological evaluations, had a Full Scale IQ of 70 or higher, and had frozen or paraffin-embedded tissue available for DNA analysis. Two patients were excluded because their memory data were outliers, resulting in a final sample size of 87. Participants ranged in age from 16 to 65 years (mean 36.26, SD 11.20) and in education from 8 to 20 years (mean 13.25, SD 2.18). The mean age of seizure onset for the group was 14.15 years (SD 9.87), and the mean duration of epilepsy was 21.84 years (SD 12.61). Twenty-two patients (25%) had at least one ε4 allele (ε4 group), and 65 patients (75%) did not have an ε4 allele (non-ε4 group). The distribution of ApoE genotypes was consistent with what is typically observed in the general population and did not deviate from Hardy–Weinberg equilibrium (table 1). There were no significant differences between the ε4 and non-ε4 groups with Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of