2014 Bulletin

26 | Bulletin vol. 28 no. 1 These studies consistently point to poorer cognitive functioning compared to a control group. Of interest, Griffith et al., (2005) compared the cognitive performance of older individuals with epilepsy (over age 60) to a comparable age MCI group, a group known to be at increased risk for conversion to AD. The epilepsy group showed a similar degree of impairment across the subscales including the Memory scale compared to the MCI group. Current Hypotheses Historically, the study of age-related changes in cognition and brain structure was conceptualized in terms of progressive decline (neurodegenerative effect). From a neuropsychological perspective, the progression hypothesis entails the possibility that cognitive decline becomes increasingly evident with increased duration of the disorder. Early neuropsychological studies supported the progression hypothesis with cognitive decline exhibited by a subset of investigated cohorts. Cognitive impairment among adults with chronic epilepsy was reported in the context of a high cumulative frequency of seizures (particularly tonic-clonic), severity of seizures, number of status episodes, early age of onset, and longer duration of epilepsy. However, more comprehensive reviews indicated that the findings were mixed and in many instances it proved difficult to isolate duration of epilepsy from other factors (Dodrill, 2004; Seidenberg et al., 2007). In contrast to the progression hypothesis, several recent papers have proposed a life-span perspective of chronic epilepsy, aging, cognition, and brain structure (Hermann et al., 2007; Helmsteador et al., 2009; Seidenberg & Hermann, 2010). From this perspective, chronic childhood onset epilepsy potentially impacts both early cognitive and brain development; an impact that is evident at time of initial diagnosis. In addition, these early outcomes in of themselves may have negative lifespan implications for academic and social-emotional development including aging effects on behavior. At this point, the data available on this issue is primarily cross- sectional, with a focus on memory, and the study of individuals many years (even decades) after the onset of their epilepsy that is often intractable to conventional AED treatment. Fortunately, there has been a few published longitudinal investigations over the past few years. Furthermore, there has been a marked increased in neuroimaging studies. Cross-sectional Studies For many years, the study of cognitive dysfunction in chronic epilepsy primarily focused on the memory impairment observed in people with temporal lobe epilepsy (TLE). More recently, however, it has become evident that a picture of more generalized cognitive dysfunction is present, even among those with focal mesial temporal lobe seizures. We compared the performance of adults with TLE divided into a group with histopathological evidence of hippocampal sclerosis to TLE participants without such evidence (Hermann et al., 1997). Findings showed considerable generalized cognitive impairment in the former group including in domains of intellectual functioning, language, and visuoperceptual functions. In addition, the group with hippocampal pathology was characterized by an earlier age of epilepsy onset and longer epilepsy duration. Oyegbile et al (2004) examined duration of epilepsy and cognition in a sample of 96 subjects with chronic temporal lobe. Neuropsychological performance was adjusted for age, gender, and education based on the scores obtained from a group of 86 healthy controls. As expected duration effects were evident; more years of epilepsy was negatively correlated with performance in memory, language, visuoperceptual, and motor tasks. Of interest, duration effects were moderated by education level. Less educated individuals showed a stronger negative relationship between cognition and duration than a more educated group. One is left to consider the possible reasons for finding generalized cognitive impairment in a focal neurological group (TLE). In addition, it is possible that the moderating effect of education level may signal the impact of epilepsy on a developing brain, and/or the accumulative effects of years of intractable epilepsy. More recent studies have provided support for the life span neurodevelopmental hypothesis. Christoph Helmstaedor and colleagues (2009) reported a comparison of age regression performance in 1156 TLE patients and 1000 controls on a measure of verbal memory and learning. Notably, the age range for the two groups went from age 6 years old to age 70 years. They did not find a linear increase of divergence in performance across the age range as would be expected based on the progression hypothesis. Rather, there were significant differences between groups evident in the youngest age group which were accentuated until ages in the 20-30 year old range, and thereafter showed a parallel trajectory (thru age 70). Baxendale et al., (2010) reported similar findings in a retrospective study of three different aged cohorts. They also suggested that duration effects may be minimal and that the early age of epilepsy onset is more important. However, both of these studies use retrospective cross-sectional designs. Longitudinal Findings We followed a cohort a cohort of chronic TLE individuals, with a mean age in the late 30's, a protracted duration of over 20 years, and a mean age of epilepsy onset of twelve years of age. They were compared to a healthy control group at two time points separated by four years. Measures of cognition and MRI scans were collected at both time points. At baseline, the chronic TLE group demonstrated significant impairment in a broad set of cognitive domains that extended beyond episodic declarative memory, and included difficulties with executive functioning, semantic memory and knowledge, language, and psychomotor ability (Hermann et al., 2002). As expected, baseline brain volumes were smaller in the TLE group in the hippocampus and other regions of the mesial temporal lobe. However, areas distal to the seizure focus (ipsilateral and contralateral) also showed smaller volumes than controls (Pulsipher et al., 2007). This may help explain the pattern of generalized cognitive impairment discussed earlier. After four years, there was no evidence of significant cognitive decline in the TLE group. Overall their mean performance was quite stable across the four year interval. However, the healthy control showed a small improvement, presumably representing a practice effect on many of the cognitive measures. When the TLE group was examined more closely, it became apparent that a distinct subset of the participants did show an adverse and significant decline in test performance, as reflected by at least a two standard deviation (lower) than expected based on regression based change scores. The percent of participants affected ranged from under 25% in most domains, but the number of participants was higher on measures of confrontation naming (38%), immediate and delayed auditory-verbal memory (38%), and speeded motor dexterity (63%). Predictors of adverse cognitive outcome also varied across cognitive domains. For example, hippocampus volume was related to memory outcome, and total white matter volume for psychomotor speed (Hermann et al., 2006). In addition, demographic variables (chronological age,

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