2014 Bulletin

Bulletin vol. 28 no. 1 | 25 Aging in Epilepsy: Cognition and Brain Structure Michael Seidenberg, Ph.D. Rosalind Franklin University of Medicine and Science, Chicago, Illinois Bruce Hermann, Ph.D. University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin Acknowledgement: Supported by NIH 3ROI-44351 The Challenge Epilepsy is the fourth most common neurological disorder, representing a diversity of syndromes of variable seizure frequency and severity and impact on cognition, behavior, and quality of life (Institute of Medicine, 2012). Many individuals with childhood epilepsy are well controlled with anti-epilepsy medication (AED), and characterized by minimal impact on cognitive and brain development. However, there is a distinct subset of individuals who remain refractory to treatment and experience a chronic and long-standing course of seizures. Given the known age-related cognitive changes as well as the structural and functional brain changes that occur, it is possible that these people are more vulnerable as they get older. In this brief paper, we provide an overview of current findings on this topic primarily focusing on work from our lab. There are three subgroups of older people of relevance for investigation. These include individuals with an onset of epilepsy at an early age (e.g., < 20 years). This is the group which is the focus of this paper. Other important subgroups include individuals who begin to have new onset recurrent seizures as adults (e.g., over age 50). Finally, there is a group of individuals with epilepsy secondary to another acute neurological event (e.g., strike, traumatic brain injury). Recent papers on these latter topics are available (Roberson et al., 2011; Lowenstein, 2009). Paucity of Research We currently know very little about the course of cognition and brain structure in aging people with childhood/adolescent onset epilepsy. This is notable as the incidence and prevalence of epilepsy in people over aged sixty has markedly increased and estimates indicate further increases can be expected. The mean incidence and prevalence rates of epilepsy in older people are 2.4 per 1000 and 10.8 per thousand, respectively. There is a lifetime risk of epilepsy of 1.6% up to age 50 years and 3.4% to age 80. In addition, there is increasing evidence of a relationship between Alzheimer's Dementia (AD) and epilepsy including high rates of co-morbidity and the possible similarity of cellular mechanisms underlying both disorders. The dearth of clinical neuropsychological research of aging and epilepsy is very evident. We offer two possible reasons for the imbalance of neuropsychological investigation directed to the younger age population compared to the elderly, both of which pertain to issues relevant to the clinical neuropsychology of epilepsy. First, the onset of epilepsy often occurs before the age of eighteen years. This is primary time point for a comprehensive diagnostic work-up including assessment of cognitive functioning to be facilitated by a network of advocacy provided by parents, health care professionals, and social agencies invested in ensuring that these children obtain the most optimal intervention services. This is particularly the case for school aged children. Unfortunately, the cost and lack of resources often make it difficult to obtain follow-up assessment unless significant academic or psychiatric difficulties are identified. Perhaps the most studied issues in the neuropsychology of epilepsy revolve around the population of TLE individuals being seen for possible surgery to relieve chronic and intractable seizures. Surgical intervention, particularly anterior temporal lobectomy (ATL) has proven to be a viable and effective intervention approach for these individuals. Neuropsychology has played a significant role in the clinical assessment of these patients both before and after surgery. Research with this population has provided important information about the neurobiological basis of cognition, particularly on the role of the hippocampus and surrounding MTL on declarative memory, language dominance, plasticity and reorganization, and material-specific memory. However, ATL is typically conducted for individuals between 20-50 years of age (mean age in the mid 30's). Thus, this population is not appropriate to study the natural course of epilepsy and aging. Growing Old with Epilepsy Several years ago, we published a paper which highlighted the relative lack of research regarding cognitive and brain structure aging in older adults with chronic epilepsy (Hermann et al., 2007). Discussed were a number of risk factors (e.g., vascular and lifestyle factors), shown to be associated with cognitive decline in aging people in the general population, risk factors that also appear to be elevated in persons with chronic epilepsy. In the general population, there is considerable evidence that vascular risk factors and vascular disease including higher rates of hypertension, ischemic heart disease, heart failure, diabetes, and cerebrovascular disease have a deleterious impact on cognitive aging. This is a concern as population-based surveys document higher rates of these medical problems in persons with epilepsy. In addition, there is considerable evidence that lifestyle habits that may protect against these risks such as physical exercise, weight control, cognitive stimulation, and social integration are less likely to characterize the lives of people. Despite these concerns, there are only a handful of published studies that have directly examined the neuropsychological functioning of epilepsy in individuals over the age of sixty.

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