Neurobiology of Epilepsy and Aging

1. Auflage 2007
ISBN: 978-0-08-048925-4
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 362 Seiten

This volume in the International Review of Neurobiology series addresses the epidemiology, pathophysiology, and treatment of epilepsy in elderly patients. Demographically, the elderly comprise both the fastest-growing segment of the U.S. population and the adult age group with the highest incidence of epilepsy, yet there are relatively few publications devoted to this clinical subgroup. The intersection of these two complex processes-epilepsy and advancing age-will have an increasing impact on medical and community care. The etiology, prognosis, and differential diagnosis of epilepsy can all be affected by the normal aging process and by the frequent comorbidities encountered in an elderly population. Chapters in this book review the effects of aging on brain function and on drug metabolism and interactions, covering the gamut of research from animal models of aging and epilepsy to clinical trials and outcomes. Topics also include the dangers of misdiagnosing status epilepticus, the special issues encountered in recruiting and retaining elderly clinical trial participants, and the use of antiepileptic drugs in the elderly. In both the clinic and the research laboratory, a better understanding of how epilepsy may differ between younger and older patients will be valuable in determining the best possible care for geriatric patients with epilepsy.

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Epilepsy in the Elderly: Scope of the Problem
Ilo E. Leppik    Epilepsy Research and Education Program, University of Minnesota, Minneapolis, Minnesota 55455, USA Abstract
The knowledge base for treating elderly persons with epilepsy is limited. There are few known knowns, many known unknowns, and probably many unknown knowns, that is, the things we know that “ain't so.” We know that the incidence and prevalence of epilepsy is higher in the elderly than any other age group, that the elderly are not a homogeneous group, that epilepsy is much more common in the nursing home population than in the community-dwelling elderly, and that antiepileptic drug (AED) use varies greatly among countries, but that in all, the older AEDs (phenytoin, phenobarbital, and carbamazepine) are the most commonly used. We also know that drugs that require hepatic metabolism for elimination are subject to pharmacokinetic changes with age and may be problematic because of drug–drug interactions. There are many known unknowns in both the basic science of brain aging and the susceptibility to epilepsy, and many clinical issues remain unresolved. Some unknown knowns (i.e., misconceptions) are that the elderly need levels of AEDs similar to those for younger adults and that AED levels do not fluctuate widely. This book is designed to help the reader understand the issues and, hopefully, to stimulate research to provide answers for the known unknowns. I Introduction
The elderly are the most rapidly growing segment of the population, and demographic trends predict that by 2050 the proportion of the population older than 60 years will be more than 30% in many developed countries (United Nations, 2001). Epidemiological studies have shown that onset of epilepsy is higher in the elderly than in any other age group (Hauser et al., 1996). With the combination of these two factors, elderly persons with epilepsy will represent an increasingly large group of patients needing expert care to maximize their quality of life and minimize health care costs. Because elderly persons with epilepsy may have different problems than younger adults, research which specifically identifies and addresses issues relevant to this population is needed. In a news briefing, knowledge was classified as “known knowns, known unknowns, and unknown unknowns” (Rumsfeld, 2002). However, the speaker left out perhaps the most critical class, the unknown knowns, or “things we know that ain't so” (Leppik, 2006b), to paraphrase Mark Twain. In medicine, this class consists of generally accepted facts that are found not to be true or applicable, after more information from research is available, and that may cause more harm than good. One example is the past practice of using aspirin to treat pain in children with hemophilia. Today, there may be many practices used in younger persons which may be inappropriate for the elderly. One cannot simplistically extrapolate knowledge gained from research done in younger patients to the elderly. Despite the magnitude of the problem, little basic and clinical research has been directed toward addressing crucial issues facing the elderly person with epilepsy (Leppik, 2006b). This chapter will review the scope of the problem and provide a context for the chapters included in this volume. II Known Knowns
A Incidence and Prevalence of Epilepsy Is Higher in the Community-Dwelling Elderly Than in Younger Adults or Children
Only recently have there been sufficient numbers of elderly in the general population to provide meaningful epidemiological data regarding the magnitude of the problem of epilepsy in the elderly. For a long time, epilepsy was considered to be primarily a disorder of children, with the incidence of epilepsy decreasing with age. However, studies have shown that the incidence of epilepsy is represented by a U-shaped curve, with the highest incidence being at both ends of the age spectrum (Cloyd et al., 2006; Hauser et al., 1996). One early study found that the incidence of seizures begins to increase after age 50 and rises to 127/100,000 person-years in those aged 60 and older (Hauser and Hesdorffer, 1990). A study reported the incidence of epilepsy to be 10.6/100,000 person-years for the ages of 45–59, 25.8/100,000 person-years for the ages of 60–74, and 101.1/100,000 person-years for the ages of 75–89 (Hussain et al., 2006). African-American subjects in this study had more than twice the incidence of epilepsy, 57.6/100,000 person-years compared to 26.1/100,000 person-years for Caucasians (Hussain et al., 2006). Among persons 75 years and older, the active epilepsy prevalence rate of persons living in the community is approximately 1.5%, about twice the rate of younger adults (Hauser et al., 1991). A study of data collected on 1,130,155 veterans aged 65 or older from 1997 to 1999 found that 20,558 of the veterans (1.8%) had a diagnosis of epilepsy (Perucca et al., 2006; Pugh et al., 2004). In the United States, approximately 181,000 persons developed epilepsy in 1995, and approximately 61,000 of these were over age 65 (Epilepsy Foundation of America, 1999). In Finland, the incidence of epilepsy decreased significantly in children and younger adults from 1986 to 2002, but increased significantly (p < 0.0001) in the elderly (Sillanpaa et al., 2006). B Prevalence and Incidence of Epilepsy Is Higher Among Nursing Home Residents Than Community-Dwelling Elderly
In the United States, all physicians’ orders must carry an indication listed by an International Classification of Diseases, Ninth Revision (ICD-9), code. Using these codes, it has been possible to link specific antiepileptic drug (AED) use to diagnoses. This is very useful because some AEDs, such as valproate and carbamazepine, are often used for conditions other than epilepsy. However, the criteria or findings used to make a diagnosis of epilepsy are not well understood. By using these codes, studies have shown that approximately 9% of nursing home residents in the United States are classified as having epilepsy or seizures (Garrard et al., 2000). A report from a study of 2001 Italian nursing home residents stated that 5.3% of the men and 4.0% of the women were being treated with an AED, but only 3.5% of the men and 2.7% of the women had a history of epileptic seizures (Galimberti et al., 2006). A study of 565 residents of a nursing home in Germany found that 4.96% had an AED prescribed, but only 3.00% had a seizure-related diagnosis (Huying et al., 2006). Thus, the use of AEDs in nursing homes in the United States is much higher than in European countries, but interestingly, the proportion of AED prescriptions for epilepsy and other conditions is similar. Also, in all countries, the prevalence of epilepsy in nursing home residents is much higher than in the community-dwelling elderly (Garrard et al., 2000). Only one study gives some indication of the incidence of epilepsy in nursing home residents; it is a study of 510 Beverly Enterprises nursing homes with 10,318 admissions over a 6-month period. On admission, 802 residents (7.8%) were using an AED. Of these, 57.7% had an epilepsy/seizure ICD-9 code, and most of the others had an indication suggesting behavioral issues. In the 3-month follow-up period, an additional 260 persons (2.7% of the admission cohort who were not using an AED) were placed on an AED, 20.9% for an epilepsy/seizure indication (Garrard et al., 2003). Thus, 54 of 9516 persons had an event resulting in a diagnosis of epilepsy/seizure within 3 months after admission. This is an incidence rate of approximately 571/100,000, or more than five times the incidence rate for the community-dwelling elderly. Another key finding of this study was that the odds ratio for being placed on an AED decreased with age. Setting 1.00 as the reference for the 65- to 74-year age group, the 75–84 cohort had an odds ratio of 0.68 (p < 0.05), and those over age 85 had an odds ratio of 0.47 (p < 0.0001) (Garrard et al., 2003). This is in marked contrast to the community-dwelling elderly, in whom the incidence of epilepsy increases with age (Hauser et al., 1996). Thus, the question arises as to whether the incidence of epilepsy actually decreases or the diagnosis is being missed in the older patient. C Retirement Age of 65 Is a Political Decision, Not Related to Medical Condition
Although age 65 is generally accepted as the age for retirement under entitlement programs, this age is somewhat arbitrary. The concept of a government-sponsored retirement system came into being during the 1880s, at a time when German Chancellor Otto von Bismarck’s political party was campaigning for reelection. For this first-ever government-sponsored entitlement program, the proposed retirement age was set at 70 years, when the average lifespan was only 48 years, but Bismarck’s party nevertheless won the election. As it became apparent that very few would collect any benefits under Bismarck’s scheme, the retirement age was reduced to 65 early in the twentieth century (http://www.ssa.gov/history/ottob.html; Social Security Administration history page). Since that time, “the elderly” have generally been defined as those 65 years or older, even though there is no medical evidence to...