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Are patients with epilepsy at greater risk for developing dementia in old age?



By Naomi Chaytor, Ph.D. and Vaishali Phatak, Ph.D.

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Normal Age-Associated Cognitive Change


The brain, like the rest of the body, undergoes changes with aging. Research suggests that total brain volume is relatively stable from individuals' twenties to their fifties and begins to gradually decline over the subsequent decades. White matter lesions and a decrease in total brain volume have been observed in normal aging. These changes in brain volume have been correlated with a decline in performance on cognitive tests. The greatest cognitive change occurs in the collection of abilities known as “fluid” intelligence. Fluid intelligence, which is defined as the brain’s inherent ability to process information, can be measured through information processing speed and the ability to manipulate new information, make decisions, and solve problems. It is generally accepted that processing speed is the most significantly affected cognitive ability in normal aging. Reduced processing speed has been closely associated with increased white matter lesions. The other fluid intelligence abilities mentioned above, including cognitive flexibility, problem solving, and reasoning, also decline with age. Some researchers argue that declines in these aspects of fluid intelligence are byproducts of reduced cognitive speed, whereas other researchers suggest that they are independent processes. Typically, individuals experience a gradual decline in their fifties and sixties and a sharper decline from their sixties onwards.

Research in memory function in older adults has indicated that learning new information is the most affected memory process. Thus older adults need more exposure or more learning trials to master new information. However, once the information has been learned, it is relatively well preserved. Other memory processes such as working memory (e.g., holding and manipulating information “online” for a few minutes) and remote memory are preserved in normal aging.

The majority of over-learned material and acquired skills (e.g., experiences learned through environmental feedback, academic skills, vocabulary, and factual knowledge) are better protected from the aging process. Typically, these abilities increase into the sixties and then remain stable into the seventies. In psychology theory, these abilities comprise “crystallized” intelligence or learned skills, knowledge, and experience; culturally, these abilities are commonly described as “wisdom.”

Overall, the good news regarding cognitive function and normal aging is that despite evidence of decreased brain volume and declining performance on certain neuropsychological tests, there is not a significant decline in functional or day-to-day activity (Tranel, Benton, & Olson, 1997), and many cognitive skills remain intact with age.

Cognitive Decline in Young Adults with Epilepsy


It is well known that a subset of patients with epilepsy have some degree of cognitive impairment. The exact nature and severity of this impairment depends on many factors, including the age of seizure onset, the location of the seizure focus (in focal epilepsy) and the nature of the seizure disorder (e.g., focal versus generalized).
A recent review of longitudinal studies assessing cognitive change over time in patients with epilepsy has found that there is evidence for progression of cognitive deficits associated with chronic epilepsy.
Common cognitive complaints include memory and word-finding problems, although all cognitive domains can be affected. An additional question concerns whether this cognitive impairment is static or if it progresses over time. A recent review of longitudinal studies assessing cognitive change over time in patients with epilepsy has found that there is evidence for progression of cognitive deficits associated with chronic epilepsy (Seidenberg, Pulsipher, & Hermann, 2007). Specifically, several studies have found that compared to healthy controls, patients with epilepsy consistently fail to demonstrate practice effects during standard neuropsychological testing. That is, while the performance of healthy controls tends to improve with the second exposure to a given test, patients with epilepsy fail to improve. In addition, at least two studies have shown frank decline in cognition on repeat testing.

This research found reliable cognitive change over a three- to four-year period, with more dramatic declines in studies following patients over ten or more years. Cognitive decline was associated with the duration of epilepsy and with the frequency of both generalized and complex partial seizures. Decline was observed most consistently in the domains of verbal memory, attention, and psychomotor speed. It is important to note that most of the patients in these longitudinal studies are young adults (under age fifty) who have intractable temporal lobe epilepsy and that the results may not generalize to other patient groups.

Epilepsy and Dementia


Dementia, unlike normal aging, consists of declines in both cognitive test performance and functional skills. A U.K. population-based study found that 11.8% of patients with epilepsy who were over the age of 64 also had a comorbid diagnosis of dementia, which was significantly higher than the 1.9% comorbidity rate in the older non-epilepsy group. The same study found that rates of dementia comorbidity were comparable in the younger epilepsy (0.3%) and non-epilepsy subjects (0.2%). A Canadian population-based study also found higher rates of dementia in patients with epilepsy. Very rarely have studies prospectively followed cognitive functioning in older epilepsy patients. One longitudinal study that followed older epilepsy patients over a three- to four-year period found a subtle memory decline (i.e., failed to show a “practice effect”) similar to the type of decline seen in younger patients with epilepsy.

As noted above, there is concern that cognitive impairment in epilepsy follows a progressive course that appears to continue into old age. However, the mechanisms that contribute to this progression remain unclear. Investigations have suggested several possible mechanisms: upregulation of amyloid precursor protein, increased inflammation, increased vascular and metabolic risk factors associated with antiepileptic medications, and lifestyle factors such as lower rates of exercise in patients with epilepsy. Further research needs to be conducted to better understand these potential etiological processes.

In the meantime, it is important for clinicians working with epilepsy patients to be aware of older patients' increased vulnerability to dementia, as patients themselves may not reliably report cognitive decline.
It is important for clinicians working with epilepsy patients to be aware of older patients' increased vulnerability to dementia, as patients themselves may not reliably report cognitive decline.
Numerous studies have found that subjective memory complaints are not well correlated with objective memory performance. Older individuals who are comparing their abilities to those of their younger selves may complain of memory difficulties but in fact may be experiencing normal age-related changes. By contrast, patients with dementia may not fully appreciate that they are experiencing memory difficulties.

How Can Neuropsychological Assessment Help?


There are many unanswered questions in the literature regarding the cognitive functioning of older adults with epilepsy. What are clinicians to do in the mean time? There are important steps that can be taken to identify and assist patients who are at risk for dementia. First, it may be helpful to conduct neuropsychological testing of middle-aged adults with poorly controlled epilepsy in order to establish a baseline for comparison as they age. Otherwise, premorbid cognitive functioning must be estimated and assessment of decline will be less precise. Formal cognitive assessment is also indicated when older adults or their family members complain of cognitive problems.
Neuropsychological testing can help differentiate normal age-related changes from more problematic decline.
Neuropsychological testing can help differentiate normal age-related changes from more problematic decline. Furthermore, some patients who complain of cognitive problems are actually experiencing mood or anxiety disorders. It can be particularly difficult to differentiate mood disorders from dementia in older adults, and mood disorders are common in patients with epilepsy. Neuropsychological assessment typically includes screening for psychopathology and may assist with differential diagnosis. Particularly concerning are patient or family reports of functional decline such as problems with cooking, household chores, paying bills, or managing medications, as these difficulties can lead to safety concerns. Routinely asking your older patients with epilepsy about these daily tasks may assist in early identification of dementia.
References

Tranel, D., Benton, A., & Olson, K. (1997). A 10-year longitudinal study of cognitive changes in elderly persons. Developmental Neuropsychology, 13, 87-96.

Seidenberg, M., Pulsipher, D., & Hermann, B. (2007). Cognitive progression in epilepsy. Neuropsychology Review, 17, 445-454.
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