University of Washington Regional Epilepsy Center at Harborview Medical Center

Are Patients with Epilepsy at Greater Risk for Developing Dementia in Old Age?
By Naomi Chaytor, Ph.D. and Vaishali Phatak, Ph.D.

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 the 20s to the 50s 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 decline on cognitive testing. The greatest cognitive change occurs in the collection of abilities known as “fluid” intelligence. Fluid intelligence is defined as the brain’s inherent ability to process information and can be measured through tasks of information processing speed, the ability to manipulate new information, decision making, and problem solving. It is generally accepted that reduced processing speed is the most significantly affected cognitive ability in normal aging and 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 decline in these aspects of fluid intelligence is a byproduct of reduced cognitive speed; whereas, other researchers suggest that they are independent processes. Typically, there is a gradual decline in the 50s and 60s and a sharper decline from the 60s onwards.

Research in memory functioning in older adults has indicated that learning new information is the most affected of the memory processes. Thus, older adults need more exposure or learning trials to learn 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 “on-line” for a few minutes) and remote memories 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 60s and then remain stable into the 70s. 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 functions 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). 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 on 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 3-4 year period, with more dramatic declines in studies following patients over 10 or more years. Cognitive decline was associated with the duration of epilepsy, as well as 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 50) who have intractable temporal lobe epilepsy and the results may not generalize to other patient groups.

Epilepsy and Dementia

Dementia, unlike normal aging, consists of decline in both cognitive test performance as well as functional skills. A U.K. population based study found 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 similarly 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 3-4 year period, had a subtle memory decline (i.e., failed to show a “practice effect”), similar to the type of declines seen in younger patients with epilepsy.

As noted above, there is concern that cognitive impairment in epilepsy follows a progressive course which appears to continue into old age. However, the mechanisms contributing to this progression remain unclear. Investigations have raised the possible mechanisms of upregulation of amyloid precursor protein, increased inflammation, increased vascular and metabolic risk factors associated with anti-epileptic 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.

Meanwhile, it is important for clinicians working with epilepsy patients to be aware of the increased vulnerability for dementia in older patients, 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 when they were younger may complain of memory difficulties but in fact may be experiencing normal age related changes. Whereas, patients with dementia may not fully appreciate that they are experiencing memory difficulties.

How Can Neuropsychological Assessment Help?

As described above, there are many unanswered questions in the literature regarding the cognitive functioning of older adults with epilepsy. So 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 obtain neuropsychological testing in 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. Further, 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, managing medications, as this can lead to safety concerns. Routinely asking your older patients with epilepsy about these daily tasks may assist in early identification of dementia.

Contact Carol Breitenbach (Patient Care Coordinator) at 206-744-2105 for information on how to refer a patient to the UW Regional Epilepsy center for a Neuropsychological Assessment.

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.