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according to research published online ahead of print Feb. 3 in Neurology. Optimizing AED therapy to reduce or prevent seizures is thus unlikely to affect cognition, according to the investigators.
Patients who take AEDs commonly report cognitive problems, but investigations into the cognitive effects of AEDs have yielded inconsistent results. “We were also interested in this association, as we often treat complex patients taking multiple or high-dose AEDs, and our patients often report cognitive dysfunction,” said Emma Foster, MBBS, an epilepsy fellow at Alfred Health and the Royal Melbourne Hospital in Victoria, Australia. “We were particularly interested to examine how much AEDs affect cognition relative to other factors. We commonly see patients in our tertiary epilepsy care unit who have had severe epilepsy for a long time or who have psychiatric disorders, and these factors may also contribute to cognitive dysfunction.”
Researchers analyzed patients admitted for video EEG monitoring
For their study, Dr. Foster and colleagues prospectively enrolled patients admitted to the Royal Melbourne Hospital’s video EEG monitoring unit between January 2009 and December 2016. Patients were included in the study if they were age 18 years or older, had been admitted for diagnostic or surgical evaluation, and had complete data for the relevant variables. Patients were prescribed AED monotherapy or polytherapy.
The researchers based epilepsy diagnoses on the 2014 International League Against Epilepsy criteria. Diagnoses of psychogenic nonepileptic seizures (PNES) were based on a consensus of epileptologists at weekly multidisciplinary clinical meetings, which was supported by evaluation of all available data. Some patients received a diagnosis of comorbid epilepsy and PNES. If data were insufficient to support a diagnosis of epilepsy or PNES, the admission was considered nondiagnostic.
All participants underwent neuropsychologic and neuropsychiatric screening. Researchers assessed patients’ objective, global cognitive function using the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG), a validated instrument. Patients responded to the Quality of Life in Epilepsy inventory (QOLIE-89) to provide a measure of subjective cognitive function. They also responded to the Hospital Anxiety and Depression Scale (HADS) to screen for mood disorders.
Dr. Foster and colleagues measured seizure frequency through patient self-report. Patients averaged their seizure frequency during the 12-month period before admission to the video EEG unit. They categorized it according to a 12-point system in which 0 denotes patients who are seizure-free and not taking AEDs and 12 denotes patients in status epilepticus. Patients with PNES used the same scale to report event frequency, although the system was not designed for this purpose.
Almost half of patients were prescribed polypharmacy
The researchers included 331 patients in their analysis. The population’s mean age was 39.3 years, and about 62% of patients were female. Approximately 47% of patients had epilepsy, 25.7% had PNES, 6.6% had comorbid epilepsy and PNES, and 20.5% had a nondiagnostic outcome. Among patients with epilepsy, most (54.5%) had temporal lobe epilepsy, followed by extratemporal focal epilepsy (32.1%) and generalized epilepsy (13.5%). The mean number of AEDs prescribed on admission was 1.6, and mean seizure or event frequency score was 7.2, which indicated 1-3 seizures per month. Mean HADS depression score was within the normal range (5.7), and mean HADS anxiety score was in the borderline range (8.2).
Approximately 45% of patients were prescribed AED polypharmacy on admission, 25.1% were prescribed AED monotherapy, and 29.9% were prescribed no AED. Levetiracetam, valproate, and carbamazepine were the most frequently prescribed AEDs. Most patients with epilepsy (73.1%) were on polypharmacy, compared with 17.6% of patients with PNES, 63.6% of patients with epilepsy and PNES, and 8.8% of nondiagnostic patients.
Older age and greater seizure frequency predicted impaired objective cognitive function. Comorbid epilepsy and PNES appeared to predict impaired objective cognitive function as well, but the data were inconclusive. No AED was a significant predictor of objective cognitive function. Higher depression and anxiety scores and greater seizure frequency predicted impaired subjective cognitive function. No AED predicted subjective cognitive function.
Future studies could address particular cognitive domains
Previous studies have suggested that treatment with topiramate predicts objective or subjective cognitive function, but Dr. Foster and colleagues did not observe this result. The current findings suggest that topiramate may have a less significant effect on cognition than the literature suggests, they wrote. In addition, more evidence is needed to fully understand the effects of clobazam, valproate, phenytoin, and gabapentin because the analysis was underpowered for these drugs.
Although NUCOG assesses global cognitive function reliably, its ability to measure particular cognitive subdomains is limited. “We aim to conduct future research investigating the complex associations between different cognitive functions, including processing speed, and specific AEDs in this heterogeneous population,” said Dr. Foster.
Despite the study’s large sample size, the researchers could not explore potential interactions between various predictor variables. “Epilepsy may interact with the aging process or with other medical conditions associated with aging, such as hypertension and diabetes, and this may increase the risk of cognitive decline,” said Dr. Foster. “Older age may also be associated with reduced capacity to metabolize drugs, increased sensitivity to the cognitive and neurological effects of drugs, less cognitive reserve, and increased likelihood of taking multiple medications, which, along with AEDs, may exert a cognitive effect.”
The current findings may reduce concerns about the effects of AEDs on cognitive function and encourage neurologists to pursue the proper dosing for optimal seizure control, wrote the authors. “However, it is possible that some individuals may be more susceptible than others to AED-related cognitive dysfunction,” said Dr. Foster. “We do not have a robust way to predict who these patients will be, and it is still good practice to make patients aware that some people experience adverse cognitive effects from AEDs. However, it needs to be emphasized that it is unlikely to be the sole reason for their cognitive impairment. Other issues, such as poor seizure control or unrecognized or undertreated mood disorders, are even more important factors for impaired cognition.”
Patients who report cognitive problems should be screened for mood disorders, Dr. Foster continued. “It would also be important to consider whether the patients’ cognitive complaints arise from subtle clinical or subclinical seizure activity and subsequent postictal periods. To investigate this [question] further, clinicians may arrange for prolonged EEG monitoring. This [monitoring] could be done in an ambulatory setting or during an inpatient admission.”
The study was conducted without external funding. Dr. Foster and other investigators reported research funding from professional associations and pharmaceutical companies that was unrelated to the study.
SOURCE: Foster E et al. Neurology. 2020 Feb 3. doi: 10.1212/WNL.0000000000009061.
according to research published online ahead of print Feb. 3 in Neurology. Optimizing AED therapy to reduce or prevent seizures is thus unlikely to affect cognition, according to the investigators.
Patients who take AEDs commonly report cognitive problems, but investigations into the cognitive effects of AEDs have yielded inconsistent results. “We were also interested in this association, as we often treat complex patients taking multiple or high-dose AEDs, and our patients often report cognitive dysfunction,” said Emma Foster, MBBS, an epilepsy fellow at Alfred Health and the Royal Melbourne Hospital in Victoria, Australia. “We were particularly interested to examine how much AEDs affect cognition relative to other factors. We commonly see patients in our tertiary epilepsy care unit who have had severe epilepsy for a long time or who have psychiatric disorders, and these factors may also contribute to cognitive dysfunction.”
Researchers analyzed patients admitted for video EEG monitoring
For their study, Dr. Foster and colleagues prospectively enrolled patients admitted to the Royal Melbourne Hospital’s video EEG monitoring unit between January 2009 and December 2016. Patients were included in the study if they were age 18 years or older, had been admitted for diagnostic or surgical evaluation, and had complete data for the relevant variables. Patients were prescribed AED monotherapy or polytherapy.
The researchers based epilepsy diagnoses on the 2014 International League Against Epilepsy criteria. Diagnoses of psychogenic nonepileptic seizures (PNES) were based on a consensus of epileptologists at weekly multidisciplinary clinical meetings, which was supported by evaluation of all available data. Some patients received a diagnosis of comorbid epilepsy and PNES. If data were insufficient to support a diagnosis of epilepsy or PNES, the admission was considered nondiagnostic.
All participants underwent neuropsychologic and neuropsychiatric screening. Researchers assessed patients’ objective, global cognitive function using the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG), a validated instrument. Patients responded to the Quality of Life in Epilepsy inventory (QOLIE-89) to provide a measure of subjective cognitive function. They also responded to the Hospital Anxiety and Depression Scale (HADS) to screen for mood disorders.
Dr. Foster and colleagues measured seizure frequency through patient self-report. Patients averaged their seizure frequency during the 12-month period before admission to the video EEG unit. They categorized it according to a 12-point system in which 0 denotes patients who are seizure-free and not taking AEDs and 12 denotes patients in status epilepticus. Patients with PNES used the same scale to report event frequency, although the system was not designed for this purpose.
Almost half of patients were prescribed polypharmacy
The researchers included 331 patients in their analysis. The population’s mean age was 39.3 years, and about 62% of patients were female. Approximately 47% of patients had epilepsy, 25.7% had PNES, 6.6% had comorbid epilepsy and PNES, and 20.5% had a nondiagnostic outcome. Among patients with epilepsy, most (54.5%) had temporal lobe epilepsy, followed by extratemporal focal epilepsy (32.1%) and generalized epilepsy (13.5%). The mean number of AEDs prescribed on admission was 1.6, and mean seizure or event frequency score was 7.2, which indicated 1-3 seizures per month. Mean HADS depression score was within the normal range (5.7), and mean HADS anxiety score was in the borderline range (8.2).
Approximately 45% of patients were prescribed AED polypharmacy on admission, 25.1% were prescribed AED monotherapy, and 29.9% were prescribed no AED. Levetiracetam, valproate, and carbamazepine were the most frequently prescribed AEDs. Most patients with epilepsy (73.1%) were on polypharmacy, compared with 17.6% of patients with PNES, 63.6% of patients with epilepsy and PNES, and 8.8% of nondiagnostic patients.
Older age and greater seizure frequency predicted impaired objective cognitive function. Comorbid epilepsy and PNES appeared to predict impaired objective cognitive function as well, but the data were inconclusive. No AED was a significant predictor of objective cognitive function. Higher depression and anxiety scores and greater seizure frequency predicted impaired subjective cognitive function. No AED predicted subjective cognitive function.
Future studies could address particular cognitive domains
Previous studies have suggested that treatment with topiramate predicts objective or subjective cognitive function, but Dr. Foster and colleagues did not observe this result. The current findings suggest that topiramate may have a less significant effect on cognition than the literature suggests, they wrote. In addition, more evidence is needed to fully understand the effects of clobazam, valproate, phenytoin, and gabapentin because the analysis was underpowered for these drugs.
Although NUCOG assesses global cognitive function reliably, its ability to measure particular cognitive subdomains is limited. “We aim to conduct future research investigating the complex associations between different cognitive functions, including processing speed, and specific AEDs in this heterogeneous population,” said Dr. Foster.
Despite the study’s large sample size, the researchers could not explore potential interactions between various predictor variables. “Epilepsy may interact with the aging process or with other medical conditions associated with aging, such as hypertension and diabetes, and this may increase the risk of cognitive decline,” said Dr. Foster. “Older age may also be associated with reduced capacity to metabolize drugs, increased sensitivity to the cognitive and neurological effects of drugs, less cognitive reserve, and increased likelihood of taking multiple medications, which, along with AEDs, may exert a cognitive effect.”
The current findings may reduce concerns about the effects of AEDs on cognitive function and encourage neurologists to pursue the proper dosing for optimal seizure control, wrote the authors. “However, it is possible that some individuals may be more susceptible than others to AED-related cognitive dysfunction,” said Dr. Foster. “We do not have a robust way to predict who these patients will be, and it is still good practice to make patients aware that some people experience adverse cognitive effects from AEDs. However, it needs to be emphasized that it is unlikely to be the sole reason for their cognitive impairment. Other issues, such as poor seizure control or unrecognized or undertreated mood disorders, are even more important factors for impaired cognition.”
Patients who report cognitive problems should be screened for mood disorders, Dr. Foster continued. “It would also be important to consider whether the patients’ cognitive complaints arise from subtle clinical or subclinical seizure activity and subsequent postictal periods. To investigate this [question] further, clinicians may arrange for prolonged EEG monitoring. This [monitoring] could be done in an ambulatory setting or during an inpatient admission.”
The study was conducted without external funding. Dr. Foster and other investigators reported research funding from professional associations and pharmaceutical companies that was unrelated to the study.
SOURCE: Foster E et al. Neurology. 2020 Feb 3. doi: 10.1212/WNL.0000000000009061.
according to research published online ahead of print Feb. 3 in Neurology. Optimizing AED therapy to reduce or prevent seizures is thus unlikely to affect cognition, according to the investigators.
Patients who take AEDs commonly report cognitive problems, but investigations into the cognitive effects of AEDs have yielded inconsistent results. “We were also interested in this association, as we often treat complex patients taking multiple or high-dose AEDs, and our patients often report cognitive dysfunction,” said Emma Foster, MBBS, an epilepsy fellow at Alfred Health and the Royal Melbourne Hospital in Victoria, Australia. “We were particularly interested to examine how much AEDs affect cognition relative to other factors. We commonly see patients in our tertiary epilepsy care unit who have had severe epilepsy for a long time or who have psychiatric disorders, and these factors may also contribute to cognitive dysfunction.”
Researchers analyzed patients admitted for video EEG monitoring
For their study, Dr. Foster and colleagues prospectively enrolled patients admitted to the Royal Melbourne Hospital’s video EEG monitoring unit between January 2009 and December 2016. Patients were included in the study if they were age 18 years or older, had been admitted for diagnostic or surgical evaluation, and had complete data for the relevant variables. Patients were prescribed AED monotherapy or polytherapy.
The researchers based epilepsy diagnoses on the 2014 International League Against Epilepsy criteria. Diagnoses of psychogenic nonepileptic seizures (PNES) were based on a consensus of epileptologists at weekly multidisciplinary clinical meetings, which was supported by evaluation of all available data. Some patients received a diagnosis of comorbid epilepsy and PNES. If data were insufficient to support a diagnosis of epilepsy or PNES, the admission was considered nondiagnostic.
All participants underwent neuropsychologic and neuropsychiatric screening. Researchers assessed patients’ objective, global cognitive function using the Neuropsychiatry Unit Cognitive Assessment Tool (NUCOG), a validated instrument. Patients responded to the Quality of Life in Epilepsy inventory (QOLIE-89) to provide a measure of subjective cognitive function. They also responded to the Hospital Anxiety and Depression Scale (HADS) to screen for mood disorders.
Dr. Foster and colleagues measured seizure frequency through patient self-report. Patients averaged their seizure frequency during the 12-month period before admission to the video EEG unit. They categorized it according to a 12-point system in which 0 denotes patients who are seizure-free and not taking AEDs and 12 denotes patients in status epilepticus. Patients with PNES used the same scale to report event frequency, although the system was not designed for this purpose.
Almost half of patients were prescribed polypharmacy
The researchers included 331 patients in their analysis. The population’s mean age was 39.3 years, and about 62% of patients were female. Approximately 47% of patients had epilepsy, 25.7% had PNES, 6.6% had comorbid epilepsy and PNES, and 20.5% had a nondiagnostic outcome. Among patients with epilepsy, most (54.5%) had temporal lobe epilepsy, followed by extratemporal focal epilepsy (32.1%) and generalized epilepsy (13.5%). The mean number of AEDs prescribed on admission was 1.6, and mean seizure or event frequency score was 7.2, which indicated 1-3 seizures per month. Mean HADS depression score was within the normal range (5.7), and mean HADS anxiety score was in the borderline range (8.2).
Approximately 45% of patients were prescribed AED polypharmacy on admission, 25.1% were prescribed AED monotherapy, and 29.9% were prescribed no AED. Levetiracetam, valproate, and carbamazepine were the most frequently prescribed AEDs. Most patients with epilepsy (73.1%) were on polypharmacy, compared with 17.6% of patients with PNES, 63.6% of patients with epilepsy and PNES, and 8.8% of nondiagnostic patients.
Older age and greater seizure frequency predicted impaired objective cognitive function. Comorbid epilepsy and PNES appeared to predict impaired objective cognitive function as well, but the data were inconclusive. No AED was a significant predictor of objective cognitive function. Higher depression and anxiety scores and greater seizure frequency predicted impaired subjective cognitive function. No AED predicted subjective cognitive function.
Future studies could address particular cognitive domains
Previous studies have suggested that treatment with topiramate predicts objective or subjective cognitive function, but Dr. Foster and colleagues did not observe this result. The current findings suggest that topiramate may have a less significant effect on cognition than the literature suggests, they wrote. In addition, more evidence is needed to fully understand the effects of clobazam, valproate, phenytoin, and gabapentin because the analysis was underpowered for these drugs.
Although NUCOG assesses global cognitive function reliably, its ability to measure particular cognitive subdomains is limited. “We aim to conduct future research investigating the complex associations between different cognitive functions, including processing speed, and specific AEDs in this heterogeneous population,” said Dr. Foster.
Despite the study’s large sample size, the researchers could not explore potential interactions between various predictor variables. “Epilepsy may interact with the aging process or with other medical conditions associated with aging, such as hypertension and diabetes, and this may increase the risk of cognitive decline,” said Dr. Foster. “Older age may also be associated with reduced capacity to metabolize drugs, increased sensitivity to the cognitive and neurological effects of drugs, less cognitive reserve, and increased likelihood of taking multiple medications, which, along with AEDs, may exert a cognitive effect.”
The current findings may reduce concerns about the effects of AEDs on cognitive function and encourage neurologists to pursue the proper dosing for optimal seizure control, wrote the authors. “However, it is possible that some individuals may be more susceptible than others to AED-related cognitive dysfunction,” said Dr. Foster. “We do not have a robust way to predict who these patients will be, and it is still good practice to make patients aware that some people experience adverse cognitive effects from AEDs. However, it needs to be emphasized that it is unlikely to be the sole reason for their cognitive impairment. Other issues, such as poor seizure control or unrecognized or undertreated mood disorders, are even more important factors for impaired cognition.”
Patients who report cognitive problems should be screened for mood disorders, Dr. Foster continued. “It would also be important to consider whether the patients’ cognitive complaints arise from subtle clinical or subclinical seizure activity and subsequent postictal periods. To investigate this [question] further, clinicians may arrange for prolonged EEG monitoring. This [monitoring] could be done in an ambulatory setting or during an inpatient admission.”
The study was conducted without external funding. Dr. Foster and other investigators reported research funding from professional associations and pharmaceutical companies that was unrelated to the study.
SOURCE: Foster E et al. Neurology. 2020 Feb 3. doi: 10.1212/WNL.0000000000009061.
FROM NEUROLOGY