NASHVILLE, TENN. – Targeting relevant sleep problems for patients with refractory temporal lobe epilepsy (TLE) improves cognition, results of a new, double-blind, randomized controlled trial suggest.
Study findings show significant improvement in REM sleep and language scores for patients with TLE who took the cholinesterase inhibitor donepezil and better slow-wave sleep and memory scores for those who took the sleep aid zolpidem.
, study investigator Garima Shukla, MBBS, MD, DM, professor, division of neurology, department of medicine, Queens University, Kingston, Ont., told this news organization.
Daytime sleepiness could be a red flag in these patients, although it could mean they just have treatable sleep apnea, said Dr. Shukla. “But if they have very poor slow-wave sleep, we could try increasing its percentage by prescribing zolpidem.”
The findings were presented at the annual meeting of the American Epilepsy Society.
Sleep, cognitive disturbances common
Sleep disturbances and cognitive disturbances are common among patients with TLE. Executive function is affected in almost all patients with refractory epilepsy, and it’s “super common” that TLE patients have memory disturbances, said Dr. Shukla.
The study included 108 patients with refractory TLE who were awaiting surgery. The patients, who had no severe comorbidities, were randomly assigned to three groups; the final number in each group was 36.
Patients in group 1 received donepezil 10 mg in the morning and a placebo at night. (Donepezil is used to treat memory loss associated with Alzheimer’s disease.)
Those in group 2 received a placebo in the morning and zolpidem 6.25 mg at night. Group 3 patients received a placebo in the morning and again at night.
The mean age of the patients was 25.4, 27.1, and 27.6 years, and the percentage of men was 63.8%, 72.2%, and 63.8% in groups 1, 2, and 3, respectively.
In all groups, patients had been experiencing about three seizures per month. The median number of antiseizure medications was two in group 1 and three in both groups 2 and 3.
Researchers evaluated sleep using the Pittsburgh Sleep Quality Index, the Epsworth Sleepiness Scale, and video polysomnography and electroencephalography.
To assess executive function, they used the Trail A & B, Stroop, and forward and backward Digit Span tests. For memory, they used the Weschler Memory Scale, and for language, the Western Aphasia Battery. They conducted follow-up evaluations at 6 months.
The results showed significant improvement in the percentage of rapid eye movement (REM) sleep in group 1 (from 14.81 at baseline to 18.21 at 6 months). In this group, the number of patients whose REM sleep percentage was less than 15 dropped significantly from 29 (of 36) to 10.
In group 2, sleep-onset latency significantly improved, and the percentage of N3 (slow-wave) sleep stage increased significantly from 25.27 to 28.74.
Regarding cognitive outcomes, backward Digit Span was significantly improved for patients in group 1. In this group, there was also a significant reduction in the time taken for Stroop A test, and there was significant improvement in language.
In group 2, there was a significant improvement in verbal and visual memory scores. There were no significant changes in group 3.
The increase in REM sleep percentage in group 1 strongly correlated with increased language and executive function scores. Similarly, in group 2, the increase in N3 sleep percentage strongly correlated with an increase in verbal memory scores.
On the basis of these observations, giving a small dose of zolpidem to a patient with “acceptable” REM sleep but very little slow-wave sleep may boost the patient’s non-REM sleep, said Dr. Shukla. “By improving non-REM sleep percentage, we will possibly help memory consolidation.”
Dr. Shukla sees this study as “a stepping-stone” to larger, multicenter trials testing “the effect of zolpidem through its impact on improving non-REM sleep percentage consolidation and its impact on memory.”
This idea veers somewhat from the traditional idea that REM sleep plays a greater role in memory consolidation, she said. “We actually found it correlates very well with language, which we have also seen in some of our anecdotal case reports.”
Patients whose language scores are very poor are “the population I would pick to target REM sleep through donepezil,” said Dr. Shukla.