The Effect of Two Benzodiazepine Receptor Agonist Hypnotics on Sleep-Dependent Memory Consolidation

Abstract

Results: ANOVA revealed a signifi cant condition effect for the WPT (p = 0.025) and a trend for the FTT (p = 0.067), which was signifi cant when sex was added to the model (p = 0.014). Improvement in memory performance following sleep was lower with bedtime dosing of zolpidem-ER compared to placebo and middle-of-the-night dosing of zaleplon. There were no differences between placebo and zaleplon. Conclusions:The results suggest that in some circumstances hypnotics may have the potential to reduce the degree of sleep-dependent memory consolidation and that drug-free sleep early in the night may ameliorate this effect. S C I E N T I F I C I N V E S T I G A T I O N SA growing body of evidence demonstrates that sleep promotes memory consolidation in healthy individuals.1-3 Numerous studies using various designs and memory tasks have consistently found that memory consolidation (i.e., improvement on a given memory task from initial training/test to retest) is significantly greater after a period of sleep than a period of wake. This is commonly referred to as sleep-dependent memory consolidation (SDMC). 4 For example, improvements on a procedural memory fi nger-tapping task were observed after a night of sleep but not after 4-, 8-, or 12-hour daytime periods without sleep. 5,6 Studies examining declarative memory consolidation, such as with a word pair association task, also demonstrate improvements in performance after sleep.7 In addition to improvements in memory following overnight sleep, memory consolidation is also enhanced during naps as short as 45 minutes. Improvements in procedural 8,9 and declarative 10 memory occur with naps, but not following similar durations of wakefulness. These fi ndings suggest that memory consolidation that occurs during wakefulness is enhanced during sleep.Synaptic plasticity, which refers to structural or functional neural changes in response to stimuli, 2 is thought to be the cellular substrate underlying the processes of memory formation and consolidation.11 Sleep has been found to enhance plasticity in animals, 12 which is consistent with the idea that sleep enhances memory consolidation. In humans, fMRI studies have shown that sleep-dependent learning of a motor skill task is accompanied by changes in multiple brain areas, BRIEF SUMMARYCurrent Knowledge/Study Rationale: Few studies have investigated the impact of hypnotic medication on sleep-dependent memory consolidation. This study compared the effect of differing time of exposure to two hypnotics on the sleep-dependent consolidation of declarative and non-declarative memory. Study Impact: This study contributes to the research surrounding sleep-dependent memory and hypnotics, indicating that hypnotic exposure during most of the night may reduce sleep-dependent memory consolidation; whereas hypnotic exposure only during the second half of the night appears to have no effect.

Sleep and Human Aging

“…Pharmacological methods using classic GABA-targeting hypnotics for selective NREM sleep enhancement have so far proved less promising in the context of aging and often fail to trigger any corresponding sleep-dependent memory benefit in the elderly, sometimes even causing amnestic effects (Feld et al, 2013; Hall-Porter et al, 2014; Mednick et al, 2013; Vienne et al, 2012). Little is currently known regarding the impact of more contemporary non-GABA-targeting sleep medications on enhancing sleep and/or cognition in the elderly populations at risk for dementia.…”

Sleep: A Novel Mechanistic Pathway, Biomarker, and Treatment Target in the Pathology of Alzheimer's Disease?

“…Although multiple GABA-targeting hypnotic and anti-convulsive drugs that increase NREM SWA in a dose-dependent manner exist 76–79 , they often fail to trigger any corresponding sleep-dependent memory benefit in the elderly, and many even have amnestic effects 77, 78, 80, 81 . Moreover, such medications have actually been associated with an increased rather than lowering of dementia risk 82 .…”

Sleep, Cognition, and Normal Aging

“…Antidepressants have been associated with REM suppression and their (lack of) impact on cognitive function was the subject of much debate a decade ago (Vertes, 2004; Walker & Stickgold, 2004; for a potential resolution, see Dresler, Kluge, Genzel, Schussler, & Steiger, 2010, and Goerke, Cohrs, Rodenbeck, & Kunz, 2014). Furthermore, there is a paradox that sleep hypnotics might improve memory consolidation (e.g., Mednick et al, 2013; but see Hall-Porter, Schweitzer, Eisenstein, Ahmed, & Walsh, 2013), while also causing anterograde amnesia or psychomotor slowing in young adults. Though clearly a complex and controversial area (Vermeeren & Coenen, 2011), we can currently ask whether common sleep medications demonstrate any benefits to memory consolidation or cognitive performance in older adults after the hypnotic effect of the medication has presumably dissipated.…”