Orla P. Hornung

The relationship between REM sleep and memory consolidation in old age and effects of cholinergic medication

BACKGROUND Recent findings in young adults suggest that rapid eye movement (REM) sleep plays a role in procedural memory consolidation. The significance of REM sleep for memory consolidation in old age has not yet been investigated. METHODS Effects of REM sleep manipulation on declarative and procedural memory consolidation were investigated in 107 healthy older adults, ages 60-82 years. Rapid eye movement sleep deprivation was achieved by REM sleep awakenings and compared with non-REM sleep awakenings. Rapid eye movement sleep augmentation was realized physiologically by REM sleep rebound and pharmacologically by administering an acetylcholinesterase inhibitor in a double-blind, placebo-controlled design. Memory performance was tested by a paired associate list and a mirror tracing task at 9:30 pm and 7:30 am with sleep intervening between 11:00 pm and 7:00 am. RESULTS Although REM sleep deprivation led to a significant reduction in total and phasic REM sleep, memory consolidation remained unaffected. Both REM sleep augmentation groups showed a significant increase in phasic REM sleep, whereas only pharmacological cholinergic REM sleep manipulation exerted a significant positive effect on procedural memory consolidation. CONCLUSIONS Because only after cholinergic stimulation of phasic REM sleep procedural memory consolidation is improved, cholinergic activation seems to be a crucial component of REM sleep-related memory consolidation in old age.

Age-related changes in sleep and memory : Commonalities and interrelationships

Aging is accompanied by changes on many different levels, including sleep and memory processes. In light of recent findings, which underline the importance of sleep for memory consolidation in young adults, the relationship between sleep and memory in older adults is of particular interest. This review takes a closer look at commonalities and interrelationships of the two aging trajectories in sleep and memory. A link between these two research domains on aging will be proposed and discussed on the basis of recent findings within the cognitive neuroscience of sleep.

Gene-environment interactions and intermediate phenotypes: early trauma and depression

This review focuses on current research developments in the study of gene by early life stress (ELS) interactions and depression. ELS refers to aversive experiences during childhood and adolescence such as sexual, physical or emotional abuse, emotional or physical neglect as well as parental loss. Previous research has focused on investigating and characterizing the specific role of ELS within the pathogenesis of depression and linking these findings to neurobiological changes of the brain, especially the stress response system. The latest findings highlight the role of genetic factors that increase vulnerability or, likewise, promote resilience to depression after childhood trauma. Considering intermediate phenotypes has further increased our understanding of the complex relationship between early trauma and depression. Recent findings with regard to epigenetic changes resulting from adverse environmental events during childhood promote current endeavors to identify specific target areas for prevention and treatment schemes regarding the long-term impact of ELS. Taken together, the latest research findings have underscored the essential role of genotypes and epigenetic processes within the development of depression after childhood trauma, thereby building the basis for future research and clinical interventions.

Manipulating REM sleep in older adults by selective REM sleep deprivation and physiological as well as pharmacological REM sleep augmentation methods.

Experimental approaches to manipulate REM sleep within the cognitive neuroscience of sleep are usually based on sleep deprivation paradigms and focus on younger adults. In the present study, a traditional selective REM sleep deprivation paradigm as well as two alternative manipulation paradigms targeting REM sleep augmentation were investigated in healthy older adults. The study sample consisted of 107 participants, male and female, between the ages of 60 and 82 years, who had been randomly assigned to five experimental groups. During the study night, a first group was deprived of REM sleep by selective REM sleep awakenings, while a second group was woken during stage 2 NREM sleep in matched frequency. Physiological REM sleep augmentation was realized by REM sleep rebound after selective REM sleep deprivation, pharmacological REM sleep augmentation by administering an acetylcholinesterase inhibitor in a double-blind, placebo-controlled design. Deprivation and augmentation paradigms manipulated REM sleep significantly, the former affecting more global measures such as REM sleep minutes and percentage, the latter more organizational aspects such as stage shifts to REM sleep, REM latency, REM density (only pharmacological augmentation) and phasic REM sleep duration. According to our findings, selective REM sleep deprivation seems to be an efficient method of REM sleep manipulation in healthy older adults. While physiological rebound-based and pharmacological cholinergic REM sleep augmentation methods both failed to affect global measures of REM sleep, their efficiency in manipulating organizational aspects of REM sleep extends the traditional scope of REM sleep manipulation methods within the cognitive neuroscience of sleep.

The Effects of Donepezil on Postlearning Sleep EEG of Healthy Older Adults

INTRODUCTION Aging is associated with cholinergic hypofunction and memory decline. Cholinergic activity also plays a crucial role in sleep-dependent memory consolidation. The acetylcholinesterase inhibitor (AChE-I) donepezil has been found to increase sleep-related procedural memory consolidation in healthy older adults in a previous study. METHODS Data of the former study were reanalyzed with regard to the effects of donepezil on the sleep EEG of healthy older adults. This analysis was conducted with a special focus on spectral parameters of sleep, which have previously been linked to plasticity-related processes during sleep, i.e., sigma and delta activity. Forty-two participants (aged: 60-77 years) received 5 mg of the AChE-I donepezil orally 30 min before bedtime in a placebo-controlled, double-blind design. Power values for EEG delta, theta, alpha1, alpha 2, sigma, beta and gamma frequency bands were calculated for stage 2 NREM sleep, SWS and REM sleep. RESULTS In line with our hypotheses, the AChE-I donepezil led to an increase in sigma activity during stage 2 NREM sleep and delta activity during slow wave sleep. CONCLUSION These results suggest that an AChE-I facilitates processes of sleep-dependent memory consolidation in older adults.

Sleep‐related memory consolidation in depression: an emerging field of research

Sleep‐related memory consolidation has received increasing attention in recent years. Because previous research has focused on healthy young adults, only very few studies have been conducted in patients with psychiatric disorders so far. The investigation of sleep‐related memory consolidation in depression offers a wide range of future research opportunities and can therefore be regarded as an emerging field of research. This article gives a short overview of current knowledge of sleep‐related memory consolidation in healthy young adults and builds a bridge to psychiatry and depression, where further research is urgently needed. Depression and Anxiety, 2008.