Sleep and Memory Consilidation in Alzheimer Disease

Alzheimer’s disease (AD), followed by vascular dementia, is the most common cause of dementia in the world, including in Taiwan. Although the real etiology of AD is still obscure, AD usually begins with memory impairment, then dysfunction in performing daily activities, such as dealing with financial affairs and self-care. In addition to cognitive impairment, AD patients usually present many behavioral psychological syndromes of dementia (BPSD), such as sleep disorders. Sleep disorders and sun-downing phenomenon, in terms of confusion in the night, have been found in transgenic AD animals. Sleep disorders, including insomnia, hypersomnia and parasomnia, such as rapid eye movement (REM) sleep behavior disorder (RBD), are commonly found in patients with neurodegenerative disorders, include AD. In our previous studies, the sleep efficiency of patients with cognitive impairment is significantly reduced. The diminishment of muscle tone, in terms of atonia, during rapid eye movement (REM) sleep, in which acetylcholine is involved, also reduced in these patients. The impacts of sleep appear in the behaviors by alternating endocrine, neuro-transmitters and intracellular molecular events. REM sleep is well known to accompany many physiological changes such as decrease of muscle tone, increase of brain activities and irregular cardiopulmonary functioning. Sleep is also important for maintaining neuro-cognitive functions, which including memory consolidation. In one of our studies, we found sleep could enhance memory consolidation and there are different memory consolidation profiles between Parkinson’s disease (PD) and non-PD controls. These sleep-related changes would also be associated with dramatic changes of the micro-environment of the brain, including gene-expression patterns and activities of neurotransmitters. Some studies supported slow wave sleep (SWS) with slow oscillations, spindles and ripples, reflecting minimum cholinergic activity, coordinate the re-activation and redistribution of hippocampus-dependent memories to neocortical sites. REM sleep, at high cholinergic and theta activity, increases in plasticity-related immediate-early gene activity and might favor the subsequent synaptic consolidation of memories in the cortex. However, the classical classification of sleep stages might be too crude for an adequate reflection of the complexity of sleep-associated processes contributing to memory consolidation. What specific sleep stages and what molecules are responsible to specific memory components still need fine grained analysis and investigation. In this proposal, including both human and animal studies, aims to clarify the memory consolidation after sleep in Alzheimer’s disease (AD), which contains persistent minimum cholinergic activity. And, it aims to explore the key molecules or biomarkers, which are involved in the memory consolidation after sleep. We will collect the real-time bio-samples precisely based on the sleep staging by use of polysomnography in human and animals. After experiments of proteomics and micro-array for studying these bio-samples, we could find few important molecules or biomarkers related to memory consolidation after sleep in AD. The results should be important for further clinical application to improve patients’ sleep and memory.