Rauchs and Schabus et al . 1 Is there a link between sleep changes and memory in Alzheimer ’ s disease ? Running title : Spindles and memory in Alzheimer ’ s disease

Aging and Alzheimer’s disease (AD) are both characterized by memory impairments and sleep changes. We investigated the potential link between these disturbances, focusing on sleep spindles, involved in memory consolidation. Two episodic memory tasks were given to young and old healthy subjects, as well as to AD patients. Post-learning sleep was recorded. Sleep spindles were globally reduced in aging and AD. AD patients also exhibited a further decrease in fast spindles. Besides, mean intensity of fast spindles was positively correlated, in AD patients, with immediate recall performance. Our results are the first report of a specific decrease in fast spindles in AD, associated with learning abilities. They also give further hints for a functional differentiation between slow and fast spindles. Key-words: slow spindles; fast spindles; aging; cognitive abilities; stage 2 sleep. in se rm -0 04 94 11 9, v er si on 1 22 J un 2 01 0 Rauchs and Schabus et al. 3 Introduction The formation of long-term memories requires a process of consolidation, which is facilitated by sleep. In the case of hippocampus-dependent declarative memories, this process appears to benefit mainly from slow-wave sleep (SWS) [1]. Recently, the focus has also been put on stage 2 sleep and more precisely on sleep spindles. Several studies have reported an increase in spindle density after verbal learning [2,3], a link between spindle activity and overnight change in declarative memory performance [4], or more general and trait-like relationships between spindle activity and measures of learning [2] or cognitive abilities [5]. Aging and Alzheimer’s disease (AD) are characterized by episodic memory impairment and changes in global sleep architecture [6]. Although modifications in the amount of sleep stages and decreases in sleep spindles are now well documented in both cases, the potential aftermaths of such changes on memory consolidation have received little attention. Mazzoni et al. [7] investigated the importance of sleep structure in aged adults and found the duration of sleep cycles, but not the amount of NREM, SWS or REM sleep, to be positively associated with morning recall performance on a declarative memory task. Backhaus et al. [8] provided evidence of a decline in sleep-dependent declarative memory consolidation in aging, associated with a decrease in SWS. Nevertheless, to the best of our knowledge, no study directly addressed this question in AD. This study aimed at investigating, in aging and AD, the potential link between episodic memory impairment and sleep changes, especially sleep spindles, in subjects free of any cholinergic medication. As recent data indicate that fast spindles may be preferentially involved in cognitive re-processing [5,9], we also investigated the potential differential effect of slow and fast spindles on memory consolidation. in se rm -0 04 94 11 9, v er si on 1 22 J un 2 01 0 Rauchs and Schabus et al. 4