Study Objectives: Emerging evidence suggests a role for sleep in contributing to the progression of Alzheimer disease (AD). Slow wave sleep (SWS) is the stage during which synaptic activity is minimal and clearance of neuronal metabolites is high, making it an ideal state to regulate levels of amyloid beta (Aβ). We thus aimed to examine relationships between concentrations of Aβ42 in the cerebrospinal fluid (CSF) and measures of SWS in cognitively normal elderly subjects. Methods: Thirty-six subjects underwent a clinical and cognitive assessment, a structural MRI, a morning to early afternoon lumbar puncture, and nocturnal polysomnography. Correlations and linear regression analyses were used to assess for associations between CSF Aβ42 levels and measures of SWS controlling for potential confounders. Resulting models were compared to each other using ordinary least squared linear regression analysis. Additionally, the participant sample was dichotomized into "high" and "low" Aβ42 groups to compare SWS bout length using survival analyses. Results: A significant inverse correlation was found between CSF Aβ42 levels, SWS duration and other SWS characteristics. Collectively, total SWA in the frontal lead was the best predictor of reduced CSF Aβ42 levels when controlling for age and ApoE status. Total sleep time, time spent in NREM1, NREM2, or REM sleep were not correlated with CSF Aβ42. Conclusions: In cognitively normal elderly, reduced and fragmented SWS is associated with increases in CSF Aβ42, suggesting that disturbed sleep might drive an increase in soluble brain Aβ levels prior to amyloid deposition.

The consolidation of spatial navigational memory during sleep is supported by electrophysiological and behavioral evidence. The features of sleep that mediate this ability may change with aging, as percentage of slow wave sleep is canonically thought to decrease with age, and slow waves are thought to help orchestrate hippocampal-neocortical dialogue that supports systems level consolidation. In this study, groups of younger and older subjects performed timed trials before and after polysomnographically recorded sleep on a 3D spatial maze navigational task. Although younger subjects performed better than older subjects at baseline, both groups showed similar improvement across pre-sleep trials. However, younger subjects experienced significant improvement in maze performance during sleep that was not observed in older subjects, without differences in morning psychomotor vigilance between groups. Older subjects had sleep quality marked by decreased amount of slow wave sleep and increased fragmentation of slow wave sleep, resulting in decreased slow wave activity. Across all subjects, frontal slow wave activity was positively correlated with both overnight change in maze performance and medial prefrontal cortical volume, illuminating a potential neuroanatomical substrate for slow wave activity changes with aging and underscoring the importance of slow wave activity in sleep-dependent spatial navigational memory consolidation.

Physiological and/or pathological implications of the dynamics of sleep stage transitions have not, to date, been investigated. We report detailed duration and transition statistics between sleep stages in healthy subjects and in others with chronic fatigue syndrome (CFS); in addition, we also compare our data with previously published results for rats. Twenty-two healthy females and 22 female patients with CFS, characterized by complaints of unrefreshing sleep, underwent one night of polysomnographic recording. We find that duration of deep sleep (stages III and IV) follows a power-law probability distribution function; in contrast, stage II sleep durations follow a stretched exponential and stage I, and REM sleep durations follow an exponential function. These stage duration distributions show a gradually increasing departure from the exponential form with increasing depth of sleep toward a power-law type distribution for deep sleep, suggesting increasing complexity of regulation of deeper sleep stages. We also find a substantial number of REM to non-REM sleep transitions in humans, while this transition is reported to be virtually nonexistent in rats. The relative frequency of this REM to non-REM sleep transition is significantly lower in CFS patients than in controls, resulting in a significantly greater relative transition frequency of moving from both REM and stage I sleep to awake. Such an alteration in the transition pattern suggests that the normal continuation of sleep in light or REM sleep is disrupted in CFS. We conclude that dynamic transition analysis of sleep stages is useful for elucidating yet-to-be-determined human sleep regulation mechanisms with pathophysiological implications.

Hippocampal electrophysiology and behavioral evidence support a role for sleep in spatial navigational memory, but the role of particular sleep stages is less clear. Although rodent models suggest the importance of rapid eye movement (REM) sleep in spatial navigational memory, a similar role for REM sleep has never been examined in humans. We recruited subjects with severe obstructive sleep apnea (OSA) who were well treated and adherent with continuous positive airway pressure (CPAP). Restricting CPAP withdrawal to REM through real-time monitoring of the polysomnogram provides a novel way of addressing the role of REM sleep in spatial navigational memory with a physiologically relevant stimulus. Individuals spent two different nights in the laboratory, during which subjects performed timed trials before and after sleep on one of two unique 3D spatial mazes. One night of sleep was normally consolidated with use of therapeutic CPAP throughout, whereas on the other night, CPAP was reduced only in REM sleep, allowing REM OSA to recur. REM disruption via this method caused REM sleep reduction and significantly fragmented any remaining REM sleep without affecting total sleep time, sleep efficiency, or slow-wave sleep. We observed improvements in maze performance after a night of normal sleep that were significantly attenuated after a night of REM disruption without changes in psychomotor vigilance. Furthermore, the improvement in maze completion time significantly positively correlated with the mean REM run duration across both sleep conditions. In conclusion, we demonstrate a novel role for REM sleep in human memory formation and highlight a significant cognitive consequence of OSA.

These results suggest that the mechanism governing NREM sleep stage transitions (from light to deep sleep) plays an important role in determining ultradian REM sleep rhythms.

These results suggest that CFS and FM may be different illnesses associated with different problems of sleep regulation.

These results suggest that dynamic sleep stage transitions constitute the basis of the formation of the ultradian rhythm of sleep; however, further elaboration of the model would be required to reduce the variability in rhythmicity.

Study Objectives We hypothesized that sleep stage dynamics are different in patients with sleep bruxism (SB) and that these changes are associated with the occurrence of rhythmic masticatory muscle activity (RMMA). Methods Fifteen healthy controls and 15 patients with SB underwent overnight polysomnography. Sleep variables and survival curves of continuous runs of each sleep stage were compared between the groups. Stage transition dynamics and the probability of stage fragmentation were analyzed for three epochs before and after the epoch with RMMA. Survival curves of continuous runs of each sleep stage, terminated with or without RMMA, were also compared. Results There were no significant differences in sleep variables between the groups, except for shorter sleep latency, shorter rapid eye movement (REM) latency, and longer total N1 duration in SB patients than in controls. REM sleep and N2 were significantly less continuous in SB patients than in controls. In the SB group, stage fragmentation probability was significantly increased for the epoch with RMMA compared with the baseline for all stages. Meanwhile, the occurrence of RMMA did not affect the continuity of N2 or REM; however, the occurrence of RMMA was preceded by more continuous N3 runs. Conclusions Sleep stage dynamics differed between SB patients and controls. RMMA does not result in sleep disruption but is likely associated with dissipation of sleep pressure. Less continuity of REM sleep in SB may provide insights into the underlying pathophysiological mechanisms of SB, which may be related to REM sleep processes such as cortical desynchronized states or brainstem activation.