**2. Sleep's role in memory**

Since, Hervey de Saint Denys published *Les Rêves et les Moyens de les Diriger* in 1867, was established that sleep benefits the retention of memory [17]*.* Rosa Heine was the first person, in 1914, who demonstrated that learning before a period of sleep results in a lower rate of forgetfulness in the following 24 hours than learning before a period of wakefulness. These results demonstrated the importance of sleep for memory. Likewise, Ellenbogen et al. showed that sleep after learning benefits the consolidation of memories and strengthens the traces of memory against future interference. Current research findings show an active sleep role in the consolidation of memory, learning and brain plasticity [18].

Sleep is defined as "a natural and reversible state of reduced response to external stimuli and relative inactivity, accompanied by decreased consciousness" [19]. Sleep has four basic states, rapid eye movement (REM), no REM sleep 1 (N1), NREM sleep 2 (N2) and NREM sleep 3 (N3). Slow wave sleep (SWS) is observed in N3. In humans, SWS predominates in the early stages of the sleep and REM in the final period, alternating in a cyclic manner. In terms of memory, forming and recovering memories is a fundamental ability to achieve adaptation. Memory functions involved different process such as encoding, consolidation and retrieval. During encoding, the stimulus results in the formation of a new memory fragment that is stabilized in consolidation process avoiding forgetting and incorporating the memory into preexisting knowledge complexes. Consolidation occurs during SWS and REM sleep stabilizes transformed memories [20, 21]. Also, it has been suggested the possibility that cholinergic tone during delayed REM sleep is necessary for the successful consolidation of memory [22, 23].

Theories that propose a differential role of the sleep stages in memory are based on the "dual process hypothesis." In this dual hypothesis, SWS has a benefit in the declarative memories of events, such as learning word lists, word pairs or spatial locations, and processing dependent on the hippocampus [24], while REM sleep, benefits the consolidation of non-declarative memories (related to procedural memory, including mirror tracing, priming, implicit memory, and the emotional modulation of memories). A complex learning task can often involve both procedural and declarative learning components (complex motor movements, language learning). Emotive and sensitive events are better evoked than neutral ones, due to stimuli of the amygdala in the process of coding in the hippocampus. Changes registered in REM sleep for patients with mood disorders and lived dreams, clarify the link between REM sleep and the increase in amygdala activity. This activity has been related with the emotive and sensitive recycling during this stage of sleep. REM sleep seems also to be related with strength and weakened of emotional memory [25]. Findings from electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) show activity in brain regions (hippocampal) correlated with REM and SWS sleep, following both declarative and procedural learning. Although other theories hypothesized that memory consolidation occurs during different sleep states [26], neural processes of memory consolidation have been

**145**

and blood-brain barrier [41].

*Cognitive Impairment and Obstructive Sleep Apnea DOI: http://dx.doi.org/10.5772/intechopen.82756*

disorders in neurocognitive impairment.

with Parkinson [23].

observed during sleep and wakefulness [27]. Additional findings show that sleep enhances memory performance in brain-damaged individuals, except in patients

The effect of sleep on memory is lasting and adaptive. Coding and initial recovery depends on the integrity of the hippocampus. The beneficial effect of sleep is linked to the interaction between slow oscillatory activity during SWS, thalamocortical sleep spindles and spontaneous reactivations of hippocampal memory [28]. In humans, slow wave sleep is correlated with hippocampus-dependent memory and REM sleep is associated with emotional memory. Currently, it is considered that an active consolidation of memory is established specifically during sleep and originates from the reactivation of newly coded memory representations that are integrated into the long-term knowledge networks. Findings from fMRI suggest that the process of consolidation in declarative memory is gradual. Then, the early activity after learning is observed in hippocampal locations, and after reinforced during sleep, long-lasting changes of memories are observed in medial prefrontal cortical activity. REM and NREM sleep are important for preservation, integration, and recollection of episodic memory [29]. In summary, sleep enhances learning of skills, semantic, episodic and emotional memories and stimulates creativity.

Some factors such as age, psychiatric and neurodegenerative conditions, sleep disruption and sleep apnea impair episodic memory [30, 31]. In patients with OSA cognitive processing, memory, vigilance, divided attention and executive functioning are affected. These deficits are observed identifying decreased ability to digest information, decreased ability to register, store, retain, and retrieve information, inability to maintain attention over the time, inability to respond to more than one task or stimuli, disorganization, emotional liability, impulsivity and difficulty maintaining motivation [32]. Beyond physiologic functions, the role of sleep in brain plasticity and memory consolidation processes is relevant, but the mechanisms involved in these processes remain to be fully understood. Therefore, it is necessary to perform future investigations to elucidate the pathophysiology of sleep

**3. Physiopathology of cognitive impairment in obstructive sleep apnea**

Neurocognitive impairment has over the years been associated with OSA but the prevalence of neurocognitive impairment in patients with OSA is not known [12]. One in four patients with OSA has neurophysiological impairment [33]. OSA patients are 7.5 to 20 times more likely to have difficulties with concentration, learning new tasks and execution monotonous tasks [34]. While current test for cognition not specifically assess impairments in OSA [35], some studies suggest that in the association between OSA and cognitive dysfunction, multitude of susceptibility and protective factors have been including, but others important factors should be considered. Susceptibility factors associated with neurocognitive impairment include: increased nocturnal awakenings, latency to REM sleep, [36, 37] changes in cerebral blood flow, neurovascular and neurotransmitter changes, intermittent hypoxemia, neuroinflammation, oxidative stress, ischemic precondition, hypercapnia [38, 39] and neural regulation in OSA [40]. Nevertheless, it is necessary to investigate the role of other factors such as genetic susceptibility, duration of OSA, hypertension, metabolic dysfunction, systemic inflammation, cerebral blood flow

Excessive daytime somnolence exhibit in patients with OSA increase the risk of cognitive decline and dementia. Sleep deprivation impair neuronal excitability, decrease myelination, produce cellular oxidative stress, misfolding of cellular

*Updates in Sleep Neurology and Obstructive Sleep Apnea*

tion of memory, learning and brain plasticity [18].

for the successful consolidation of memory [22, 23].

**2. Sleep's role in memory**

language do not seem compromised, [12] whereas others demonstrated to psychomotor function is affected by OSA and this domain does not improve with CPAP therapy [13]. Although the cognitive impairment in individuals with OSA is largely recognized as mild cognitive impairment, [14] OSA has also recognized as modifiable risk for dementia, neuropsychiatric disorders and stroke [15, 16]. However, the pathophysiology of cognitive impairment in adults with OSA is complex and the whole mechanisms involved in cognitive deficit have not been clarified yet.

Since, Hervey de Saint Denys published *Les Rêves et les Moyens de les Diriger* in 1867, was established that sleep benefits the retention of memory [17]*.* Rosa Heine was the first person, in 1914, who demonstrated that learning before a period of sleep results in a lower rate of forgetfulness in the following 24 hours than learning before a period of wakefulness. These results demonstrated the importance of sleep for memory. Likewise, Ellenbogen et al. showed that sleep after learning benefits the consolidation of memories and strengthens the traces of memory against future interference. Current research findings show an active sleep role in the consolida-

Sleep is defined as "a natural and reversible state of reduced response to external

Theories that propose a differential role of the sleep stages in memory are based on the "dual process hypothesis." In this dual hypothesis, SWS has a benefit in the declarative memories of events, such as learning word lists, word pairs or spatial locations, and processing dependent on the hippocampus [24], while REM sleep, benefits the consolidation of non-declarative memories (related to procedural memory, including mirror tracing, priming, implicit memory, and the emotional modulation of memories). A complex learning task can often involve both procedural and declarative learning components (complex motor movements, language learning). Emotive and sensitive events are better evoked than neutral ones, due to stimuli of the amygdala in the process of coding in the hippocampus. Changes registered in REM sleep for patients with mood disorders and lived dreams, clarify the link between REM sleep and the increase in amygdala activity. This activity has been related with the emotive and sensitive recycling during this stage of sleep. REM sleep seems also to be related with strength and weakened of emotional memory [25]. Findings from electroencephalogram (EEG) and functional magnetic resonance imaging (fMRI) show activity in brain regions (hippocampal) correlated with REM and SWS sleep, following both declarative and procedural learning. Although other theories hypothesized that memory consolidation occurs during different sleep states [26], neural processes of memory consolidation have been

stimuli and relative inactivity, accompanied by decreased consciousness" [19]. Sleep has four basic states, rapid eye movement (REM), no REM sleep 1 (N1), NREM sleep 2 (N2) and NREM sleep 3 (N3). Slow wave sleep (SWS) is observed in N3. In humans, SWS predominates in the early stages of the sleep and REM in the final period, alternating in a cyclic manner. In terms of memory, forming and recovering memories is a fundamental ability to achieve adaptation. Memory functions involved different process such as encoding, consolidation and retrieval. During encoding, the stimulus results in the formation of a new memory fragment that is stabilized in consolidation process avoiding forgetting and incorporating the memory into preexisting knowledge complexes. Consolidation occurs during SWS and REM sleep stabilizes transformed memories [20, 21]. Also, it has been suggested the possibility that cholinergic tone during delayed REM sleep is necessary

**144**

observed during sleep and wakefulness [27]. Additional findings show that sleep enhances memory performance in brain-damaged individuals, except in patients with Parkinson [23].

The effect of sleep on memory is lasting and adaptive. Coding and initial recovery depends on the integrity of the hippocampus. The beneficial effect of sleep is linked to the interaction between slow oscillatory activity during SWS, thalamocortical sleep spindles and spontaneous reactivations of hippocampal memory [28]. In humans, slow wave sleep is correlated with hippocampus-dependent memory and REM sleep is associated with emotional memory. Currently, it is considered that an active consolidation of memory is established specifically during sleep and originates from the reactivation of newly coded memory representations that are integrated into the long-term knowledge networks. Findings from fMRI suggest that the process of consolidation in declarative memory is gradual. Then, the early activity after learning is observed in hippocampal locations, and after reinforced during sleep, long-lasting changes of memories are observed in medial prefrontal cortical activity. REM and NREM sleep are important for preservation, integration, and recollection of episodic memory [29]. In summary, sleep enhances learning of skills, semantic, episodic and emotional memories and stimulates creativity.

Some factors such as age, psychiatric and neurodegenerative conditions, sleep disruption and sleep apnea impair episodic memory [30, 31]. In patients with OSA cognitive processing, memory, vigilance, divided attention and executive functioning are affected. These deficits are observed identifying decreased ability to digest information, decreased ability to register, store, retain, and retrieve information, inability to maintain attention over the time, inability to respond to more than one task or stimuli, disorganization, emotional liability, impulsivity and difficulty maintaining motivation [32]. Beyond physiologic functions, the role of sleep in brain plasticity and memory consolidation processes is relevant, but the mechanisms involved in these processes remain to be fully understood. Therefore, it is necessary to perform future investigations to elucidate the pathophysiology of sleep disorders in neurocognitive impairment.
