Clinical reviewSleep and Alzheimer's disease
Introduction
Changes in sleep are part of the normal aging process, with increasing sleep fragmentation, nighttime awakenings and greater tendency for daytime sleep. Dementia causes further degeneration of sleep patterns [1]. While there are various types of dementia, Alzheimer's disease (AD) is the most common form. The prevalence of AD is rapidly increasing and will probably further rise dramatically within the next decades as growing numbers of people are living older.
Although progressive deterioration of memory, language, and intellect are the classic hallmarks of AD, sleep disturbance is a common and often highly disruptive behavioral symptom associated with AD. Epidemiological studies have reported that up to 45% of patients with AD have sleep disturbances [2], ∗[3]. These neurobehavioral symptoms may appear at an early stage of the AD process but seem to be usually correlated to a more severe cognitive decline ∗[3], ∗[4]. Sleep disturbances can be as stressful for patients and caregivers as the dementia itself and are a major risk factor for early institutionalization [5], [6].
The origin of sleep disturbances in AD is thought to be multi-factorial. Degeneration of neural pathways that regulate sleep–wake patterns and sleep architecture as well as somatic or psychiatric co-morbidities may contribute to sleep alterations ∗[3], [7]. In return, sleep disorders may exacerbate cognitive symptoms through impairment of sleep-dependent memory consolidation processes [8], [9]. Recently, a link between sleep characteristics and cognitive decline in the elderly has been suggested, emphasizing the fact that sleep and cognition are closely related [10], [11], ∗[12].
This article will review sleep changes with normal aging and AD, common pathologies of sleep and their relation with AD, and the influence of AD treatment on sleep. The consequences of sleep disturbances in AD and their management will be discussed thereafter. Finally, recommendations as to areas in which future research is needed will be proposed.
Section snippets
Age-related changes in sleep
There are age-related, normal changes that occur in sleep architecture and sleep patterns. Decrease in sleep quality during the aging process is well documented. The frequent complaints of “poor sleep” in elderly include increased sleep latency, difficulty with sleep maintenance, frequent nighttime and early morning awakenings [13]. Objective modifications of sleep architecture on polysomnographic studies are represented by a reduction of total sleep time and sleep efficiency. The number of
Sleep disturbances associated with Alzheimer's disease
Sleep disturbances represent an early component of AD and the severity of this sleep disruption appears to parallel the severity of dementia ∗[4], [30].
Sleep-related breathing disorders
Interactions between SRBD and dementia are complex. Obstructive sleep apnea and hypopnea (OSAH) has been shown to be associated not only with impairment of many cognitive functions, including attention and executive tasks, but also memory, even if some authors argue that the relationship between SRBD and cognitive function may only be mediated by the effect of SRBD on daytime sleepiness ∗[69], [70], [71]. Recently, SRBD have also been highlighted as an independent risk factor for cognitive
Cholinesterase inhibitor treatments and sleep
Degeneration of the cholinergic system including the sub-systems involved in cognitive functions is thought to participate in the symptomatic expression of AD [94]. Acetylcholine plays a key role in memory functions and its concentration is closely related to vigilance states, as it increases during wakefulness and REM sleep, and decreases during SWS. Acetylcholinesterase inhibitors, by replenishing acetylcholine in the central nervous system of AD patients should have beneficial effects on
Sleep and cognition in AD patients
Sleep disorders are often considered as clinical neuropsychiatric symptoms of AD. Nevertheless given the critical role of sleep in memory consolidation, alterations of sleep in AD patients may represent in itself an aggravating factor for amnestic symptoms [8]. Indeed, even if age-related changes in the cognitive function of sleep have been reported, many learning abilities seem to be improved with specific sleep stages in the elderly (cf Section Sleep and normal aging). The mechanisms by which
Management of sleep disorders in AD
Management of sleep disorders in patients with AD consists in pharmacological and/or non-pharmacological measures, aims to ameliorate the quality of life of patients and caregivers and so may result in postponing institutionalization [2].
Conclusion and future directions
Sleep disturbances are frequent in AD and have significant impact on patients and caregivers. Future research is needed to clarify the contribution of the various genetic, neurodegenerative and environmental factors to sleep impairment, then testing the effectiveness on sleep of various interventions targeting these processes. Experimental and epidemiological evidence for close reciprocal interaction between cognitive decline and sleep alteration are growing but long-term longitudinal studies
Acknowledgments
The authors have no conflict of interest to declare.
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