Elsevier

Sleep Medicine Reviews

Volume 26, April 2016, Pages 21-32
Sleep Medicine Reviews

Clinical review
The relationship between sleep and cognition in Parkinson's disease: A meta-analysis

https://doi.org/10.1016/j.smrv.2015.04.003Get rights and content

Summary

It is well established that sleep disorders have neuropsychological consequences in otherwise healthy people. Studies of night-time sleep problems and cognition in Parkinson's disease (PD), however, paint a mixed picture, with many reporting no relationship between sleep problems and neuropsychological performance. This review aimed to meta-analyse this research and to examine the factors underlying these mixed results. A literature search was conducted of published and unpublished studies, resulting in 16 papers that met inclusion criteria. Data were analysed in the domains of: global cognitive function; memory (general, long-term verbal recognition, long-term verbal recall); and executive function (general, shifting, updating, inhibition, generativity, fluid reasoning).

There was a significant effect of sleep on global cognitive function, long-term verbal recall, long-term verbal recognition, shifting, updating, generativity, and fluid reasoning.

Although there are effects on memory and executive function associated with poor sleep in PD, the effects were driven by a small number of studies. Numerous methodological issues were identified. Further studies are needed reliably to determine whether disturbed sleep impacts on cognition via mechanisms of hypoxia, hypercapnia, sleep fragmentation, chronic sleep debt or decreased REM and/or slow wave sleep in PD, as this may have important clinical implications.

Introduction

Parkinson's disease (PD) is classified as a movement disorder, but non-motor symptoms are common and have a profound effect on patient experience and quality of life [1]. Up to a decade before the first motor symptoms emerge, patients often experience significant sleep disruption [2]. Sleep quality is strongly correlated with health related quality of life [3] and the impact of PD treatment (levodopa and dopamine agonists) on the sleep–wake cycle is an area of debate, with treatment effects varying between patients and compounds [4], [5].

Sleep disorders affect up to 98% of PD patients [6]. A range of sleep disturbances are common in PD, including insomnia, sleep fragmentation, sleep related breathing disorders (SRBD), hallucinations, nightmares, narcolepsy, REM sleep behaviour disorder (RBD) and non-REM parasomnias [7]. Similar to other neurodegenerative diseases (e.g. Alzheimer's disease) [8], significant sleep problems occur in PD, alongside significant cognitive dysfunction. This is noteworthy as cognitive impairment greatly increases disease burden [9]. Moreover, sleep problems have been shown to contribute to neuropsychological deficits in otherwise healthy people [10], [11], [12]. The cognitive changes observed in early to moderate PD are primarily deficits in executive function (EF) and memory [13], [14], [15]. These are the same domains affected in those with SRBD [16] and in insomnia [17]. SRBD causes sleep fragmentation and hypoxia, leading to daytime tiredness and cognitive deficits [18]. Daytime tiredness has an effect on attention and motivation, affecting neuropsychological test performance [10], and ability to manage daytime activities [19]. Diminished slow wave sleep (SWS) is thought to interfere with the capacity to learn new information [20] and to lead to specific deficits in spatial learning [21].

Given that sleep problems are almost universal in PD, and that they are associated with cognitive impairment even when experienced in isolation, this suggests that the neuropsychological deficits in mild to moderate PD may be compounded by chronic sleep debt or consistently fragmented sleep. That is, cognitive impairment may not only arise directly through the pathology of PD, but also indirectly via the mechanism of chronic sleep disruption. Studies of night-time sleep problems and cognition in PD, however, paint a mixed picture, with many reporting no relationship between sleep problems and neuropsychological performance. Critical appraisal of this literature, taking account of sample size and methodology is needed, as no such synthesis has been conducted.

This meta-analysis systematically examined the relationship between sleep and cognition in PD. The objectives of this study were: 1) to identify whether there are specific cognitive deficits associated with sleep problems (insomnia, sleep fragmentation, SRBD, hallucinations, nightmares, narcolepsy, RBD, and non-REM parasomnias) in PD and 2) which neuropsychological tests are sensitive to sleep-associated cognitive impairment in PD. We analysed, separately, measures of global cognitive function, EF and memory. Additionally, we analysed the sub-domains of memory: long-term verbal recall and long-term verbal recognition and the sub-domains of EF: shifting, updating, inhibition, generativity and fluid reasoning.

Section snippets

Search strategy

Electronic search of Medline, PsychInfo, PubMed, Proquest: Theses and Dissertations and Web of Science: Conference Proceedings databases to 19/12/2013 was conducted, restricted to papers in English, supplemented by hand searches of reference lists from included and seminal papers.

Fig. 1 list search terms which produced a total of 2283 papers. Following exclusion of duplicates and irrelevant reports, judging by title and abstract screening, 43 papers were retained for full-text evaluation. Two

Description of studies

From the 2283 articles initially identified, 16 studies met inclusion criteria. Study details, including methodology and methodological issues, can be found in Table S1.

Across these 16 studies, there were 1882 people with PD. The average age was 66.28 ± 8.65 y, and the average time since diagnosis was 7.17 ± 6.04 y. All studies were conducted in a clinical setting. Mean united Parkinson's disease rating scale (UPDRS) scores were provided for 10 studies, while either mean or median Hoehn and

Discussion

This meta-analysis indicates that, relative to those without sleep problems, people with PD who experience sleep problems demonstrate poorer cognitive performance. Poor sleepers had poorer performance on tests of global cognitive ability such as the Mattis dementia rating scale, and the SCOPA-Cog. When cognition was measured using brief or compound measures (such as the MMSE to measure global cognitive ability, the FAB to measure EF and memory or EF summary scores), no significant effects of

Conflicts of interest

The authors have no conflicts of interest to declare.

References (81)

  • J.G. Goldman et al.

    Dissociations among daytime sleepiness, nighttime sleep, and cognitive status in Parkinson's disease

    Park Relat Disord

    (2013 Sep)
  • L. Plomhause et al.

    Rapid eye movement sleep behavior disorder in treatment-naïve Parkinson disease patients

    Sleep Med

    (2013)
  • A. Sadeh

    The role and validity of actigraphy in sleep medicine: an update

    Sleep Med Rev

    (2011 Aug)
  • J.D. Edinger et al.

    Slow-wave sleep and waking cognitive performance II: findings among middle-aged adults with and without insomnia complaints

    Physiol Behav

    (2000)
  • J. Mouret

    Differences in Sleep in Patients with Parkinson's disease

    Electroencephalogr Clin Neurophysiol

    (1975)
  • B. Kaszás et al.

    Sensitivity and specificity of Addenbrooke's cognitive examination, mattis dementia rating scale, frontal assessment battery and mini mental state examination for diagnosing dementia in Parkinson's disease

    Park Relat Disord

    (2012 Jun)
  • R.D. Chervin et al.

    Obstructive sleep apnea and related disorders

    Neurol Clin

    (1996 Aug)
  • K.R. Chaudhuri et al.

    Non-motor symptoms of Parkinson's disease: dopaminergic pathophysiology and treatment

    Lancet Neurol

    (2009 May)
  • K.R. Chaudhuri et al.

    The nondeclaration of nonmotor symptoms of Parkinson's disease to health care professionals: an international study using the nonmotor symptoms questionnaire

    Mov Disord

    (2010 Apr 30)
  • T. Scaravilli et al.

    Health-related quality of life and sleep disorders in Parkinson's disease

    Neurol Sci

    (2003 Oct)
  • A. Romigi et al.

    Effect of cabergoline added to levodopa treatment on sleep-wake cycle in idiopathic Parkinson's disease: an open label 24-hour polysomnographic study

    J Neural Transm

    (2006)
  • C.H. Adler et al.

    Sleep issues in Parkinson's disease

    Neurology

    (2005)
  • C.L. Comella

    Sleep disorders in Parkinson's disease: an overview

    Mov Disord

    (2007 Sep)
  • M.V. Vitiello et al.

    Sleep disturbances in patients with Alzheimer's disease: epidemiology, pathophysiology and treatment

    CNS Drugs

    (2001)
  • P. Barone et al.

    The PRIAMO study: a multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson's disease

    Mov Disord

    (2009 Aug 15)
  • M.S. Aloia et al.

    Neuropsychological sequelae of obstructive sleep apnea-hypopnea syndrome: a critical review

    J Int Neuropsychol Soc

    (2004 Sep)
  • A.M. Owen et al.

    Fronto-striatal cognitive deficits at different stages of Parkinson’S disease

    Brain

    (1992)
  • D. Muslimovic et al.

    Cognitive profile of patients with newly diagnosed Parkinson's disease

    Neurology

    (2005)
  • R.S. Bucks et al.

    Neurocognitive function in obstructive sleep apnoea: a meta-review

    Respirology

    (2013 Jan)
  • D.W. Beebe et al.

    Obstructive sleep apnea and the prefrontal cortex: towards a comprehensive model linking nocturnal upper airway obstruction to daytime cognitive and behavioral deficits

    J Sleep Res

    (2002 Mar)
  • K. Kuriyama

    Multiple Causality in the impairment of daytime functioning associated with Insomnia: is it time to reconsider insomnia subtypes?

    J Sleep Disord Ther

    (2013)
  • A. Yoritaka et al.

    Parkinson's disease with and without REM sleep behaviour disorder: are there any clinical differences?

    Eur Neurol

    (2009 Jan)
  • P. Bugalho et al.

    Clinical features associated with REM sleep behavior disorder symptoms in the early stages of Parkinson's disease

    J Neurol

    (2011 Jan)
  • A. Wallace et al.

    Memory and obstructive sleep apnea: a meta-analysis

    Sleep

    (2013 Feb)
  • M. Olaithe et al.

    Executive dysfunction in OSA before and after treatment: a meta-analysis

    Sleep

    (2013)
  • E. Sinforiani et al.

    REM sleep behavior disorder, hallucinations, and cognitive impairment in Parkinson's disease

    Mov Disord

    (2006 Apr)
  • R. Nardone et al.

    Functional evaluation of central cholinergic circuits in patients with Parkinson's disease and REM sleep behavior disorder: a TMS study

    J Neural Transm

    (2013 Mar)
  • D. Verbaan et al.

    Prevalence and clinical profile of restless legs syndrome in Parkinson's disease

    Mov Disord

    (2010 Oct 15)
  • K. Stavitsky et al.

    The impact of sleep quality on cognitive functioning in Parkinson's disease

    J Int Neuropsychol Soc

    (2012 Jan)
  • S.L. Naismith et al.

    Neuropsychological functioning in Parkinson's disease: differential relationships with self-reported sleep-wake disturbances

    Mov Disord

    (2011 Jul)
  • Cited by (44)

    • Analysis of slow and fast sleep spindle properties in Parkinson's disease – A comparative EEG study

      2022, International Journal of Psychophysiology
      Citation Excerpt :

      In the early phase, PD patients show slight executive dysfunctions, but two-thirds of them develop dementia over 20 years (Braak et al., 2003; Zgaljardic et al., 2003). Even sleep disorders and changes in sleep macro- and microstructure themselves might cause cognitive decline in PD (Pushpanathan et al., 2014). The role of NREM sleep, particularly slow-wave sleep in declarative memory reactivation and consolidation has already been confirmed (Rasch and Born, 2013).

    • Sleep and affective disorders in relation to Parkinson's disease risk among older women from the Women's Health Initiative

      2022, Journal of Affective Disorders
      Citation Excerpt :

      The role played by sleep in PD risk remains controversial. To date, epidemiological evidence has been mostly limited to small case-control studies focused on PD NMS and to longitudinal studies that examined self-reported sleep-related symptoms rather than diagnosed sleep disorders (Liu et al., 2018; Mao et al., 2018; Mao et al., 2017; Pushpanathan et al., 2016; Wang et al., 2017; Wu et al., 2016). According to Vallee and colleagues, the main risk factor for PD is aging which can be detrimental to cellular homeostasis and lead to metabolic abnormalities such as neuroinflammation and oxidative stress which are in turn driven by circadian rhythms (Vallee et al., 2020).

    • Sleep alterations are related to cognitive symptoms in Parkinson's disease: A 24-hour ambulatory polygraphic EEG study

      2022, International Journal of Psychophysiology
      Citation Excerpt :

      The other domains of cognitive dysfunction are involved only in the latter course of the disease with further spread of the pathology (Braak et al., 2003; Zgaljardic et al., 2003). There are studies suggesting correlation between sleep disturbance and cognitive dysfunction in PD: significant relationship was found between bad sleep quality and impaired long-term verbal recall, recognition, as well as memory and executive functions (Pushpanathan et al., 2014). Excessive daytime sleepiness (EDS), which is common in PD might be also presumed to worsen cognitive performance, particularly executive function (Bolitho et al., 2013).

    View all citing articles on Scopus

    The most important references are denoted by an asterisk.

    View full text