Elsevier

Neurobiology of Aging

Volume 36, Issue 2, February 2015, Pages 1083-1090
Neurobiology of Aging

Regular article
Sleep spindles in Parkinson's disease may predict the development of dementia

https://doi.org/10.1016/j.neurobiolaging.2014.09.009Get rights and content

Abstract

Sleep disturbances and cognitive impairment are common non-motor manifestations of Parkinson's disease (PD). Recent studies suggest that sleep spindles and slow waves play a role in brain plasticity mechanisms and are associated with cognitive performance. However, it remains unknown whether these sleep parameters could serve as markers of cognitive decline in PD. Therefore, we examined whether alterations in sleep spindles and slow waves at baseline visit were associated with increased likelihood of developing dementia at follow-up in PD. Sixty-eight nondemented PD patients (64.9 ± 8.8 years old; 46 men) participated in the study, along with 47 healthy individuals (65.0 ± 10.6 years old; 30 men). All participants underwent baseline polysomnographic recording and a comprehensive neuropsychological assessment. Sleep spindles (12–15 Hz) and slow waves (>75 μV and <4 Hz) were automatically detected on all-night non-rapid eye movement sleep electroencephalography. At follow-up (mean: 4.5 years later), 18 PD patients developed dementia (70.2 ± 7.6 years old; 13 men) and 50 remained dementia-free (63.0 ± 8.5 years old; 33 men). Sleep spindle density and amplitude were lower in PD patients who converted to dementia compared with both patients who remained dementia-free and controls, mostly in posterior cortical regions (p < 0.05). Dementia-free PD patients were intermediate between dementia patients and controls, with lower baseline sleep spindle density in all cortical areas compared with controls (p < 0.01). In demented PD patients, lower sleep spindle amplitude in parietal and occipital areas was associated with poorer visuospatial abilities. Although slow wave amplitude was lower in PD patients compared with controls (p < 0.0001), no difference was observed between those who developed or did not develop dementia. Results demonstrate non-rapid eye movement sleep electroencephalographic abnormalities in PD patients. Sleep spindle activity was particularly impaired in PD patients who developed dementia, with a more posterior topographic pattern. Sleep spindle alterations are associated with later development of dementia in PD, and thus may serve as an additional marker of cognitive decline in these patients.

Introduction

Nonmotor symptoms, such as autonomic, neuropsychiatric, sensory, sleep, and cognitive dysfunctions, are now recognized as central features of Parkinson's disease (PD; Chaudhuri et al., 2006, Chaudhuri et al., 2011). In cross-sectional studies, approximately one-third of PD patients have dementia (Aarsland and Kurz, 2010). Prospective studies have reported that over 20 years of the disease, up to 75% of PD patients eventually develop dementia (Hely et al., 2008). Certain risk factors (age, depression, apathy, hallucinations, mild cognitive impairment, rapid eye movement sleep behavior disorder [RBD], and akinetic-rigid subtype of PD) and biomarkers (electroencephalography [EEG], magnetic resonance imaging, magnetoencephalography, and genetic anomalies) of dementia have been identified in PD (Aarsland and Kurz, 2010, Klassen et al., 2011, Olde Dubbelink et al., 2014, Postuma et al., 2012, Svenningsson et al., 2012). However, it remains unknown whether specific EEG sleep characteristics could predict cognitive decline in PD.

There is increasing evidence for a relationship between sleep and cognition in normal and pathologic aging (Fogel et al., 2012). EEG events during non-rapid eye movement (N-REM) sleep, including slow waves (>75 μV and <4 Hz) and sleep spindles (approximately 12–15 Hz), may contribute to brain plasticity (Fogel et al., 2012, Lafortune et al., 2014, Schabus et al., 2006, Steriade, 2006). Recent studies in patients with mild cognitive impairment and Alzheimer's disease found altered N-REM sleep EEG characteristics (Rauchs et al., 2008, Westerberg et al., 2012). To date, few studies have investigated N-REM sleep oscillations in PD, with inconsistent results. Most found lower sleep spindles in PD patients (Christensen et al., 2014, Emser et al., 1988, Puca et al., 1973), except for one (Happe et al., 2004), and none investigated slow waves in this population. Some studies had methodological shortcomings (e.g., no healthy control group, EEG analyses performed only during a portion of the night, use of visual detection only for sleep spindles, PD not diagnosed according to standard clinical criteria and so forth), and none determined whether sleep spindles differed with scalp topography or whether they were related to cognitive status. Because N-REM sleep oscillations are associated with cognitive functioning, their alteration might predict dementia development in PD.

The aim of this study was to examine whether baseline N-REM sleep EEG alterations are associated with increased likelihood of developing dementia on prospective follow-up assessment in PD patients.

Section snippets

Participants

Patients were recruited from our ongoing longitudinal study on sleep in PD. All patients who underwent a baseline neuropsychological examination and one night of polysomnographic recordings in the sleep laboratory with at least 1 follow-up examination at a minimum of 2 years after the baseline visit were included in the study. Control subjects were recruited by word of mouth and through newspaper advertisements (and were used for baseline comparisons only). The hospital's ethical committee

Demographic, clinical, and polysomnographic characteristics

Initially, 82 patients were enrolled in the baseline cohort. Fourteen patients (17%) could not be assessed at follow-up: 8 had died, 2 refused the reassessment, and 1 was unreachable. Moreover, baseline EEG recordings for 3 patients were unusable for analysis because of significant artifacts. Consequently, 68 PD patients (83%) met inclusion criteria and were prospectively followed; 41 patients (60%; 17% developed dementia and 83% remained dementia-free) underwent a comprehensive

Discussion

Compared with both healthy controls and patients who remained dementia free, PD patients who later developed dementia showed marked sleep spindle alterations at baseline, including lower sleep spindle density and amplitude, mainly in posterior cortical regions. Sleep spindle frequency was also lower in PD patients who developed dementia compared with controls, and supplementary analyses showed that fast sleep spindles were altered in PD patients with dementia, with a global effect across all

Conclusions

Our results suggest that sleep spindles are considerably impaired in PD, according to a more posterior topographic pattern. Alterations in sleep spindle activity are related to dementia development in PD and are therefore a potential marker of cognitive decline in this population. Future neuroimaging studies should explore the relationships between N-REM sleep oscillations and structural and functional alterations in PD.

Disclosure statement

The authors have no actual or potential conflicts of interest.

Acknowledgements

This study was supported by grants from the Canadian Institutes of Health Research, Canada (MOP-84482; Jean-François Gagnon, Ronald B. Postuma, and Julie Carrier) and the Fonds de Recherche du Québec - Santé, Canada (Jean-François Gagnon, Ronald B. Postuma, and Julie Carrier). Véronique Latreille and Josie-Anne Bertrand were supported by a scholarship from the Canadian Institutes of Health Research, Canada, and Marjolaine Lafortune was supported by a scholarship from the Fonds de Recherche du

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