Regular articleSleep spindles in Parkinson's disease may predict the development of dementia
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
References (60)
- et al.
The cholinergic system and Parkinson disease
Behav. Brain Res.
(2011) - et al.
Association between dopaminergic medications and nocturnal sleep in early-stage Parkinson’s disease
Parkinsonism Relat. Disord.
(2013) - et al.
Non-motor symptoms of Parkinson’s disease: diagnosis and management
Lancet Neurol.
(2006) - et al.
Parkinson’s disease: the non-motor issues
Parkinsonism Relat. Disord.
(2011) - et al.
Decreased sleep spindle density in patients with idiopathic REM sleep behavior disorder and patients with Parkinson’s disease
Clin. Neurophysiol.
(2014) Metabolic brain networks in neurodegenerative disorders: a functional imaging approach
Trends Neurosci.
(2009)- et al.
‘‘Mini-mental state.” A practical method for grading the cognitive state of patients for the clinician
J. Psychiatr. Res.
(1975) - et al.
Neuropsychological and clinical heterogeneity of cognitive impairment and dementia in patients with Parkinson’s disease
Lancet Neurol.
(2010) - et al.
Thalamic cholinergic innervation is spared in Alzheimer disease compared to Parkinsonian disorders
Neurosci. Lett.
(2012) - et al.
Non-rapid eye movement sleep characteristics in idiopathic REM sleep behavior disorder
J. Neurol. Sci.
(2011)