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

In healthy individuals and those with insomnia, poor sleep quality is associated with decrements in performance on tests of cognition, especially executive function. Sleep disturbances and cognitive deficits are both prevalent in Parkinson's disease (PD). Sleep problems occur in over 75% of patients, with sleep fragmentation and decreased sleep efficiency being the most common sleep complaints, but their relation to cognition is unknown. We examined the association between sleep quality and cognition in PD. In 35 non-demented individuals with PD and 18 normal control adults (NC), sleep was measured using 24-hr wrist actigraphy over 7 days. Cognitive domains tested included attention and executive function, memory and psychomotor function. In both groups, poor sleep was associated with worse performance on tests of attention/executive function but not memory or psychomotor function. In the PD group, attention/executive function was predicted by sleep efficiency, whereas memory and psychomotor function were not predicted by sleep quality. Psychomotor and memory function were predicted by motor symptom severity. This study is the first to demonstrate that sleep quality in PD is significantly correlated with cognition and that it differentially impacts attention and executive function, thereby furthering our understanding of the link between sleep and cognition.Published versio

Circadian rest-activity rhythms predict cognitive function in early Parkinson's disease independently of sleep

BACKGROUND: Cognitive impairment is a common and debilitating symptom of Parkinson's disease (PD), and its etiology is likely multifactorial. One candidate mechanism is circadian disruption. Although there is evidence of circadian abnormalities in PD, no studies have directly assessed their association with cognitive impairment. OBJECTIVES: Investigate whether circadian rest-activity rhythm is associated with cognitive function in PD independently of sleep. METHODS: Thirty-five participants with PD wore wrist actigraph monitors and completed sleep diaries for 7 to 10 days, then underwent neuropsychological testing. Rest-activity rhythm was characterized using nonparametric circadian rhythm analysis of actigraphy data. Objective sleep parameters were also estimated using actigraphy data. Hierarchical regression models assessed the independent contributions of sleep and rest-activity rhythm to cognitive performance. RESULTS: Less stable day-to-day rest-activity rhythm was associated with poorer executive, visuospatial, and psychomotor functioning, but not with memory. Hierarchical regressions showed that interdaily stability's contribution to cognitive performance was independent of sleep's contributions. Whereas sleep contributed to executive function, but not psychomotor or visuospatial performance, rest-activity rhythm stability significantly contributed to variance in all three of these domains, uniquely accounting for 14.4% to 17.6% of their performance variance. CONCLUSIONS: Our findings indicate that circadian rest-activity rhythm is associated with cognitive impairment independently of sleep. This suggests the possible utility of rest-activity rhythm as a biomarker for circadian function in PD. Future research should explore interventions to stabilize behavioral rhythms in order to strengthen circadian function, which, in turn, may reduce cognitive impairment in PD.R00 HL102241 - NHLBI NIH HHS; R01 AG048108 - NIA NIH HHSAccepted manuscrip

Seeking for a fingerprint: analysis of point processes in actigraphy recording

Motor activity of humans displays complex temporal fluctuations which can be characterized by scale-invariant statistics, thus documenting that structure and fluctuations of such kinetics remain similar over a broad range of time scales. Former studies on humans regularly deprived of sleep or suffering from sleep disorders predicted change in the invariant scale parameters with respect to those representative for healthy subjects. In this study we investigate the signal patterns from actigraphy recordings by means of characteristic measures of fractional point processes. We analyse spontaneous locomotor activity of healthy individuals recorded during a week of regular sleep and a week of chronic partial sleep deprivation. Behavioural symptoms of lack of sleep can be evaluated by analysing statistics of duration times during active and resting states, and alteration of behavioural organization can be assessed by analysis of power laws detected in the event count distribution, distribution of waiting times between consecutive movements and detrended fluctuation analysis of recorded time series. We claim that among different measures characterizing complexity of the actigraphy recordings and their variations implied by chronic sleep distress, the exponents characterizing slopes of survival functions in resting states are the most effective biomarkers distinguishing between healthy and sleep-deprived groups.Comment: Communicated at UPON2015, 14-17 July 2015, Barcelona. 21 pages, 11 figures; updated: figures 4-7, text revised, expanded Sec. 1,3,

Sleep and circadian rhythms in the acute phase of moderate to severe traumatic brain injury

Les traumatismes craniocérébraux (TCC) sont la principale cause d’invalidité chez les jeunes adultes, engendrant d’importantes séquelles cognitives, physiologiques et comportementales. Les perturbations du cycle veille-sommeil sont parmi les symptômes les plus persistants à la suite d’un TCC et pourraient nuire à la récupération. En effet, le sommeil est nécessaire à l’apprentissage, la plasticité cérébrale et la génération de nouveaux neurones dans le cerveau adulte. Les observations cliniques suggèrent que ces perturbations apparaissent dès les premières semaines suivant le TCC et pourraient suggérer une altération de l’horloge circadienne. Cependant, aucune étude n’a encore documenté comment les perturbations du cycle veille-sommeil émergent et évoluent dans la phase aiguë du TCC, ni leur association à la récupération fonctionnelle et cognitive à court-terme. Conséquemment, cette thèse vise à caractériser le sommeil et les rythmes circadiens des patients hospitalisés avec un TCC modéré ou sévère et déterminer si les perturbations du cycle veille-sommeil sont causées par un dérèglement de l’horloge circadienne. Pour ce faire, nous avons utilisé des mesures objectives et quantitatives de sommeil et des rythmes circadiens, incluant l’actigraphie, la polysomnographie (PSG) et la mélatonine, dès la phase d’éveil aux soins intensif. Afin de comprendre le rôle du TCC dans ces perturbations, nous avons comparé les patients TCC à des patients hospitalisés avec blessures orthopédiques graves, sans TCC. Ce protocole a mené à cinq articles de recherche. En premier lieu, nous démontrons que le cycle veille-sommeil des patients TCC est sévèrement perturbé, mais s’améliore chez 50% d’entre eux au cours de leur séjour hospitalier. Les patients avec une amélioration de la consolidation du cycle veille-sommeil ont un meilleur fonctionnement cognitif et fonctionnel au congé de l’hôpital. Ensuite, dans une étude de cas, nous démontrons qu’un patient TCC peut avoir un cycle veille-sommeil complètement différent dans un même environnement, selon son stade de récupération. Notre troisième article confirme que la consolidation du cycle veille-sommeil évolue en synchronie avec la récupération de la conscience et des fonctions cognitives dans la phase aiguë du TCC. Notre quatrième article compare le sommeil des patients TCC à celui des blessés orthopédiques graves, sans TCC, en utilisant un système de PSG ambulatoire au chevet. Nous démontrons que, contrairement à notre hypothèse, le sommeil des patients TCC comprend tous les éléments et stades d’un sommeil normal. Cependant, ces patients s’endorment plus tôt et ont un sommeil de plus longue durée, mais plus fragmenté, que les patients sans TCC. Dans les deux groupes, le sommeil est de mauvaise qualité, reflétant probablement l’effet de facteurs non-spécifiques associés avec les blessures physiques et l’environnement hospitalier. Conséquemment, la PSG en phase aiguë permet difficilement de distinguer les patients TCC des patients sans TCC. Notre dernier article confirme que les patients avec TCC ont une consolidation du cycle veille-sommeil et une qualité de sommeil nocturne inférieures à celles des patients sans TCC, ce qui confirme le rôle du TCC dans les perturbations du cycle veille-sommeil. Cependant, malgré ces perturbations plus sévères, les patients TCC ont un rythme normal de la mélatonine et celui-ci n’est pas associé aux perturbations observées. Cet article suggère que des mécanismes neuronaux autres que l’horloge circadienne seraient responsables des perturbations du cycle veille-sommeil à la suite d’un TCC. Cette thèse est la première à évaluer le sommeil et le fonctionnement de l’horloge circadienne de patients hospitalisés avec un TCC modéré ou sévère ayant atteint la stabilité médicale. En isolant le rôle du TCC de celui du traumatisme physique et du milieu hospitalier, ces études contribuent à comprendre les caractéristiques, les conséquences et la pathophysiologie des perturbations du cycle veille-sommeil à la suite d’un TCC, ouvrant la voie à de possibles interventions visant à améliorer le sommeil et optimiser la récupération.Traumatic brain injuries (TBI) are the leading cause of disability among young adults, causing debilitating cognitive, psychological and behavioural impairments. Sleep-wake disturbances (SWD) are among the most persistent sequelae following TBI, and could impede recovery. Indeed, sleep is essential to learning, plasticity and neurogenesis. Clinical observations suggest that these disturbances arise in the first weeks following injury, and could suggest a circadian disturbance. However, no study has yet documented how SWD arise and evolve in the acute phase of TBI, or how they are associated to short-term cognitive and functional recovery. Consequently, this thesis aims to characterize the sleep and circadian rhythms of patients hospitalized with moderate or severe TBI, and determine whether SWD are caused by a deregulation of the circadian clock. To achieve this goal, we used objective and quantitative measures of sleep and circadian rhythms including actigraphy, polysomnography (PSG), and melatonin, beginning in the awakening stage in the Intensive Care Unit. In order to understand the specific role of TBI on SWD, we compared TBI patients to other hospitalized trauma patients, without TBI. Our comprehensive study protocol led to five research articles. First, we show that the sleep-wake cycle of TBI patients is severely disturbed, but improves for 50% of patients during their hospital stay. Patients whose sleep-wake cycle consolidation improves have better cognitive and functional outcome at hospital discharge. Then, in a single case study, we demonstrate how a patient can have drastically different sleep-wake patterns in the same environment, according to recovery stage. In our third research article, we show that the consolidation of sleep and wake states evolves synchronously with the recovery of consciousness and cognition in the acute phase of TBI. Our fourth article compares the sleep of TBI patients to that of non-TBI trauma patients using ambulatory PSG at bedside. Contrary to our hypothesis, TBI patients have normal sleep elements and normal proportions of each sleep stages. However, they have earlier sleep onset and longer nighttime sleep duration, but with greater fragmentation, than non-TBI patients. In both groups, sleep quality is poor, which most likely reflects non-specific factors associated with the physical trauma and hospital environment. Therefore, PSG reveals little information able to distinguish TBI patients from other non-TBI trauma patients at this stage post-injury. Our final article shows that TBI patients have poorer sleep-wake cycle consolidation and nighttime sleep quality than non-TBI patients, confirming the role of the TBI in altering sleep and wake states. However, despite having more severe SWD, TBI patients have a normal melatonin rhythm, and this rhythm is not associated with the observed SWD. This article suggests that neural mechanisms other than the circadian clock may be responsible for post-TBI SWD. This thesis is the first to investigate the sleep and circadian clock of hospitalized moderate to severe TBI patients who are medically stable. By isolating the role of the injured brain from that of overall trauma and the hospital setting, these studies contribute to understanding the characteristics, consequences and pathophysiology of post-TBI SWD, unlocking the possibility to design interventions aiming to improve sleep and optimize recovery

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

In healthy individuals and those with insomnia, poor sleep quality is associated with decrements in performance on tests of cognition, especially executive function. Sleep disturbances and cognitive deficits are both prevalent in Parkinson's disease (PD). Sleep problems occur in over 75% of patients, with sleep fragmentation and decreased sleep efficiency being the most common sleep complaints, but their relation to cognition is unknown. We examined the association between sleep quality and cognition in PD. In 35 non-demented individuals with PD and 18 normal control adults (NC), sleep was measured using 24-hr wrist actigraphy over 7 days. Cognitive domains tested included attention and executive function, memory and psychomotor function. In both groups, poor sleep was associated with worse performance on tests of attention/executive function but not memory or psychomotor function. In the PD group, attention/executive function was predicted by sleep efficiency, whereas memory and psychomotor function were not predicted by sleep quality. Psychomotor and memory function were predicted by motor symptom severity. This study is the first to demonstrate that sleep quality in PD is significantly correlated with cognition and that it differentially impacts attention and executive function, thereby furthering our understanding of the link between sleep and cognition.Published versio

Naturally-occurring sleep choice and time of day effects on p-beauty contest outcomes

We explore the behavioral consequences of sleep loss and time-of-day (circadian) effects on a particular type of decision making. Subject sleep is monitored for the week prior to a decision experiment, which is then conducted at 8 a.m. or 8 p.m. A validated circadian preference instrument allows us to randomly assign subjects to a more or less preferred time-of-day session. The well-known p-beauty contest (a.k.a., the guessing game) is administered to examine how sleep loss and circadian mismatch affect subject reasoning and learning. We find that the subject responses are consistent with significantly lower levels of iterative reasoning when ‘sleep deprived’ or at non-optimal times-of-day. A non-linear effect is estimated to indicate that too much sleep also leads to choices consistent with lower levels of reasoning, with an apparent optimum at close to 7 hours sleep per night. However, repeated play shows that sleep loss and non-optimal times-of-day do not affect learning or adaptation in response to information feedback. Our results apply to environments where anticipation is important, such as in coordination games, stock trading, driving, etc. These findings have important implications for the millions of adults considered sleep deprived, as well as those employed in shift work occupations. Key Words:

Combining Cardiac Monitoring with Actigraphy Aids Nocturnal Arousal Detection during Ambulatory Sleep Assessment in Insomnia

Study Objectives: The objective assessment of insomnia has remained difficult. Multisensory devices collecting heart rate (HR) and motion are regarded as the future of ambulatory sleep monitoring. Unfortunately, reports on altered average HR or heart rate variability (HRV) during sleep in insomnia are equivocal. Here, we evaluated whether the objective quantification of insomnia improves by assessing state-related changes in cardiac measures. Methods: We recorded electrocardiography, posture, and actigraphy in 33 people without sleep complaints and 158 patients with mild to severe insomnia over 4 d in their home environment. At the microscale, we investigated whether HR changed with proximity to gross (body) and small (wrist) movements at nighttime. At the macroscale, we calculated day-night differences in HR and HRV measures. For both timescales, we tested whether outcome measures were related to insomnia diagnosis and severity. Results: At the microscale, an increase in HR was often detectable already 60 s prior to as well as following a nocturnal chest, but not wrist, movement. This increase was slightly steeper in insomnia and was associated with insomnia severity, but future EEG recordings are necessary to elucidate whether these changes occur prior to or simultaneously with PSG-indicators of wakefulness. At the macroscale, we found an attenuated cardiac response to sleep in insomnia: patients consistently showed smaller day-night differences in HR and HRV. Conclusions: Incorporating state-related changes in cardiac features in the ambulatory monitoring of sleep might provide a more sensitive biomarker of insomnia than the use of cardiac activity averages or actigraphy alone

Expression of interferon-inducible chemokines and sleep/wake changes during early encephalitis in experimental African trypanosomiasis

Background: Human African trypanosomiasis or sleeping sickness, caused by the parasite Trypanosoma brucei, leads to neuroinflammation and characteristic sleep/wake alterations. The relationship between the onset of these alterations and the development of neuroinflammation is of high translational relevance, but remains unclear. This study investigates the expression of interferon (IFN)-γ and IFN-inducible chemokine genes in the brain, and the levels of CXCL10 in the serum and cerebrospinal fluid prior to and during the encephalitic stage of trypanosome infection, and correlates these with sleep/wake changes in a rat model of the disease. Methodology/Principal findings: The expression of genes encoding IFN-γ, CXCL9, CXCL10, and CXCL11 was assessed in the brain of rats infected with Trypanosoma brucei brucei and matched controls using semi-quantitative end-point RT-PCR. Levels of CXCL10 in the serum and cerebrospinal fluid were determined using ELISA. Sleep/wake states were monitored by telemetric recording. Using immunohistochemistry, parasites were found in the brain parenchyma at 14 days post-infection (dpi), but not at 6 dpi. Ifn-γ, Cxcl9, Cxcl10 and Cxcl11 mRNA levels showed moderate upregulation by 14 dpi followed by further increase between 14 and 21 dpi. CXCL10 concentration in the cerebrospinal fluid increased between 14 and 21 dpi, preceded by a rise in the serum CXCL10 level between 6 and 14 dpi. Sleep/wake pattern fragmentation was evident at 14 dpi, especially in the phase of wake predominance, with intrusion of sleep episodes into wakefulness. Conclusions/Significance: The results show a modest increase in Cxcl9 and Cxcl11 transcripts in the brain and the emergence of sleep/wake cycle fragmentation in the initial encephalitic stage, followed by increases in Ifn-γ and IFN-dependent chemokine transcripts in the brain and of CXCL10 in the cerebrospinal fluid. The latter parameter and sleep/wake alterations could provide combined humoral and functional biomarkers of the early encephalitic stage in African trypanosomiasis