Sleep in everyday life - relationship to mood and performance in young and older adults: a study protocol.

Laboratory based sleep deprivation studies demonstrate that lack of sleep impairs well-being and performance ability, but suggest that these effects are mitigated in older adults. Yet, much less is known whether day-to-day variations of sleep have similar consequences in the context of everyday life. This project uses an intensive longitudinal design to investigate the occurrence of day-to-day variations in sleep and their impact on mood and performance in everyday life and to examine whether effects differ between young and older adults. We aim to include 160 young (18-30 years) and 160 older adults (55-75 years) to complete a 21-day experience sampling method (ESM) protocol. During the ESM period, participants are asked to fill in (i) a brief morning questionnaire, (ii) 8 short daytime questionnaires addressing momentary well-being, sleepiness, stress, and mind wandering, followed by a 1 min cognitive task and (iii) a brief evening questionnaire, all delivered via a mobile phone application. Sleep will be measured using self-reports (daily questions) and objectively with wrist actigraphy. The impact of adult age on mean levels and intraindividual variability of sleep will be analyzed using mixed-effects location scale models. The impact of sleep on daily cognitive performance will be analyzed using multilevel linear mixed models. The relationship of sleep to mean values and variability of positive and negative affect in young and older adults will be analyzed using mixed-effects location scale modeling. The overarching purpose of the project is improving the current knowledge on the occurrence of day-to-day variations in sleep and their relationship to performance as well as positive and negative affect in young and older adults.

Implicit Motor Sequence Learning in People with Mild to Moderate Parkinson's Disease: Behavior and Related Brain Function.

BACKGROUND: Deficits in motor learning could be an important explanation for the balance and gait impairments characteristic of people with Parkinson's disease (PD). Empirical studies often report that so-called implicit motor sequence learning is impaired in people with PD, but the results are inconclusive. Altered brain activity during implicit motor sequence learning has also been reported for people with PD in comparison to healthy individuals. OBJECTIVE: To investigate implicit motor sequence learning and associated neural correlates in individuals with mild to moderate PD. METHODS: Fifty-seven participants with PD and 34 healthy participants, all ≥60 years of age, performed the serial reaction time task (SRTT) during the acquisition of functional magnetic resonance imaging (fMRI) data. We analyzed the SRTT as a measure of implicit motor sequence learning in two complementary ways. We analyzed the task-induced fMRI data within regions of interest (ROIs) as well as functional connectivity between ROIs. RESULTS: We found a significant group difference in SRTT performance indicating that the participants with PD had a somewhat lower level of implicit motor sequence learning than the healthy participants. Exploratory analyses suggested that impairments in implicit motor sequence learning for people with PD might be due to a lower learning rate. We did not find any significant group differences in the fMRI data. CONCLUSION: Our exploratory finding of a lower implicit motor learning rate in PD could have important implications for how people with PD should practice new motor tasks and physical exercise. Future studies need to confirm this finding with hypothesis-driven analyses.

Unraveling Parkinson's disease heterogeneity using subtypes based on multimodal data.

BACKGROUND: Parkinson's disease (PD) is a clinically and neuroanatomically heterogeneous neurodegenerative disease characterized by different subtypes. To this date, no studies have used multimodal data that combines clinical, motor, cognitive and neuroimaging assessments to identify these subtypes, which may provide complementary, clinically relevant information. To address this limitation, we subtyped participants with mild-moderate PD based on a rich, multimodal dataset of clinical, cognitive, motor, and neuroimaging variables. METHODS: Cross-sectional data from 95 PD participants from our randomized EXPANd (EXercise in PArkinson's disease and Neuroplasticity) controlled trial were included. Participants were subtyped using clinical, motor, and cognitive assessments as well as structural and resting-state MRI data. Subtyping was done by random forest clustering. We extracted information about the subtypes by inspecting their neuroimaging profiles and descriptive statistics. RESULTS: Our multimodal subtyping analysis yielded three PD subtypes: a motor-cognitive subtype characterized by widespread alterations in brain structure and function as well as impairment in motor and cognitive abilities; a cognitive dominant subtype mainly impaired in cognitive function that showed frontoparietal structural and functional changes; and a motor dominant subtype impaired in motor variables without any brain alterations. Motor variables were most important for the subtyping, followed by gray matter volume in the right medial postcentral gyrus. CONCLUSIONS: Three distinct PD subtypes were identified in our multimodal dataset. The most important features to subtype PD participants were motor variables in addition to structural MRI in the sensorimotor region. These findings have the potential to improve our understanding of PD heterogeneity, which in turn can lead to personalized interventions and rehabilitation.

Behavioural and neuroplastic effects of a double-blind randomised controlled balance exercise trial in people with Parkinson's disease.

Balance dysfunction is a disabling symptom in people with Parkinson's disease (PD). Evidence suggests that exercise can improve balance performance and induce neuroplastic effects. We hypothesised that a 10-week balance intervention (HiBalance) would improve balance, other motor and cognitive symptoms, and alter task-evoked brain activity in people with PD. We performed a double-blind randomised controlled trial (RCT) where 95 participants with PD were randomised to either HiBalance (n = 48) or a control group (n = 47). We found no significant group by time effect on balance performance (b = 0.4 95% CI [-1, 1.9], p = 0.57) or on our secondary outcomes, including the measures of task-evoked brain activity. The findings of this well-powered, double-blind RCT contrast previous studies of the HiBalance programme but are congruent with other double-blind RCTs of physical exercise in PD. The divergent results raise important questions on how to optimise physical exercise interventions for people with PD.Preregistration clinicaltrials.gov: NCT03213873.

Effects of a Highly Challenging Balance Training Program on Motor Function and Brain Structure in Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is characterized by motor deficits and brain alterations having a detrimental impact on balance, gait, and cognition. Intensive physical exercise can induce changes in the neural system, potentially counteracting neurodegeneration in PD and improving clinical symptoms. OBJECTIVE: This randomized controlled trial investigated effects of a highly challenging, cognitively demanding, balance and gait training (HiBalance) program in participants with PD on brain structure. METHODS: 95 participants were assigned to either the HiBalance or an active control speech training program. The group-based interventions were performed in 1-hour sessions, twice per week over a 10-week period. Participants underwent balance, gait, cognitive function, and structural magnetic resonance imaging assessments before and after the interventions. Voxel-based morphometry was analyzed in 34 HiBalance and 31 active controls. Additionally, structural covariance networks were assessed. RESULTS: There was no significant time by group interaction between the HiBalance and control training in balance, gait, or brain volume. Within-HiBalance-group analyses showed higher left putamen volumes post-training. In repeated measures correlation a positive linear, non-significant relationship between gait speed and putamen volume was revealed. In the HiBalance group we found community structure changes and stronger thalamic-cerebellar connectivity in structural covariance networks. Neither brain volume changes nor topology changes were found for the active controls after the training. CONCLUSION: Thus, subtle structural brain changes occur after balance and gait training. Future studies need to determine whether training modifications or other assessment methods lead to stronger effects.

Measuring implicit sequence learning and dual task ability in mild to moderate Parkinson´s disease: A feasibility study.

We investigated the feasibility aspects of two choice reaction time tasks designed to assess implicit sequence learning and dual task ability in individuals with mild to moderate Parkinson's disease in comparison to healthy individuals. Twelve individuals with mild to moderate Parkinson's disease and 12 healthy individuals, all ≥ 60 years of age, were included. A serial reaction time task was used as a measure of implicit sequence learning and a similar task but with the addition of a simple counting task, was used as a measure of dual task ability. We have present thorough descriptive statistics of the data but we have refrained from any inferential statistics due to the small sample size. All participants understood the task instructions and the difficulty level of both tasks was deemed acceptable. There were indications of task fatigue that demand careful choices for how best to analyse the data from such tasks in future trials. Ceiling effects were present in several accuracy outcomes, but not in the reaction time outcomes. Overall, we found both tasks to be feasible to use in samples of individuals with mild to moderate Parkinson's disease and healthy older individuals.

Feasibility Aspects of Exploring Exercise-Induced Neuroplasticity in Parkinson's Disease: A Pilot Randomized Controlled Trial.

BACKGROUND: Recent studies indicate that exercise can induce neuroplastic changes in people with Parkinson's disease (PwPD). Reports of feasibility outcomes from existing pilot trials however are, of date, insufficient to enable replication by others in larger definitive trials. OBJECTIVE: To evaluate trial design for a definitive trial by exploring process and scientific feasibility. METHODS: The trial design was a parallel-group RCT pilot with a 1 : 1 allocation ratio to either HiBalance or an active control group (HiCommunication). Both groups received one-hour sessions twice weekly, plus home exercises weekly, for 10 weeks. Participants with mild-to-moderate Parkinson's disease (PD) were recruited via advertisement. Assessment included physical performance, structural and functional MRI, blood sampling, neuropsychological assessment, and speech/voice assessment. Process and scientific feasibility were monitored throughout the study. Process feasibility involved recruitment, participant acceptability of assessments and interventions, assessment procedures (focus on imaging, blood sampling, and dual-task gait analysis), and blinding procedures. Scientific feasibility involved trends in outcome response and safety during group training and home exercises. Data are presented in median, minimum, and maximum values. Changes from pre- to postintervention are reported descriptively. RESULTS: Thirteen participants were included (4 women, mean age 69.7 years), with a recruitment rate of 31%. Attendance rates and follow-up questionnaires indicated that both groups were acceptable to participate. Image quality was acceptable; however, diplopia and/or sleepiness were observed in several participants during MRI. With regard to dual-task gait performance, there appeared to be a ceiling effect of the cognitive tasks with seven participants scoring all correct answers at pretest. Blinding of group allocation was successful for one assessor but was broken for half of participants for the other. CONCLUSIONS: The overall trial design proved feasible to perform, but further strengthening ahead of the definitive RCT is recommended, specifically with respect to MRI setup, cognitive dual-tasks during gait, and blinding procedures. This trial is registered with NCT03213873.

No evidence for any effect of multiple sessions of frontal transcranial direct stimulation on mood in healthy older adults.

The dorsolateral prefrontal cortex (DLPFC) is part of a network important for emotional regulation and the possibility of modulating activity in this region with transcranial direct current stimulation (TDCS) to change mood has gained great interest, particularly for application in clinical populations. Whilst results in major depressive disorder have been promising, less is known about the effects of TDCS on mood in non-clinical populations. We hypothesized that multiple sessions of anodal TDCS applied over the left DLPFC would enhance mood, primarily as measured by the Profile of Mood States questionnaire, in healthy older adults. In addition, in an exploratory analysis, we examined the potentially moderating role of working memory training. Working memory, just like emotional regulation, taxes the DLPFC, which suggests that engaging in a working memory task whilst receiving TDCS may have a different effect on activity in this region and consequently mood. A total of 123 participants between 65 and 75 years of age were randomly assigned to receive either 20 sessions of TDCS, with or without working memory training, or 20 sessions sham stimulation, with or without working memory training. We found no support for enhancement of mood due to TDCS in healthy older adults, with or without cognitive training and conclude that the TDCS protocol used is unlikely to improve mood in non-depressed older individuals.

The EXPANd trial: effects of exercise and exploring neuroplastic changes in people with Parkinson's disease: a study protocol for a double-blinded randomized controlled trial.

BACKGROUND: Parkinson's disease (PD) affects many physiological systems essential for balance control. Recent studies suggest that intensive and cognitively demanding physical exercise programs are capable of inducing plastic brain changes in PD. We have developed a highly challenging balance training (the HiBalance) program that emphasizes critical aspects of balance control through progressively introducing more challenging exercises which incorporates dual-tasking. Earlier studies have shown it to be effective in improving balance, gait and dual-tasking. The study design has thereafter been adjusted to link intervention-induced behavioral changes to brain morphology and function. Specifically, in this randomized controlled trial, we will determine the effects of the HiBalance program on balance, gait and cognition and relate this to task-evoked functional MRI (fMRI), as well as brain-derived neurotrophic factor (BDNF) in participants with mild-moderate PD. METHODS: One hundred participants with idiopathic PD, Hoehn & Yahr stage 2 or 3, ≥ 60 years of age, ≥ 21 on Montreal Cognitive Assessment will be recruited in successive waves and randomized into either the HiBalance program or to an active control group (the HiCommunication program, targeting speech and communication). Both interventions will be performed in small groups, twice a week with 1 h sessions for 10 weeks. In addition, a 1 h, once a week, home exercise program will also be performed. A double-blinded design will be used. At the pre- and post-assessments, participants will be assessed on balance (main outcome), gait, cognitive functions, physical activity, voice/speech function, BDNF in serum and fMRI (3 T Philips) during performance of motor-cognitive tasks. DISCUSSION: Since there is currently no cure for PD, findings of neuroplastic brain changes in response to exercise would revolutionize the way we treat PD, and, in turn, provide new hope to patients for a life with better health, greater independence and improved quality of life. TRIAL REGISTRATION: ClincalTrials.gov: NCT03213873, first posted July 11, 2017.