Use of nonintrusive sensor-based information and communication technology for real-world evidence for clinical trials in dementia

Cognitive function is an important end point of treatments in dementia clinical trials. Measuring cognitive function by standardized tests, however, is biased toward highly constrained environments (such as hospitals) in selected samples. Patient-powered real-world evidence using information and communication technology devices, including environmental and wearable sensors, may help to overcome these limitations. This position paper describes current and novel information and communication technology devices and algorithms to monitor behavior and function in people with prodromal and manifest stages of dementia continuously, and discusses clinical, technological, ethical, regulatory, and user-centered requirements for collecting real-world evidence in future randomized controlled trials. Challenges of data safety, quality, and privacy and regulatory requirements need to be addressed by future smart sensor technologies. When these requirements are satisfied, these technologies will provide access to truly user relevant outcomes and broader cohorts of participants than currently sampled in clinical trials

The Relationship Between Sleep Disturbances and Episodic Memory in Older Adults.

Impaired episodic memory in older adults has been posited to be related to sleep disturbances which are revealed by self-reported questionnaires and objective devices but the relationship between these two measured results is unclear. Sleep disturbances have been tied to declines in attention, executive function, and cognitive reserve, which may contribute to impaired episodic memory. However, how sleep disturbances relate to these cognitive functions and in turn influence episodic memory remains unclear. Age and depressive symptoms are correlated with sleep disturbances and episodic memory decline in older adults; however, the role of age and depressive symptoms in explaining the relationship between sleep disturbances and episodic memory remains unclear The specific aims were (a) to determine the conceptual structure of sleep disturbances in older adults; and (b) to determine the relationship between sleep disturbances and episodic memory in older adults, including the roles of attention, executive function, cognitive reserve, depressive symptoms, and aging in the relationship. This descriptive study included a convenience sample of (N=62) older adults (age 60-88). Two sleep questionnaires and actigraphy were used to measure sleep; the Hopkins Verbal Learning Test-Revised was used to assess episodic memory; the CogState computerized battery was used to evaluate attention and executive function; and the Wide Range Achievement Test 4-Reading subtest was used to measure cognitive reserve. Descriptive statistics, Pearson’s correlation, exploratory factor analysis, and hierarchical multiple regression analyses were conducted to analyze data. Self-reported sleep disturbances significantly correlated with objective sleep time and wakefulness during sleep periods, but this relationship was only substantial for objective sleep time. In older adults, more objective difficulty in falling and staying asleep, better executive function, more cognitive reserve and unexpectedly, higher level of daytime sleepiness explained better episodic memory after controlling for the covariates. The influence of sleep disturbances on episodic memory was stronger among those participants with more, as compared to less depressive symptoms. The study results suggest some possible directions to develop sleep interventions to prevent episodic memory declines in older adults. Future studies may focus on improving daytime sleepiness and difficulty in falling and staying asleep to prevent episodic memory declines.PhDNursingUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/113327/1/anyun_1.pd

The effect of bright light on sleep in nursing home patients with dementia

Background: Up to 70% of nursing home patients with dementia suffer from disrupted sleep, often characterized by multiple awakenings at night and excessive daytime sleep. Sleep disruption may have negative effects on the cognition, mood, behaviour, and well-being of nursing home patients, while also representing a challenge for nursing home staff. However, few sleep scales are developed and validated specifically for the nursing home setting. Sleep problems among nursing home patients are frequently treated by medications, which are associated with severe side effects, including daytime sleepiness, and an increased risk of falls. Thus, there is a need for non-pharmacological interventions to improve sleep in this population. Bright light treatment (BLT) may represent such an intervention, providing increased light exposure aiming to impact sleep, circadian rhythmicity, mood, and/or behaviour. Light is the most important zeitgeber to the circadian system, and consequently has a significant impact on sleep-wake behaviour. Unfortunately, studies have reported low indoor light levels in nursing homes, which in combination with dementia-related neuropathology and age-related reductions in light sensitivity, are likely to contribute to sleep problems in this population. The aim of this thesis was to investigate whether increasing daytime light exposure, by means of BLT, can improve sleep in nursing home patients with dementia, and also to address methodological challenges in this field of research. Methods: Paper 1 is a systematic review of the literature, focusing on the methodological features of the included studies, in addition to their findings. Paper 2 and 3 are based on data from the DEM.LIGHT trial; a cluster-randomized placebo-controlled trial conducted in Norwegian nursing homes, including 69 patients. The intervention comprised a diurnal cycle of ambient light with a maximum of 1,000 lux and 6,000 Kelvin (K) from 10:00-15:00, administered using light emitting diode (LED) light. Before and after this interval, the light levels gradually increased/decreased in lux and K. In the placebo condition, standard light levels were maintained at 150-300 lux and approximately 3,000 K throughout the day. The intervention and placebo lights were installed in the common rooms of the included nursing home units. Outcomes were measured at baseline and at follow-up at week 8, 16, and 24. Paper 2 was a validation study of a proxy-rated sleep scale, using the baseline data from the DEM. LIGHT trial. Actigraphy was used as the reference standard. Paper 3 reported on the sleep outcomes of the trial, which were the primary outcomes. Results: Paper 1 found that there are promising, though inconsistent, results regarding the effect of BLT on sleep and circadian rhythmicity in dementia. Large heterogeneity in terms of interventions, study designs, population characteristics, and outcome measurement tools may explain some of the inconsistencies of results across studies. Paper 2 showed that the proxy-rated Sleep Disorder Inventory (SDI) had satisfactory internal consistency and convergent validity. Using actigraphy as the reference standard, the SDI was termed clinically useful, and we suggested a cut-off score of five or more as defining disrupted sleep in nursing home patients with dementia. These results should be interpreted keeping in mind that actigraphy have some important weaknesses, such as underestimating wake time. Paper 3 evaluated the effects of the BLT on sleep and found an improvement in sleep according to the SDI scores in the intervention group, as compared to the control group, from baseline to week 16 and baseline to week 24. There was no effect in terms of sleep measured by actigraphy. Conclusion: In summary, this thesis found that the evidence for an effect of BLT on sleep in nursing home patients with dementia is promising, but equivocal. Importantly, the research field faces some important methodological challenges, such as accurately measuring sleep. The SDI may represent a valid tool to measure sleep in the nursing home setting, which may be used both by researchers and by practitioners. Although the results of this thesis are not conclusive regarding the effect of BLT on sleep in nursing home patients with dementia, it may represent a step forward in understanding the potential value of BLT in this population, and may lay the ground for further investigation. The lack of an improvement on the SDI at week 8 indicates that the effect of BLT may take a long time to manifest in this population.Doktorgradsavhandlin

Sleep and the risk of neurodegenerative disease : a population-based approach

In this thesis we investigate the role of sleep in the risk of neurodegenerative disease. We use data from the Rotterdam Study, a prospective cohort study in the general populatio

ACTIGRAPHIC ASSESSMENT OF SLEEP-ACTIVITY CYCLE IN PHYSIOPATHOLOGY: EXPERIMENTAL AND METHODOLOGICAL STUDIES

The principal objective of my research during my PhD has been the investigation of the rest-activity circadian rhythms in physiopathology, dealing with both experimental and methodological issues. On the experimental side, the focus of my research program was centered on the investigation of the rest-activity circadian rhythms in patients with binge eating disorders. On the methodological side, my activity was aimed at exploring the relationships between the actigraphy-based assessment of circadian rhythmicity and the questionnaire-based assessment of circadian typology. The thesis is organized in 11 Chapters. Chapter 1 provides a short introduction to chronobiology and to the components of a circadian rhythm. Chapter 2 describes the two most common methods used to evaluate the circadian rhythmicity, namely actigraphy and self-administered questionnaires. These two approaches have remarkable strengths and weaknesses. Actigraphy is a non-invasive method (usually based on a small, wearable actigraphic unit) that allows one to monitor the activity levels during the 24 hours, to detect the rest-activity circadian rhythm, to evaluate the activity levels during the nocturnal sleep and to assess the quality and quantity of sleep by specific sleep parameters. One alternative approach to assessment of the circadian typology of a subject is based on self-administered questionnaires. Questionnaires are obviously less objective than actigraphy-based assessments, but have the advantage of being simple and cost-effective. Chapter 3 provides a general overview of all the research projects I have taken part in throughout my PhD course. This chapter has been written with the reader in mind and aims to succinctly describe the structure and function of the subsequent chapters, 4 through 11. In Chapters 4 to 7, I will focus on the experimental core of my research activity during my PhD course, which is the chronobiological investigation of obese patients suffering from binge eating disorder. First, I will provide an overview of the features characterizing this disorder. Then, I will describe three experimental studies that were carried out in these patients with the purpose of i): quantifying their rest-activity circadian rhythm (RARs); ii) describing their sleep behaviour; iii) evaluating the effectiveness of a physical activity program as an auxiliary therapeutic approach to the traditional treatment for BED. In Chapters 8 to 10, I will illustrate the methodological core of my research activity during my PhD which aims to develop predictive formulas - based on linear regression - enabling investigators to use the questionnaire-based assessment of circadian typology (Morningness-Eveningness Questionnaire, MEQ) as a surrogate of the actigraphy-based assessment of circadian rhythmicity. A methodological project of this kind was successful is showing that both MEQ and its reduced version rMEQ are appropriate for the prediction of the actigraphy-based acrophase and this may prove useful when actigraphy-based measurements are not applicable, in so far as they result either too complex or time-consuming. Chapter 11, the final chapter, is concerned with providing concise summaries of the other studies I have been involved in during my PhD course. Seven experimental studies are described in relation to: i) the influence of chronotype on circadian rhythm (RARs), on sleep, on physical activity and on cardiac autonomic function; ii) the effects of aerobic physical activity on sleep and on markers of insulin resistance in breast cancer women; iii) the effects of short and prolonged exposure to cave environments on human physiology. The thesis also comprises an appendix containing the list of all the scientific papers that I co-authored in the course of my PhD thesis. The list reports both the published and the submitted articles

The rotterdam study: 2014 objectives and design update

The Rotterdam Study is a prospective cohort study ongoing since 1990 in the city of Rotterdam in The Netherlands. The study targets cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, oncological, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. The findings of the Rotterdam Study have been presented in over a 1,000 research articles and reports (see www.erasmus-epidemiology.nl/rotterdamstudy). This article gives the rationale of the study and its design. It also presents a summary of the major findings and an update of the objectives and methods

THE IMPACT OF ACUTE EXERCISE AND SLEEP QUALITY ON EXECUTIVE FUNCTION: THE POTENTIAL MEDIATING EFFECTS OF FUNCTIONAL CONNECTIVITY IN OLDER ADULTS

Background: Although, improved longevity is a major public health accomplishment, the prevalence of chronic disease, including cognitive impairment, increases with age. Insufficient sleep and physical inactivity exacerbate chronic disease and may accelerate the onset of dementia. While a cure remains elusive, a growing body of evidence demonstrates that exercise training facilitates better sleep and enhanced cognition. Exercise-altered patterns of neural activity, including resting state functional connectivity (rsFC) and task-based functional activation, likely coincide with and may facilitate cognitive improvements in the aging brain. Purpose: This study sought to examine the joint impact of acute exercise and sleep quality on executive function in older adults. We also aimed to determine the degree to which exercise-induced changes in prefrontal rsFC influence the relationship between sleep and executive function performance/functional activation. Methods: Using a within subjects counter-balanced design, 21 participants (aged 55-85) underwent at least three days of objective sleep monitoring (actigraphy), followed by two experimental visits on separate days. During each visit, participants engaged in 30-minutes of rest or exercise followed immediately by resting state and task-based functional MRI. After the MRI scanning session, participants completed several executive function assessments. Neuroimaging and behavioral data were processed using AFNI (version 17.1.06) and SPSS (version 23), respectively. Results: Repeated measures ANOVA and multivariate linear regression revealed two significant voxel-wise interactions in the (L) precuneus. Our findings demonstrated that acute exercise increased prefrontal rsFC and functional activation in long sleepers (> 7.5 hours/night), while decreasing these parameters for individuals with less total sleep time. Moreover, these results correspond to behavioral data demonstrating that acute exercise and adequate sleep improved select aspects of executive function performance, while decreasing inhibitory control in short sleepers alone (< 7.5 hours). Conclusion: These findings suggest that the effects of acute exercise on prefrontal rsFC are similar, or even related, to the effects of acute exercise on conflict-dependent functional activation, and that this relationship may depend on sleep duration. Moreover, our results imply that although acute exercise elicited improved executive function for those with adequate sleep, it may weaken already vulnerable, and perhaps fatigued, executive function networks among short sleepers