The effect of bright light on rest-activity rhythms and behavioural and psychological symptoms of dementia

De fleste som lever med demens har også atferdsmessige- og psykologiske symptomer ved demens (APSD) som for eksempel depresjon, angst, agitasjon, og søvnforstyrrelser. APSD påvirker livskvalitet og pleiebehov. Aktivitetsrytmen er ofte endret hos personer med demens. For eksempel kan søvn og våkenhet forekomme uregelmessig, med rastløshet og atferdsforstyrrelser på kvelds- og nattestid, og søvn på dagtid. Forstyrrelser i søvn og våkenhet har negative konsekvenser for daglig fungering, kognisjon, og affekt. I tillegg er det trolig at denne typen problemer gjenspeiler forstyrrelse av den endogene cirkadiane rytmen. APSD, inkludert søvnproblemer, behandles ofte medikamentelt, på tross av at slik behandling har begrenset effekt og kan medføre alvorlige bivirkninger. Lys påvirker den cirkadiane rytmen, og kan i tillegg ha en innvirkning på våkenhet og humør. Disse omtales som ikke-visuelle effekter av lys. Lysterapi er en ikke-medikamentell behandling som ifølge noen tidligere studier kan ha en positiv effekt på affekt, agitasjon, søvnforstyrrelser og aktivitetsrytmer hos personer med demens, men resultatene fra ulike studier har ikke vært entydige. Målet med denne avhandlingen var å undersøke effekten av lysterapi på APSD og aktivitetsrytmer, gjennom en klynge-randomisert placebo-kontrollert studie over 24 uker – DEM.LIGHT studien. Et sekundært mål, og et forarbeid til hovedstudien, var å undersøke lysforholdene ved demensenheter på sykehjem. Artikkel 1 presenterte en undersøkelse av lys på 15 demensenheter i Bergen kommune, gjennomført ved to årstider og med lysmålinger i ulike retninger. Lysmålingene ble sammenlignet med grenseverdier basert på anbefalinger og tidligere forskning. Lysverdiene ble oppgitt i måleenheter som er relevante for ikkevisuelle effekter av lys. Artikkel 2 og 3 rapporterte resultater fra DEM.LIGHTstudien, gjennomført på 8 sykehjem med 69 deltagere. Intervensjonen besto av takmonterte LED-lys i fellesstuen på 4 demensenheter, som gav lys av ulik styrke og fargetemperatur gjennom dagen. Maksimalt nivå for intervensjonen var ~1000 lx og 6000 K, mellom kl. 10:00 og 15:00, målt vertikalt 1.2 m over gulvet. Kontrollgruppen (4 demensenheter) hadde standard innendørsbelysning (~150–300 lx, 3000 K). Data ble innhentet ved baseline, og etter 8, 16 og 24 uker. Artikkel 2 undersøkte effekten av lysbehandlingen på aktivitetsrytmer registrert med aktigrafi, og artikkel 3 undersøkte effekten på proxy-vurderte APSD-mål (Cornell Scale for Depression in Dementia, CSDD og Neuropsychiatric Inventory – Nursing Home Version, NPI-NH). Effekten av behandlingen ble analysert ved bruk av blandede regresjonsmodeller (multilevel models), med demensstadium (Functional Assessment Staging Tool, FAST skåre) ved baseline som en a priori bestemt kovariat. I tillegg ble baselineskårer på utfallsmålene inkludert som kovariater i analysene til artikkel 3. I artikkel 1 fant vi at de fleste målingene av lyset på demensenhetene var under terskelverdiene, uavhengig av årstid og måleretning. I artikkel 2 fant vi ingen forbedring av aktivitetsrytmen etter BLT hos personer med demens når vi korrigerte for multippel testing. Uten slik korreksjon var akrofasen (tidspunktet for aktivitetrytmens makspunkt) signifikant mindre forsinket (med en time) i uke 16 i intervensjonsgruppen sammenlignet med kontrollgruppen. Artikkel 3 rapporterte blandede resultater for effekten av lysintervensjonen på APSD. Det var en signifikant effekt på underskalaer som måler affektive symptomer i uke 16, men ikke i uke 8 eller 24, etter korreksjon for multippel testing. Det var en signifikant effekt på CSDD og NPI-NH total-skårer i uke 16 før, men ikke etter, korreksjon for multippel testing. Det var ingen signifikant effekt på andre underskalaer. Oppsummert peker funnene fra artikkel 1 mot at lyset på demensenheter er utilstrekkelig sett opp mot terskelverdier for ikke-visuelle effekter av lys. Likevel var resultatene fra DEM.LIGHT-studien, som økte belysningen på demensenheter, blandede. Basert på disse resultatene kan vi ikke anbefale takmontert lysterapi ved demensenheter. Det er imidlertid flere metodologiske utfordringer og karakteristikker ved utvalget som begrenser generaliserbarheten til disse funnene.Most people living with dementia have behavioural and psychological symptoms of dementia (BPSD), such as depression, anxiety, agitation, and disturbed sleep, that strongly affect well-being and care needs. The rest-activity rhythm (RAR), i.e., the diurnal pattern of activity, is often altered in individuals with dementia. Sleep and wakefulness may, for instance, occur at irregular intervals, characterised by restlessness and behavioural disturbances at night, and napping during the day. This disruption of the sleep-wake pattern is detrimental to functioning and well-being. It is also thought to reflect deterioration of the endogenous circadian rhythm. Pharmacotherapy is often used to treat BPSD, including sleep disturbances, but has limited efficacy and is associated with severe side effects. Light influences the circadian rhythm, and can also have effects on alertness and mood. These are collectively referred to as non-image forming (NIF) effects of light. Bright light treatment (BLT) is a non-pharmacological intervention that has been found to improve affective symptoms, agitation, sleep disorders, and RARs in people with dementia in some studies, but results have been mixed. The main aim of this thesis was to investigate the effect of BLT on RARs and BPSD in a 24-week cluster randomised controlled trial - the DEM.LIGHT trial (ClinicalTrials.gov identifier: NCT03357328). A secondary aim, and preparation for the trial, was to investigate the illumination in nursing home dementia units. Paper 1 was a field study investigating nursing home illumination in 15 dementia units across seasons and gaze directions. Measured illuminances were compared to thresholds suggested by industry standards and research, and measurement units relevant to NIF effects of light were used. Paper 2 and 3 reported results from the DEM.LIGHT trial, conducted at 8 dementia units, with 69 participants. In the intervention group (4 units), ceiling mounted LED-panels provided ambient light of varying illuminance and correlated colour temperature throughout the day, with a peak of ~1000 lx and 6000 K (measured vertically at 1.2 m) between 10:00 and 15:00. In the control group (4 units), standard indoor light of ~150–300 lx, 3000 K was used. Data were collected at baseline and at 8, 16, and 24 weeks. Paper 2 investigated the effect of the intervention on actigraphy-measured RARs, and paper 3 investigated the effect on proxy-rated BPSD measures: the Cornell Scale for Depression in Dementia (CSDD) and the Neuropsychiatric Inventory - Nursing Home Version (NPI-NH). Treatment effects were analysed using multilevel regression models, with dementia stage (score on the Functional Assessment Staging Tool, FAST) at baseline as a pre-determined covariate. In addition, baseline scores on the outcome measures were included as covariates in the models in paper 3. In paper 1 we found that, regardless of season and gaze direction, nearly all measured illuminances in dementia units fell below the thresholds. In paper 2, we found that there was no effect of BLT on RAR outcomes in people with dementia when controlling for multiple testing. Without controlling for multiple testing, the acrophase (i.e., timing of the activity peak) was significantly less delayed (by one hour) in the intervention group compared to the control group, in week 16. Paper 3 found mixed results for the effect of BLT on BPSD. There was a significant reduction of scores on affective subscales in the intervention group in week 16, but not at other follow-ups, after controlling for multiple testing. There was a significant effect on the NPI-NH and CSDD total scores in week 16 before, but not after, controlling for multiple testing. There were no significant effects on other subscales. In conclusion, the findings in paper 1 suggest that illumination in dementia units is inadequate compared to thresholds suggested for NIF effects of light. However, the results of the DEM.LIGHT trial, which increased the indoor illumination in dementia units, were mixed. Based on our results, we cannot make clear recommendations regarding the use of ambient BLT in dementia units. Several methodological challenges and sample characteristics may limit the generalisability of these results.Doktorgradsavhandlin

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

Detection of melatonin-onset in real settings via wearable sensors and artificial intelligence : a pilot study

Circadian rhythms modulate physiological and behavioral processes of approximately 24-h periodicity. Alterations in the circadian timing system may lead to cardiovascular, metabolic or neurological diseases, cancers and sleep disorders, as well as to disruption of quality of life. Circadian rhythms can be tracked via laboratory tests measuring hormones in salivary, urinary or blood samples, which are collected in controlled environments. These tests are unsuitable for continuous monitoring in real-life, being expensive and time consuming, producing discrete information (i.e., few values per day) and requiring controlled environmental conditions (e.g., exposure to light can alter the samples). Thus, there is a need to develop non-invasive methods and tools to track circadian rhythms in real-life conditions

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

Sensing Technology to Monitor Behavioral and Psychological Symptoms and to Assess Treatment Response in People With Dementia. A Systematic Review

Background: The prevalence of dementia is expected to rapidly increase in the next decades, warranting innovative solutions improving diagnostics, monitoring and resource utilization to facilitate smart housing and living in the nursing home. This systematic review presents a synthesis of research on sensing technology to assess behavioral and psychological symptoms and to monitor treatment response in people with dementia. Methods: The literature search included medical peer-reviewed English language publications indexed in Embase, Medline, Cochrane library and Web of Sciences, published up to the 5th of April 2019. Keywords included MESH terms and phrases synonymous with “dementia”, “sensor”, “patient”, “monitoring”, “behavior”, and “therapy”. Studies applying both cross sectional and prospective designs, either as randomized controlled trials, cohort studies, and case-control studies were included. The study was registered in PROSPERO 3rd of May 2019. Results: A total of 1,337 potential publications were identified in the search, of which 34 were included in this review after the systematic exclusion process. Studies were classified according to the type of technology used, as (1) wearable sensors, (2) non-wearable motion sensor technologies, and (3) assistive technologies/smart home technologies. Half of the studies investigated how temporarily dense data on motion can be utilized as a proxy for behavior, indicating high validity of using motion data to monitor behavior such as sleep disturbances, agitation and wandering. Further, up to half of the studies represented proof of concept, acceptability and/or feasibility testing. Overall, the technology was regarded as non-intrusive and well accepted. Conclusions: Targeted clinical application of specific technologies is poised to revolutionize precision care in dementia as these technologies may be used both by patients and caregivers, and at a systems level to provide safe and effective care. To highlight awareness of legal regulations, data risk assessment, and patient and public involvement, we propose a necessary framework for sustainable ethical innovation in healthcare technology. The success of this field will depend on interdisciplinary cooperation and the advance in sustainable ethic innovation.publishedVersio

Statistical learning for the analysis of multimodal sleep in older men

Introduction: Sleep is essential for human development and maintaining physical and mental health. Sleep disturbances have long been known to be associated with mental illness, metabolic, neurological or other systems diseases. Knowing what factors are associated with sleep quality and sleep-wake homeostasis is important for the study of sleep disorders and may potentially inform new treatment strategies to preserve patients' normal sleep-wake cycle. The present study aims to identify what actigraphic measures, self-reported sleep variables, and other chronic diseases, medications are related to the percentage of slow-wave sleep and delta power spectra in older men. Method: Categorical variables are summarized using frequencies and percentages. For continuous variables, means and standard deviations are computed, and distributions are displayed in histograms. Possible correlations among variables are examined by a matrix of scatterplots and Pearson correlation coefficients. The LASSO is used for feature selection in multiple linear regression models and multiple imputation used to overcome missing data. Results: The past month sleep hours (β=0.0896, p<0.05), kidney diseases (β=0.161, p<0.05) and oral corticosteroids (β=0.148, p<0.05) are significantly positively associated with percentage of deep sleep, while sleep apnea severity (β=-0.0043, p<0.001), age ( = -0.0042, p<0.01), Benzodiazepine use ( -0.155, p<0.001), NSAIDS use (β=-0.0418, p<0.05), and race(β=-0.0476, p<0.01) are negatively associated when controlling other variables’ effect. Cognitive function (β=0.0015, p<0.001), and oral corticosteroids (β=0.0733, p<0.01) are positively related to delta power, while sleep apnea severity (β=-0.0011, p<0.001), age ( = -0.0013, p<0.05), mean sleep minutes (-0.0002, p<0.001) , BMI (-0.031, p<0.001), Diabetes (β=-0.0404, p<0.001), Benzodiazepine use ( -0.061, p<0.001), and the consumption of alcoholic beverages (β=-0.0125, p<0.05) are negatively related to delta power when controlling other covariates. Conclusions: Our study suggested several factors are either positively or negatively associated with the percentage of deep sleep and delta power. Most of the factors affect the percentage of slow-wave sleep and delta power in the same direction. Public Health Significance: These analyses may provide important messages for future study and potential medical interventions application

Events of daily living classification on an ambient assisted living environment

Dissertação de mestrado em Engenharia Eletrónica Industrial e ComputadoresPopulation ageing is a global demographic challenge and countries all around the world are facing significant pressure on their health and social care systems in order to mitigate the effects of it. The emerging social aspect introduced some crucial challenges to society and greater demands on the actual health care sector, which led to the emergence and increased integration of agefriendly innovative welfare technological-based care services for safe and independent ageing, including the assisted living technologies based on Ambient Intelligence (AmI) paradigm and Pervasive HealthCare. The Ambient Assisted Living (AAL) systems intend to provide caregivers with a detailed overview of their Events of Daily Living (EDL), which constitutes a clinical criteria to evaluate activity limitations. This dissertation addresses these challenges and contributes to the Ambient Assisted Living research, by means of a holistic solution composed of a beyond the state-of-the-art AAL technologies, representing a novel approach to assist in the investigation and on the modeling of a subset of Events of Daily Living (EDL), for sustaining independent living and a continual naturalistic assessment of health. The investigation was focused on 1) developing a multisensorial pervasive Research Data Acquistion (RDA) Platform with embedded Ambient Intelligence (AmI), 2) COTS to verify their validity and reliability for healthcare applications. The proposed solution has been thoroughly evaluated in the Ambient Assisted Living Laboratory that showed its effectiveness classifying EDL through the application of the AAL paradigm in the real world.O envelhecimento populacional é um desafio demográfico global e os países em todo o mundo estão sob com enorme pressão nos seus sistemas de saúde a fim de mitigar os efeitos que poderão advir. O aspecto social emergente introduziu alguns desafios cruciais para a sociedade e uma maior sobrecarga no setor de saúde, o que levou ao surgimento e aumento da integração de serviços inovadores de assistência social, de modo a que haja um envelhecimento seguro e independente, incluindo as tecnologias de assistência à vida com base no paradigma de Ambient Intelligence (AmI) e no Pervasive HealthCare, os sistemas de Ambient Assisted Living (AAL). Eles pretendem fornecer aos profissionais de saúde uma visão detalhada de seu Events of Daily Living (EDL), que constitui um critério clínico para avaliar as limitações da atividade. Para enfrentar estes desafios, esta dissertação contribui para a pesquisa na área de Ambient Assisted Living, por meio de uma solução holística composta por uma tecnologia além das tecnologias state-of-the-art, representando uma nova abordagem para auxiliar na investigação e na modelação de um subconjunto de Events of Daily Living (EDL), para sustentar uma vida independente e uma avaliação naturalística contínua da saúde. A investigação foi focada em 1) desenvolver uma plataforma multisensorial pervasiva Research Data Acquistion (RDA) com Ambient Intelligence (AmI), 2) COTS para verificar a sua validade e fiabilidade para aplicações de assistência médica. A solução proposta foi avaliada no Ambient Assisted Living Laboratory, que mostrou bastante eficácia ao classificar EDL através da aplicação do paradigma AAL no mundo real

MyRoom: A user-centred model of affective responsive architecture

Can my immediate physical environment affect how I feel? The instinctive answer to this question must be a resounding “yes”. What might seem a throwaway remark is increasingly borne out by research in environmental and behavioural psychology, and in the more recent discipline of Evidence-Based Design. Research outcomes are beginning to converge with findings in neuroscience and neurophysiology, as we discover more about how the human brain and body functions, and reacts to environmental stimuli. What we see, hear, touch, and sense affects each of us psychologically and, by extension, physically, on a continual basis. The physical characteristics of our daily environment thus have the capacity to profoundly affect all aspects of our functioning, from biological systems to cognitive ability. This has long been understood on an intuitive basis, and utilised on a more conscious basis by architects and other designers. Recent research in evidence-based design, coupled with advances in neurophysiology, confirm what have been previously held as commonalities, but also illuminate an almost frightening potential to do enormous good, or alternatively, terrible harm, by virtue of how we make our everyday surroundings. The thesis adopts a design methodology in its approach to exploring the potential use of wireless sensor networks in environments for elderly people. Vitruvian principles of “commodity, firmness and delight” inform the research process and become embedded in the final design proposals and research conclusions. The issue of person-environment fit becomes a key principle in describing a model of continuously-evolving responsive architecture which makes the individual user its focus, with the intention of promoting wellbeing. The key research questions are: What are the key system characteristics of an adaptive therapeutic single-room environment? How can embedded technologies be utilised to maximise the adaptive and therapeutic aspects of the personal life-space of an elderly person with dementia?