Phenotypic divergence in sleep and circadian cycles linked by affective state and environmental risk related to psychosis.

STUDY OBJECTIVES: Environmental cues influence circadian rhythm timing and neurochemicals involved in the regulation of affective behavior. How this interplay makes them a probable nonspecific risk factor for psychosis is unclear. We aimed to identify the relationship between environmental risk for psychosis and circadian timing phenotypes sampled from the general population. METHODS: Using an online survey, we devised a cumulative risk exposure score for each of the 1898 survey respondents based on 23 empirically verified transdiagnostic risks for psychosis, three dimensions of affect severity, psychotic-like experiences, and help-seeking behavior. Quantitative phenotyping of sleep and circadian rhythms was undertaken using at-home polysomnography, melatonin and cortisol profiles, and 3-week rest-activity behavior in individuals with a high-risk exposure load (top 15% of survey respondents, n = 22) and low-risk exposure load (bottom 15% of respondents, n = 22). RESULTS: Psychiatric symptoms were present in 100% of the high-load participants and 14% of the low-load participants. Compared to those with a low-load, high-load participants showed a later melatonin phase which was reflected by a greater degree of dispersion in circadian timing. Phase relationships between later circadian melatonin phase and later actigraphic sleep onsets were maintained and these were strongly correlated with self-reported sleep mid-points. No differences were identified from polysomnography during sleep between groups. CONCLUSION: Distinguishing circadian timing from other sleep phenotypes will allow adaptation for dosage of time-directed intervention, useful in stabilizing circadian timekeeping physiology and potentially reducing the multisystemic disruption in mental health disorders.

Individual differences in slow wave sleep architecture relate to variation in white matter microstructure across adulthood.

Sleep plays a key role in supporting brain function and resilience to brain decline. It is well known that sleep changes substantially with aging and that aging is associated with deterioration of brain structure. In this study, we sought to characterize the relationship between slow wave slope (SWslope)-a key marker of sleep architecture and an indirect proxy of sleep quality-and microstructure of white matter pathways in healthy adults with no sleep complaints. Participants were 12 young (24-27 years) and 12 older (50-79 years) adults. Sleep was assessed with nocturnal electroencephalography (EEG) and the Pittsburgh Sleep Quality Index (PSQI). White matter integrity was assessed using tract-based spatial statistics (TBSS) on tensor-based metrics such as Fractional Anisotropy (FA) and Mean Diffusivity (MD). Global PSQI score did not differ between younger (n = 11) and older (n = 11) adults (U = 50, p = 0.505), but EEG revealed that younger adults had a steeper SWslope at both frontal electrode sites (F3: U = 2, p < 0.001, F4: U = 4, p < 0.001, n = 12 younger, 10 older). There were widespread correlations between various diffusion tensor-based metrics of white matter integrity and sleep SWslope, over and above effects of age (n = 11 younger, 9 older). This was particularly evident for the corpus callosum, corona radiata, superior longitudinal fasciculus, internal and external capsule. This indicates that reduced sleep slow waves may be associated with widespread white matter deterioration. Future studies should investigate whether interventions targeted at improving sleep architecture also impact on decline in white matter microstructure in older adults.

Extracting Circadian and Sleep Parameters from Longitudinal Data in Schizophrenia for the Design of Pragmatic Light Interventions.

Sleep and circadian rhythm dysfunction is prevalent in schizophrenia, is associated with distress and poorer clinical status, yet remains an under-recognized therapeutic target. The development of new therapies requires the identification of the primary drivers of these abnormalities. Understanding of the regulation of sleep-wake timing is now sufficiently advanced for mathematical model-based analyses to identify the relative contribution of endogenous circadian processes, behavioral or environmental influences on sleep-wake disturbance and guide the development of personalized treatments. Here, we have elucidated factors underlying disturbed sleep-wake timing by applying a predictive mathematical model for the interaction of light and the circadian and homeostatic regulation of sleep to actigraphy, light, and melatonin profiles from 20 schizophrenia patients and 21 age-matched healthy unemployed controls, and designed interventions which restored sleep-circadian function. Compared to controls, those with schizophrenia slept longer, had more variable sleep timing, and received significantly fewer hours of bright light (light > 500 lux), which was associated with greater variance in sleep timing. Combining the model with the objective data revealed that non 24-h sleep could be best explained by reduced light exposure rather than differences in intrinsic circadian period. Modeling implied that late sleep offset and non 24-h sleep timing in schizophrenia can be normalized by changes in environmental light-dark profiles, without imposing major lifestyle changes. Aberrant timing and intensity of light exposure patterns are likely causal factors in sleep timing disturbances in schizophrenia. Implementing our new model-data framework in clinical practice could deliver personalized and acceptable light-dark interventions that normalize sleep-wake timing.

Do environmental risk factors for the development of psychosis distribute differently across dimensionally assessed psychotic experiences?

Psychotic experiences (PE) are associated with poorer functioning, higher distress and the onset of serious mental illness. Environmental exposures (e.g. childhood abuse) are associated with the development of PE. However, which specific exposures convey risk for each type or dimension of PE has rarely been explored. The Oxford Wellbeing Life and Sleep (OWLS) survey includes 22 environmental risk factors for psychosis and was designed to examine how environmental risks are associated with specific dimensions of PE. Multivariate logistic regression models were fit using these risk factors to predict six dimensions of PE (perceptual abnormalities, persecutory ideation, bizarre ideas, cognitive disorganisation, delusional mood and negative symptoms). Models were built using only 70% of the data, and then fit to the remaining data to assess their generalisability and quality. 1789 (27.2% men; mean age = 27.6; SD = 10.9) survey responses were analysed. The risk factors predictive of the most PE were anxiety, social withdrawal during childhood and trauma. Cannabis and depression predicted three dimensions with both predicting bizarre ideas and persecutory ideation. Psychological abuse and sleep quality each predicted two dimensions (persecutory ideation and delusional mood). Risk factors predicting one PE dimension were age (predicting cognitive disorganisation), physical abuse (bizarre ideas), bullying and gender (persecutory ideation); and circadian phase (delusional mood). These results lend support for a continuum of psychosis, suggesting environmental risks for psychotic disorders also increase the risk of assorted dimensions of PE. Furthermore, it advocates the use of dimensional approaches when examining environmental exposures for PE given that environmental risks distribute differently across dimensions.

Revisiting nocturnal heart rate and heart rate variability in insomnia: A polysomnography-based comparison of young self-reported good and poor sleepers.

Primary insomnia is often considered a disorder of 24-hr hyperarousal. Numerous attempts have been made to investigate nocturnal heart rate (HR) and its variability (HRV) as potential pathophysiological hallmarks of altered arousal levels in insomnia, with mixed results. We have aimed to overcome some of the pitfalls of previous studies by using a young, medication-free, age- and gender-matched population consisting of 43 students aged 18-30 years half with a subthreshold insomnia complaint. We employed at-home ambulatory polysomnography and compared this attenuated insomnia group to a good sleeping group. The poor sleepers had significantly higher wake after sleep onset, arousal count, mean HR in all sleep stages (with the exception of Stage 1) and lower sleep efficiency. Consistent with previous research, we also found a significant group-by-sleep stage interaction in the prediction of nocturnal HR, highlighting the insomnia group to have a lower wake-sleep HR reduction compared to good sleepers. When restricting our analyses to insomnia with objectively determined short sleep duration, we found significantly lower standard deviation of RR intervals (SDNN; a measure of HRV) compared to good sleepers. Taken together, this lends credence to the hyperarousal model of insomnia and may at least partially explain the increased prevalence of cardiovascular morbidity and mortality observed in patients with insomnia.

The Role of Daylight for Humans: Gaps in Current Knowledge.

Daylight stems solely from direct, scattered and reflected sunlight, and undergoes dynamic changes in irradiance and spectral power composition due to latitude, time of day, time of year and the nature of the physical environment (reflections, buildings and vegetation). Humans and their ancestors evolved under these natural day/night cycles over millions of years. Electric light, a relatively recent invention, interacts and competes with the natural light-dark cycle to impact human biology. What are the consequences of living in industrialised urban areas with much less daylight and more use of electric light, throughout the day (and at night), on general health and quality of life? In this workshop report, we have classified key gaps of knowledge in daylight research into three main groups: (I) uncertainty as to daylight quantity and quality needed for "optimal" physiological and psychological functioning, (II) lack of consensus on practical measurement and assessment methods and tools for monitoring real (day) light exposure across multiple time scales, and (III) insufficient integration and exchange of daylight knowledge bases from different disciplines. Crucial short and long-term objectives to fill these gaps are proposed.

INTERGROWTH-21st Project international INTER-NDA standards for child development at 2 years of age: an international prospective population-based study.

OBJECTIVES: To describe the construction of the international INTERGROWTH-21st Neurodevelopment Assessment (INTER-NDA) standards for child development at 2 years by reporting the cognitive, language, motor and behaviour outcomes in optimally healthy and nourished children in the INTERGROWTH-21st Project. DESIGN: Population-based cohort study, the INTERGROWTH-21st Project. SETTING: Brazil, India, Italy, Kenya and the UK. PARTICIPANTS: 1181 children prospectively recruited from early fetal life according to the prescriptive WHO approach, and confirmed to be at low risk of adverse perinatal and postnatal outcomes. PRIMARY MEASURES: Scaled INTER-NDA domain scores for cognition, language, fine and gross motor skills and behaviour; vision outcomes measured on the Cardiff tests; attentional problems and emotional reactivity measured on the respective subscales of the preschool Child Behaviour Checklist; and the age of acquisition of the WHO gross motor milestones. RESULTS: Scaled INTER-NDA domain scores are presented as centiles, which were constructed according to the prescriptive WHO approach and excluded children born preterm and those with significant postnatal/neurological morbidity. For all domains, except negative behaviour, higher scores reflect better outcomes and the threshold for normality was defined as ≥10th centile. For the INTER-NDA's cognitive, fine motor, gross motor, language and positive behaviour domains these are ≥38.5, ≥25.7, ≥51.7, ≥17.8 and ≥51.4, respectively. The threshold for normality for the INTER-NDA's negative behaviour domain is ≤50.0, that is, ≤90th centile. At 22-30 months of age, the cohort overlapped with the WHO motor milestone centiles, showed low postnatal morbidity (<10%), and vision outcomes, attentional problems and emotional reactivity scores within the respective normative ranges. CONCLUSIONS: From this large, healthy and well-nourished, international cohort, we have constructed, using the WHO prescriptive methodology, international INTER-NDA standards for child development at 2 years of age. Standards, rather than references, are recommended for population-level screening and the identification of children at risk of adverse outcomes.

Sleep, insomnia, and depression.

Since ancient times it is known that melancholia and sleep disturbances co-occur. The introduction of polysomnography into psychiatric research confirmed a disturbance of sleep continuity in patients with depression, revealing not only a decrease in Slow Wave Sleep, but also a disinhibition of REM (rapid eye movement) sleep, demonstrated as a shortening of REM latency, an increase of REM density, as well as total REM sleep time. Initial hopes that these abnormalities of REM sleep may serve as differential-diagnostic markers for subtypes of depression were not fulfilled. Almost all antidepressant agents suppress REM sleep and a time-and-dose-response relationship between total REM sleep suppression and therapeutic response to treatment seemed apparent. The so-called Cholinergic REM Induction Test revealed that REM sleep abnormalities can be mimicked by administration of cholinomimetic agents. Another important research avenue is the study of chrono-medical timing of sleep deprivation and light exposure for their positive effects on mood in depression. Present day research takes the view on insomnia, i.e., prolonged sleep latency, problems to maintain sleep, and early morning awakening, as a transdiagnostic symptom for many mental disorders, being most closely related to depression. Studying insomnia from different angles as a transdiagnostic phenotype has opened many new perspectives for research into mechanisms but also for clinical practice. Thus, the question is: can the early and adequate treatment of insomnia prevent depression? This article will link current understanding about sleep regulatory mechanisms with knowledge about changes in physiology due to depression. The review aims to draw the attention to current and future strategies in research and clinical practice to the benefits of sleep and depression therapeutics.

Impact of Diabetic Retinopathy on Sleep, Mood, and Quality of Life.

Purpose: Diabetic retinopathy (DR) is associated with retinal neuronal and vascular damage. DR has previously been shown to affect the photosensitive retinal ganglion cells (pRGCs). PRGCs are essential for the entrainment of circadian rhythms; thus, DR progression could lead to worsening sleep quality and mood. We investigate the relationship between increasing DR severity, and its impact on sleep quality and mood. Methods: A total of 430 participants with DR, and 303 healthy controls with no ocular disease or preexisting sleep disorders were recruited. DR severity was grouped as follows: 1, mild nonproliferative (NPDR); 2, moderate/severe NPDR; and 3, proliferative diabetic retinopathy (PDR). Sleep, mood, and quality of life were assessed using the Pittsburgh Sleep Quality Index (PSQI), quality of life (SF-36), and Hospital Anxiety and Depression Score (HADS) questionnaires. Data were analyzed by severity of DR, and correlated with sleep, QOL, and mood and compared to controls. Results: No significant difference between PSQI scores in the DR group or the control group was identified despite severity of DR. Mean anxiety and depression scores were within the normal range for both groups. Despite a lower general health and physical function, the DR group had lower anxiety scores than controls. Conclusions: These data show that even in severe DR, sleep quality is similar to controls. However, this could be explained by the majority of individuals in this study having good visual acuities in the better eye with a residual population of pRGCs remaining unaffected by DR.

Validation of 'Somnivore', a Machine Learning Algorithm for Automated Scoring and Analysis of Polysomnography Data.

Manual scoring of polysomnography data is labor-intensive and time-consuming, and most existing software does not account for subjective differences and user variability. Therefore, we evaluated a supervised machine learning algorithm, SomnivoreTM, for automated wake-sleep stage classification. We designed an algorithm that extracts features from various input channels, following a brief session of manual scoring, and provides automated wake-sleep stage classification for each recording. For algorithm validation, polysomnography data was obtained from independent laboratories, and include normal, cognitively-impaired, and alcohol-treated human subjects (total n = 52), narcoleptic mice and drug-treated rats (total n = 56), and pigeons (n = 5). Training and testing sets for validation were previously scored manually by 1-2 trained sleep technologists from each laboratory. F-measure was used to assess precision and sensitivity for statistical analysis of classifier output and human scorer agreement. The algorithm gave high concordance with manual visual scoring across all human data (wake 0.91 ± 0.01; N1 0.57 ± 0.01; N2 0.81 ± 0.01; N3 0.86 ± 0.01; REM 0.87 ± 0.01), which was comparable to manual inter-scorer agreement on all stages. Similarly, high concordance was observed across all rodent (wake 0.95 ± 0.01; NREM 0.94 ± 0.01; REM 0.91 ± 0.01) and pigeon (wake 0.96 ± 0.006; NREM 0.97 ± 0.01; REM 0.86 ± 0.02) data. Effects of classifier learning from single signal inputs, simple stage reclassification, automated removal of transition epochs, and training set size were also examined. In summary, we have developed a polysomnography analysis program for automated sleep-stage classification of data from diverse species. Somnivore enables flexible, accurate, and high-throughput analysis of experimental and clinical sleep studies.

Investigation of the impact of total sleep deprivation at home on the number of intrusive memories to an analogue trauma.

Sleep enhances the consolidation of memory; however, this property of sleep may be detrimental in situations where memories of an event can lead to psychopathology, such as following a traumatic event. Intrusive memories of trauma are emotional memories that spring to mind involuntarily and are a core feature of post-traumatic stress disorder. Total sleep deprivation in a hospital setting on the first night after an analogue trauma (a trauma film) led to fewer intrusive memories compared to sleep as usual in one study. The current study aimed to test an extension of these findings: sleep deprivation under more naturalistic conditions-at home. Polysomnographic recordings show inconsistent sleep deprivation was achieved at home. Fewer intrusive memories were reported on day 1 after the trauma film in the sleep-deprived condition. On day 2 the opposite was found: more intrusive memories in the sleep-deprived condition. However, no significant differences were found with the removal of two participants with extreme values and no difference was found in the total number of intrusive memories reported in the week following the trauma film. Voluntary memory of the trauma film was found to be slightly impaired in the sleep deprivation condition. In conclusion, compared to our eariler findings using total sleep deprivation in a hospital setting, in the current study the use of inconsistent sleep deprivation at home does not replicate the pattern of results on reducing the number of intrusive memories. Considering the conditions under which sleep deprivation (naturalistic versus hospital) was achieved requires further examination.

Developmental pathways towards mood disorders in adult life: Is there a role for sleep disturbances?

INTRODUCTION: Mood disorders are among the most prevalent and serious mental disorders and rank high among to the leading global burdens of disease. The developmental psychopathology framework can offer a life course perspective on them thus providing a basis for early prevention and intervention. Sleep disturbances, are considered risk factors for mood disorders across childhood, adolescence and adulthood. Assuming that sleep disturbances may play a pivotal role in the pathogenesis of mood disorders from a life course point of view, we reviewed the data on developmental pathways towards mood disorders in adult life in relation to sleep disturbances. METHOD: From February 2017, a systematic search was conducted in PubMed, PsycINFO and Embase electronic databases for literature on developmental pathways to mood disorders in adult life in relation to sleep disturbances and to 1) pre-natal stress, 2) early brain developmental processes, and 3) temperaments, character and attachment style. RESULTS: Eleven, 54 and 15 articles were respectively selected. CONCLUSIONS: Experimental and clinical studies revealed that exposure to prenatal/early life stress results in sleep disturbances such as poor sleep and altered circadian regulation phases and may predict or even precipitate mood disorders in adulthood. Chronic sleep disruption may interfere with neuronal plasticity, connectivity and the developing brain thus contributing to the development of mood disorders. In addition sleep and circadian dysregulations have been shown to be related to those temperaments, character and attachment styles which are considered precursors of mood disorders. Sleep and circadian behaviours may serve as early targets regarding mood disorders.

Schizotypy and Performance on an Insight Problem-Solving Task: The Contribution of Persecutory Ideation.

Insight problem solving is thought to underpin creative thought as it incorporates both divergent (generating multiple ideas and solutions) and convergent (arriving at the optimal solution) thinking approaches. The current literature on schizotypy and creativity is mixed and requires clarification. An alternate approach was employed by designing an exploratory web-based study using only correlates of schizotypal traits (paranoia, dissociation, cognitive failures, fantasy proneness, and unusual sleep experiences) and examining which (if any) predicted optimal performance on an insight problem-solving task. One hundred and twenty-one participants were recruited online from the general population and completed the number reduction task. The discovery of the hidden rule (HR) was used as a measure of insight. Multivariate logistic regression analyses highlighted persecutory ideation to best predict the discovery of the HR (OR = 1.05; 95% CI 1.01-1.10, p = 0.017), with a one-point increase in persecutory ideas corresponding to the participant being 5% more likely to discover the HR. This result suggests that persecutory ideation, above other schizotypy correlates, may be involved in insight problem solving.

Chronotype and environmental light exposure in a student population.

In humans and most other species, changes in the intensity and duration of light provide a critical set of signals for the synchronisation of the circadian system to the astronomical day. The timing of activity within the 24 h day defines an individual's chronotype, i.e. morning, intermediate or evening type. The aim of this study was to investigate the associations between environmental light exposure, due to geographical location, on the chronotype of university students. Over 6 000 university students from cities in the Northern Hemisphere (Oxford, Munich and Groningen) and Southern Hemisphere (Perth, Melbourne and Auckland) completed the Munich ChronoType Questionnaire. In parallel, light measures (daily irradiance, timing of sunrise and sunset) were compiled from satellite or ground stations at each of these locations. Our data shows that later mid-sleep point on free days (corrected for oversleep on weekends MFSsc) is associated with (i) residing further from the equator, (ii) a later sunset, (iii) spending more time outside and (iv) waking from sleep significantly after sunrise. However, surprisingly, MSFsc did not correlate with daily light intensity at the different geographical locations. Although these findings appear to contradict earlier studies suggesting that in the wider population increased light exposure is associated with an earlier chronotype, our findings are derived exclusively from a student population aged between 17 and 26 years. We therefore suggest that the age and occupation of our population increase the likelihood that these individuals will experience relatively little light exposure in the morning whilst encountering more light exposure later in the day, when light has a delaying effect upon the circadian system.

Sleep, circadian rhythms, and schizophrenia: where we are and where we need to go.

PURPOSE OF REVIEW: The review is designed to give an overview of the latest developments in research exploring the relationship between sleep and psychosis, with particular attention paid to the evidence for a causal relationship between the two. RECENT FINDINGS: The most interesting avenues currently in pursuit are focused upon sleep spindle deficits which may hallmark an endophenotype; explorations of the continuum of psychotic experiences, and experimental manipulations to explore the evidence for bidirectional causality; inflammatory markers, psychosis and sleep disturbances and finally, treatment approaches for sleep in psychosis and the subsequent impact on positive experiences. SUMMARY: Globally, large surveys and tightly controlled sleep deprivation or manipulation experiments provide good evidence for a cause-and-effect relationship between sleep and subclinical psychotic experiences. The evidence for cause-and-effect using a interventionist-causal model is more ambiguous; it would appear treating insomnia improves psychotic experiences in an insomnia cohort but not in a cohort with schizophrenia. This advocates the necessity for mechanism-driven research with dimensional approaches and in depth phenotyping of circadian clock-driven processes and sleep regulating functions. Such an approach would lead to greater insight into the dynamics of sleep changes in healthy and acute psychosis brain states.

Deep clinical and biological phenotyping of the preterm birth and small for gestational age syndromes: The INTERBIO-21 st Newborn Case-Control Study protocol.

Background: INTERBIO-21 st is Phase II of the INTERGROWTH-21 st Project, the population-based, research initiative involving nearly 70,000 mothers and babies worldwide coordinated by Oxford University and performed by a multidisciplinary network of more than 400 healthcare professionals and scientists from 35 institutions in 21 countries worldwide. Phase I, conducted 2008-2015, consisted of nine complementary studies designed to describe optimal human growth and neurodevelopment, based conceptually on the WHO prescriptive approach. The studies generated a set of international standards for monitoring growth and neurodevelopment, which complement the existing WHO Child Growth Standards. Phase II aims to improve the functional classification of the highly heterogenous preterm birth and fetal growth restriction syndromes through a better understanding of how environmental exposures, clinical conditions and nutrition influence patterns of human growth from conception to childhood, as well as specific neurodevelopmental domains and associated behaviors at 2 years of age. Methods: In the INTERBIO-21 st Newborn Case-Control Study, a major component of Phase II, our objective is to investigate the mechanisms potentially responsible for preterm birth and small for gestational age and their interactions, using deep phenotyping of clinical, growth and epidemiological data and associated nutritional, biochemical, omic and histological profiles. Here we describe the study sites, population characteristics, study design, methodology and standardization procedures for the collection of longitudinal clinical data and biological samples (maternal blood, umbilical cord blood, placental tissue, maternal feces and infant buccal swabs) for the study that was conducted between 2012 and 2018 in Brazil, Kenya, Pakistan, South Africa, Thailand and the UK. Discussion: Our study provides a unique resource for the planned analyses given the range of potentially disadvantageous exposures (including poor nutrition, pregnancy complications and infections) in geographically diverse populations worldwide. The study should enhance current medical knowledge and provide new insights into environmental influences on human growth and neurodevelopment.

The interaction between subclinical psychotic experiences, insomnia and objective measures of sleep.

Investigations into schizophrenia have revealed a high incidence of comorbidity with disturbed sleep and circadian timing. Acknowledging this comorbidity on a dimensional level, we tested prospectively whether subclinical psychotic symptoms are more prevalent in individuals with insomnia. An insomnia group (n=21) and controls (n=22) were recruited on their subjective sleep quality, recorded actigraphically for 3weeks and assessed for psychotic-like experiences with The Prodromal Questionnaire-16. Using multivariate Poisson regression analyses, we found that objective and subjective sleep measures interact to predict the highest risk for psychotic experiences. Objective measures of sleep and statistical modelling are rarely used in either clinical trials or practice for schizophrenia, yet this study highlights their value in these areas.

Insight into the Role of Photoreception and Light Intervention for Sleep and Neuropsychiatric Behaviour in the Elderly.

Light exerts influences on many physiological and behavioural functions in humans. These functions can be described as image-forming (IF) and non-image forming (NIF) visual processes, both originating in the retina of the eye. Image-forming refers to vision; the process of detecting and distinguishing shapes and colour of objects. Non-image forming refers to detecting level of light intensity or brightness of ambient space, which affects basal physiology such as cycles of rest and activity or the endocrine system. Rod and cone photoreceptors in the outer retinal layer are most important for imageforming vision, while non-image forming functions depend upon additional input from the photopigment melanopsin, which is expressed in retinal ganglion cells (RGC) that makes these cells photosensitive (pRGC). Projections of these pRGCs convey light-induced electrical impulses to a number of brain regions. Visual acuity and colour contrast naturally diminishes with age but dementia often has major effects on the visual processing systems, which impact on the quality of life. The ability of humans to manipulate their light exposure has the immediate potential to either create problems with human physiology (as in shift workers) or to compensate physiological disadvantages (of IF and NIF visual impairment). This mini-review describes the impact of aging on the function of the eye with respect to nonimage forming effects of light, summarises light intervention studies for sleep and neuropsychiatric symptoms and considers implications from photoreceptor-weighted light intensities for biologically effective light intervention and lighting solutions for patients with dementia.

Sleep-Wake Patterns and Cognition of Older Adults with Amnestic Mild Cognitive Impairment (aMCI): A Comparison with Cognitively Healthy Adults and Moderate Alzheimer's Disease Patients.

OBJECTIVE: Age-related cognitive impairment and the prevalence of neurodegenerative disease contribute to decreasing quality of life in affected individuals and their families as well as demand considerable societal responsibility. Sleep supports overall brain activity and contributes to both physical and mental health. As a result, sleep is an attractive target for exploring ways to promote health in accelerated cognitive aging. The aims of this study were to characterise cognitive performance and sleepwake behaviour in older adults with different degrees of cognitive impairment. METHODS: Cognitive ability in a variety of domains of amnestic mild cognitive impairment (aMCI) individuals, moderate AD patients and cognitively healthy adults was assessed with the Mini-Mental-State- Examination and five computerised tests (CANTABeclipse™). It was imperative to exclude mixed diagnosis, comorbidities (psychiatric, neurological, sleep disorders), anti-dementia medication, institutionalised subjects, and to study participants within their home to minimise confounders. Sleep profiles were assessed with the Jupiter Sleep Questionnaire and Pittsburgh Sleep Quality Index completed by participants and carers. Participants' sleep-wake activity was monitored for three weeks using a wrist-worn actigraph and a semi-standardised diary. Groups were compared according to their diagnostic category and then pooled to correlate sleep data with cognitive performance. RESULTS: Mild cognitive impairment in aMCI individuals was reflected in domains of verbal and visuospatial memory but not attentional capacity or episodic memory. All self-reported and objective measures of sleep quality and sleep quantity of the aMCIs were within the normal range and comparable to those of cognitively healthy controls. Moderate AD patients scored significantly lower on all cognitive tests and had lower rest-activity amplitudes and distinctively longer nightly sleep periods that were not associated with sleep disorders, sleep medication or poor sleep efficiency. Self-rated and actigraphic quality of sleep was equally good (i.e. 90% sleep efficiency) in all groups. CONCLUSION: This investigation is of clinical importance, because major confounding variables were excluded. The lack of comorbidities might be responsible for the absence of sundown syndrome and sleep disturbances commonly reported in AD patients. Whether there is interdependence between progressive decline in cognition and long sleep duration remains elusive. Future studies should address whether prolonged sleep at night and decreased day-time activity can be altered to delay the progression of cognitive decline.

Slow wave sleep and accelerated forgetting.

We investigated whether the benefit of slow wave sleep (SWS) for memory consolidation typically observed in healthy individuals is disrupted in people with accelerated long-term forgetting (ALF) due to epilepsy. SWS is thought to play an active role in declarative memory in healthy individuals and, furthermore, electrographic epileptiform activity is often more prevalent during SWS than during wakefulness or other sleep stages. We studied the relationship between SWS and the benefit of sleep for memory retention using a word-pair associates task. In both the ALF and the healthy control groups, sleep conferred a memory benefit. However, the relationship between the amount of SWS and sleep-related memory benefits differed significantly between the groups. In healthy participants, the amount of SWS correlated positively with sleep-related memory benefits. In stark contrast, the more SWS, the smaller the sleep-related memory benefit in the ALF group. Therefore, contrary to its role in healthy people, SWS-associated brain activity appears to be deleterious for memory in patients with ALF.