Neuropsychiatric studies of sleep and 24-hour activity rhythms

__Abstract__ In Nederland ervaart tot 40% van de bevolking slaapklachten, regelmatig staan deze problemen in verband met andere gezondheidsklachten. Slaap is een wisselwerking tussen twee processen. Als eerste is er de slaapbehoefte, deze wordt grotendeels bepaald door hoe lang iemand wakker is. Als tweede is er het circadiaans ritme, dit is het ongeveer 24-uur durende dag-nacht ritme van het lichaam. In deze studie hebben wij onderzocht hoe verstoringen in slaap en het 24-uurs ritme van beweging samenhangen met de lichamelijke en geestelijke gezondheid in het ERGO-onderzoek. Het onderzoek laat zien dat naarmate mensen ouder worden ze een stabieler 24-uurs ritme hebben, maar het ritme ook meer gefragmenteerd wordt, dat wil zeggen dat het vermogen om langer in een actieve of non-actieve staat te blijven beperkt is. Echter, uit ons onderzoek blijkt ook dat zowel onstabiele als meer gefragmenteerde ritmes de levensduur verkorten. Waarschijnlijk reflecteren verstoringen in het 24-uurs ritme veranderingen in de biologische klok, mogelijk zijn ze een indicatie voor een slechte gezondheid. Het hebben van stabiele ritmes op oudere leeftijd zou, bewust of onbewust, een strategie kunnen zijn voor het omgaan met een slechtere gezondheid. Ook de geestelijke gezondheid hangt samen met veranderingen in slaap en 24-uurs ritmes. De resultaten demonstreren dat verstoringen in de slaap vooral in verband staan met slechtere prestaties op geheugen- en taaltaken, terwijl verstoringen in het 24-uurs ritme vooral in verband staat met een verminderde snelheid en een verminderde uitvoer van complexere taken. Ook bleek uit het onderzoek dat 24-uurs ritmes verstoord zijn in personen met depressie- en angstklachten. Daarentegen werden bij mensen met klachten van depressie geen veranderingen gezien in de globale kenmerken van slaap, zoals de objectief gemeten slaapduur, de tijd die het kost om in slaap te vallen en de ernst van slaap apneu. Specifieke kenmerken van de slaap, zoals de hoeveelheid snelle oogbewegingen in de REM-slaap, waren echter wel veranderd in personen die depressie rapporteren. Ook hoe mensen hun slaapkwaliteit ervaren is afhankelijk van de hoeveelheid depressie- en angstklachten. Als laatste bestudeerden we slaap en het 24-uurs ritme in relatie tot het functioneren van de hypothalamus-hypofyse-bijnier as, dit is een systeem in de hersenen wat onder andere van belang is voor stress. De resultaten lieten zien dat dit systeem gerelateerd was aan zowel slaapduur, een verstoord ritme e

24-h Activity Rhythms and Health in Older Adults

__Purpose of Review:__ Circadian rhythms, including 24-h activity rhythms, change with age. Disturbances in these 24-h activity rhythms at older age have also been implied in various diseases. This review evaluates recent findings on 24-h activity rhythms and disease in older adults. __Recent Findings:__ Growing evidence supports that 24-h activity rhythm disturbances at older age are related to the presence and/or progression of disease. Longitudinal and genetic work even suggests a potential causal contribution of disturbed 24-h activity rhythms to disease development. Interventional studies targeting circadian and 24-h activity rhythms demonstrate that 24-h rhythmicity can be improved, but the effect of improving 24-h rhythmicity on disease risk or progression remains to be shown. __Summary:__ Increasing evidence suggests that 24-h activity rhythms are involved in age-related diseases. Further studies are needed to assess causality, underlying mechanisms, and the effects of treating disturbed 24-h activity rhythms on age-related disease

Sleep disturbance and intrusive memories after presenting to the emergency department following a traumatic motor vehicle accident: an exploratory analysis

Background: Sleep disturbances are common after traumatic events and have been hypothesized to be a risk factor in the development of psychopathology such as that associated with posttraumatic stress disorder (PTSD). Objective: To assess the association between intrusive memories, a core clinical feature of PTSD, and self-reported sleep disturbance shortly after experiencing or witnessing a motor vehicle accident, and whether a brief behavioural intervention (trauma reminder cue and Tetris gameplay) reduced sleep disturbance post-trauma. Method: The exploratory analyses included 71 participants (mean age 39.66, standard deviation 16.32; 37 women, 52.1%) enrolled in a previously published proof-of-concept randomized controlled trial. Participants were recruited from the emergency department after experiencing or witnessing a traumatic motor vehicle accident. Intrusive memories were assessed with a daily paper-and-pen diary for one week post-trauma, and sleep disturbances with three questions from the Impact of Event Scale-Revised assessing problems initiating sleep, problems maintaining sleep and dreams about the event at one week and one month post-trauma. Missing data were imputed 15 times. Results: The total number of intrusive memories during the first week post-trauma suggested weak to moderate pooled intercorrelations with problems initiating and maintaining sleep. An ordinal regression using imputed data suggested that the intervention had no effect on sleep disturbances, while completers only analyses suggested an improvement in problems maintaining sleep at one week. Conclusions: This exploratory study suggested that experiencing early intrusive memories is related to sleep disturbances. Sleep disturbance might be a particularly important construct to assess in studies involving intrusive memories post-trauma

Sleep, 24-h activity rhythms, and plasma markers of neurodegenerative disease

Sleep and 24-h activity rhythm disturbances are associated with development of neurodegenerative diseases and related pathophysiological processes in the brain. We determined the cross-sectional relation of sleep and 24-h activity rhythm disturbances with plasma-based biomarkers that might signal neurodegenerative disease, in 4712 middle-aged and elderly non-demented persons. Sleep and a

Sleep and 24-h activity rhythms in relation to cortisol change after a very low-dose of dexamethasone

The hypothalamic-pituitary-adrenal (HPA) axis plays an important role in sleep. Nevertheless, the association of sleep and its 24-h organization with negative feedback control of the HPA axis has received limited attention in population-based studies. We explored this association in 493 mid

Associations of the 24-h activity rhythm and sleep with cognition: A population-based study of middle-aged and elderly persons

Background: Cognitive functioning changes with age, sleep, and the circadian rhythm. We investigated whether these factors are independently associated with different cognitive domains assessed in middle-aged and elderly persons. Methods: In 1723 middle-aged and elderly persons (age 62 ± 9.4 years, mean ± standard deviation, SD) of the Rotterdam Study, we collected actigraphy recordings of on average 138 h. Actigraphy was used to quantify 24-h rhythms by calculating the stability of the rhythm over days and the fragmentation of the rhythm. Sleep parameters including total sleep time, sleep-onset latency, and wake after sleep onset were also estimated from actigraphy. Cognitive functioning was assessed with the word learning test (WLT), word fluency test (WFT), letter digit substitution task (LDST), and Stroop color word test (Stroop). Results: Persons with less stable 24-h rhythms performed worse on the LDST (. B = 0.42 per SD increase, p = 0.004) and the Stroop interference trial (. B = -1.04 per SD increase, p = 0.003) after full adjustment. Similarly, persons with more fragmented rhythms performed worse on the LDST (. B = -0.47 per SD increase, p = 0.002) and the Stroop (.

Sleep and resting-state functional magnetic resonance imaging connectivity in middle-aged adults and the elderly: A population-based study

Sleep problems increase with ageing. Increasing evidence suggests that sleep problems are not only a consequence of age-related processes, but may independently contribute to developing vascular or neurodegenerative brain disease. Yet, it remains unclear what mechanisms underlie the impact sleep problems may have on brain health in the general middle-aged and elderly population. Here, we studied sleep's relation to brain functioning in 621 participants (median age 62 years, 55% women) from the population-based Rotterdam Study. We investigated cross-sectional associations of polysomnographic and subjectively measured aspects of sleep with intrinsic neural activity measured with resting-state functional magnetic resonance imaging on a different day. We investigated both functional connectivity between regions and brain activity (blood-oxygen-level-dependent signal amplitude) within regions, hierarchically towards smaller topographical levels. We found that longer polysomnographic total sleep time is associated with lower blood-oxygen-level-dependent signal amplitude in (pre)frontal regions. No objective or subjective sleep parameters were associated with functional connectivity between or within resting-state networks. The findings may indicate a pathway through which sleep, in a ‘real-life’ population setting, impacts brain activity or regional brain activity determines t

The Risk of Dementia in Relation to Cognitive and Brain Reserve

Background: Individual differences in the risk to develop dementia remain poorly understood. These differences may partly be explained through reserve, which is the ability to buffer cognitive decline due to neuropathology and age. Objective: To determine how much early and late–life cognitive reserve (CR) and brain reserve (BR) contribute to the risk of dementia. Methods: 4,112 dementia-free participants (mean age = 66.3 years) from the Rotterdam Study were followed up for on average 6.0 years. Early-life CR and BR were defined as attained education and intracranial volume, respectively. Late-life CR was derived through variance decomposition based on cognition. Late-life BR was set as the total non-lesioned brain volume divided by intracranial volume. Results: Higher early-life CR (hazard ratio = 0.48, 95% CI = [0.21; 1.06]) but not early-life BR associated with a lower risk of incident dementia. Higher late-life CR (hazard ratio = 0.57, 95% CI = [0.48; 0.68]) and late-life BR (hazard ratio = 0.54, 95% CI = [0.43; 0.68]) also showed lower levels of dementia. Combining all proxies into one model attenuated the association between early-life CR and dementia (hazard ratio = 0.56, 95% CI = [0.25; 1.25]) whereas the other associations were unaffected. These findings were stable upon stratification for sex, age, and APOE ɛ4. Finally, high levels of l

The very low-dose dexamethasone suppression test in the general population: A cross-sectional study

Determinants of the hypothalamic-pituitary-adrenal (HPA) axis functioning are increasingly explored in population-based studies. However, functional tests measuring the negative feedback of the HPA axis cannot easily be implemented into large observational studies. Furthermore, high doses of dexamethasone often completely suppress the HPA axis in healthy persons. This study aimed to detect the effects of the health, lifestyle and sociodemographic factors, psychiatric problems and cognitive functions on the negative feedback of the HPA axis using a very low-dose (0.25 mg) dexamethasone suppression test (DST). We evaluated the associations of several determinants with the saliva cortisol concentrations after dexamethasone intake in a confounder-adjusted model also corrected for baseline saliva cortisol concentrations in the Rotterdam Study, a large population-based study (N = 1822). We found that female sex, low income, lack of exercise, instrumental disability and smoking were all independently associated with stronger suppression of the HPA axis. Even though there were no linear associations between psychiatric measures and cortisol suppression, we found that depressive symptoms and anxiety disorders were more common in persons with non-suppression of cortisol. Conversely, psychotropic medication use was related to enhanced suppression of cortisol after DST. In this large study, we found that female gender, low socioeconomic status and poor health were all related to suppression of the HPA axis. Non-linear associations were detected between the suppression of the HPA axis and common psychiatric disorders in community-dwelling persons

The longitudinal association of actigraphy-estimated sleep with grief in middle-aged and elderly persons

Most people experience grief after a loss, about 10% develop complicated grief, often accompanied by sleep complaints. Yet, the role of objectively estimated poor sleep remains unclear. Therefore, we assessed the cross-sectional and longitudinal association of actigraphy-estimated sleep with grief. We included 1,776 participants (mean age: 61.8 ± 8.9 years, 55% women) of a prospective population-based cohort. Of 1,471 participants (83%) repeated measures of grief were available (median follow-up 6 years, inter quartile range 5.6–6.3). At baseline, sleep was objectively estimated using actigraphy (mean duration 6.0 ± 0.8days). At baseline and follow-up, participants were asked about significant losses and completed the Dutch Inventory of Complicated Grief (17 items, cut-off ≥22). At baseline 1,521 (86%) participants experienced no grief, 44 (2%) acute grief (<6 months, any grief score), 158 (9%) non-complicated grief (≥6 months, grief score<22), and 53 (3%) complicated grief (≥6 months, grief score≥22). In those indicating any grief (n = 255), low sleep efficiency (B = −0.16, 95%CI = −0.30;-0.02), long sleep onset latency (B = 0.07, 95%CI = 0.01; 0.14), and long wake after sleep onset (B = 0.06, 95%CI = 0.01; 0.10) were cross-sectionally associated with more grief symptoms. Over time, those with a short total sleep time (OR = 0.59, 95%CI = 0.39; 0.91), low sleep efficiency (OR = 0.95, 95%CI = 0.91; 0.99), long sleep onset latency (OR = 1.02, 95%CI = 1.00; 1.04), and long wake after sleep onset (OR = 1.02, 95%CI = 1.00; 1.03) at baseline more often experienced complicated grief than non-complicated grief at follow-up. This study suggests that objectively estimated poor sleep is associated with grief over time. Poor sleep might not only accompany grief, but also be a risk factor for developing complicated grief after a loss