Publications by authors named "Annemarie I Luik"

68 Publications

Psychosocial factors and cancer incidence (PSY-CA): Protocol for individual participant data meta-analyses.

Brain Behav 2021 Sep 2:e2340. Epub 2021 Sep 2.

Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht and Utrecht University, Utrecht, the Netherlands.

Objectives: Psychosocial factors have been hypothesized to increase the risk of cancer. This study aims (1) to test whether psychosocial factors (depression, anxiety, recent loss events, subjective social support, relationship status, general distress, and neuroticism) are associated with the incidence of any cancer (any, breast, lung, prostate, colorectal, smoking-related, and alcohol-related); (2) to test the interaction between psychosocial factors and factors related to cancer risk (smoking, alcohol use, weight, physical activity, sedentary behavior, sleep, age, sex, education, hormone replacement therapy, and menopausal status) with regard to the incidence of cancer; and (3) to test the mediating role of health behaviors (smoking, alcohol use, weight, physical activity, sedentary behavior, and sleep) in the relationship between psychosocial factors and the incidence of cancer.

Methods: The psychosocial factors and cancer incidence (PSY-CA) consortium was established involving experts in the field of (psycho-)oncology, methodology, and epidemiology. Using data collected in 18 cohorts (N = 617,355), a preplanned two-stage individual participant data (IPD) meta-analysis is proposed. Standardized analyses will be conducted on harmonized datasets for each cohort (stage 1), and meta-analyses will be performed on the risk estimates (stage 2).

Conclusion: PSY-CA aims to elucidate the relationship between psychosocial factors and cancer risk by addressing several shortcomings of prior meta-analyses.
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http://dx.doi.org/10.1002/brb3.2340DOI Listing
September 2021

Substitutions of physical activity, sedentary behaviour and sleep: associations with mental health in middle-aged and elderly persons.

J Epidemiol Community Health 2021 Jul 22. Epub 2021 Jul 22.

Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, Zuid-Holland, Netherlands

Background: Physical activity, sedentary behaviour and sleep are potential risk factors of mental health disorders, but previous studies have not considered the dependency between these activity domains. Therefore, we examined the associations of reallocations of time among older adults' physical activity, sedentary behaviour and sleep with depressive and anxiety symptoms using compositional isotemporal substitution analyses.

Methods: We included 1943 participants (mean age 71 years, SD: 9; 52% women) from the population-based Rotterdam Study. Between 2011 and 2016, we collected accelerometer data (mean duration 5.8 days, SD: 0.4) on physical activity, sedentary behaviour and sleep and self-reported data on depressive symptoms and anxiety.

Results: A reallocation of 30 min more moderate-to-vigorous physical activity was associated with a -0.55 (95% CI -1.04 to -0.06) points lower depressive symptoms score when replacing sleep and a -0.59 (95% CI -1.06 to -0.12) points lower score when replacing sedentary behaviour, but not when replacing light physical activity (-0.70, 95% CI -1.63 to 0.24). No associations were found for anxiety.

Conclusion: Replacing sedentary behaviour or sleep with more moderate-to-vigorous physical activity was associated with less depressive symptoms, suggesting that mainly intensive types of physical activity are important for middle-aged and older adults in relation to depressive symptoms.
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http://dx.doi.org/10.1136/jech-2020-215883DOI Listing
July 2021

Diagnostic Validity of the Sleep Condition Indicator to Screen for Diagnostic and Statistical Manual-5 Insomnia Disorder in Patients with Parkinson's Disease.

Eur Neurol 2021 28;84(5):333-339. Epub 2021 Jun 28.

Sleep & Circadian Neuroscience Institute, Department of Epidemiology, Nuffield Department of Clinical Neurosciences, Erasmus MC University Medical Center, Rotterdam, Netherlands and University of Oxford, Oxford, United Kingdom.

Background: Insomnia is a highly common sleep disorder in patients with Parkinson's disease (PD). Yet, no screening questionnaires following the Diagnostic and Statistical Manual-5 (DSM-5) criteria have been validated in PD patients.

Objectives: We assessed the validity and reliability of the French version of the sleep condition indicator (SCI), in patients with PD.

Methods: In a sample of 65 patients (46% women, mean age 63.8 ± 7.9 years) with PD, but without dementia, insomnia was assessed with a clinical interview and the SCI. Statistical analyses were performed to determine the reliability, construct validity, and divergent validity of the SCI. In addition, an explanatory factor analysis was performed to assess the underlying structure of the SCI.

Results: Of the 65 patients (mean duration PD 9.7 ± 6.9 years), 51% met the criteria for insomnia disorder when measured with a clinical interview. The mean SCI score was 18.05 ± 8.3. The internal consistency (α = 0.89) of the SCI was high. Using the previously defined cutoff value of ≤16, the area under the receiver operating characteristic curve was 0.86 with a sensitivity of 86% and a specificity of 87%. Exploratory factor analysis showed a 2-factor structure with a focus on sleep and daytime effects. Additionally, good construct and divergent validity were demonstrated.

Conclusion: The SCI can be used as a valid and reliable screener for DSM-5 insomnia disorder in PD patients. Due to its short length, it is useful in both clinical practice and scientific research.
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http://dx.doi.org/10.1159/000508185DOI Listing
June 2021

Cross-sectional and Longitudinal Associations Between Tinnitus and Mental Health in a Population-Based Sample of Middle-aged and Elderly Persons.

JAMA Otolaryngol Head Neck Surg 2021 Aug;147(8):708-716

Department of Otorhinolaryngology, Head and Neck Surgery, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.

Importance: Tinnitus is a common disorder, but its impact on daily life varies widely in population-based samples. It is unclear whether this interference in daily life is associated with mental health problems that are commonly detected in clinical populations.

Objective: To investigate the association of tinnitus and its interference in daily life with symptoms of depression and anxiety and poor sleep quality in a population-based sample of middle-aged and elderly persons in a cross-sectional analysis and during a 4-year follow-up.

Design, Setting, And Participants: This cohort study evaluated data from the population-based Rotterdam Study of individuals 40 years or older living in Rotterdam, the Netherlands. Between 2011 and 2016, data on tinnitus were obtained during a home interview at least once for 6128 participants. Participants with information on depressive and anxiety symptoms and self-rated sleep quality, with Mini-Mental State Examination scores indicating unimpaired cognition, and with repeatedly obtained tinnitus and mental health outcome data were included. Data analyses were conducted between September 2019 and April 2020.

Main Outcomes And Measures: The presence of tinnitus and its interference with daily life were assessed during a home interview. Depressive symptoms were assessed with the Center for Epidemiologic Studies-Depression, anxiety symptoms with the Hospital Anxiety and Depression Scale, and sleep quality with the Pittsburgh Sleep Quality Index. Linear regression analyses and linear mixed models adjusted for relevant confounders were used to assess the cross-sectional and longitudinal association of tinnitus with mental health.

Results: Of 5418 complete-case participants (mean [SD] age, 69.0 [9.8] years; 3131 [57.8%] women), 975 (mean [SD] age, 71.7 [4.5] years; 519 [53.2%] women) had repeated measurements available for follow-up analyses. Compared with participants without tinnitus and participants with nonbothersome tinnitus, participants with tinnitus interfering with daily life reported more depressive (difference, 0.20; 95% CI, 0.11-0.28) and anxiety (difference, 0.15; 95% CI, 0.08-0.22) symptoms and poorer sleep quality (difference, 0.10; 95% CI, 0.03-0.16). Compared with participants without tinnitus, participants with nonbothersome tinnitus also reported more depressive (difference, 0.06; 95% CI, 0.03-0.09) and anxiety (difference, 0.05; 95% CI, 0.02-0.07) symptoms and poorer sleep quality (difference, 0.05; 95% CI, 0.03-0.08). Individuals indicating more interference with daily life reported having more mental health problems. During a mean follow-up of 4.4 years (range, 3.5-5.1 years), participants with tinnitus reported more anxiety symptoms and poorer sleep quality than those without tinnitus.

Conclusions And Relevance: Findings of this population-based cohort study indicate that tinnitus was associated with more mental health problems in middle-aged and elderly persons in the general population, in particular when tinnitus interfered with daily life but not solely. Over time, more severe tinnitus was associated with an increase in anxiety symptoms and poor sleep quality. This outcome suggests that mental health problems may be part of the burden of tinnitus, even among individuals who do not report their tinnitus interfering with daily life.
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http://dx.doi.org/10.1001/jamaoto.2021.1049DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193541PMC
August 2021

ENIGMA-Sleep: Challenges, opportunities, and the road map.

J Sleep Res 2021 Apr 28:e13347. Epub 2021 Apr 28.

Department of Sleep and Cognition, Netherlands Institute for Neuroscience (NIN), an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, The Netherlands.

Neuroimaging and genetics studies have advanced our understanding of the neurobiology of sleep and its disorders. However, individual studies usually have limitations to identifying consistent and reproducible effects, including modest sample sizes, heterogeneous clinical characteristics and varied methodologies. These issues call for a large-scale multi-centre effort in sleep research, in order to increase the number of samples, and harmonize the methods of data collection, preprocessing and analysis using pre-registered well-established protocols. The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) consortium provides a powerful collaborative framework for combining datasets across individual sites. Recently, we have launched the ENIGMA-Sleep working group with the collaboration of several institutes from 15 countries to perform large-scale worldwide neuroimaging and genetics studies for better understanding the neurobiology of impaired sleep quality in population-based healthy individuals, the neural consequences of sleep deprivation, pathophysiology of sleep disorders, as well as neural correlates of sleep disturbances across various neuropsychiatric disorders. In this introductory review, we describe the details of our currently available datasets and our ongoing projects in the ENIGMA-Sleep group, and discuss both the potential challenges and opportunities of a collaborative initiative in sleep medicine.
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http://dx.doi.org/10.1111/jsr.13347DOI Listing
April 2021

Multi-ancestry genome-wide gene-sleep interactions identify novel loci for blood pressure.

Mol Psychiatry 2021 Apr 15. Epub 2021 Apr 15.

Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

Long and short sleep duration are associated with elevated blood pressure (BP), possibly through effects on molecular pathways that influence neuroendocrine and vascular systems. To gain new insights into the genetic basis of sleep-related BP variation, we performed genome-wide gene by short or long sleep duration interaction analyses on four BP traits (systolic BP, diastolic BP, mean arterial pressure, and pulse pressure) across five ancestry groups in two stages using 2 degree of freedom (df) joint test followed by 1df test of interaction effects. Primary multi-ancestry analysis in 62,969 individuals in stage 1 identified three novel gene by sleep interactions that were replicated in an additional 59,296 individuals in stage 2 (stage 1 + 2 P < 5 × 10), including rs7955964 (FIGNL2/ANKRD33) that increases BP among long sleepers, and rs73493041 (SNORA26/C9orf170) and rs10406644 (KCTD15/LSM14A) that increase BP among short sleepers (P < 5 × 10). Secondary ancestry-specific analysis identified another novel gene by long sleep interaction at rs111887471 (TRPC3/KIAA1109) in individuals of African ancestry (P = 2 × 10). Combined stage 1 and 2 analyses additionally identified significant gene by long sleep interactions at 10 loci including MKLN1 and RGL3/ELAVL3 previously associated with BP, and significant gene by short sleep interactions at 10 loci including C2orf43 previously associated with BP (P < 10). 2df test also identified novel loci for BP after modeling sleep that has known functions in sleep-wake regulation, nervous and cardiometabolic systems. This study indicates that sleep and primary mechanisms regulating BP may interact to elevate BP level, suggesting novel insights into sleep-related BP regulation.
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http://dx.doi.org/10.1038/s41380-021-01087-0DOI Listing
April 2021

Investigating the relationships between unfavourable habitual sleep and metabolomic traits: evidence from multi-cohort multivariable regression and Mendelian randomization analyses.

BMC Med 2021 Mar 18;19(1):69. Epub 2021 Mar 18.

Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands.

Background: Sleep traits are associated with cardiometabolic disease risk, with evidence from Mendelian randomization (MR) suggesting that insomnia symptoms and shorter sleep duration increase coronary artery disease risk. We combined adjusted multivariable regression (AMV) and MR analyses of phenotypes of unfavourable sleep on 113 metabolomic traits to investigate possible biochemical mechanisms linking sleep to cardiovascular disease.

Methods: We used AMV (N = 17,368) combined with two-sample MR (N = 38,618) to examine effects of self-reported insomnia symptoms, total habitual sleep duration, and chronotype on 113 metabolomic traits. The AMV analyses were conducted on data from 10 cohorts of mostly Europeans, adjusted for age, sex, and body mass index. For the MR analyses, we used summary results from published European-ancestry genome-wide association studies of self-reported sleep traits and of nuclear magnetic resonance (NMR) serum metabolites. We used the inverse-variance weighted (IVW) method and complemented this with sensitivity analyses to assess MR assumptions.

Results: We found consistent evidence from AMV and MR analyses for associations of usual vs. sometimes/rare/never insomnia symptoms with lower citrate (- 0.08 standard deviation (SD)[95% confidence interval (CI) - 0.12, - 0.03] in AMV and - 0.03SD [- 0.07, - 0.003] in MR), higher glycoprotein acetyls (0.08SD [95% CI 0.03, 0.12] in AMV and 0.06SD [0.03, 0.10) in MR]), lower total very large HDL particles (- 0.04SD [- 0.08, 0.00] in AMV and - 0.05SD [- 0.09, - 0.02] in MR), and lower phospholipids in very large HDL particles (- 0.04SD [- 0.08, 0.002] in AMV and - 0.05SD [- 0.08, - 0.02] in MR). Longer total sleep duration associated with higher creatinine concentrations using both methods (0.02SD per 1 h [0.01, 0.03] in AMV and 0.15SD [0.02, 0.29] in MR) and with isoleucine in MR analyses (0.22SD [0.08, 0.35]). No consistent evidence was observed for effects of chronotype on metabolomic measures.

Conclusions: Whilst our results suggested that unfavourable sleep traits may not cause widespread metabolic disruption, some notable effects were observed. The evidence for possible effects of insomnia symptoms on glycoprotein acetyls and citrate and longer total sleep duration on creatinine and isoleucine might explain some of the effects, found in MR analyses of these sleep traits on coronary heart disease, which warrant further investigation.
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http://dx.doi.org/10.1186/s12916-021-01939-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7971964PMC
March 2021

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

J Psychiatr Res 2021 05 25;137:66-72. Epub 2021 Feb 25.

Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, the Netherlands; Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center Rotterdam, the Netherlands. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jpsychires.2021.02.042DOI Listing
May 2021

Design and overview of the Origins of Alzheimer's Disease Across the Life course (ORACLE) study.

Eur J Epidemiol 2021 Jan 16;36(1):117-127. Epub 2020 Dec 16.

Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.

Brain development and deterioration across the lifespan are integral to the etiology of late-life neurodegenerative disease. Factors that influence the health of the adult brain remain to be elucidated and include risk factors, protective factors, and factors related to cognitive and brain reserve. To address this knowledge gap we designed a life-course study on brain health, which received funding through the EU ERC Programme under the name Origins of Alzheimer's Disease Across the Life course (ORACLE) Study. The ORACLE Study is embedded within Generation R, a prospective population-based cohort study of children and their parents, and links this with the Rotterdam Study, a population-based study in middle-aged and elderly persons. The studies are based in Rotterdam, the Netherlands. Generation R focuses on child health from fetal life until adolescence with repeated in-person examinations, but has also included data collection on the children's parents. The ORACLE Study aims to extend the parental data collection in nearly 2000 parents with extensive measures on brain health, including neuroimaging, cognitive testing and motor testing. Additionally, questionnaires on migraine, depressive symptoms, sleep, and neurological family history were completed. These data allow for the investigation of longitudinal influences on adult brain health as well as intergenerational designs involving children and parents. As a secondary focus, the sampling is enriched by mothers (n = 356) that suffered from hypertensive disorders during pregnancy in order to study brain health in this high-risk population. This article provides an overview of the rationale and the design of the ORACLE Study.
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http://dx.doi.org/10.1007/s10654-020-00696-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847463PMC
January 2021

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

Sci Rep 2020 11 26;10(1):20691. Epub 2020 Nov 26.

Department of Epidemiology, Erasmus MC, University Medical Center, Doctor Molewaterplein 40, 3015 GD, Rotterdam, The Netherlands.

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 activity rhythms were measured using the Pittsburgh Sleep Quality Index and actigraphy. Simoa assays were used to measure plasma levels of neurofilament light chain, and additionally β-amyloid 40, β-amyloid 42, and total-tau. We used linear regression, adjusting for relevant confounders, and corrected for multiple testing. We found no associations of self-rated sleep, actigraphy-estimated sleep and 24-h activity rhythms with neurofilament light chain after confounder adjustment and correction for multiple testing, except for a non-linear association of self-rated time in bed with neurofilament light chain (P = 2.5*10). Similarly, we observed no significant associations with β-amyloid 40, β-amyloid 42, and total-tau after multiple testing correction. We conclude that sleep and 24-h activity rhythm disturbances were not consistently associated with neuronal damage as indicated by plasma neurofilament light chain in this population-based sample middle-aged and elderly non-demented persons. Further studies are needed to determine the associations of sleep and 24-h activity rhythm disturbances with NfL-related neuronal damage.
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http://dx.doi.org/10.1038/s41598-020-77830-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692474PMC
November 2020

Sleep characteristics across the lifespan in 1.1 million people from the Netherlands, United Kingdom and United States: a systematic review and meta-analysis.

Nat Hum Behav 2021 01 16;5(1):113-122. Epub 2020 Nov 16.

Research Institute of Child Development and Education, University of Amsterdam, Amsterdam, the Netherlands.

We aimed to obtain reliable reference charts for sleep duration, estimate the prevalence of sleep complaints across the lifespan and identify risk indicators of poor sleep. Studies were identified through systematic literature search in Embase, Medline and Web of Science (9 August 2019) and through personal contacts. Eligible studies had to be published between 2000 and 2017 with data on sleep assessed with questionnaires including ≥100 participants from the general population. We assembled individual participant data from 200,358 people (aged 1-100 years, 55% female) from 36 studies from the Netherlands, 471,759 people (40-69 years, 55.5% female) from the United Kingdom and 409,617 people (≥18 years, 55.8% female) from the United States. One in four people slept less than age-specific recommendations, but only 5.8% slept outside of the 'acceptable' sleep duration. Among teenagers, 51.5% reported total sleep times (TST) of less than the recommended 8-10 h and 18% report daytime sleepiness. In adults (≥18 years), poor sleep quality (13.3%) and insomnia symptoms (9.6-19.4%) were more prevalent than short sleep duration (6.5% with TST < 6 h). Insomnia symptoms were most frequent in people spending ≥9 h in bed, whereas poor sleep quality was more frequent in those spending <6 h in bed. TST was similar across countries, but insomnia symptoms were 1.5-2.9 times higher in the United States. Women (≥41 years) reported sleeping shorter times or slightly less efficiently than men, whereas with actigraphy they were estimated to sleep longer and more efficiently than man. This study provides age- and sex-specific population reference charts for sleep duration and efficiency which can help guide personalized advice on sleep length and preventive practices.
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http://dx.doi.org/10.1038/s41562-020-00965-xDOI Listing
January 2021

The interrelatedness of chronic cough and chronic pain.

Eur Respir J 2021 05 6;57(5). Epub 2021 May 6.

Dept of Respiratory Medicine, Ghent University Hospital, Ghent, Belgium.

Since chronic cough has common neurobiological mechanisms and pathophysiology with chronic pain, both clinical disorders might be interrelated. Hence, we examined the association between chronic cough and chronic pain in adult subjects in the Rotterdam Study, a large prospective population-based cohort study.Using a standardised questionnaire, chronic pain was defined as pain lasting up to 6 months and grouped into a frequency of weekly/monthly or daily pain. Chronic cough was described as daily coughing for at least 3 months duration. The longitudinal and cross-sectional associations were investigated bi-directionally.Of 7141 subjects in the study, 54% (n=3888) reported chronic pain at baseline. The co-prevalence of daily chronic pain and chronic cough was 4.4%. Chronic cough was more prevalent in subjects with daily and weekly/monthly chronic pain compared with those without chronic pain (13.8% and 10.3% 8.2%; p<0.001). After adjustment for potential confounders, prevalent chronic pain was significantly associated with incident chronic cough (OR 1.47, 95% CI 1.08-1.99). The association remained significant in subjects with daily chronic pain (OR 1.49, 95% CI 1.06-2.11) with a similar effect estimate, albeit non-significant in those with weekly/monthly chronic pain (OR 1.43, 95% CI 0.98-2.10). After adjustment for covariables, subjects with chronic cough had a significant risk of developing chronic pain (OR 1.63, 95% CI 1.02-2.62) compared with those without chronic cough.Chronic cough and chronic pain confer risk on each other among adult subjects, indicating that both conditions might share common risk factors and/or pathophysiologic mechanisms.
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http://dx.doi.org/10.1183/13993003.02651-2020DOI Listing
May 2021

Ethical Considerations in Screening for Rapid Eye Movement Sleep Behavior Disorder in the General Population.

Mov Disord 2020 11 15;35(11):1939-1944. Epub 2020 Sep 15.

Department of Medical Ethics, Philosophy and History of Medicine, Erasmus MC University Medical Center Rotterdam, Rotterdam, the Netherlands.

Clinical studies have shown that up to 90% of patients with idiopathic rapid eye movement sleep behavior disorder (RBD) will eventually be diagnosed with a clinical α-synucleinopathy. Because of this high conversion rate, screening for RBD is often performed to identify eligible participants for studies aimed at elucidating the prodromal phase of α-synucleinopathies. However, screening for RBD, especially in the general population, raises many ethical dilemmas. In light of the existing ethical literature and our experience in establishing a screening approach for RBD in the Rotterdam Study, we discuss ethical dilemmas when screening for RBD in population-based studies. We conclude that informing study participants about the reason for invitation and the possible trajectory that lies ahead when participating is essential. However, participants should not be troubled unnecessarily by giving them detailed information about possible diagnoses or associated disease risks. © 2020 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28262DOI Listing
November 2020

Insomnia as a mediating therapeutic target for depressive symptoms: A sub-analysis of participant data from two large randomized controlled trials of a digital sleep intervention.

J Sleep Res 2021 02 18;30(1):e13140. Epub 2020 Aug 18.

Big Health Inc., San Francisco, California, USA.

Insomnia predicts the onset of depression, commonly co-presents with depression and often persists following depression remission. However, these conditions can be challenging to treat concurrently using depression-specific therapies. Cognitive behavioural therapy for insomnia may be an appropriate treatment to improve both insomnia and depressive symptoms. We examined the effects of a fully-automated digital cognitive behavioural therapy intervention for insomnia (Sleepio) on insomnia and depressive symptoms, and the mediating role of sleep improvement on depressive symptoms in participants from two randomized controlled trials of digital cognitive behavioural therapy for insomnia. We also explored potential moderators of intervention effects. All participants met criteria for probable insomnia disorder and had clinically significant depressive symptomatology (PHQ-9 ≥ 10; n = 3,352). Individuals allocated to treatment in both trials were provided access to digital cognitive behavioural therapy. Digital cognitive behavioural therapy significantly improved insomnia (p < .001; g = 0.76) and depressive symptoms (p < .001; g = 0.48) at post-intervention (weeks 8-10), and increased the odds (OR = 2.9; 95% CI = 2.34, 3.65) of clinically significant improvement in depressive symptoms (PHQ-9 < 10). Improvements in insomnia symptoms at mid-intervention mediated 87% of the effects on depressive symptoms at post-intervention. No variables moderated effectiveness outcomes, suggesting generalizability of these findings. Our results suggest that effects of digital cognitive behavioural therapy for insomnia extend to depressive symptoms in those with clinically significant depressive symptomatology. Insomnia may, therefore, be an important therapeutic target to assist management of depressive symptoms.
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http://dx.doi.org/10.1111/jsr.13140DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8150672PMC
February 2021

Trajectories of Cognitive and Motor Function Between Ages 45 and 90 Years: A Population-Based Study.

J Gerontol A Biol Sci Med Sci 2021 01;76(2):297-306

Department of Epidemiology, Erasmus MC-University Medical Center Rotterdam, The Netherlands.

Background: To establish trajectories of cognitive and motor function, and to determine the sequence of change across individual tests in community-dwelling individuals aged 45-90 years.

Method: Between 1997 and 2016, we repeatedly assessed cognitive function with 5 tests in 9514 participants aged 45-90 years from the population-based Rotterdam Study. Between 1999 and 2016, we measured motor function with 3 tests in 8297 participants. All participants were free from dementia, stroke, and parkinsonism. We assessed overall and education-specific cognitive and motor trajectories using linear mixed models with age as time scale. Next, we determined the sequence of change across individual tests.

Results: The number of assessments per participant ranged between 1 and 6 (mean interval, years [SD]: 5.1 [1.4]) for cognitive function, and 1 and 4 (5.4 [1.4]) for motor function. Cognitive and motor trajectories declined linearly between ages 45 and 65 years, followed by steeper declines after ages 65-70 years. Lower educated participants had lower cognitive function at age 45 years (baseline), and declined faster on most cognitive, but not on motor tests than higher educated participants. Up to a 25-year age difference between the fastest and slowest declining test scores was observed.

Conclusions: On a population-level, cognitive and motor function decline similarly. Compared to higher educated individuals, lower educated individuals had lower cognitive function at baseline, and a faster rate of decline thereafter. These educational-effects were not seen for motor function. These findings benefit the understanding of the natural course of cognitive and motor function during aging, and highlight the role of education in the preservation of cognitive but not motor function.
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http://dx.doi.org/10.1093/gerona/glaa187DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812437PMC
January 2021

The Risk of Dementia in Relation to Cognitive and Brain Reserve.

J Alzheimers Dis 2020 ;77(2):607-618

Department of Epidemiology, Erasmus MC University Medical Center Rotterdam, the Netherlands.

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 APOEɛ4. Finally, high levels of late-life CR and BR provided additive protection against dementia.

Conclusion: The findings illustrate the importance of late-life over early-life reserve in understanding the risk of dementia, and show the need to study CR and BR conjointly.
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http://dx.doi.org/10.3233/JAD-200264DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7592692PMC
September 2021

Actigraphy-estimated sleep and 24-hour activity rhythms and the risk of dementia.

Alzheimers Dement 2020 09 19;16(9):1259-1267. Epub 2020 Jun 19.

Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.

Introduction: We investigated and compared associations of objective estimates of sleep and 24-hour activity rhythms using actigraphy with risk of dementia.

Methods: We included 1322 non-demented participants from the prospective, population-based Rotterdam Study cohort with valid actigraphy data (mean age 66 ± 8 years, 53% women), and followed them for up to 11.2 years to determine incident dementia.

Results: During follow-up, 60 individuals developed dementia, of which 49 had Alzheimer's disease (AD). Poor sleep as indicated by longer sleep latency, wake after sleep onset, and time in bed and lower sleep efficiency, as well as an earlier "lights out" time, were associated with increased risk of dementia, especially AD. We found no associations of 24-hour activity rhythms with dementia risk.

Discussion: Poor sleep, but not 24-hour activity rhythm disturbance, is associated with increased risk of dementia. Actigraphy-estimated nighttime wakefulness may be further targeted in etiologic or risk prediction studies.
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http://dx.doi.org/10.1002/alz.12122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7984295PMC
September 2020

Objectives, design and main findings until 2020 from the Rotterdam Study.

Eur J Epidemiol 2020 May 4;35(5):483-517. Epub 2020 May 4.

Department of Epidemiology, Erasmus University Medical Center, PO Box 2040, 3000 CA, Rotterdam, The Netherlands.

The Rotterdam Study is an ongoing prospective cohort study that started in 1990 in the city of Rotterdam, The Netherlands. The study aims to unravel etiology, preclinical course, natural history and potential targets for intervention for chronic diseases in mid-life and late-life. The study focuses on cardiovascular, endocrine, hepatic, neurological, ophthalmic, psychiatric, dermatological, otolaryngological, locomotor, and respiratory diseases. As of 2008, 14,926 subjects aged 45 years or over comprise the Rotterdam Study cohort. Since 2016, the cohort is being expanded by persons aged 40 years and over. The findings of the Rotterdam Study have been presented in over 1700 research articles and reports. This article provides an update on the rationale and design of the study. It also presents a summary of the major findings from the preceding 3 years and outlines developments for the coming period.
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http://dx.doi.org/10.1007/s10654-020-00640-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7250962PMC
May 2020

Prevalence of benzodiazepines and benzodiazepine-related drugs exposure before, during and after pregnancy: A systematic review and meta-analysis.

J Affect Disord 2020 05 5;269:18-27. Epub 2020 Mar 5.

Epidemiological and Social Psychiatric Research Institute, Department of Psychiatry, Erasmus University Medical Centre Rotterdam, Rotterdam, the Netherlands.

Background: Maternal use of benzodiazepines during pregnancy is common and has increased over the last decades. In this systematic review and meta-analysis, we studied the literature to estimate the worldwide use of benzodiazepines before, during and after pregnancy, which could help to estimate benzodiazepine exposure and to prioritize and guide future investigations.

Methods: We systematically searched Embase, Medline Ovid, Web of Science and Cochrane Central up until July 2019 for studies reporting on benzodiazepine use before (12 months), during and after pregnancy (12 months). Random effects meta-analysis was conducted to calculate pooled prevalence estimates, as well as stratified according to substantive variables.

Results: We identified 32 studies reporting on 28 countries, together reporting on 7,343,571 pregnancies. The worldwide prevalence of benzodiazepine use/prescriptions during pregnancy was 1.9% (95%CI 1.6%-2.2%; I 97.48%). Highest prevalence was found in the third trimester (3.1%; 95%CI 1.8%-4.5%; I 99.83%). Lorazepam was the most frequently used/prescribed benzodiazepine (1.5%; 95%CI 0.5%-2.5%; I 99.87%). Highest prevalence was found in Eastern Europe (14.0%; 95%CI 12.1%-15.9%; I 0.00%).

Limitations: All analyses revealed considerable heterogeneity.

Conclusions: Our meta-analysis confirmed that benzodiazepine use before, during and after pregnancy is prevalent. The relatively common use of benzodiazepines with possible risks for both mother and (unborn) child is worrying and calls for prescription guidelines for women, starting in the preconception period. Given the substantial proportion of children exposed to benzodiazepines in utero, future research should continue to study the short- and long-term safety of maternal benzodiazepine use during pregnancy and to explore non-pharmacological alternative treatments.
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http://dx.doi.org/10.1016/j.jad.2020.03.014DOI Listing
May 2020

The effects of digital cognitive behavioral therapy for insomnia on cognitive function: a randomized controlled trial.

Sleep 2020 09;43(9)

Oxford Centre for Human Brain Activity, Wellcome Centre for Integrative Neuroimaging, Department of Psychiatry, University of Oxford, Oxford, UK.

Study Objectives: We sought to examine the impact of digital cognitive behavioral therapy (dCBT) for insomnia on both self-reported cognitive impairment and objective cognitive performance.

Methods: The Defining the Impact of Sleep improvement on Cognitive Outcomes (DISCO) trial was an online, two-arm, single-blind, randomized clinical trial of dCBT versus wait-list control. Participants were aged 25 years and older, met DSM-5 diagnostic criteria for insomnia disorder, and reported difficulties with concentration or memory. Assessments were carried out online at baseline, and 10 and 24 weeks post-randomization. The primary outcome measure was self-reported cognitive impairment, assessed with the British Columbia Cognitive Complaints Inventory (BC-CCI). Secondary outcomes included tests of cognitive performance, insomnia symptoms, cognitive failures, fatigue, sleepiness, depression, and anxiety.

Results: Four hundred and ten participants with insomnia were recruited and assigned to dCBT (N = 205) or wait-list control (N = 205). At 10 weeks post-randomization the estimated adjusted mean difference for the BC-CCI was -3.03 (95% CI: -3.60, -2.47; p < 0.0001, d = -0.86), indicating that participants in the dCBT group reported less cognitive impairment than the control group. These effects were maintained at 24 weeks (d = -0.96) and were mediated, in part, via reductions in insomnia severity and increased sleep efficiency. Treatment effects in favor of dCBT, at both 10 and 24 weeks, were found for insomnia severity, sleep efficiency, cognitive failures, fatigue, sleepiness, depression, and anxiety. We found no between-group differences in objective tests of cognitive performance.

Conclusions: Our study shows that dCBT robustly decreases self-reported cognitive impairment at post-treatment and these effects are maintained at 6 months.
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http://dx.doi.org/10.1093/sleep/zsaa034DOI Listing
September 2020

Long-term benefits of digital cognitive behavioural therapy for insomnia: Follow-up report from a randomized clinical trial.

J Sleep Res 2020 08 28;29(4):e13018. Epub 2020 Feb 28.

Sleep and Circadian Neuroscience Institute, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK.

Digital cognitive behavioural therapy (dCBT) is an effective treatment for chronic insomnia and also improves well-being and quality of life (QoL). We assessed whether these benefits are sustained and if the effects of dCBT extend to the use of sleep medication and healthcare. In total 1,711 adults (48.0 ± 13.8 years, 77.6% female) with complaints of chronic insomnia participated in a previously published randomized controlled trial (ISRCTN 60530898) comparing dCBT (n = 853) with sleep hygiene education (SHE, n = 858). At weeks 0, 4, 8, 24, 36 and 48, we assessed functional health (Patient-Reported Outcomes Measurement Information System: Global Health Scale); psychological well-being (Warwick-Edinburgh Mental Well-being Scale) and sleep-related QoL (Glasgow Sleep Impact Index), prescribed and non-prescribed sleep medication use, and healthcare utilization. At week 25, those who received SHE at baseline were offered dCBT. dCBT improved functional health (difference: 2.45, 95% confidence interval [CI]: 2.03; 2.88, Cohen's d: 0.50, p < .001), psychological well-being (difference: 4.34, 95% CI: 3.70; 4.98, Cohen's d: 0.55, p < .001) and sleep-related QoL (difference: -44.61, 95%CI: -47.17; -42.05, Cohen's d: -1.44, p < .001) at week 48 compared to baseline. At week 24 dCBT, compared to SHE, also reduced use of prescription and non-prescription sleep medication up to week 24 (adjusted rate ratio [RR]: 0.64, 95% CI: 0.42; 0.97, p = .037 and adjusted RR: 0.52, 95% CI: 0.37; 0.74, p < .0001, respectively), but not healthcare utilization. Uncontrolled follow-up suggests that these effects were sustained for non-prescribed sleep medication (RR: 0.52, 95% CI: 0.40; 0.67, p < .001). In conclusion, this study suggests that dCBT results in sustained benefits to insomnia and its daytime outcomes.
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http://dx.doi.org/10.1111/jsr.13018DOI Listing
August 2020

Digital Cognitive Behavioral Therapy for Insomnia in Women With Chronic Migraines.

Headache 2020 05 28;60(5):902-915. Epub 2020 Feb 28.

Department of Neurology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.

Objective/background: Insomnia commonly co-occurs with chronic migraines (CM). Non-pharmacological treatments for insomnia in CM patients remain understudied. This is a proof-of-concept study, which aims to evaluate the feasibility, acceptability, and preliminary efficacy of a digital cognitive behavioral therapy for insomnia (dCBT-I) for individuals with CM and insomnia (CM-I) in the United States.

Methods: We recruited 42 females with CM-I symptoms from a U.S.-based observational cohort and from the general population via advertisements. Within a multiple baseline design, participants were randomized to receive dCBT-I after 2, 4, or 6 weeks of completing baseline sleep diaries. DCBT-I was scrutinized against benchmarks for completion rates (≥90% to complete dCBT-I), acceptability (≥80% to find dCBT-I acceptable), and posttreatment changes in insomnia symptoms (≥50% indicating a clinically relevant improvement in their insomnia symptoms). As a secondary measure, we also reported percentage of individuals reverting to episodic migraines.

Results: Out of 42 randomized, 35 (83.3%) completed dCBT-I within the 12 weeks provided. Of these completers, 33 (94.3%) reported being satisfied (n = 16) or very satisfied (n = 17) with treatment. Additionally, 65.7% of completers responded to treatment as per universally accepted criteria for insomnia. Lastly, 34% of completers reverted from CM to episodic migraine.

Conclusion: This study provides evidence for the feasibility and acceptability of dCBT-I in patients with CM-I complaints. Effects of improving insomnia and migraines were suggested. These results indicate that a randomized controlled trial is needed to determine the efficacy of dCBT-I in CM patients.
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http://dx.doi.org/10.1111/head.13777DOI Listing
May 2020

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

J Sleep Res 2020 10 26;29(5):e12999. Epub 2020 Feb 26.

Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.

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 total sleep time.
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http://dx.doi.org/10.1111/jsr.12999DOI Listing
October 2020

Is digital cognitive behavioural therapy for insomnia effective in treating sub-threshold insomnia: a pilot RCT.

Sleep Med 2020 02 5;66:174-183. Epub 2019 Nov 5.

Department of Psychology, Goldsmiths, University of London, London, UK. Electronic address:

Objective/background: Many patients find cognitive behavioral therapy for insomnia (CBT-I) useful. However, it is currently unknown if those with sub-threshold insomnia also benefit. Here we assessed whether CBT-I is both feasible and acceptable in participants with sub-threshold insomnia. The primary aims were to evaluate participation rates and treatment acceptability, and to establish an effect size for symptom improvement.

Patients/methods: A total of 199 female participants (M 20 ± 5 years) took part. Following baseline assessments, participants were randomly allocated to either a six-week digital CBT-I intervention or a six-week control group receiving puzzles. Additional assessments were performed three-weeks, six-weeks, and six-months later.

Results: Participation rates at each survey assessment wave did not differ between the groups (ps > 0.140), though adherence to completing each weekly task was lower in the CBT-I group, p = 0.02. Treatment acceptability was high (M (SD) = 33.61 (4.82), theoretical range 6-42). The CBT-I group showed greater improvement in insomnia symptoms at the end of the intervention compared to the control group (p = 0.013, d = 0.42), with significant variation in outcome (M = 4.69, SD = 5.41). Sub-threshold participants showed a similar pattern of results, whilst those meeting insomnia criteria showed a smaller between-group difference. CBT-I led to improvements in anxiety, paranoia and perceived stress between baseline and end of intervention. Changes in insomnia symptoms were mediated by cognitions about sleep and somatic pre-sleep arousal.

Conclusions: CBT-I provides a benefit even in sub-threshold insomnia. CBT-I may be useful to tackle insomnia symptoms even when they are sub-threshold.
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http://dx.doi.org/10.1016/j.sleep.2019.10.007DOI Listing
February 2020

Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration.

Nat Commun 2019 11 12;10(1):5121. Epub 2019 Nov 12.

Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands.

Both short and long sleep are associated with an adverse lipid profile, likely through different biological pathways. To elucidate the biology of sleep-associated adverse lipid profile, we conduct multi-ancestry genome-wide sleep-SNP interaction analyses on three lipid traits (HDL-c, LDL-c and triglycerides). In the total study sample (discovery + replication) of 126,926 individuals from 5 different ancestry groups, when considering either long or short total sleep time interactions in joint analyses, we identify 49 previously unreported lipid loci, and 10 additional previously unreported lipid loci in a restricted sample of European-ancestry cohorts. In addition, we identify new gene-sleep interactions for known lipid loci such as LPL and PCSK9. The previously unreported lipid loci have a modest explained variance in lipid levels: most notable, gene-short-sleep interactions explain 4.25% of the variance in triglyceride level. Collectively, these findings contribute to our understanding of the biological mechanisms involved in sleep-associated adverse lipid profiles.
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http://dx.doi.org/10.1038/s41467-019-12958-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851116PMC
November 2019

Association of Sleep Problems and Melatonin Use in School-aged Children.

JAMA Pediatr 2019 Sep;173(9):883-885

Department of Child and Adolescent Psychiatry, Erasmus University Medical Center-Sophia Children's Hospital, Rotterdam, the Netherlands.

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http://dx.doi.org/10.1001/jamapediatrics.2019.2084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6646973PMC
September 2019

The prospective association of objectively measured sleep and cerebral white matter microstructure in middle-aged and older persons.

Sleep 2019 10;42(10)

Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.

Study Objectives: Poor sleep may destabilize axonal integrity and deteriorate cerebral white matter. In middle-aged and older adults sleep problems increase alongside structural brain changes, but the temporal relation between these processes is poorly understood. We studied longitudinal associations between sleep and cerebral white matter microstructure.

Methods: One thousand one persons (59.3 ± 7.9 years, 55% women) were followed across 5.8 years (3.9-10.8). Total sleep time (TST, hours), sleep efficiency (SE, percentage), sleep onset latency (SOL, minutes), and wake after sleep onset (WASO, minutes) were measured at baseline using a wrist-worn actigraph. White matter microstructure (global and tract-specific fractional anisotropy [FA] and mean diffusivity [MD]) was measured twice with diffusion tensor imaging (DTI).

Results: Poor sleep was associated with worse white matter microstructure up to 7 years later but did not predict trajectories of DTI over time. Longer TST was associated with higher global FA (β = 0.06, 95% CI: 0.01 to 0.12), but not with MD. Persons with higher SE had higher global FA (β = 0.01, 95% CI: 0.002 to 0.01) and lower MD (β = -0.01, 95% CI: -0.01 to -0.0004). Consistently, those with more WASO had lower global FA (β = -0.003, 95% CI: -0.005 to -0.001) and higher MD (β = 0.002, 95% CI: 0.0004 to 0.004). Global findings seemed to be driven by microstructural alterations in the cingulum, anterior forceps of corpus callosum, projection and association tracts.

Conclusions: Middle-aged and older persons with more WASO, lower SE and shorter TST have worse microstructure of cerebral white matter. Microstructural alterations are most pronounced projection and association tracts, in the cingulum, and in the anterior forceps of corpus callosum.
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http://dx.doi.org/10.1093/sleep/zsz140DOI Listing
October 2019

Digital Delivery of Cognitive Behavioral Therapy for Insomnia.

Curr Psychiatry Rep 2019 06 4;21(7):50. Epub 2019 Jun 4.

Department of Clinical Psychology, University of Amsterdam, Amsterdam, Netherlands.

Purpose Of Review: Digital cognitive behavioral therapy (dCBT) has been available for over a decade. We reviewed the evidence that accumulated over the past 5 years and discuss the implications for introducing dCBT into standard healthcare.

Recent Findings: Studies have consistently supported the use of dCBT to treat insomnia. Evidence is now demonstrating large short-term effects and smaller long-term effects up to 1.5 years after treatment across populations with various co-occurring health problems. The effects also extend into a range of psychological well-being factors. Mediators and moderators have been studied to understand mechanisms and create new opportunities to enhance effectiveness and reduce dropout. Incorporating personalized guidance in dCBT may further enhance effectiveness. The evidence for dCBT for insomnia is strong and suggests that dCBT is ready for application in standard healthcare. Further research, digital innovation, and development of effective implementation methods are required to ensure dCBT fulfills its potential.
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http://dx.doi.org/10.1007/s11920-019-1041-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546653PMC
June 2019

Sleep and risk of parkinsonism and Parkinson's disease: a population-based study.

Brain 2019 07;142(7):2013-2022

Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.

Sleep disturbances may signal presence of prodromal parkinsonism, including Parkinson's disease. Whether general sleep quality or duration in otherwise healthy subjects is related to the risk of parkinsonism remains unclear. We hypothesized that both worse self-reported sleep quality and duration, as well as a longitudinal deterioration in these measures, are associated with the risk of parkinsonism, including Parkinson's disease. In the prospective population-based Rotterdam Study, we assessed sleep quality and duration with the Pittsburgh Sleep Quality Index in 7726 subjects (mean age 65 years, 57% female) between 2002 and 2008, and again in 5450 subjects between 2009 and 2014. Participants were followed until 2015 for a diagnosis of parkinsonism and Parkinson's disease. Outcomes were assessed using multiple modalities: interviews, physical examination, and continuous monitoring of pharmacy records and medical records of general practitioners. We used Cox regression to associate sleep, and changes in sleep over time, with incident parkinsonism and Parkinson's disease, adjusting for age, sex, education and smoking status. Over 64 855 person-years in 13 years of follow-up (mean: 8.4 years), 75 participants developed parkinsonism, of whom 47 developed Parkinson's disease. We showed that within the first 2 years of follow-up, worse sleep quality {hazard ratio (HR) 2.38 per standard deviation increase [95% confidence interval (CI 0.91-6.23)]} and shorter sleep duration [HR 0.61 per standard deviation increase (95% CI 0.31-1.21)] related to a higher risk of parkinsonism. Associations of worse sleep quality [HR 3.86 (95% CI 1.19-12.47)] and shorter sleep duration [HR 0.48 (95% CI 0.23-0.99)] with Parkinson's disease were more pronounced, and statistically significant, compared to parkinsonism. This increased risk disappeared with longer follow-up duration. Worsening of sleep quality [HR 1.76 per standard deviation increase (95% CI 1.12-2.78)], as well as shortening of sleep duration [HR 1.72 per standard deviation decrease (95% CI 1.08-2.72)], were related to Parkinson's disease risk in the subsequent 6 years. Therefore, we argue that in the general population, deterioration of sleep quality and duration are markers of the prodromal phase of parkinsonism, including Parkinson's disease.
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http://dx.doi.org/10.1093/brain/awz113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6911221PMC
July 2019

Genetic studies of accelerometer-based sleep measures yield new insights into human sleep behaviour.

Nat Commun 2019 04 5;10(1):1585. Epub 2019 Apr 5.

Genetics of Complex Traits, College of Medicine and Health, University of Exeter, Exeter, EX2 5DW, UK.

Sleep is an essential human function but its regulation is poorly understood. Using accelerometer data from 85,670 UK Biobank participants, we perform a genome-wide association study of 8 derived sleep traits representing sleep quality, quantity and timing, and validate our findings in 5,819 individuals. We identify 47 genetic associations at P < 5 × 10, of which 20 reach a stricter threshold of P < 8 × 10. These include 26 novel associations with measures of sleep quality and 10 with nocturnal sleep duration. The majority of identified variants associate with a single sleep trait, except for variants previously associated with restless legs syndrome. For sleep duration we identify a missense variant (p.Tyr727Cys) in PDE11A as the likely causal variant. As a group, sleep quality loci are enriched for serotonin processing genes. Although accelerometer-derived measures of sleep are imperfect and may be affected by restless legs syndrome, these findings provide new biological insights into sleep compared to previous efforts based on self-report sleep measures.
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http://dx.doi.org/10.1038/s41467-019-09576-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451011PMC
April 2019
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