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1.
Alzheimers Res Ther ; 14(1): 8, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35022067

RESUMO

BACKGROUND: Adherence to the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet has been linked to a decreased risk of dementia, but reverse causality and residual confounding by lifestyle may partly account for this link. We aimed to address these issues by studying the associations over cumulative time periods, which may provide insight into possible reverse causality, and by using both historical and more contemporary dietary data as this could give insight into confounding since historical data may be less affected by lifestyle factors. METHODS: In the population-based Rotterdam Study, dietary intake was assessed using validated food frequency questionnaires in 5375 participants between 1989 and 1993 (baseline I) and in a largely non-overlapping sample in 2861 participants between 2009 and 2013 (baseline II). We calculated the MIND diet score and studied its association with the risk of all-cause dementia, using Cox models. Incident all-cause dementia was recorded until 2018. RESULTS: During a mean follow-up of 15.6 years from baseline I, 1188 participants developed dementia. A higher MIND diet score at baseline I was associated with a lower risk of dementia over the first 7 years of follow-up (hazard ratio (HR) [95% confidence interval (CI)] per standard deviation (SD) increase, 0.85 [0.74, 0.98]), but associations disappeared over longer follow-up intervals. The mean follow-up from baseline II was 5.9 years during which 248 participants developed dementia. A higher MIND diet score at baseline II was associated with a lower risk of dementia over every follow-up interval, but associations slightly attenuated over time (HR [95% CI] for 7 years follow-up per SD increase, 0.76 [0.66, 0.87]). The MIND diet score at baseline II was more strongly associated with the risk of dementia than the MIND diet score at baseline I. CONCLUSION: Better adherence to the MIND diet is associated with a decreased risk of dementia within the first years of follow-up, but this may in part be explained by reverse causality and residual confounding by lifestyle. Further research is needed to unravel to which extent the MIND diet may affect the risk of dementia.

2.
Genome Biol ; 23(1): 24, 2022 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-35031073

RESUMO

BACKGROUND: Epigenetic clocks use DNA methylation (DNAm) levels of specific sets of CpG dinucleotides to accurately predict individual chronological age. A popular application of these clocks is to explore whether the deviation of predicted age from chronological age is associated with disease phenotypes, where this deviation is interpreted as a potential biomarker of biological age. This wide application, however, contrasts with the limited insight in the processes that may drive the running of epigenetic clocks. RESULTS: We perform a functional genomics analysis on four epigenetic clocks, including Hannum's blood predictor and Horvath's multi-tissue predictor, using blood DNA methylome and transcriptome data from 3132 individuals. The four clocks result in similar predictions of individual chronological age, and their constituting CpGs are correlated in DNAm level and are enriched for similar histone modifications and chromatin states. Interestingly, DNAm levels of CpGs from the clocks are commonly associated with gene expression in trans. The gene sets involved are highly overlapping and enriched for T cell processes. Further analysis of the transcriptome and methylome of sorted blood cell types identifies differences in DNAm between naive and activated T and NK cells as a probable contributor to the clocks. Indeed, within the same donor, the four epigenetic clocks predict naive cells to be up to 40 years younger than activated cells. CONCLUSIONS: The ability of epigenetic clocks to predict chronological age involves their ability to detect changes in proportions of naive and activated immune blood cells, an established feature of immuno-senescence. This finding may contribute to the interpretation of associations between clock-derived measures and age-related health outcomes.

3.
ERJ Open Res ; 8(1)2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35036418

RESUMO

Background: Increasing evidence suggests that sarcopenia and a higher systemic immune-inflammation index (SII) are linked with morbidity in patients with COPD. However, whether these two conditions contribute to all-cause mortality in middle-aged and older patients with COPD or asthma is unclear. Therefore, we investigated the association between sarcopenia, SII, COPD or asthma and all-cause mortality in a large-scale population-based setting. Methods: Between 2009 and 2014, 4482 participants (aged >55 years; 57.3% female) from the population-based Rotterdam Study were included. COPD and asthma patients were diagnosed clinically and based on spirometry. Six study groups were defined according to the presence or absence of COPD or asthma and sarcopenia. Cox regression models were used to assess all-cause mortality in the study groups, adjusted for sex, age, body mass index, SII, smoking, oral corticosteroid use and comorbidities. In addition, all participants were categorised into sex-specific quartiles of SII, and mortality in these groups was compared. Results: Over a median follow-up of 6.1 years (interquartile range 5.0-7.2 years), 466 (10.4%) persons died. Independent of the presence of sarcopenia, participants with COPD had a higher risk of all-cause mortality (hazard ratio (HR) 2.13, 95% CI 1.46-3.12 and HR 1.70, 95% CI 1.32-2.18 for those with and without sarcopenia, respectively). Compared to lower SII levels, higher SII levels increased mortality risk even in people without sarcopenia, COPD or asthma. Conclusion: Middle-aged and older people with COPD, higher SII levels or sarcopenia had an independently increased mortality risk. Our study suggests prognostic usefulness of routinely evaluating sarcopenia and SII in older people with COPD or asthma.

4.
J Am Heart Assoc ; 11(1): e023967, 2022 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34970920

RESUMO

Background Limited population-based data on the (sex-specific) link between subclinical measures of peripheral atherosclerosis and new-onset atrial fibrillation (AF) exist. Methods and Results Subclinical measures of peripheral atherosclerosis including carotid intima-media thickness (cIMT), carotid plaque, and ankle-brachial index (ABI) were assessed at baseline and follow-up examinations. A total of 12 840 participants free of AF at baseline from the population-based Rotterdam Study were included. Cox proportional hazards models and joint models, adjusted for cardiovascular risk factors, were used to determine the associations between baseline and longitudinal measures of cIMT, carotid plaque, and ABI with new-onset AF. During a median follow-up of 9.2 years, 1360 incident AF cases occurred among 12 840 participants (mean age 65.2 years, 58.3% women). Higher baseline cIMT (fully-adjusted hazard ratio [HR], 95% CI, 1.81, 1.21-2.71; P=0.0042), presence of carotid plaque (fully-adjusted HR, 95% CI, 1.19, 1.04-1.35; P=0.0089), lower ABI (fully-adjusted HR, 95% CI, 1.57, 1.14-2.18; P=0.0061) and longitudinal measures of higher cIMT (fully-adjusted HR, 95% CI, 2.14, 1.38-3.29; P=0.0021), presence of carotid plaque (fully-adjusted HR, 95% CI, 1.61, 1.12-2.43; P=0.0112), and lower ABI (fully-adjusted HR, 95% CI, 4.43, 1.83-10.49; P=0.0007) showed significant associations with new-onset AF in the general population. Sex-stratified analyses showed that the associations for cIMT, carotid plaque, and ABI were mostly prominent among women. Conclusions Baseline and longitudinal subclinical measures of peripheral atherosclerosis (carotid atherosclerosis, and lower extremity peripheral atherosclerosis) were significantly associated with an increased risk of new-onset AF, especially among women. Registration URL: https://www.trialregister.nl, https://www.apps.who.int/trialsearch/; Unique identifier: NL6645/NTR6831.

5.
Hum Mol Genet ; 2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34875050

RESUMO

Telomeres are repetitive DNA sequences located at the end of chromosomes, which are associated to biological aging, cardiovascular disease, cancer, and mortality. Lipid and fatty acid metabolism have been associated with telomere shortening. We have conducted an in-depth study investigating the association of metabolic biomarkers with telomere length (LTL). We performed an association analysis of 226 metabolic biomarkers with LTL using data from 11 775 individuals from six independent population-based cohorts (BBMRI-NL consortium). Metabolic biomarkers include lipoprotein lipids and subclasses, fatty acids, amino acids, glycolysis measures and ketone bodies. LTL was measured by quantitative polymerase chain reaction or FlowFISH. Linear regression analysis was performed adjusting for age, sex, lipid-lowering medication and cohort-specific covariates (model 1) and additionally for body mass index (BMI) and smoking (model 2), followed by inverse variance-weighted meta-analyses (significance threshold pmeta = 6.5x10-4). We identified four metabolic biomarkers positively associated with LTL, including two cholesterol to lipid ratios in small VLDL (S-VLDL-C % and S-VLDL-ce %) and two omega-6 fatty acid ratios (FAw6/FA and LA/FA). After additionally adjusting for BMI and smoking, these metabolic biomarkers remained associated with LTL with similar effect estimates. In addition, cholesterol esters in very small VLDL (XS-VLDL-ce) became significantly associated with LTL (p = 3.6x10-4). We replicated the association of FAw6/FA with LTL in an independent dataset of 7845 individuals (p = 1.9x10-4). To conclude, we identified multiple metabolic biomarkers involved in lipid and fatty acid metabolism that may be involved in LTL biology. Longitudinal studies are needed to exclude reversed causation.

6.
J Alzheimers Dis ; 2021 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-34864674

RESUMO

BACKGROUND: Cognitive reserve aims to explain individual differences in the susceptibility to the functional impact of dementia in the presence of equal amount of neuropathological damage. It is thought to be shaped by a combination of innate individual differences and lifetime exposures. Which determinants are associated with cognitive reserve remains unknown. OBJECTIVE: The objective of this study was to investigate the associations of sociodemographic, lifestyle, physical, and psychosocial determinants with cognitive reserve, and potential sex differences. METHODS: This cross-sectional study included 4,309 participants from the Rotterdam Study (mean age 63.9±10.7) between 2006-2016. Participants completed five cognitive tests and a brain MRI-scan. Cognitive reserve was defined as a latent variable that captures variance common across five cognitive tests, while adjusting for demographic and MRI-inferred neuropathological factors. The associations of potential determinants and cognitive reserve, adjusted for relevant confounders, were assessed with structural equation models. RESULTS: Current smoking (adjusted mean difference: -0.31, 95%confidence interval -0.42; -0.19), diabetes mellitus (-0.25, -0.40; -0.10) and depressive symptoms (-0.07/SD, -0.12; -0.03) were associated with a lower cognitive reserve whereas alcohol use (0.07/SD, 0.03; 0.12) was associated with higher cognitive reserve. Only smoking was associated with cognitive reserve in both men and women. Employment, alcohol use, diabetes, history of cancer, COPD, and depressive symptoms were only associated with cognitive reserve in women. CONCLUSION: Our study found that current smoking, diabetes mellitus, and depressive symptoms were associated with a lower cognitive reserve, whereas more alcohol use was associated with a higher cognitive reserve, but with clear differences between men and women.

7.
Kidney Int Rep ; 6(12): 3054-3063, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34901574

RESUMO

Introduction: Kidney function declines with age, but its determinants in the general population remain incompletely understood. We investigated the rate and determinants of kidney function decline in the general population. Methods: Participants with information on kidney function were selected from a population-based cohort study. Joint models were used to investigate the evolution of the estimated glomerular filtration rate (eGFR, expressed in ml/min per 1.73 m2 per year) and the urine albumin-to-creatinine ratio (ACR, expressed in mg/g per year) with age. We stratified for 8 potential determinants of kidney function decline, including sex, cardiovascular risk factors, and cardiovascular disease. Results: We included 12,062 participants with 85,922 eGFR assessments (mean age 67.0 years, 58.7% women) and 3522 participants with 5995 ACR measurements. The annual eGFR decline was 0.82 and the ACR increase was 0.05. All determinants appeared detrimental for eGFR and ACR, except for prediabetes and higher body mass index which proved only detrimental for ACR. In participants without the determinants, eGFR decline was 0.75 and ACR increase was 0.002. Higher baseline eGFR but faster eGFR decline with age was detected in men (0.92 vs. 0.75), smokers (0.90 vs. 0.75), and participants with diabetes (1.07 vs. 0.78). Conclusion: We identify prediabetes, smoking, and blood pressure as modifiable risk factors for kidney function decline. As with diabetes, hyperfiltration seems important in accelerated kidney function decline in men and smokers. The interpretation of kidney function decline may require adjustment for age and sex to prevent overdiagnosis of chronic kidney disease in aging populations.

8.
J Parkinsons Dis ; 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34897101

RESUMO

BACKGROUND: The immune system is known to be involved in Parkinson's disease (PD) pathogenesis, but the temporal relationship between peripheral immune responses and PD remains unknown. OBJECTIVE: We determined the association between peripheral immune cell numbers, C-Reactive protein (CRP), and prevalent as well as incident PD. METHODS: This study was embedded in the population-based setting of the Rotterdam Study. We repeatedly measured peripheral immune cell numbers (differential leukocyte count and platelet count, granulocyte-to-lymphocyte ratio [GLR], platelet-to-lymphocyte ratio [PLR], and adapted systemic immune-inflammation index [adapted SII]) and CRP between 1990 and 2016. Participants were continuously followed-up for PD until 2018. We estimated the association of the markers with prevalent and incident PD using logistic regression models and joint models, respectively. Models were adjusted for age, sex, smoking, body mass index, and medication use. Odds ratios (OR) and hazard ratios (HR) are shown per doubling of the marker. RESULTS: A total of 12,642 participants were included in this study. The mean age (standard deviation) was 65.1 (9.8) years and 57.5%were women. Participants with a higher lymphocyte count were less likely to have prevalent PD (adjusted OR: 0.34, 95%CI 0.17-0.68). Participants with a higher GLR, PLR, and adapted SII were more likely to have prevalent PD, but these effects were explained by the lymphocyte count. The peripheral immune cell numbers and CRP were not significantly associated with the risk of incident PD. CONCLUSION: We found participants with a higher lymphocyte count to be less likely to have prevalent PD, but we did not find an association between peripheral immune cell numbers nor CRP and the risk of incident PD.

9.
Neurology ; 2021 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-34965968

RESUMO

BACKGROUND AND OBJECTIVES: Although there is evidence of disruption in acute cerebrovascular and cardiovascular care during the COVID-19 pandemic, its downstream effect in primary care is less clear. We investigated how the pandemic affected utilization of cerebrovascular and cardiovascular care in general practices (GPs) and determined changes in GP-recorded diagnoses of selected cerebrovascular and cardiovascular outcomes. METHODS: From electronic health records of 166,929 primary care patients aged 30 or over within the Rotterdam region, the Netherlands, we extracted the number of consultations related to cerebrovascular and cardiovascular care, and first diagnoses of selected cerebrovascular and cardiovascular risk factors (hypertension, diabetes, lipid disorders), conditions and events (angina, atrial fibrillation, TIA, myocardial infarction, stroke). We quantified changes in those outcomes during the first COVID-19 wave (March-May 2020) and thereafter (June-December 2020) by comparing them to the same period in 2016-2019. We also estimated the number of potentially missed diagnoses for each outcome. RESULTS: The number of GP consultations related to cerebrovascular and cardiovascular care declined by 38% (0.62, 95% CI: 0.56-0.68) during the first wave, as compared to expected counts based on pre-pandemic levels. Substantial declines in the number of new diagnoses were observed for cerebrovascular events: 37% for TIA (0.63, 0.41-0.96), and 29% for stroke (0.71, 0.59 to 0.84), while no significant changes were observed for cardiovascular events (myocardial infarction (0.91, 0.74-1.14), angina (0.77, 0.48-1.25)). The counts across individual diagnoses recovered following June 2020, but the number of GP consultations related to cerebrovascular and cardiovascular care remained lower than expected also throughout the June-December period (0.93, 0.88-0.98). DISCUSSION: While new diagnoses of acute cardiovascular events remained stable during the COVID19 pandemic, diagnoses of cerebrovascular events declined substantially compared to pre-pandemic levels, possibly due to incorrect perception of risk by patients. These findings emphasize the need to improve symptom recognition of cerebrovascular events among the general public and to encourage urgent presentation despite any physical distancing measures.

10.
BMC Med ; 19(1): 266, 2021 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-34727949

RESUMO

BACKGROUND: Observational studies suggest interconnections between thyroid status, metabolism, and risk of coronary artery disease (CAD), but causality remains to be proven. The present study aimed to investigate the potential causal relationship between thyroid status and cardiovascular disease and to characterize the metabolomic profile associated with thyroid status. METHODS: Multi-cohort two-sample Mendelian randomization (MR) was performed utilizing genome-wide significant variants as instruments for standardized thyrotropin (TSH) and free thyroxine (fT4) within the reference range. Associations between TSH and fT4 and metabolic profile were investigated in a two-stage manner: associations between TSH and fT4 and the full panel of 161 metabolomic markers were first assessed hypothesis-free, then directional consistency was assessed through Mendelian randomization, another metabolic profile platform, and in individuals with biochemically defined thyroid dysfunction. RESULTS: Circulating TSH was associated with 52/161 metabolomic markers, and fT4 levels were associated with 21/161 metabolomic markers among 9432 euthyroid individuals (median age varied from 23.0 to 75.4 years, 54.5% women). Positive associations between circulating TSH levels and concentrations of very low-density lipoprotein subclasses and components, triglycerides, and triglyceride content of lipoproteins were directionally consistent across the multivariable regression, MR, metabolomic platforms, and for individuals with hypo- and hyperthyroidism. Associations with fT4 levels inversely reflected those observed with TSH. Among 91,810 CAD cases and 656,091 controls of European ancestry, per 1-SD increase of genetically determined TSH concentration risk of CAD increased slightly, but not significantly, with an OR of 1.03 (95% CI 0.99-1.07; p value 0.16), whereas higher genetically determined fT4 levels were not associated with CAD risk (OR 1.00 per SD increase of fT4; 95% CI 0.96-1.04; p value 0.59). CONCLUSIONS: Lower thyroid status leads to an unfavorable lipid profile and a somewhat increased cardiovascular disease risk.


Assuntos
Doenças Cardiovasculares , Tireotropina , Adulto , Idoso , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Feminino , Humanos , Lipídeos , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Tiroxina , Adulto Jovem
11.
J Alzheimers Dis ; 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34842183

RESUMO

BACKGROUND: Poor social health is likely associated with cognitive decline and risk of dementia; however, studies show inconsistent results. Additionally, few studies separate social health components or control for mental health. OBJECTIVE: To investigate whether loneliness and social support are independently associated with cognitive decline and risk of dementia, and whether depressive symptoms confound the association. METHODS: We included 4,514 participants from the population-based Rotterdam Study (RS; aged 71±7SD years) followed up to 14 years (median 10.8, interquartile range 7.4-11.6), and 2,112 participants from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K; aged 72±10SD years) followed up to 10 years (mean 5.9±1.6SD). At baseline, participants were free of major depression and scored on the Mini-Mental State Examination (MMSE) ≥26 for RS and ≥25 for SNAC-K. We investigated loneliness, perceived social support, and structural social support (specifically marital status and number of children). In both cohorts, dementia was diagnosed and cognitive function was repeatedly assessed with MMSE and a global cognitive factor (g-factor). RESULTS: Loneliness was prospectively associated with a decline in the MMSE in both cohorts. Consistently, persons who were lonely had an increased risk of developing dementia (RS: HR 1.34, 95%CI 1.08-1.67; SNAC-K: HR 2.16, 95%CI 1.12-4.17). Adjustment for depressive symptoms and exclusion of the first 5 years of follow-up did not alter results. Neither perceived or structural social support was associated with cognitive decline or dementia risk. CONCLUSION: Loneliness, not social support, predicted cognitive decline and incident dementia independently of depressive symptoms.

12.
Hum Mol Genet ; 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34791242

RESUMO

The interocular distance, or orbital telorism, is a distinctive craniofacial trait that also serves as a clinically informative measure. While its extremes, hypo- and hypertelorism, have been linked to monogenic disorders and are often syndromic, little is known about the genetic determinants of interocular distance within the general population. We derived orbital telorism measures from cranial magnetic resonance imaging (MRI) by calculating the distance between the eyeballs' center of gravity, which showed a good reproducibility with an intraclass correlation coefficient of 0.991 (95% confidence interval 0.985-0.994). Heritability estimates were 76% (standard error = 12%) with a family-based method (N = 364), and 39% (standard error = 2.4%) with a single nucleotide polymorphism-based method (N = 34 130), and were unaffected by adjustment for height (model II), and intracranial volume (model III) or head width (model IV). Genome-wide association studies in 34 130 European individuals identified 56 significantly associated genomic loci (P < 5 x 10-8) across four different models of which 46 were novel for facial morphology, and overall these findings replicated in an independent sample (N = 10 115) with telorism-related horizontal facial distance measures. Genes located nearby these 56 identified genetic loci were 4.9-fold enriched for Mendelian hypotelorism and hypertelorism genes, underlining their biological relevance. This study provides novel insights into the genetic architecture underlying interocular distance in particular, and the face in general, and explores its potential for applications in a clinical setting.

13.
Atherosclerosis ; 337: 27-34, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34757268

RESUMO

BACKGROUND AND AIMS: The sex-specific contributions of arterial calcification to atherosclerotic cardiovascular disease (ASCVD) risk prediction and stratification in the light of recent modifications by cardiovascular prevention guidelines remain unclear. We assessed the sex-specific value of calcification in different arteries, beyond the Pooled Cohort Equations (PCE) risk factors, for 10-year ASCVD risk prediction. METHODS: From 2003 to 2006, participants from the population-based Rotterdam Study (n = 2167) underwent CT to quantify coronary artery calcification (CAC), aortic arch calcification (AAC), extracranial (ECAC) and intracranial carotid artery calcification (ICAC). Follow-up for ASCVD was complete on January 1, 2015. We refitted the PCE (base model), and categorized participants into low (<5%), borderline (5%-7.5%), intermediate (7.5%-20%), and high (≥20%) ASCVD risk. We extended the models with calcifications and calculated c-statistics and net reclassification improvements for events (NRIe) and non-events (NRIne). RESULTS: CAC predicted ASCVD in women [hazard-ratio (95%-CI) per 1-SD: 1.40 (1.14-1.73)] and men [1.62 (1.27-1.93)]. After addition of CAC to the base model, the c-statistic improved from 0.71 to 0.72 in women; from 0.65 to 0.68 in men. Addition of CAC led to NRIe of 14.3% in women, 4.8% in men and NRIne of 1.5% in women, 15.1% in men. Only in women, ICAC predicted ASCVD [hazard-ratio (95%-CI) per 1-SD: 1.62 (1.26-2.08)], and improved the model (c-statistic from 0.71 to 0.73, NRIe: 9.8% and NRIne: 5.9%). CONCLUSIONS: Assessment of CAC improves ASCVD risk prediction and stratification. In women, the added value of ICAC for ASCVD risk prediction is comparable to that of CAC.

14.
Cortex ; 145: 315-326, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34781092

RESUMO

Orbital telorism, the interocular distance, is clinically informative and in extremes is considered a minor physical anomaly. While its extremes, hypo- and hypertelorism, have been linked to disorders often related to cognitive ability, little is known about the neural correlates of normal variation of telorism within the general population. We derived measures of orbital telorism from cranial magnetic resonance imaging (MRI) by calculating the distance between the eyeball center of gravity in two population-based datasets (N = 5,653, N = 29,824; mean age 64.66, 63.75 years). This measure was found to be related to grey matter tissue density within numerous regions of the brain, including, but surprisingly not limited to, the frontal regions, in both positive and negative directions. Additionally, telorism was related to several cognitive functions, such as Purdue pegboard test (Beta, P-value (CI95%) -.02, 1.63 × 10-7 (-.03:-.01)) and fluid intelligence (.02, 4.75 × 10-6 (.01:0.02)), with some relationships driven by individuals with a smaller orbital telorism. This is reflective of the higher prevalence of hypotelorism in developmental disorders, specifically those that accompany lower cognitive lower functioning. This study suggests, despite previous links only made in clinical extremes, that orbital telorism holds some relation to structural brain development and cognitive function in the general population. This relationship is likely driven by shared developmental periods.

15.
PLoS Med ; 18(11): e1003854, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34813591

RESUMO

BACKGROUND: During the Coronavirus Disease 2019 (COVID-19) pandemic, the number of consultations and diagnoses in primary care and referrals to specialist care declined substantially compared to prepandemic levels. Beyond deferral of elective non-COVID-19 care by healthcare providers, it is unclear to what extent healthcare avoidance by community-dwelling individuals contributed to this decline in routine healthcare utilisation. Moreover, it is uncertain which specific symptoms were left unheeded by patients and which determinants predispose to healthcare avoidance in the general population. In this cross-sectional study, we assessed prevalence of healthcare avoidance during the pandemic from a patient perspective, including symptoms that were left unheeded, as well as determinants of healthcare avoidance. METHODS AND FINDINGS: On April 20, 2020, a paper COVID-19 survey addressing healthcare utilisation, socioeconomic factors, mental and physical health, medication use, and COVID-19-specific symptoms was sent out to 8,732 participants from the population-based Rotterdam Study (response rate 73%). All questionnaires were returned before July 10, 2020. By hand, prevalence of healthcare avoidance was subsequently verified through free text analysis of medical records of general practitioners. Odds ratios (ORs) for avoidance were determined using logistic regression models, adjusted for age, sex, and history of chronic diseases. We found that 1,142 of 5,656 included participants (20.2%) reported having avoided healthcare. Of those, 414 participants (36.3%) reported symptoms that potentially warranted urgent evaluation, including limb weakness (13.6%), palpitations (10.8%), and chest pain (10.2%). Determinants related to avoidance were older age (adjusted OR 1.14 [95% confidence interval (CI) 1.08 to 1.21]), female sex (1.58 [1.38 to 1.82]), low educational level (primary education versus higher vocational/university 1.21 [1.01 to 1.46), poor self-appreciated health (per level decrease 2.00 [1.80 to 2.22]), unemployment (versus employed 2.29 [1.54 to 3.39]), smoking (1.34 [1.08 to 1.65]), concern about contracting COVID-19 (per level increase 1.28 [1.19 to 1.38]) and symptoms of depression (per point increase 1.13 [1.11 to 1.14]) and anxiety (per point increase 1.16 [1.14 to 1.18]). Study limitations included uncertainty about (perceived) severity of the reported symptoms and potentially limited generalisability given the ethnically homogeneous study population. CONCLUSIONS: In this population-based cross-sectional study, 1 in 5 individuals avoided healthcare during lockdown in the COVID-19 pandemic, often for potentially urgent symptoms. Healthcare avoidance was strongly associated with female sex, fragile self-appreciated health, and high levels of depression and anxiety. These results emphasise the need for targeted public education urging these vulnerable patients to timely seek medical care for their symptoms to mitigate major health consequences.

16.
Geroscience ; 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34750718

RESUMO

Seasonal variation in cognitive function and underlying cerebral hemodynamics in humans has been suggested, but not consistently shown in previous studies. We assessed cognitive function in 10,276 participants from the population-based Rotterdam Study, aged 45 years and older without dementia, at baseline and at subsequent visits between 1999 and 2016. Seasonality of five cognitive test scores and of a summary measure of global cognition were determined, as well as of brain perfusion. Using linkage with medical records, we also examined whether a seasonal variation was present in clinical diagnoses of dementia. We found a seasonal variation of global cognition (0.05 standard deviations [95% confidence interval: 0.02-0.08]), the Stroop reading task, the Purdue Pegboard test, and of the delayed world learning test, with the best performance in summer months. In line with these findings, there were fewer dementia diagnoses of dementia in spring and summer than in winter and fall. We found no seasonal variation in brain perfusion. These findings support seasonality of cognition, albeit not explained by brain perfusion.

17.
Pharmacogenomics J ; 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34616002

RESUMO

Digoxin is characterized by a small therapeutic window and a QT-interval shortening effect. Moreover, it has been shown that the genetic variants of the nitric oxide synthase-1 adaptor protein (NOS1AP) gene are associated with QT-interval prolongation. We investigated whether the rs10494366 variant of the NOS1AP gene decreases the QT-interval shortening effect of digoxin in patients using this drug. We included 10,057 individuals from the prospective population-based cohort of the Rotterdam Study during a median of 12.2 (interquartile range (IQR) 6.7-18.1) years of follow-up. At study entry, the mean age was 64 years and almost 59% of participants were women. A total of 23,179 ECGs were longitudinally recorded, of which 334 ECGs were from 249 individuals on digoxin therapy. The linear mixed model analysis was used to estimate the effect of the rs10494366 variant on the association between digoxin use and QT-interval duration, adjusted for age, sex, RR interval, diabetes, heart failure, and history of myocardial infarction. In non-users of digoxin, the GG genotype was associated with a significant 6.5 ms [95% confidence interval (CI) 5.5; 7.5] longer QT-interval duration than the TT variant. In current digoxin users, however, the GG variant was associated with a significantly -23.9 [95%CI -29.5; -18.5] ms shorter mean QT-interval duration than in those with the TT variant with -15.9 [95%CI -18.7; -13.1]. This reduction was strongest in the high digoxin dose category [≥0.250 mg/day] with the GG genotype group, with -40.8 [95%CI -52.5; -29.2] ms changes compared to non-users. Our study suggests that the minor homozygous GG genotype group of the NOS1AP gene rs10494366 variant is associated with a paradoxical increase of the QT-interval shortening effect of digoxin in a population of European ancestry.

18.
J Am Geriatr Soc ; 2021 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-34664261

RESUMO

BACKGROUND: Various clinical studies have provided estimates of life expectancy of patients with mild cognitive impairment (MCI) from outpatient clinics, but whether these apply to community-dwelling individuals at home or in primary care is uncertain. METHODS: Within the population-based Rotterdam Study, we studied life expectancy with and without dementia in 648 community-dwelling persons with MCI and 6410 without MCI. Participants aged 60 years and older were assessed for MCI at baseline (2002-2014) and subsequently followed for the onset of dementia and death. We used multistate life tables to determine age-specific life expectancy with and without dementia by sex, educational attainment, and MCI subtype. RESULTS: Total life expectancy for MCI ranged from 21.4 years (95% CI: 19.0-23.6) at age 60 to 2.6 years (1.6-3.6) at age 95. With advancing age, an increasing proportion of these years was lived with dementia (2.9 years [1.8-4.0] at age 60; 1.2 [0.2-2.2] at age 95). Women and higher educated individuals lived longer and lived more years with dementia. No differences in total life expectancy were observed by MCI subtype, although individuals with amnestic MCI lived a larger proportion of those years with dementia. CONCLUSIONS: Prognosis of MCI, in terms of life years lived with and without dementia, is more favorable in the general population than described in prior clinical observations, due likely to a substantial proportion of individuals with MCI in the clinic not seeking medical attention in an earlier stage.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34634119

RESUMO

CONTEXT: Whether thyroid dysfunction is related to altered brain circulation in the general population remains unknown. OBJECTIVE: We determined the association of thyroid hormones with different markers of brain circulation within community-dwelling elderly. DESIGN: Three subcohorts of the Rotterdam Study, starting in 1989, 2000 and 2006 respectively. SETTING: Population-based. PATIENTS OR OTHER PARTICIPANTS: A total of 5,142 participants (mean age, 63.8 years; 55.4% women), underwent venapuncture to measure serum thyroid-stimulating hormone (TSH), free thyroxine (FT4). MAIN OUTCOME MEASURES: Between 2005 and 2015, all participants underwent phase-contrast brain magnetic resonance imaging to assess global brain perfusion (mL of blood flow/100 mL of brain/min). Arteriolar retinal calibers were assessed using digitized images of stereoscopic fundus color transparencies in 3,105 participants as markers of microcirculation. We investigated associations of TSH, FT4 with brain circulation measures using (non-)linear regression models. Results. FT4 (in pmol/L) levels had an inverse u-shaped association with global brain perfusion, such that high and low levels of FT4 were associated with lower global brain perfusion compared to middle levels of FT4. The difference in global brain perfusion between high FT4 levels (25 pmol/L) and middle FT4 levels (FT4 = 15 pmol/L; P non-linearity = 0.002) was up to -2.44 mL (95% confidence interval (95%CI)= -4.31; -0.56). Similarly, higher and lower levels of FT4, compared with middle FT4 levels, were associated with arteriolar retinal vessels (mean difference up to -2.46 µm, 95%CI -4.98; 0.05 for lower FT4). CONCLUSIONS: These results suggest that thyroid dysfunction could lead to brain diseases such as stroke or dementia through a suboptimal brain circulation that is potentially modifiable.

20.
J Alzheimers Dis ; 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34690139

RESUMO

BACKGROUND: The burden of dementia is changing due to population aging and changes in incidence and risk factor profiles. Reliable projections of future disease burden require accurate estimates of disease duration across different stages of dementia severity. OBJECTIVE: To provide an overview of current evidence on severity stage and disease duration in patients with dementia. METHODS: We reviewed the literature on duration of mild cognitive impairment (MCI), dementia, and various dementia severity stages. Data on study setting, country, sample size, severity stages, dementia type, and definition of disease duration was collected. Weighted averages and Q-statistics were calculated within severity stages and duration definitions. RESULTS: Of 732 screened articles, 15 reported the duration of one or more severity stages and only half of those reported severity stage onset to conversion to the following stage. In those studies, MCI, very mild dementia, and mild dementia stages lasted 3-4 years and moderate and severe dementia stages lasted 1-2 years. Information on the disease duration was reported in 93 (13%) of screened articles and varied from 1 to 17 years. Reporting of dementia severity stage and disease duration in the literature was highly heterogeneous, which was accounted for only in part by dementia type, study setting, or continent of data collection. CONCLUSION: The duration of dementia disease stages shortens with advancing stage. However, reliable modelling of future dementia burden and informing of intervention strategies will require more consistently reported duration estimates from studies that follow individuals longitudinally throughout their entire disease course.

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