Long-term association of pregnancy and maternal brain structure: the Rotterdam Study

The peripartum period is the highest risk interval for the onset or exacerbation of psychiatric illness in women’s lives. Notably, pregnancy and childbirth have been associated with short-term structural and functional changes in the maternal human brain. Yet the long-term effects of pregnancy on maternal brain structure remain unknown. We investigated a large population-based cohort to examine the association between parity and brain structure. In total, 2,835 women (mean age 65.2 years; all free from dementia, stroke, and cortical brain infarcts) from the Rotterdam Study underwent magnetic resonance imaging (1.5 T) between 2005 and 2015. Associations of parity with global and lobar brain tissue volumes, white matter microstructure, and markers of vascular brain disease were examined using regression models. We found that parity was associated with a larger global gray matter volume (β = 0.14, 95% CI = 0.09–0.19), a finding that persisted following adjustment for sociodemographic factors. A non-significant dose-dependent relationship was observed between a higher number of childbirths and larger gray matter volume. The gray matter volume association with parity was globally proportional across lobes. No associations were found regarding white matter volume or integrity, nor with markers of cerebral small vessel disease. The current findings suggest that pregnancy and childbirth are associated with robust long-term changes in brain structure involving a larger global gray matter volume that persists for decades. Future studies are warranted to further investigate the mechanism and physiological relevance of these differences in brain morphology.

Subclinical Measures of Peripheral Atherosclerosis and the Risk of New‐Onset Atrial Fibrillation in the General Population: the Rotterdam Study

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.

Circulatory MicroRNAs in Plasma and Atrial Fibrillation in the General Population: The Rotterdam Study

Background: MicroRNAs (miRNAs), small non-coding RNAs regulating gene expression, have been shown to play an important role in cardiovascular disease. However, limited population-based data regarding the relationship between circulatory miRNAs in plasma and atrial fibrillation (AF) exist. Moreover, it remains unclear if the relationship differs by sex. We therefore aimed to determine the (sex-specific) association between plasma circulatory miRNAs and AF at the population level. Methods: Plasma levels of miRNAs were measured using a targeted next-generation sequencing method in 1999 participants from the population-based Rotterdam Study. Logistic regression and Cox proportional hazards models were used to assess the associations of 591 well-expressed miRNAs with the prevalence and incidence of AF. Models were adjusted for cardiovascular risk factors. We further examined the link between predicted target genes of the identified miRNAs. Results: The mean age was 71.7 years (57.1% women), 98 participants (58 men and 40 women) had prevalent AF at baseline. Moreover, 196 participants (96 men and 100 women) developed AF during a median follow-up of 9.0 years. After adjusting for multiple testing, miR-4798-3p was significantly associated with the odds of prevalent AF among men (odds ratio, 95% confidence interval, 0.39, 0.24–0.66, p-value = 0.000248). No miRNAs were significantly associated with incident AF. MiR-4798-3p could potentially regulate the expression of a number of AF-related genes, including genes involved in calcium and potassium handling in myocytes, protection of cells against oxidative stress, and cardiac fibrosis. Conclusions: Plasma levels of miR-4798-3p were significantly associated with the odds of prevalent AF among men. Several target genes in relation to AF pathophysiology could potentially be regulated by miR-4798-3p that warrant further investigations in future experimental studies.

Comparison of cerebral blood flow in subjects with and without chronic obstructive pulmonary disease from the population-based Rotterdam Study

ObjectivesPatients with chronic obstructive pulmonary disease (COPD) are at increased risk of cerebrovascular disease, which might be associated with decreases in cerebral blood flow. Since studies examining cerebral blood flow in COPD remain scarce and are limited by sample size, we aimed to study cerebral blood flow in participants with and without COPD.DesignObservational cohort study.SettingPopulation-based Rotterdam Study.Participants4177 participants (age 68.0±8.5 years; 53% females) with and without COPD.Predictor variableSpirometry and pulmonary diffusing capacity.Outcome measuresCerebral blood flow by two-dimensional phase-contrast cerebral MRI.ResultsCompared with subjects with normal spirometry (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ≥0.7 and FEV1 ≥80%), multivariable adjusted cerebral blood flow (mL/min) was preserved in subjects with COPD Global initiative for Chronic Obstructive Lung Disease (GOLD1) (FEV1/FVC <0.7 and FEV1 ≥80%), but significantly lower in subjects with COPD GOLD2-3 (FEV1/FVC <0.7 and FEV1 <80%), even after adjustment for cardiovascular comorbidities. In sex-stratified analyses, this difference in cerebral blood flow was statistically significant in women but not in men. Cerebral blood flow was lowest in subjects with FEV1, FVC and diffusion lung capacity for carbon monoxide % predicted values in the lowest quintile, even after adjustment for cardiovascular comorbidities and cardiac function.ConclusionWe observed a lowered cerebral blood flow in subjects with COPD GOLD2-3.

Seasonality of cognitive function in the general population: the Rotterdam Study

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.

Diet Quality and Risk of Parkinson’s Disease: The Rotterdam Study

The Mediterranean diet has been associated with the risk of Parkinson’s disease (PD), but limited research has been performed on other dietary patterns. We studied the relationship between overall diet quality and PD risk in the general population. We included 9414 participants from the Rotterdam Study, a prospective population-based study in the Netherlands. Diet was defined using a Dutch diet quality score, a Mediterranean diet score and data-driven dietary patterns constructed with principal component analysis (PCA). During an average follow-up of 14.1 years, PD was diagnosed in 129 participants. We identified a ‘Prudent’, ‘Unhealthy’ and ‘Traditional Dutch’ pattern from the PCA. We found a possible association between the Mediterranean diet (Hazard ratio (HR) per standard deviation (SD) 0.89 (95% confidence interval (CI) 0.74–1.07)), the ‘Prudent’ pattern (HR per SD 0.81 (95% CI 0.61–1.08)) and the risk of PD. However, no associations with PD risk were found for the Dutch diet quality score (HR per SD 0.93 (95% CI 0.77–1.12)), the ‘Unhealthy’ pattern (HR per SD 1.05 (95% CI 0.85–1.29)) or the ‘Traditional Dutch’ pattern (HR per SD 0.90 (95% CI 0.69–1.17)). In conclusion, our results corroborate previous findings of a possible protective effect of the Mediterranean diet. Further research is warranted to study the effect of other dietary patterns on PD risk.