The scans of people with Alzheimer's disease showed the greatest overall difference from the scans of individuals of the same age without neurological diseases, closely followed by scans from ...patients with mild cognitive impairment or schizophrenia. The large sample size and the virtually complete age range of Bethlehem and colleagues’ study could ultimately inform clinical practice for patients outside of the memory clinic setting with more accurate estimations of brain volumetrics against normative reference data. ...the work by Bethlehem and colleagues has brought us one important step closer to understanding what is healthy in structural brain development and brain ageing, which in time will help us to better recognise what is unhealthy.
Increasing evidence suggests that atherosclerotic plaque composition rather than plaque size is linked to ischemic cardiovascular events, yet largescale population-based data in asymptomatic ...individuals remain scarce.
This study sought to investigate carotid plaque composition in relation to incident stroke and coronary heart disease (CHD) in a population-based setting.
Between 2007 and 2012, 1,349 persons (mean age 72 years, 49.5% women) from the population-based Rotterdam Study who were free from a history of stroke or CHD, in whom carotid ultrasonography showed subclinical atherosclerosis, and who underwent high-resolution magnetic resonance imaging of the carotid arteries to assess plaque characteristics. These included the presence of specific plaque components (intraplaque hemorrhage IPH, lipid-rich necrotic core, and calcification), and measures of plaque size (maximum plaque thickness and presence of stenosis of more than 30%). Individuals were continuously followed for the occurrence of stroke or CHD until January 1, 2015. The authors used Cox regression models to assess the association of the plaque characteristics with the incidence of stroke and CHD, with adjustments for age, sex, and cardiovascular risk factors.
During a median of 5.1 years’ follow-up for stroke and 4.8 years for CHD, 51 individuals had a stroke and 83 developed CHD. Independent of maximum plaque thickness and cardiovascular risk factors, the presence of IPH was associated with incident stroke and CHD (fully adjusted hazard ratio: 2.42 95% confidence interval: 1.30 to 4.50, and 1.95 95% confidence interval: 1.20 to 3.14). Presence of a lipid-rich necrotic core and calcification were not associated with stroke or CHD.
The presence of IPH in the carotid atherosclerotic plaque is an independent risk factor for stroke and CHD. These findings indicate the promise of IPH as a marker of plaque vulnerability in healthy persons with subclinical atherosclerosis.
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The variation between images obtained with different scanners or different imaging protocols presents a major challenge in automatic segmentation of biomedical images. This variation especially ...hampers the application of otherwise successful supervised-learning techniques which, in order to perform well, often require a large amount of labeled training data that is exactly representative of the target data. We therefore propose to use transfer learning for image segmentation. Transfer-learning techniques can cope with differences in distributions between training and target data, and therefore may improve performance over supervised learning for segmentation across scanners and scan protocols. We present four transfer classifiers that can train a classification scheme with only a small amount of representative training data, in addition to a larger amount of other training data with slightly different characteristics. The performance of the four transfer classifiers was compared to that of standard supervised classification on two magnetic resonance imaging brain-segmentation tasks with multi-site data: white matter, gray matter, and cerebrospinal fluid segmentation; and white-matter-/MS-lesion segmentation. The experiments showed that when there is only a small amount of representative training data available, transfer learning can greatly outperform common supervised-learning approaches, minimizing classification errors by up to 60%.
BACKGROUND AND PURPOSE—Blood pressure (BP) variability may increase the risk of stroke and dementia. It remains inconclusive whether BP variability is associated with cerebral small vessel disease, a ...common and potentially devastating subclinical disease that contributes significantly to both stroke and dementia.
METHODS—A systematic review and meta-analysis of prospective cohort studies that examined the association between BP variability and the presence or progression of established markers of cerebral small vessel disease, including white matter hyperintensities, lacunes, and microbleeds on magnetic resonance imaging. We searched MEDLINE, EMBASE, and Web of Science. Ten studies met the criteria for qualitative synthesis and 7 could be included in the meta-analysis. Data were synthetized using random-effect models.
RESULTS—These studies included a total of 2796 individuals aged 74 (mean) ±4 (SD) years, with a median follow-up of 4.0 years. A one SD increase in systolic BP variability was associated with increased odds of the presence or progression of white matter hyperintensities (odds ratio, 1.26 95% CI, 1.06–1.50). The association of systolic BP variability with the presence of lacunes (odds ratio, 0.93 95% CI, 0.74–1.16) and the presence of microbleeds (odds ratio, 1.13 95% CI, 0.89–1.44) were not statistically significant.
CONCLUSIONS—A larger BP variability may be associated with a higher risk of having a higher burden of white matter hyperintensities. Targeting large BP variability has the potential to prevent cerebral small vessel disease and thereby reducing the risk of stroke and dementia. The potential issue of reverse causation and the heterogeneity in the assessment of cerebral small vessel disease markers should be better addressed in future studies.
Cortical superficial siderosis describes a distinct pattern of blood-breakdown product deposition limited to cortical sulci over the convexities of the cerebral hemispheres, sparing the brainstem, ...cerebellum and spinal cord. Although cortical superficial siderosis has many possible causes, it is emerging as a key feature of cerebral amyloid angiopathy, a common and important age-related cerebral small vessel disorder leading to intracerebral haemorrhage and dementia. In cerebral amyloid angiopathy cohorts, cortical superficial siderosis is associated with characteristic clinical symptoms, including transient focal neurological episodes; preliminary data also suggest an association with a high risk of future intracerebral haemorrhage, with potential implications for antithrombotic treatment decisions. Thus, cortical superficial siderosis is of relevance to neurologists working in neurovascular, memory and epilepsy clinics, and neurovascular emergency services, emphasizing the need for appropriate blood-sensitive magnetic resonance sequences to be routinely acquired in these clinical settings. In this review we focus on recent developments in neuroimaging and detection, aetiology, prevalence, pathophysiology and clinical significance of cortical superficial siderosis, with a particular emphasis on cerebral amyloid angiopathy. We also highlight important areas for future investigation and propose standards for evaluating cortical superficial siderosis in research studies.
The gap between predicted brain age using magnetic resonance imaging (MRI) and chronological age may serve as a biomarker for early-stage neurodegeneration. However, owing to the lack of large ...longitudinal studies, it has been challenging to validate this link. We aimed to investigate the utility of such a gap as a risk biomarker for incident dementia using a deep learning approach for predicting brain age based on MRI-derived gray matter (GM). We built a convolutional neural network (CNN) model to predict brain age trained on 3,688 dementia-free participants of the Rotterdam Study (mean age 66 ± 11 y, 55% women). Logistic regressions and Cox proportional hazards were used to assess the association of the age gap with incident dementia, adjusted for age, sex, intracranial volume, GM volume, hippocampal volume, white matter hyperintensities, years of education, and APOE ε4 allele carriership. Additionally, we computed the attention maps, which shows which regions are important for age prediction. Logistic regression and Cox proportional hazard models showed that the age gap was significantly related to incident dementia (odds ratio OR = 1.11 and 95% confidence intervals CI = 1.05–1.16; hazard ratio HR = 1.11, and 95% CI = 1.06–1.15, respectively). Attention maps indicated that GM density around the amygdala and hippocampi primarily drove the age estimation. We showed that the gap between predicted and chronological brain age is a biomarker, complimentary to those that are known, associated with risk of dementia, and could possibly be used for early-stage dementia risk screening.
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.
BACKGROUND:Cerebral hypoperfusion has previously been associated with mild cognitive impairment and dementia in various cross-sectional studies, but whether hypoperfusion precedes neurodegeneration ...is unknown. We prospectively determined the association of cerebral perfusion with subsequent cognitive decline and development of dementia.
METHODS:Between 2005 and 2012, we measured cerebral blood flow by 2-dimensional phase-contrast magnetic resonance imaging in participants of the population-based Rotterdam Study without dementia. We determined the association of cerebral perfusion (mL/100mL/min) with risk of dementia (until 2015) using a Cox model, adjusting for age, sex, demographics, cardiovascular risk factors, and apolipoprotein E genotype. We repeated analyses for Alzheimer disease and accounting for stroke. We used linear regression to determine change in cognitive performance during 2 consecutive examination rounds in relation to perfusion. Finally, we investigated whether associations were modified by baseline severity of white matter hyperintensities.
RESULTS:Of 4759 participants (median age 61.3 years, 55.2% women) with a median follow-up of 6.9 years, 123 participants developed dementia (97 Alzheimer disease). Lower cerebral perfusion was associated with higher risk of dementia (adjusted hazard ratio, 1.31; 95% confidence interval per standard deviation decrease, 1.07–1.61), similar for Alzheimer disease only, and unaltered by accounting for stroke. Risk of dementia with hypoperfusion was higher with increasing severity of white matter hyperintensities (with severe white matter hyperintensities; hazard ratio, 1.54; 95% confidence interval, 1.11–2.14). At cognitive reexamination after on average 5.7 years, lower baseline perfusion was associated with accelerated decline in cognition (global cognitionβ=−0.029, P=0.003), which was similar after excluding those with incident dementia, and again most profound in individuals with higher volume of white matter hyperintensities (P value for interaction=0.019).
CONCLUSIONS:Cerebral hypoperfusion is associated with accelerated cognitive decline and an increased risk of dementia in the general population.
•Literature reports that long-term meditators show altered brain activations and structure.•Post-MBSR, prefrontal cortex, insula, cingulate cortex and hippocampus show similar results to traditional ...meditation.•In addition, the amygdala shows earlier deactivation, less gray matter and better connectivity.•These changes indicate a neuronal working mechanism of MBSR.
The objective of the current study was to systematically review the evidence of the effect of secular mindfulness techniques on function and structure of the brain. Based on areas known from traditional meditation neuroimaging results, we aimed to explore a neuronal explanation of the stress-reducing effects of the 8-week Mindfulness Based Stress Reduction (MBSR) and Mindfulness Based Cognitive Therapy (MBCT) program.
We assessed the effect of MBSR and MBCT (N=11, all MBSR), components of the programs (N=15), and dispositional mindfulness (N=4) on brain function and/or structure as assessed by (functional) magnetic resonance imaging. 21 fMRI studies and seven MRI studies were included (two studies performed both).
The prefrontal cortex, the cingulate cortex, the insula and the hippocampus showed increased activity, connectivity and volume in stressed, anxious and healthy participants. Additionally, the amygdala showed decreased functional activity, improved functional connectivity with the prefrontal cortex, and earlier deactivation after exposure to emotional stimuli.
Demonstrable functional and structural changes in the prefrontal cortex, cingulate cortex, insula and hippocampus are similar to changes described in studies on traditional meditation practice. In addition, MBSR led to changes in the amygdala consistent with improved emotion regulation. These findings indicate that MBSR-induced emotional and behavioral changes are related to functional and structural changes in the brain.
Gyrification of the cerebral cortex changes with aging and relates to development of cognitive function during early life and midlife. Little is known about how gyrification relates to age and ...cognitive function later in life. We investigated this in 4397 individuals (mean age: 63.5 years, range: 45.7 to 97.9) from the Rotterdam Study, a population-based cohort. Global and local gyrification were assessed from T1-weighted images. A measure for global cognition, the g-factor, was calculated from five cognitive tests. Older age was associated with lower gyrification (mean difference per year = −0.0021; 95% confidence interval = −0.0025; −0.0017). Non-linear terms did not improve the models. Age related to lower gyrification in the parietal, frontal, temporal and occipital regions, and higher gyrification in the medial prefrontal cortex. Higher levels of the g-factor were associated with higher global gyrification (mean difference per g-factor unit = 0.0044; 95% confidence interval = 0.0015; 0.0073). Age and the g-factor did not interact in relation to gyrification (p > 0.05). The g-factor bilaterally associated with gyrification in three distinct clusters. The first cluster encompassed the superior temporal gyrus, the insular cortex and the postcentral gyrus, the second cluster the lingual gyrus and the precuneus, and the third cluster the orbitofrontal cortex. These clusters largely remained statistically significant after correction for cortical surface area. Overall, the results support the notion that gyrification varies with aging and cognition during and after midlife, and suggest that gyrification is a potential marker for age-related brain and cognitive decline beyond midlife.
•Older age associates with lower cortical gyrification during and after midlife.•Age and gyrification relate linearly during adulthood, not non-linearly.•Gyrification of the medial prefrontal cortex increases with age after midlife.•Cognitive function associates with gyrification in the frontal and temporal lobes.
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