The manifestation of cognitive and physical impairment in stroke patients before the acute event suggests accumulating subclinical vascular pathology in the brain. We investigated whether impairments ...in cognitive and physical functioning were associated with an increased stroke risk. Between 2002 and 2008, 8,519 stroke-free non-demented participants from the population-based Rotterdam Study underwent cognition and physical assessments including Mini-Mental State Examination, 15-word learning test, Stroop test, letter-digit substitution test, verbal fluency test, Purdue pegboard test and questionnaires on basic and instrumental activities of daily living (BADL; IADL). Principal component analysis was used to derive global cognition (G-factor). Incident stroke was assessed through continuous monitoring of medical records until 2016. Among 8,519 persons (mean age 66.0 years; 57.8% women), 489 suffered a stroke during mean follow-up of 8.7 years (SD: 2.9). Worse G-factor was associated with higher stroke risk (Hazard Ratio 1.21, 95% CI: 1.06-1.38), largely driven by unspecified stroke. Likewise, worse scores on 15-word learning test, Stroop test, Purdue pegboard test, IADL, and BADL were associated with higher risk of stroke. Thus both worse cognitive and physical functioning were associated with a higher stroke risk, in particular unspecified stroke and persons with worse memory, information processing, executive function, and motor function.
Additive manufacturing (AM) has gained significant attention due to its ability to drive technological development as a sustainable, flexible, and customizable manufacturing scheme. Among the various ...AM techniques, direct ink writing (DIW) has emerged as the most versatile 3D printing technique for the broadest range of materials. DIW allows printing of practically any material, as long as the precursor ink can be engineered to demonstrate appropriate rheological behavior. This technique acts as a unique pathway to introduce design freedom, multifunctionality, and stability simultaneously into its printed structures. Here, a comprehensive review of DIW of complex 3D structures from various materials, including polymers, ceramics, glass, cement, graphene, metals, and their combinations through multimaterial printing is presented. The review begins with an overview of the fundamentals of ink rheology, followed by an in‐depth discussion of the various methods to tailor the ink for DIW of different classes of materials. Then, the diverse applications of DIW ranging from electronics to food to biomedical industries are discussed. Finally, the current challenges and limitations of this technique are highlighted, followed by its prospects as a guideline toward possible futuristic innovations.
The comprehensive review comprises recent development in direct‐ink‐writing (DIW) 3D printing technology for the development of 3D structures from various materials such as polymers, ceramics, glass, cement, graphene, metals, and multimaterials. The work describes the fundamentals and engineering of ink rheology required for DIW. In addition, a multitude of applications, current challenges, and future prospects of the technology are discussed.
Dementia is among the leading causes of death and disability. Due to the ageing population, its prevalence is expected to nearly triple worldwide by 2050, urging the development of preventive and ...curative interventions. Various modifiable risk factors have been identified in community-based cohort studies, but insight into the underlying pathophysiological mechanisms is lacking. Clinical trials have thus far failed in the development of disease-modifying therapy in patients with dementia, thereby triggering a shift of focus toward the presymptomatic phase of disease. The extensive preclinical disease course of Alzheimer's disease warrants reliable, easily obtainable biomarkers to aid in timely application of preventive strategies, selecting participants for neuroprotective trials, and disease monitoring in trials and clinical practice. Biomarker and drug discovery may yield the fruits from technology-driven developments in the field of genomics, epigenetics, metabolomics, and brain imaging. In that context, bridging the gap between translational and population research may well prove a giant leap toward development of successful preventive and curative interventions against dementia.
To investigate whether dementia incidence has changed over the last 2 decades.
We compared dementia incidence in 2 independent subcohorts of persons aged 60-90 years from the Rotterdam Study, a ...population-based cohort study. The first subcohort started in 1990 (n = 5,727), the second in 2000 (n = 1,769). Participants were dementia-free at baseline and followed for at maximum 5 years. We calculated age-adjusted dementia incidence rates for the 2 subcohorts in total, in 10-year age strata, and for men and women separately. We also compared mortality rates, differences in prevalence of vascular risk factors, and medication use. Finally, we compared brain volumes and the extent of cerebral small vessel disease in participants who underwent brain imaging 5 years after the baseline examinations.
In the 1990 subcohort (25,696 person-years), 286 persons developed dementia, and in the 2000 subcohort (8,384 person-years), 49 persons. Age-adjusted dementia incidence rates were consistently, yet nonsignificantly, lower in the 2000 subcohort in all strata, reaching borderline significance in the overall analysis (incidence rate ratio 0.75, 95% confidence interval CI 0.56-1.02). Mortality rates were also lower in the 2000 subcohort (rate ratio 0.63, 95% CI 0.52-0.77). The prevalence of hypertension and obesity significantly increased between 1990 and 2000. This was paralleled by a strong increase in use of antithrombotics and lipid-lowering drugs. Participants in 2005-2006 had larger total brain volumes (p < 0.001) and less cerebral small vessel disease (although nonsignificant in men) than participants in 1995-1996.
Although the differences in dementia incidence were nonsignificant, our study suggests that dementia incidence has decreased between 1990 and 2005.
Cerebral microbleeds are frequently found in the general elderly population and may reflect underlying vascular disease, but their role in cognitive function is unknown.
We investigated the ...association between cerebral microbleeds and performance in multiple cognitive domains in 3,979 persons without dementia (mean age, 60.3 years). Mini-Mental State Examination (MMSE) score and neuropsychological tests were used to assess global cognition and the following cognitive domains: memory, information processing speed, executive function, and motor speed. We used number of microbleeds as continuous variable, and additionally distinguished between persons with no microbleeds, 1 microbleed, 2-4 microbleeds, and ≥5 microbleeds. The association of microbleeds with different cognitive domains was estimated using linear regression models. Additional adjustments were made for vascular risk factors, brain atrophy, and other imaging markers of cerebral small vessel disease. We stratified analyses by location of microbleeds.
A higher number of microbleeds was associated with lower MMSE score and worse performance on tests of information processing speed and motor speed. When analyzed per category, presence of 5 or more microbleeds was associated with worse performance in all cognitive domains, except memory. These associations were most robust in participants with strictly lobar microbleeds, whereas after additional adjustments associations disappeared for deep or infratentorial microbleeds.
Presence of numerous microbleeds, especially in a strictly lobar location, is associated with worse performance on tests measuring cognitive function, even after adjustments for vascular risk factors and other imaging markers of small vessel disease. These results suggest an independent role for microbleed-associated vasculopathy in cognitive impairment.
Cerebral microbleeds are focal deposits of hemosiderin that can be visualized with MRI. Little is known on their prevalence in the general population and on their etiology. It has been suggested ...that, in analogy to spontaneous intracranial hemorrhage, the etiology of microbleeds differs according to their location in the brain, with lobar microbleeds being caused by cerebral amyloid angiopathy and deep or infratentorial microbleeds resulting from hypertension and atherosclerosis. We investigated the prevalence of and risk factors for microbleeds in the general population aged 60 years and older.
This study is based on 1,062 persons (mean age 69.6 years) from the population-based Rotterdam Scan Study. MRI was performed at 1.5 T and included a sequence optimized to increase the conspicuity of microbleeds. We assessed the relation of APOE genotype, cardiovascular risk factors, and markers of small vessel disease to the presence and location of microbleeds with multiple logistic regression.
Overall prevalence of cerebral microbleeds was high and increased with age from 17.8% in persons aged 60-69 years to 38.3% in those over 80 years. APOE epsilon 4 carriers had significantly more often strictly lobar microbleeds than noncarriers. In contrast, cardiovascular risk factors and presence of lacunar infarcts and white matter lesions were associated with microbleeds in a deep or infratentorial location but not in a lobar location.
The prevalence of cerebral microbleeds is high. Our data support the hypothesis that strictly lobar microbleeds are related to cerebral amyloid angiopathy, whereas microbleeds in a deep or infratentorial location result from hypertensive or atherosclerotic microangiopathy.
The contribution of sex hormones to micro- and macrovascular damage might differ among women and men. In particular, little is known about the association between sex hormones and small vessel ...disease. Therefore, we examined the association of total oestradiol, total testosterone, free-androgen index (FAI), dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), and androstenedione levels with micro- and macrovascular diseases.
This cross-sectional study included 2950 women and 2495 men from the population-based Rotterdam Study. As proxy of microvascular damage, we measured diameters of retinal arterioles and venules. Markers of macrovascular damage included carotid intima-media thickness and carotid plaque, coronary artery calcification (CAC), and peripheral artery disease. Linear and logistic regression models were used and adjusted for age, cardiovascular risk factors, and years since menopause. Associations with microvasculature: In women, total testosterone mean difference per 1-unit increase in natural-log transformed total testosterone (95% confidence interval, CI): 2.59 (0.08-5.09) and androstenedione 4.88 (1.82-7.95) and in men DHEAS 2.80 (0.23-5.37) and androstenedione 5.83 (2.19-9.46) were associated with larger venular caliber. Associations with markers of large vessel disease: In women, higher total testosterone -0.29 (-0.56 to -0.03), FAI -0.33 (-0.56 to -0.10), and androstenedione levels -0.33 (-0.64 to -0.02) were associated with lower CAC burden and FAI odds ratio (95% CI): 0.82 (0.71-0.94) was associated with lower prevalence of plaque.
A more androgenic profile was associated with more microvascular damage in both women and men. Among women, however, higher androgen levels were also associated with less macrovascular damage. Our findings suggest that androgens might have distinct effects on the vasculature, depending on the vascular bed and stages of the atherosclerosis process.
Objective To evaluate differences in first manifestations of cardiovascular disease between men and women in a competing risks framework.Design Prospective population based cohort study.Setting ...People living in the community in Rotterdam, the Netherlands.Participants 8419 participants (60.9% women) aged ≥55 and free from cardiovascular disease at baseline.Main outcome measures First diagnosis of coronary heart disease (myocardial infarction, revascularisation, and coronary death), cerebrovascular disease (stroke, transient ischaemic attack, and carotid revascularisation), heart failure, or other cardiovascular death; or death from non-cardiovascular causes. Data were used to calculate lifetime risks of cardiovascular disease and its first incident manifestations adjusted for competing non-cardiovascular death.Results During follow-up of up to 20.1 years, 2888 participants developed cardiovascular disease (826 coronary heart disease, 1198 cerebrovascular disease, 762 heart failure, and 102 other cardiovascular death). At age 55, overall lifetime risks of cardiovascular disease were 67.1% (95% confidence interval 64.7% to 69.5%) for men and 66.4% (64.2% to 68.7%) for women. Lifetime risks of first incident manifestations of cardiovascular disease in men were 27.2% (24.1% to 30.3%) for coronary heart disease, 22.8% (20.4% to 25.1%) for cerebrovascular disease, 14.9% (13.3% to 16.6%) for heart failure, and 2.3% (1.6% to 2.9%) for other deaths from cardiovascular disease. For women the figures were 16.9% (13.5% to 20.4%), 29.8% (27.7% to 31.9%), 17.5% (15.9% to 19.2%), and 2.1% (1.6% to 2.7%), respectively. Differences in the number of events that developed over the lifespan in women compared with men (per 1000) were −7 for any cardiovascular disease, −102 for coronary heart disease, 70 for cerebrovascular disease, 26 for heart failure, and −1 for other cardiovascular death; all outcomes manifested at a higher age in women. Patterns were similar when analyses were restricted to hard atherosclerotic cardiovascular disease outcomes, but absolute risk differences between men and women were attenuated for both coronary heart disease and stroke.Conclusions At age 55, though men and women have similar lifetime risks of cardiovascular disease, there are considerable differences in the first manifestation. Men are more likely to develop coronary heart disease as a first event, while women are more likely to have cerebrovascular disease or heart failure as their first event, although these manifestations appear most often at older ages.
Highlights ► We investigated the association of age with gait, focusing on normal walking, turning and tandem walking, in 1500 persons. ► Gait can be summarized in seven independent factors. ► Rhythm ..., Variability , Phases , Pace and Base of Support represent normal walking. ► Additionally, Turning and Tandem provide incremental information on gait beyond normal walking. ► Variability , Phases and Tandem have the strongest association with age and are the earliest to deteriorate.
Both normal aging and neurodegenerative disorders such as Alzheimer's disease (AD) cause morphological changes of the brain. It is generally difficult to distinguish these two causes of morphological ...change by visual inspection of magnetic resonance (MR) images. To facilitate making this distinction and thus aid the diagnosis of neurodegenerative disorders, we propose a method for developing a spatio-temporal model of morphological differences in the brain due to normal aging. The method utilizes groupwise image registration to characterize morphological variation across brain scans of people with different ages. To extract the deformations that are due to normal aging we use partial least squares regression, which yields modes of deformations highly correlated with age, and corresponding scores for each input subject. Subsequently, we determine a distribution of morphologies as a function of age by fitting smooth percentile curves to these scores. This distribution is used as a reference to which a person's morphology score can be compared. We validate our method on two different datasets, using images from both cognitively normal subjects and patients with Alzheimer disease (AD). Results show that the proposed framework extracts the expected atrophy patterns. Moreover, the morphology scores of cognitively normal subjects are on average lower than the scores of AD subjects, indicating that morphology differences between AD subjects and healthy subjects can be partly explained by accelerated aging. With our methods we are able to assess accelerated brain aging on both population and individual level. A spatio-temporal aging brain model derived from 988 T1-weighted MR brain scans from a large population imaging study (age range 45.9–91.7y, mean age 68.3y) is made publicly available at www.agingbrain.nl.
•A model to assess morphological differences in the brain due to aging is developed.•The method can assess accelerated brain aging on population and individual level.•The model derived from 988 MR brain is made publicly available at www.agingbrain.nl.
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