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Background: Plasma amyloid-β (Aβ) levels are increasingly studied as a potential, accessible marker of cognitive impairment and dementia. The most common plasma Aβ isoforms, i.e., Aβ1-40 and Aβ1-42 have been linked with risk of Alzheimer's disease. However, it remains under-explored whether plasma Aβ levels including novel Aβ1-38 relate to vascular brain disease and cognition in a preclinical-phase of dementiaObjective:To examine the association of plasma Aβ levels (i.e., Aβ1-38, Aβ1-40, and Aβ1-42) with markers of cerebral small vessel disease (SVD) and cognition in a large population-based setting.Methods: We analyzed plasma Aβ1 levels in 1201 subjects from two independent cohorts of the Rotterdam Study. Markers of SVD [lacunes, white matter hyperintensity (WMH) volume] were assessed on brain MRI (1.5T). Cognition was assessed by a detailed neuropsychological battery. In each cohort, the association of Aβ levels with SVD and cognition was performed using regression models. Estimates were then pooled across cohorts using inverse variance meta-analysis with fixed effects.Results: Higher levels of plasma Aβ1-38, Aβ1-40, Aβ1-42, and Aβ1-40/ Aβ1-42 ratio were associated with increasing lacunar and microbleeds counts. Moreover, higher levels of Aβ1-40 and Aβ1-40/ Aβ1-42 were significantly associated with larger WMH volumes. With regard to cognition, a higher level of Aβ1-38 Aβ1-40 and Aβ1-40/ Aβ1-42 was related to worse performance on cognitive test specifically in memory domain.Conclusion: Higher plasma levels of Aβ levels are associated with subclinical markers of vascular disease and poorer memory. Plasma Aβ levels thus mark the presence of vascular brain pathology. [ABSTRACT FROM AUTHOR]

Radiomics applied in MRI has shown promising results in classifying prostate cancer lesions. However, many papers describe single-center studies without external validation. The issues of using radiomics models on unseen data have not yet been sufficiently addressed. The aim of this study is to evaluate the generalizability of radiomics models for prostate cancer classification and to compare the performance of these models to the performance of radiologists. Multiparametric MRI, photographs and histology of radical prostatectomy specimens, and pathology reports of 107 patients were obtained from three healthcare centers in the Netherlands. By spatially correlating the MRI with histology, 204 lesions were identified. For each lesion, radiomics features were extracted from the MRI data. Radiomics models for discriminating high-grade (Gleason score ≥ 7) versus low-grade lesions were automatically generated using open-source machine learning software. The performance was tested both in a single-center setting through cross-validation and in a multi-center setting using the two unseen datasets as external validation. For comparison with clinical practice, a multi-center classifier was tested and compared with the Prostate Imaging Reporting and Data System version 2 (PIRADS v2) scoring performed by two expert radiologists. The three single-center models obtained a mean AUC of 0.75, which decreased to 0.54 when the model was applied to the external data, the radiologists obtained a mean AUC of 0.46. In the multi-center setting, the radiomics model obtained a mean AUC of 0.75 while the radiologists obtained a mean AUC of 0.47 on the same subset. While radiomics models have a decent performance when tested on data from the same center(s), they may show a significant drop in performance when applied to external data. On a multi-center dataset our radiomics model outperformed the radiologists, and thus, may represent a more accurate alternative for malignancy prediction. [ABSTRACT FROM AUTHOR]

Background: Transcatheter aortic valve implantation (TAVI) is a minimally invasive, life-saving treatment for patients with severe aortic valve stenosis that improves quality of life. We examined cardiac output and cerebral blood flow in patients undergoing TAVI to test the hypothesis that improved cardiac output after TAVI is associated with an increase in cerebral blood flow., Design: Prospective cohort study., Setting: European high-volume tertiary multidisciplinary cardiac care., Participants: Thirty-one patients (78.3 ± 4.6 years; 61% female) with severe symptomatic aortic valve stenosis., Measurements: Noninvasive prospective assessment of cardiac output (L/min) by inert gas rebreathing and cerebral blood flow of the total gray matter (mL/100 g per min) using arterial spin labeling magnetic resonance imaging in resting state less than 24 hours before TAVI and at 3-month follow-up. Cerebral blood flow change was defined as the difference relative to baseline., Results: On average, cardiac output in patients with severe aortic valve stenosis increased from 4.0 ± 1.1 to 5.4 ± 2.4 L/min after TAVI (P = .003). The increase in cerebral blood flow after TAVI strongly varied between patients (7% ± 24%; P = .41) and related to the increase in cardiac output, with an 8.2% (standard error = 2.3%; P = .003) increase in cerebral blood flow per every additional liter of cardiac output following the TAVI procedure., Conclusion: Following TAVI, there was an association of increase in cardiac output with increase in cerebral blood flow. These findings encourage future larger studies to determine the influence of TAVI on cerebral blood flow and cognitive function., (© 2020 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Objective: The disconnectivity hypothesis postulates that partial loss of connecting white matter fibers between brain regions contributes to the development of dementia. Using diffusion MRI to quantify global and tract-specific white matter microstructural integrity, we tested this hypothesis in a longitudinal population-based study., Methods: Global and tract-specific fractional anisotropy (FA) and mean diffusivity (MD) were obtained in 4,415 people without dementia (mean age 63.9 years, 55.0% women) from the prospective population-based Rotterdam Study with brain MRI between 2005 and 2011. We modeled the association of these diffusion measures with risk of dementia (follow-up until 2016) and with changes on repeated cognitive assessment after on average 5.4 years, adjusting for age, sex, education, macrostructural MRI markers, depressive symptoms, cardiovascular risk factors, and APOE genotype., Results: During a median follow-up of 6.8 years, 101 participants had incident dementia, of whom 83 had clinical Alzheimer disease (AD). Lower global values of FA and higher values of MD were associated with an increased risk of dementia (adjusted hazard ratio [95% confidence interval (CI)] per SD increase for MD 1.79 [1.44-2.23] and FA 0.65 [0.52-0.80]). Similarly, lower global values of FA and higher values of MD related to more cognitive decline in people without dementia (difference in global cognition per SD increase in MD [95% CI] was -0.04 [-0.07 to -0.01]). Associations were most profound in the projection, association, and limbic system tracts., Conclusions: Structural disconnectivity is associated with an increased risk of dementia and more pronounced cognitive decline in the general population., (© 2020 American Academy of Neurology.)

Structural brain markers are studied extensively in the field of neurodegeneration, but are thought to occur rather late in the process. Functional measures such as functional connectivity are gaining interest as potentially more subtle markers of neurodegeneration. However, brain structure and function are also affected by 'normal' brain ageing. More information is needed on how functional connectivity relates to aging, particularly in the absence of overt neurodegenerative disease. We investigated the association of age with resting-state functional connectivity in 2878 non-demented persons between 50 and 95 years of age (54.1% women) from the population-based Rotterdam Study. We obtained nine well-known resting state networks using data-driven methodology. Within the anterior default mode network, ventral attention network, and sensorimotor network, functional connectivity was significantly lower with older age. In contrast, functional connectivity was higher with older age within the visual network. Between resting state networks, we found patterns of both increases and decreases in connectivity in approximate equal proportions. Our results reinforce the notion that the aging brain undergoes a reorganization process, and serves as a solid basis for exploring functional connectivity as a preclinical marker of neurodegenerative disease., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Purpose- In the general population, we investigated the association of a recently developed cerebral small vessel disease (CSVD) sum score with stroke, dementia, and mortality. Methods- One thousand six hundred fifty-one stroke-free and nondemented participants (mean age, 73.3 years; 54.5% women) of the population-based Rotterdam Study underwent brain magnetic resonance imaging (1.5T) in 2005-2011 and were followed for stroke, dementia, and mortality until 2016-2017. The CSVD sum score was composed by counting the presence of 4 magnetic resonance imaging markers (white matter hyperintensities, lacunes, cerebral microbleeds, and perivascular spaces; range, 0-4). We determined the association of the CSVD score with risk of stroke, dementia, and mortality using Cox models, adjusting for age, sex, and other Framingham Stroke Risk Profile predictors. Additionally, we assessed mortality as a competing risk for stroke and dementia and calculated absolute risk estimates for all outcomes. Results- During a mean follow-up of 7.2 years, 66 participants developed stroke, 76 developed dementia, and 306 died. The Framingham Stroke Risk Profile-adjusted hazard ratios of 1 point higher sum score were 1.54 (95% CI, 1.16-2.03) for stroke, 1.25 (95% CI, 0.95-1.64) for dementia, and 1.15 (95% CI, 1.01-1.31) for mortality. No significant differences were seen for subdistribution hazard ratios for stroke and dementia. A higher CSVD score yielded higher absolute risk estimates for all outcomes, calculated during 10 years. Conclusions- The CSVD score is a practical measure of global vascular brain injury. A higher sum score on magnetic resonance imaging is associated with higher risk of suffering a stroke, developing dementia, and death.

To determine the association between meditation and yoga practice, experienced stress, and amygdala and hippocampal volume in a large population-based study. This study was embedded within the population-based Rotterdam Study and included 3742 participants for cross-sectional association. Participants filled out a questionnaire assessing meditation practice, yoga practice, and experienced stress, and underwent a magnetic resonance scan of the brain. 2397 participants underwent multiple brain scans, and were assessed for structural change over time. Amygdala and hippocampal volumes were regions of interest, as these are structures that may be affected by meditation. Multivariable linear regression analysis and mixed linear models were performed adjusted for age, sex, educational level, intracranial volume, cardiovascular risk, anxiety, depression and stress. 15.7% of individuals participated in at least one form of practice. Those who performed meditation and yoga practices reported significantly more stress (mean difference 0.2 on a 1-5 scale, p < .001) and more depressive symptoms (mean difference 1.03 on CESD, p = .015). Partaking in meditation and yoga practices was associated with a significantly lower right amygdala volume (β = - 31.8 mm 3 , p = .005), and lower left hippocampus volume (β = - 75.3 mm 3 , p = .025). Repeated measurements using linear mixed models showed a significant effect over time on the right amygdala of practicing meditation and yoga (β = - 24.4 mm 3 , SE 11.3, p = .031). Partaking in meditation and yoga practice is associated with more experienced stress while it also helps cope with stress, and is associated with smaller right amygdala volume.

Objective: To investigate the association of brain volumes, white matter lesion (WML) volumes, and lacunes, with cognitive decline in a population-based cohort of nondemented persons., Methods: Within the Rotterdam Study, 3624 participants underwent brain magnetic resonance imaging. Cognition was evaluated at baseline (2005 to 2009) and at the follow-up visit (2011 to 2013). We used a test battery that tapped into domains of executive function, information processing speed, motor speed, and memory. The volumetric measures assessed were total brain volume, lobar (gray matter and white matter) volumes, and hippocampal volumes. We also studied the association of WML volumes and lacunes with cognitive decline using linear regression models., Results: Total brain volume was associated with decline in global cognition, information processing, and motor speed (P<0.001) in analyses controlled for demographic and vascular factors. Specifically, smaller frontal and parietal lobes were associated with decline in information processing and motor speed, and smaller temporal and parietal lobes were associated with decline in general cognition and motor speed (P<0.001 for all tests). Total WML volume was associated with decline in executive function. Lobar WML volume, hippocampal volume, and lacunes were not associated with cognitive decline., Conclusions: Lower brain volume is associated with subsequent cognitive decline. Although lower total brain volume was significantly associated with decline in global cognition, specific lobar volumes were associated with decline in certain cognitive domains.

Purpose: To determine longitudinally the rate of change in diffusion-tensor imaging (DTI) parameters of white matter microstructure with aging and to investigate whether cardiovascular risk factors influence this longitudinal change., Materials and Methods: This prospective population-based cohort study was approved by a dedicated ethics committee overseen by the national government, and all participants gave written informed consent. Community-dwelling participants without dementia were examined by using a research-dedicated 1.5-T magnetic resonance (MR) imager on two separate visits that were, on average, 2.0 years apart. Among 810 persons who were eligible for imaging at baseline, longitudinal imaging data were available for 501 persons (mean age, 69.9 years; age range, 64.1-91.1 years). Changes in normal-appearing white matter DTI characteristics in the tract centers were analyzed globally to investigate diffuse patterns of change and then locally by using voxelwise multilinear regression. The influence of cardiovascular risk factors was assessed by treating them as additional determinants in both analyses., Results: Over the 2.0-year follow-up interval, global fractional anisotropy (FA) decreased by 0.0042 (P < .001), while mean diffusivity (MD) increased by 8.1 × 10(-6) mm(2)/sec (P < .001). Voxelwise analysis of the brain white matter skeleton showed an average decrease of 0.0082 (Pmean = .002) in FA in 57% of skeleton voxels. The sensorimotor pathway, however, showed an increase of 0.0078 (Pmean = .009) in FA. MD increased by 10.8 × 10(-6)mm(2)/sec (Pmean < .001) on average in 79% of white matter skeleton voxels. Additionally, white matter degeneration was more pronounced in older persons. Cardiovascular risk factors were generally not associated with longitudinal changes in white matter microstructure., Conclusion: Longitudinal diffusion analysis indicates widespread microstructural deterioration of the normal-appearing white matter in normal aging, with relative sparing of sensorimotor fibers., ((©) RSNA, 2015 Online supplemental material is available for this article.)

Imaging plays an essential role in research on neurological diseases in the elderly. The Rotterdam Scan Study was initiated as part of the ongoing Rotterdam Study with the aim to elucidate the causes of neurological disease by performing imaging of the brain in a prospective population-based setting. Initially, in 1995 and 1999, random subsamples of participants from the Rotterdam Study underwent neuroimaging, whereas from 2005 onwards MRI has been implemented into the core protocol of the Rotterdam Study. In this paper, we discuss the background and rationale of the Rotterdam Scan Study. Moreover, we describe the imaging protocol, image post-processing techniques, and the main findings to date. Finally, we provide recommendations for future research, which will also be topics of investigation in the Rotterdam Scan Study.

Background: Loss of brain white matter microstructure is presumed to be an early sign of neurodegenerative disease. Yet, little is known on microstructural changes of various white matter tracts with normal aging., Methods: In 4532 nondemented elderly persons, we studied age-related changes in tract-specific diffusion characteristics for 25 tracts using probabilistic tractography. We studied how diffusion differs across tracts with aging, whether this depends on macrostructural white matter changes, and whether cardiovascular risk factors affect microstructure., Results: With increasing age, loss of microstructural organization occurred in association, commissural and limbic tracts. White matter lesions and atrophy each partially explained this loss. We observed worse microstructure with severe hypertension, current smoking and diabetes mellitus, independent from age and macrostructural white matter changes., Conclusions: Microstructure of white matter tracts changes with age, and may mark neurodegeneration more sensitively than white matter lesion load and atrophy. Cardiovascular factors relate to loss in microstructural organization., (Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the association between cardiac function and the risk of stroke and dementia in elderly free of clinical cardiac disease. Additionally, we investigated the relation between cardiac function and MRI markers of subclinical cerebrovascular disease., Methods: This study was conducted within the population-based Rotterdam Study. A total of 3,291 participants (60.8% female, age-range 58-98 years) free of coronary heart disease, heart failure, atrial fibrillation, stroke, and dementia underwent echocardiography in 2002-2005 to measure cardiac function. Follow-up finished in 2012. In 2005-2006, a random subset of 577 stroke-free people without dementia underwent brain MRI on which infarcts and white matter lesion volume were assessed., Results: During 21,785 person-years of follow-up, 164 people had a stroke and during 19,462 person-years of follow-up, 208 people developed dementia. Measures of better diastolic function, such as higher E/A ratio, were associated with a lower risk of stroke (hazard ratio [HR] 0.82; 95% confidence interval [CI] 0.69; 0.98) and dementia (HR 0.82; 95% CI 0.70; 0.96). Better systolic function, measured as higher fractional shortening, was only associated with a lower risk of stroke (HR 0.84; 95% CI 0.72; 0.98). Better diastolic function was related to a lower prevalence of silent infarcts on MRI, especially lacunar infarcts., Conclusions: In elderly free of clinical cardiac disease, worse diastolic function is associated with clinical stroke, dementia, and silent infarcts on MRI, whereas worse systolic function is related only to clinical stroke. These findings can form the basis for future research on the utility of cardiac function as potential intervention target for prevention of neurologic diseases., (© 2015 American Academy of Neurology.)

Background: It is unknown whether the cerebellum affects cognitive function in an aging community-dwelling population. In a population-based study on 3745 nondemented individuals aged 45 years and above, we investigated the relationship between cerebellar volume and cognitive function., Methods: Brain volumes were obtained using automatic tissue segmentation of magnetic resonance imaging scans. Cognitive functioning was assessed using MMSE and cognitive compound scores of global cognition, executive function, information processing speed, memory, and motor speed. Linear regression modeling was used to study the associations between cerebellar volumes and cognitive measures, independent of cerebral volumes., Results: We found a relationship between larger cerebellar volume and better global cognition, executive function, information processing speed, and motor speed. After adjustment for cerebral volume, only cerebellar gray matter volume remained borderline significantly associated with global cognition and information processing speed. After Bonferroni correction, the few associations found between cerebellar volume and cognition disappeared., Conclusions: We only found a minor relationship between larger cerebellar volume and better cognition in healthy older adults, which further attenuated after correcting for cerebral volume. Our findings support the notion that cerebellar volume has an influence on cognition in aging, but that it is not the major leading structure.

Objective: To investigate whether the presence of cerebral microbleeds, which present as focal lesions on imaging, is associated with a diffuse loss of white matter microstructural integrity in the brain., Methods: In the prospective, population-based Rotterdam Scan Study, a total of 4,493 participants underwent brain MRI to determine microbleed status. With diffusion tensor imaging, global fractional anisotropy (FA) and mean diffusivity (MD) were measured in normal-appearing white matter. Multiple linear regression models, adjusted for age, sex, cardiovascular risk factors, white matter lesions, and infarcts, were applied to investigate the independent association between microbleeds and organization of brain white matter. Analyses were repeated after stratification by APOE ε4 carriership., Results: Presence of microbleeds was related to a lower mean FA and higher mean MD, in a dose-dependent manner, and was already apparent for a single microbleed (standardized FA: -0.13, 95% confidence interval -0.21 to -0.05; MD: 0.12, 95% confidence interval 0.05 to 0.19). For lobar microbleeds, alterations in diffusion tensor imaging measurements were solely driven by APOE ε4 carriers., Conclusions: Presence of microbleeds relates to poorer microstructural integrity of brain white matter, even after adjusting for cardiovascular risk and other markers of cerebral small-vessel disease. Our data suggest that microbleeds reflect diffuse brain pathology, even when only a single microbleed is present.

Cerebral small-vessel disease is thought to contribute to brain atrophy, but it remains unclear whether it affects the gray matter and white matter atrophy differentially. Retinal vessels provide a direct measure to study cerebral small-vessel disease in vivo. In a cohort of 1065 persons (mean age, 67.5 y and 51% women), from the population-based Rotterdam Study, we investigated how retinal vascular calibers relate to brain atrophy and to gray matter and white matter atrophy separately. Retinal arteriolar and venular calibers were semiautomatically measured on digitized fundus transparencies. Using automated quantification of MRI scans, we obtained whole-brain volume and volumes of gray matter and white matter. Both narrower arteriolar and wider venular calibers were associated with smaller brain volume, independent from each other. These associations were primarily driven by smaller white matter volume, whereas no associations were seen for gray matter volume. Adjustments for cardiovascular risk factors attenuated the results, but wider venular caliber remained borderline significantly associated with smaller white matter volume. Our data provide evidence that cerebral small-vessel disease contributes to brain atrophy primarily by affecting the cerebral white matter.

High blood pressure is considered an important risk factor for cerebral white matter lesions (WMLs) in the aging population. In a longitudinal population-based study of 665 nondemented persons, we investigated the longitudinal relationship of systolic blood pressure, diastolic blood pressure, and pulse pressure with annual progression of WMLs. Means of blood pressure were calculated over a 5-year period before longitudinal MRI scanning. WML progression was subsequently measured on 2 scans 3.5 years apart. We performed analyses with linear regression models and evaluated adjustments for age, sex, cardiovascular risk factors, and baseline WML volume. In addition, we evaluated whether treatment of hypertension is related to less WML progression. Both systolic and diastolic blood pressures were significantly associated with annual WML progression (regression coefficient [95% confidence interval], 0.08 [0.03; 0.14] mL/y and 0.09 [0.03; 0.15] mL/y per SD increase in systolic and diastolic blood pressure, respectively). Pulse pressure was also significantly associated with WML progression, but not independent from hypertension. After adjustment for baseline WML volume, only systolic blood pressure remained significantly associated: 0.05 (0.00; 0.09) mL/y per SD increase. People with uncontrolled untreated hypertension had significantly more WML progression than people with uncontrolled treated hypertension (difference [95% confidence interval], 0.12 [0.00; 0.23] mL/y). The present study further establishes high blood pressure to precede WMLs and implies that hypertension treatment could reduce WML progression in the general population.

Background: Uric acid has been associated with focal vascular brain disease. However, it is unknown whether uric acid also relates to global brain changes such as brain atrophy. We therefore studied the relation of uric acid to brain atrophy and whether this is accompanied by worse cognitive function., Methods: In 814 persons of the population-based Rotterdam Study (mean age 62.0 years), we studied the relation of uric acid levels to brain tissue atrophy and cognition using linear regression models adjusted for age, sex and putative confounders. Brain atrophy was assessed using automated processing of magnetic resonance imaging. Cognition was assessed using a validated neuropsychological test battery and we computed compound scores of cognitive domains., Results: Higher uric acid levels were associated with white matter atrophy [difference in Z-score of white matter volume per standard deviation increase in uric acid: -0.07 (95% CI: -0.12; -0.01)], but not with gray matter atrophy. This was particularly marked when comparing hyperuricemic to normouricemic persons [Z-score difference: -0.27 (-0.43; -0.11)]. Worse cognition was primarily found in persons with hyperuricemia [-0.28 (-0.48; -0.08)]., Conclusions: Hyperuricemia is related to white matter atrophy and worse cognition., (Copyright © 2013 S. Karger AG, Basel.)

In a population-based study of 3962 community-dwelling nondemented elderly we investigated the relation of age, sex, cardiovascular risk factors, and the presence of infarcts with cerebellar volume, and its interrelationship with cerebral volumes. Cerebellar and cerebral gray and white matter were segmented using Freesurfer version 4.5 (http://surfer.nmr.mgh.harvard.edu/). We used linear regression analyses to model the relationship between age, sex, cardiovascular risk factors, brain infarcts, white matter lesions (WMLs) and cerebellar and cerebral volume. Smaller cerebellar volumes with increasing age were mainly driven by loss of white matter. Diabetes, higher serum glucose and lower cholesterol levels were related to smaller cerebellar volume. No association was found between hypertension, smoking, apolipoprotein E (ApoE) genotype, and cerebellar volume. Supratentorial lacunar infarcts and WMLs were related to smaller cerebellar volume. Infratentorial infarcts were related to smaller cerebellar white matter volume and total cerebral volume. This study suggests that determinants of cerebellar volume do not entirely overlap with those established for cerebral volume. Furthermore, presence of infarcts or WMLs in the cerebrum can affect cerebellar volume., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The purpose of this study was to validate automated atherosclerotic plaque measurements in carotid arteries from CT angiography (CTA). We present an automated method (three initialization points are required) to measure plaque components within the carotid vessel wall in CTA. Plaque components (calcifications, fibrous tissue, lipids) are determined by different ranges of Hounsfield Unit values within the vessel wall. On CTA scans of 40 symptomatic patients with atherosclerotic plaque in the carotid artery automatically segmented plaque volume, calcified, fibrous and lipid percentages were 0.97 ± 0.51 cm(3), 10 ± 11%, 63 ± 10% and 25 ± 5%; while manual measurements by first observer were 0.95 ± 0.60 cm(3), 14 ± 16%, 63 ± 13% and 21 ± 9%, respectively and manual measurement by second observer were 1.05 ± 0.75 cm(3), 11 ± 12%, 61 ± 11% and 27 ± 10%. In 90 datasets, significant associations were found between age, gender, hypercholesterolemia, diabetes, smoking and previous cerebrovascular disease and plaque features. For both automated and manual measurements, significant associations were found between: age and calcium and fibrous tissue percentage; gender and plaque volume and lipid percentage; diabetes and calcium, smoking and plaque volume; previous cerebrovascular disease and plaque volume. Significant associations found only by the automated method were between age and plaque volume, hypercholesterolemia and plaque volume and diabetes and fibrous tissue percentage. Significant association found only by the manual method was between previous cerebrovascular disease and percentage of fibrous tissue. Automated analysis of plaque composition in the carotid arteries is comparable with the manual analysis and has the potential to replace it.

Neuroimaging plays an important role in etiologic research on neurological diseases in the elderly. The Rotterdam Scan Study was initiated as part of the ongoing Rotterdam Study with the aim to unravel causes of neurological disease by performing neuroimaging in a population-based longitudinal setting. In 1995 and 1999 random subsets of the Rotterdam Study underwent neuroimaging, whereas from 2005 onwards MRI has been implemented into the core protocol of the Rotterdam Study. In this paper, we discuss the background and rationale of the Rotterdam Scan Study. We also describe the imaging protocol and post-processing techniques, and highlight the main findings to date. Finally, we make recommendations for future research, which will also be the main focus of investigation in the Rotterdam Scan Study.

Background: Cross-sectional studies have shown an association between vascular brain disease and depression. Longitudinal data are scarce. In a population-based study we investigated this relationship both cross-sectionally and longitudinally., Methods: Brain MRIs were administered to 479 persons aged 60-90 years at baseline (1995-1996). Brain atrophy, white matter lesions and brain infarcts are all markers of vascular brain disease. At baseline and at follow-up examinations, we also identified persons with depressive symptoms and syndromes using the Center for Epidemiological Studies Depression Scale and psychiatric interviews. Medical records were continuously monitored to identify incident depression. Follow-up was complete until October 2005., Results: At baseline, 36 persons had depressive symptoms. Brain atrophy, white matter lesions, and infarcts were associated with presence of depressive symptoms. During follow-up, 92 persons developed depressive symptoms, 35 of whom were categorized as having depressive syndrome. There was no association of any MRI marker with incident depressive symptoms or syndromes., Conclusions: Markers of vascular brain disease were associated with depression cross-sectionally. However, when these markers and risk of depression were assessed longitudinally, no relationship was found.

Efficiently obtaining a reliable coronary artery centerline from computed tomography angiography data is relevant in clinical practice. Whereas numerous methods have been presented for this purpose, up to now no standardized evaluation methodology has been published to reliably evaluate and compare the performance of the existing or newly developed coronary artery centerline extraction algorithms. This paper describes a standardized evaluation methodology and reference database for the quantitative evaluation of coronary artery centerline extraction algorithms. The contribution of this work is fourfold: (1) a method is described to create a consensus centerline with multiple observers, (2) well-defined measures are presented for the evaluation of coronary artery centerline extraction algorithms, (3) a database containing 32 cardiac CTA datasets with corresponding reference standard is described and made available, and (4) 13 coronary artery centerline extraction algorithms, implemented by different research groups, are quantitatively evaluated and compared. The presented evaluation framework is made available to the medical imaging community for benchmarking existing or newly developed coronary centerline extraction algorithms.

Context: The role of macrostructural white matter changes, such as atrophy and white matter lesions, in cognitive decline is increasingly being recognized. However, in the elderly population, these macrostructural changes do not account for all variability in cognition. Measures reflecting white matter microstructural integrity may provide additional information to investigate the relation between white matter changes and cognition., Objective: To study the relation between white matter integrity and cognition in the general elderly population, using diffusion tensor imaging and taking into account macrostructural white matter changes., Design: Cross-sectional population-based study., Setting: A general community in the Netherlands., Participants: A population-based sample of 860 persons, older than 60 years, free of dementia. We performed multisequence magnetic resonance imaging, which included diffusion tensor imaging, and extensive neuropsychological testing. Fractional anisotropy, mean diffusivity, and directional diffusivities were measured globally in white matter lesions and normal-appearing white matter., Main Outcome Measures: Performance on neuropsychological tests in the following cognitive domains: memory, executive function, information processing speed, global cognition, and motor speed., Results: Regardless of macrostructural white matter changes, a higher mean diffusivity or higher axial and radial diffusivities within white matter lesions or normal-appearing white matter were related to worse performance on tasks assessing information processing speed and global cognition. In addition, diffusivity within white matter lesions related to memory, while in normal-appearing white matter, it furthermore related to executive function. Lower mean fractional anisotropy in white matter lesions or normal-appearing white matter related to worse information processing speed and motor speed., Conclusions: Microstructural integrity of both white matter lesions and normal-appearing white matter is associated with cognitive function, regardless of white matter atrophy and white matter lesion volume. This suggests that measuring white matter integrity has added value beyond macrostructural assessment of white matter changes to study the relation between white matter and cognition.

Cerebral hypoperfusion has been associated with worse cognitive function. We investigated the association between cerebral blood flow and cognition and whether this association is independent of brain volume. In 892 participants, aged 60 to 91 years, of the population-based Rotterdam Scan study, we measured total cerebral blood flow (tCBF) and brain volume using magnetic resonance imaging. Lower tCBF was associated with worse information-processing speed, executive function, and global cognition. However, after correcting tCBF for brain volume, these associations disappeared. The association between tCBF and cognition may be mediated or confounded by brain atrophy. Future studies on tCBF should take into account brain atrophy.

Background and Purpose: Poor kidney function, as measured by glomerular filtration rate (GFR), is closely associated with presence of glomerular small vessel disease. Given the hemodynamic similarities between the vascular beds of the kidney and the brain, we hypothesized an association between kidney function and markers of cerebral small vessel disease on MRI. We investigated this association in a population-based study of elderly persons., Methods: We measured GFR using the Cockcroft-Gault equation in 484 participants (60 to 90 years of age) from the Rotterdam Scan Study. Using automated MRI-analysis we measured global as well as lobar and deep volumes of gray matter and white matter, and volume of WML. Lacunar infarcts were rated visually. Volumes of deep white matter and WML and presence of lacunar infarcts reflected cerebral small vessel disease. We used linear and logistic regression models to investigate the association between GFR and brain imaging parameters. Analyses were adjusted for age, sex, and additionally for cardiovascular risk factors., Results: Persons with lower GFR had less deep white matter volume (difference in standardized volume per SD decrease in GFR: -0.15 [95% CI -0.26 to -0.04]), more WML (difference per SD decrease in GFR: 0.14 [95% CI 0.03 to 0.25]), and more often lacunar infarcts, although the latter was not significant. GFR was not associated with gray matter volume or lobar white matter volume. Additional adjustment for cardiovascular risk factors yielded similar results., Conclusions: Impaired kidney function is associated with markers of cerebral small vessel disease as assessed on MRI.