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Pooling of multicenter brain imaging data is a trend in studies on ageing related brain diseases. This poses challenges to MR-based brain segmentation. The performance across different field strengths of three widely used automated methods for brain volume measurements was assessed in the present study. Ten subjects (mean age: 64 years) were scanned on 1.5T and 3T MRI on the same day. We determined robustness across field strength (i.e., whether measured volumes between 3T and 1.5T scans in the same subjects were similar) for SPM12, Freesurfer 5.3.0 and FSL 5.0.7. As a frame of reference, 3T MRI scans from 20 additional subjects (mean age: 71 years) were segmented manually to determine accuracy of the methods (i.e., whether measured volumes corresponded with expert-defined volumes). Total brain volume (TBV) measurements were robust across field strength for Freesurfer and FSL (mean absolute difference as % of mean volume ≤ 1%), but less so for SPM (4%). Gray matter (GM) and white matter (WM) volume measurements were robust for Freesurfer (1%; 2%) and FSL (2%; 3%) but less so for SPM (5%; 4%). For intracranial volume (ICV), SPM was more robust (2%) than FSL (3%) and Freesurfer (9%). TBV measurements were accurate for SPM and FSL, but less so for Freesurfer. For GM volume, SPM was accurate, but accuracy was lower for Freesurfer and FSL. For WM volume, Freesurfer was accurate, but SPM and FSL were less accurate. For ICV, FSL was accurate, while SPM and Freesurfer were less accurate. Brain volumes and ICV could be measured quite robustly in scans acquired at different field strengths, but performance of the methods varied depending on the assessed compartment (e.g., TBV or ICV). Selection of an appropriate method in multicenter brain imaging studies therefore depends on the compartment of interest.

Introduction We aimed to establish sex differences in vascular brain damage of memory clinic patients with possible vascular cognitive impairment (VCI). Methods A total of 860 memory clinic patients (aged 67.7 ± 8.5; 46% female) with cognitive complaints and vascular brain damage (ie, possible VCI) from the prospective TRACE‐VCI (Utrecht‐Amsterdam Clinical Features and Prognosis in Vascular Cognitive Impairment) cohort study with 2‐year follow‐up were included. Age‐adjusted female‐to‐male differences were calculated with general linear models, for demographic variables, vascular risk factors, clinical diagnosis, cognitive performance, and brain magnetic resonance imaging markers. Results We found no difference in age nor distribution of clinical diagnoses between females and males. Females performed worse on the MMSE (Mini‐Mental State Examination) and CAMCOG (Cognitive and Self‐Contained Part of the Cambridge Examination for Mental Disorders of the Elderly). Females had a larger white matter hyperintensity volume, while males more often showed (lacunar) infarcts. There was no difference in microbleed prevalence. Males had smaller normalized total brain and gray matter volumes. During follow‐up, occurrence of cognitive decline and institutionalization was comparable, but mortality was higher in males. Discussion Our results suggest that susceptibility and underlying etiology of VCI might differ by sex. Males seem to have more large vessel brain damage compared to females that have more small vessel brain damage.

Introduction It is unknown whether different types of small vessel disease (SVD), differentially relate to brain atrophy and if co‐occurring Alzheimer's disease pathology affects this relation. Methods In 725 memory clinic patients with SVD (mean age 67 ± 8 years, 48% female) we compared brain volumes of those with moderate/severe white matter hyperintensities (WMHs; n = 326), lacunes (n = 132) and cerebral microbleeds (n = 321) to a reference group with mild WMHs (n = 197), also considering cerebrospinal fluid (CSF) amyloid status in a subset of patients (n = 488). Results WMHs and lacunes, but not cerebral microbleeds, were associated with smaller gray matter (GM) volumes. In analyses stratified by CSF amyloid status, WMHs and lacunes were associated with smaller total brain and GM volumes only in amyloid‐negative patients. SVD‐related atrophy was most evident in frontal (cortical) GM, again predominantly in amyloid‐negative patients. Discussion Amyloid status modifies the differential relation between SVD lesion type and brain atrophy in memory clinic patients.

White matter hyperintensities (WMHs) are a common manifestation of cerebral small vessel disease, that is increasingly studied with large, pooled multicenter datasets. This data pooling increases statistical power, but poses challenges for automated WMH segmentation. Although there is extensive literature on the evaluation of automated WMH segmentation methods, such evaluations in a multicenter setting are lacking. We performed WMH segmentations in sixty patients scanned on six different magnetic resonance imaging (MRI) scanners (10 patients per scanner) using five freely available and fully-automated WMH segmentation methods (Cascade, kNN-TTP, Lesion-TOADS, LST-LGA and LST-LPA). Different MRI scanner vendors and field strengths were included. We compared these automated WMH segmentations with manual WMH segmentations as a reference. Performance of each method both within and across scanners was assessed using spatial and volumetric correspondence with the reference segmentations by Dice’s similarity coefficient (DSC) and intra-class correlation coefficient (ICC) respectively. We found the best performance, both within and across scanners, for kNN-TTP, followed by LST-LPA and LST-LGA, with worse performance for Lesion-TOADS and Cascade. Our findings can serve as a guide for choosing a method and also highlight the importance to further improve and evaluate consistency of methods in a multicenter setting.

Vascular Cognitive Impairment (VCI) refers to cognitive dysfunction due to vascular brain injury, as a single cause or in combination with other, often neurodegenerative, etiologies. VCI is a broad construct that captures a heterogeneous patient population both in terms of cognitive and noncognitive symptoms and in terms of etiology and prognosis. This provides a challenge when applying this construct in clinical practice. This paper presents the rationale and design of the TRACE-VCI study, which investigates the clinical features and prognosis of VCI in a memory clinic setting. The TRACE-VCI project is an observational, prospective cohort study of 861 consecutive memory clinic patients with possible VCI. Between 2009 and 2013, patients were recruited through the Amsterdam Dementia Cohort of the VU University Medical Centre (VUMC) (N=665) and the outpatient memory clinic and VCI cohort of the University Medical Centre Utrecht (UMCU) (N=196). We included all patients attending the clinics with magnetic resonance imaging (MRI) evidence of vascular brain injury. Patients with a primary etiology other than vascular brain injury or neurodegeneration were excluded. Patients underwent an extensive 1-day memory clinic evaluation including an interview, physical and neurological examination, assessment of biomarkers (including those for Alzheimer-type pathologies), extensive neuropsychological testing, and an MRI scan of the brain. For prognostic analyses, the composite primary outcome measure was defined as accelerated cognitive decline (change of clinical dementia rating ≥1 or institutionalization) or (recurrent) major vascular events or death over the course of 2 years. The mean age at baseline was 67.7 (SD 8.5) years and 46.3% of patients (399/861) were female. At baseline, the median Clinical Dementia Rating was 0.5 (interquartile range [IQR] 0.5-1.0) and the median Mini-Mental State Examination score was 25 (IQR 22-28). The clinical diagnosis at baseline was dementia in 52.4% of patients (451/861), mild cognitive impairment in 24.6% (212/861), and no objective cognitive impairment in the remaining 23.0% (198/861). The TRACE-VCI study represents a large cohort of well-characterized patients with VCI in a memory clinic setting. Data processing and collection for follow-up are currently being completed. The TRACE-VCI study will provide insight into the clinical features of memory clinic patients that meet VCI criteria and establish key prognostic factors for further cognitive decline and (recurrent) major vascular events.

Background: Patients with transient ischaemic attacks (TIAs) or minor disabling ischaemic stroke associated with an internal carotid artery (ICA) occlusion have a high risk of recurrent stroke in case of compromised cerebral blood flow. Recent studies showed that increased oxygen extraction fraction measured by positron emission tomography (PET) is still an independent predictor of subsequent stroke under current medical treatment, but PET facilities are not widely available. Transcranial Doppler (TCD) ultrasonography CO 2 reactivity is a cheap and non-invasive alternative to measure haemodynamic compromise. The aim of our study was to investigate whether TCD CO 2 reactivity is an independent predictor of recurrent ischaemic stroke in a large cohort of patients with symptomatic ICA occlusion in a time where rigorous control of vascular risk factors has been widely implemented in clinical practice. Methods: Between July 1995 and December 2009, we included consecutive patients with TIAs or minor disabling ischaemic stroke (modified Rankin Scale ≤3) associated with ICA occlusion who were referred to the University Medical Centre Utrecht, The Netherlands. All patients were treated with antiplatelet therapy and received rigorous control of vascular risk factors, including statins, treatment for diabetes and hypertension and lifestyle advices. CO 2 reactivity was measured with TCD within 3 months after presentation. We determined the predictive value of TCD CO 2 reactivity for recurrent ischaemic stroke using Cox proportional hazard analysis. Results: We included 201 patients with a median follow-up time of 7.1 years. Mean CO 2 reactivity was 15% (±20 standard deviation). The annual rate for ipsilateral ischaemic stroke was 2.2% [95% confidence interval (CI) 1.4-3.2] and for any recurrent stroke 3.2% (95% CI 2.3-4.4). We did not find a significant relationship between CO 2 reactivity and the risk of ipsilateral [hazard ratio (HR) for every increase in percentage point 1.01, 95% CI 0.99-1.02] or any recurrent ischaemic stroke (HR 1.01, 95% CI 0.998-1.02). Multivariable analysis showed a significant relationship with history of stroke (HR 4.0, 95% CI 1.8-9.0) for ipsilateral recurrent stroke, and age (HR for increase per year 1.05, 95% CI 1.01-1.09) and a history of stroke (HR 3.4, 95% CI 1.7-6.6) for any recurrent stroke. Conclusions: In patients with TIAs or non-disabling stroke associated with occlusion of the carotid artery, the long-term annual risk of stroke is generally low with careful control of vascular risk factors. Impaired CO 2 reactivity measured within 3 months after presentation does not identify the subgroup of patients at high risk of recurrent ischaemic stroke.