22 Chapter 2 (25)). The MMSE was used as a screening for dementia in order to exclude severely cognitively impaired participants. The study was approved by the medical ethics committee (Medical Ethical Committee Utrecht nr. 14/469). Written informed consent was obtained from all participants. 2.3.2 Procedure and demographics All participants were invited to the hospital before surgery for questionnaires and MRI scanning. Demographic data and medical his- tory questionnaires, and MMSE scores were obtained prior to surgery. Symptoms of anxiety and depression were assessed using the hospital and depression scale (HADS). Scores equal to or above 8 on the depression subscale were considered indicative of depressive symptoms.12 American Society of Anesthesiologists (ASA) classification scores were performed before surgery by anesthesiologists in training. 2.3.3 Cardiovascular risk factors Demographic data and data concerning cardiovascular risk factors was collected using questionnaires and medical history records. Diabetes (type I&II), hypertension and hyperlipidemia were registered in the database if they were known by the subject, and treated. BMI in kg/m3 was collected as an additional cardiovascular risk factor. Obesity was defined as a BMI equal to or above 30 kg/m3. 2.3.4 MRI scans The scans were performed before surgery on a Philips Achieva 3 Tesla MRI system. The standardized MRI scan protocol included a 3D T1-weighted sequence (voxel size = 1.0 × 1.0 × 1.0 mm3; TR/TE = 7.9/4.5 ms) and a 3D fluid-attenuated inversion recovery (FLAIR) sequence (voxel size = 1.11 × 1.11 × 0.56 mm3; TR/TE/TI = 4800/125/1650 ms). 2.3.5 WMH volume, type and shape Two categories of WMH were automatically determined: ‘deep’ WMH, and ‘periventricular/confluent’ WMH. WMH volumes were calculated automatically using validated methods.7 Based on the WMH segmentation data, the mean values per WMH shape marker (solidity, convexity, concavity index, fractal dimension for periventricular/confluent WMH; fractal dimension and eccentricity for deep WMH) were calculated for each participant with an in-house developed method.7 The image processing pipeline is illustrated in Figure 2.1. Statistical parametric mapping (SPM version 12; Wellcome Institute of Neurology University College London, UK, http://www.fil.ion.ucl.ac. uk/spm/doc/) in MATLAB (The MathWorks, Inc., Natick, Massachusetts, United States) was used to register 3D FLAIR images to 3D T1weighted images. Intracranial volume was calculated using the SPM12 with the option
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