Journal Article

Clinical associations of T2-weighted lesion load and lesion location in small vessel disease: Insights from a large prospective cohort study

Seifert, Christian L., Radue, Ernst-Wilhelm, Gaetano, Laura, Altermatt, Anna, Wuerfel, Jens, Bauer, Lorena, Kappos, Ludwig, Magon, Stefano, Poppert, Holger, Sprenger, Till, Hartmann, Julia, Gnahn, Hans, Feurer, Regina

2019

Overview

Subcortical T2-weighted (T2w) lesions are very common in older adults and have been associated with dementia. However, little is known about the strategic lesion distribution and how lesion patterns relate to vascular risk factors and cognitive impairment. The aim of this study was to analyze the association between T2w lesion load and location, vascular risk factors, and cognitive impairment in a large cohort of older adults. 1017 patients participating in a large prospective cohort study (INtervention project on cerebroVAscular disease and Dementia in the district of Ebersberg, INVADE II) were analyzed. Cerebral T2w white matter and deep grey matter lesions, the so-called white matter hyperintensities (WMHs), were outlined semi-automatically on fluid attenuated inversion recovery images and normalized to standard stereotaxic space (MNI152) by non-linear registration. Patients were assigned to either a low-risk or a high-risk group. The risk assessment considered ankle brachial index, intima media thickness, carotid artery stenosis, atrial fibrillation, previous cerebro-/cardiovascular events and peripheral artery disease as well as a score based on cholesterol levels, blood pressure and smoking. Separate lesion distributions were obtained for the two risk groups and compared using voxel-based lesion-symptom mapping. Moreover, we assessed the relation between lesion location and cognitive impairment (demographically adjusted z-scores of the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery Plus, CERAD-NAB Plus) using voxel-based statistics (α = 0.05). A total of 878 out of 1017 subjects (86%) had evaluable MRI data and were included in the analyses (mean age: 68.2 ± 7.6 years, female: 515). Patients in the high-risk group were characterized by a significantly higher age, a higher proportion of men, a higher lesion load (p < 0.001), and a worse performance in some of the cognitive subdomain scores (p < 0.05). Voxels with significant associations to the subjects' cerebrovascular risk profiles were mainly found at locations of the corpus callosum, superior corona radiata, superior longitudinal fasciculus, internal and external capsule, and putamen. While several cognitive domains have shown significant associations with the participants’ total lesion burden (p < 0.05), no focal WMH locations were found to be associated with cognitive impairment. Age, gender, several cognitive scores, and WMH lesion load were shown to be significantly associated with vascular risk factors in a population of older, but cognitively preserved adults. Vascular risk factors seem to promote lesion formation most severely at well-defined locations. While lesion load showed weak associations to some cognitive scores, no focal locations causing specific cognitive disturbances were identified in this large cohort of older adults. •Study of association between T2w lesion load and location, vascular risk factors, cognition.•Increased vascular risk reflected in higher age, proportion of men, lesion load, cognitive disturbances.•Periventricular lesions significantly associated with vascular risk factors.•Total lesion burden but not focal locations partially explain cognitive disturbances.

• Publisher: Elsevier Inc,Elsevier Limited
• Subject: Age / Aged / Alzheimer's disease / Ankle / Blood pressure / Brain / Cardiovascular disease / Carotid artery / Cerebral Small Vessel Diseases - complications / Cerebral Small Vessel Diseases - diagnostic imaging / Cerebral Small Vessel Diseases - pathology / Cerebral Small Vessel Diseases - physiopathology / Cerebrovascular diseases / Cholesterol / Cognition / Cognition & reasoning / Cognitive ability / Cognitive Dysfunction - diagnostic imaging / Cognitive Dysfunction - etiology / Cognitive Dysfunction - physiopathology / Cohort analysis / Corpus callosum / Dementia / Dementia disorders / Family medical history / Female / Fibrillation / Humans / Lesion probability mapping / Lesions / Magnetic resonance imaging / Magnetic Resonance Imaging - methods / Male / Middle Aged / Neurodegenerative diseases / Neuroimaging - methods / NMR / Nuclear magnetic resonance / Older people / Prospective Studies / Putamen / Risk assessment / Risk Factors / Risk groups / Small vessel disease / Smoking / Stenosis / Substantia alba / Substantia grisea / Vascular diseases / Vascular risk / White Matter - diagnostic imaging / White Matter - pathology / White matter hyperintensity