Free water determines diffusion alterations and clinical status in cerebral small vessel disease

Duering, Marco; Finsterwalder, Sofia; Baykara, Ebru; Tuladhar, Anil Man; Gesierich, Benno; Konieczny, Marek J.; Malik, Rainer; Franzmeier, Nicolai; Ewers, Michael; Jouvent, Eric; Biessels, Geert Jan; Schmidt, Reinhold; Leeuw, Frank-Erik de; Pasternak, Ofer and Dichgans, Martin (2018): Free water determines diffusion alterations and clinical status in cerebral small vessel disease. In: Alzheimers & Dementia, Vol. 14, No. 6: pp. 764-774

Abstract

Introduction: Diffusion tensor imaging detects early tissue alterations in Alzheimer's disease and cerebral small vessel disease (SVD). However, the origin of diffusion alterations in SVD is largely unknown. Methods: To gain further insight, we applied free water (FW) imaging to patients with genetically defined SVD (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy [CADASIL], n = 57), sporadic SVD (n = 444), and healthy controls (n = 28). We modeled freely diffusing water in the extracellular space (FW) and measures reflecting fiber structure (tissue compartment). We tested associations between these measures and clinical status (processing speed and disability). Results: Diffusion alterations in SVD were mostly driven by increased FW and less by tissue compartment alterations. Among imaging markers, FW showed the strongest association with clinical status (R-2 up to 34%, P < .0001). Findings were consistent across patients with CADASIL and sporadic SVD. Discussion: Diffusion alterations and clinical status in SVD are largely determined by extracellular fluid increase rather than alterations of white matter fiber organization.

• Item Type: Journal article
• EU Funded Grant Agreement Number: info:eu-repo/grantAgreement/EC/H2020/666881
• EU Projects: Horizon 2020 > RIA - Research and Innovation action > SVDs-at-target - Small Vessel Diseases from a therapeutic perspective: Targets for intervention. Affected pathways and mechanistic exploitation for prevention of stroke dementia
• Faculties: Medicine > Munich Cluster for Systems Neurology (SyNergy); Medicine > Institute for Stroke and Dementia Research (ISD)
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 1552-5260
• Language: English
• DFG: Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198