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Free Water Determines Diffusion Alterations and Clinical Status in Cerebral Small Vessel Disease

1Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany. Electronic address:
2Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
3University Paris Diderot, DHU NeuroVasc Sorbonne, Paris, France
4Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
5Department of Neurology, Medical University of Graz, Graz, Austria.
6Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Publication Date:
Alzheimers Dement
Volume Number:
Issue Number:
Alzheimers Dement. 2018 Jun;14(6):764-74.
PubMed ID:
Brain atrophy, Diffusion tensor imaging, Disability, Free water, Lacunes, Processing speed, Small vessel disease, Structural imaging, Vascular cognitive impairment, White matter hyperintensities
Appears in Collections:
P41 EB015902/EB/NIBIB NIH HHS/United States
R01 MH108574/MH/NIMH NIH HHS/United States
Generated Citation:
Duering M., Finsterwalder S., Baykara E., Tuladhar A.M., Gesierich B., Konieczny M.J., Malik R., Franzmeier N., Ewers M., Jouvent E., Biessels G.J., Schmidt R., de Leeuw F-E., Pasternak O., Dichgans M. Free Water Determines Diffusion Alterations and Clinical Status in Cerebral Small Vessel Disease. Alzheimers Dement. 2018 Jun;14(6):764-74. PMID: 29406155. PMCID: PMC5994358.
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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 (R2 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.