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Alzheimers Dement. 2018 Jun;14(6):764-774. doi: 10.1016/j.jalz.2017.12.007. Epub 2018 Feb 16.

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

Author information

1
Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany. Electronic address: marco.duering@med.uni-muenchen.de.
2
Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany.
3
Department of Neurology, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
4
Univ Paris Diderot, DHU NeuroVasc Sorbonne Paris Cité, UMR-S 1161 INSERM, Paris, France; Department of Neurology, Assistance publique - hôpitaux de Paris (AP-HP), Lariboisière Hospital, Paris, France.
5
Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
6
Department of Neurology, Medical University of Graz, Graz, Austria.
7
Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
8
Institute for Stroke and Dementia Research, University Hospital, LMU Munich, Munich, Germany; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany; German Center for Neurodegenerative Diseases (DZNE), Munich, Germany.

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 (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.

KEYWORDS:

Brain atrophy; Diffusion tensor imaging; Disability; Free water; Lacunes; Processing speed; Small vessel disease; Structural imaging; Vascular cognitive impairment; White matter hyperintensities

PMID:
29406155
PMCID:
PMC5994358
[Available on 2019-06-01]
DOI:
10.1016/j.jalz.2017.12.007

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