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230 Scientific Programme 22. European Stroke Conference © 2013 S. Karger AG, Basel 4 Brain imaging Multiparametric MR imaging shows that increased water mobility is the predominant abnor-mality in brain white matter hyperintensities S. Muñoz Maniega1, M.C. Valdés Hernández2, N.A. Royle3, B.S. Aribisala4, C. Murray5, A.J. Gow6, J.D. Clayden7, J.M. Starr8, M.E. Bastin9, I.J. Deary10, J.M. Wardlaw11 University of Edinburgh, Edinburgh, UNITED KINGDOM1, University of Edinburgh, Edin-burgh, UNITED KINGDOM2, University of Edinburgh, Edinburgh, UNITED KINGDOM3, Univer-sity of Edinburgh, Edinburgh, UNITED KINGDOM4, University of Edinburgh, Edinburgh, UNIT-ED KINGDOM5, University of Edinburgh, Edinburgh, UNITED KINGDOM6, University College London, London, UNITED KINGDOM7, University of Edinburgh, Edinburgh, UNITED KING-DOM8, University of Edinburgh, Edinburgh, UNITED KINGDOM9, University of Edinburgh, Edinburgh, UNITED KINGDOM10, University of Edinburgh, Edinburgh, UNITED KINGDOM11 Background White matter hyperintensities (WMH) are commonly seen on MRI brain images of older people and are related to cerebrovascular disease. Here, to characterise WMH, we evaluate MR imaging param-eters that are thought to represent white matter integrity, myelination, water content and mobility. Methods Using MRI data of 676 subjects (358 men; mean age 72.7, SD 0.7) we created masks of WMH and normal-appearing white matter (NAWM) using a validated tool (www.sourceforge.net/projects/ bric1936/). We measured diffusion fractional anisotropy (FA), mean diffusivity (MD), magnetisation transfer ratio (MTR) and T1 relaxation time parameters in each. We calculated mean values of each parameter for each tissue type and tested for differences between NAWM and WMH. We used logis-tic regression to determine which parameter best predicted WMH. Results We observed a wider range of the parameter values in WMH than in NAWM. FA and MTR were significantly lower whereas MD and T1 were higher in WMH (p<0.0001), table 1, with MD provid-ing the largest difference between NAWM and WMH. Logistic regression on each individual pa-rameter showed that mean MD differentiated best between NAWM and WMH, predicting 94.2% of the lesions using a threshold of 0.749 10-3 mm2/s. The effect of varying this threshold is shown in the ROC curve (Fig 1), with an area under the curve (AUC) of 0.982 for MD. Conclusion Multimodal imaging shows that increased water mobility (MD) is the main feature in WMH, where-as axonal integrity (FA) and myelination (MTR) were less affected. Thus the demyelination and axonal loss described pathologically may be a late change. The wider range of values also indicates a spectrum of tissue damage in WMH. Further work is required to determine the order of changes, and whether the increase in interstitial fluid in WMH results from ischaemia or blood-brain barrier dysfunction. Table 1 Mean valu-es NAWM WMH p Cohen’s d FA 0.338 ± 0.024 0.299 ± 0.042 < 0.0001 1.13 MD 0.692 ± 0.034 0.833 ± 0.061 < 0.0001 -2.85 MTR 56.80 ± 0.99 54.37 ± 1.51 < 0.0001 1.91 T1 1.002 ± 0.092 1.086 ± 0.117 < 0.0001 -0.80 3 Brain imaging Iron deposition in the brain is associated with declining cognition and increasing white matter damage in older subjects M.C. Valdés Hernández1, M. Allerhand2, A. Glatz3, L. Penke4, B.S. Aribisala5, S. Munoz Manie-ga6, N.A. Royle7, C. Murray8, A.J. Gow9, M.E. Bastin10, I.J. Deary11, J.M. Wardlaw12 Brain Research Imaging Centre, University of Edinburgh, Edinburgh, UNITED KINGDOM1, Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UNITED KINGDOM2, University of Edinburgh, Edinburgh, UNITED KINGDOM3, University of Edinburgh, Edinburgh, UNITED KINGDOM4, Brain Research Imaging Centre, University of Edin-burgh, Edinburgh, UNITED KINGDOM5, Brain Research Imaging Centre, University of Edinburgh, Edinburgh, UNITED KINGDOM6, University of Edinburgh, Edinburgh, UNITED KINGDOM7, University of Edinburgh, Edinburgh, UNITED KINGDOM8, Heriot-Watt University, Edinburgh, UNITED KINGDOM9, University of Edinburgh, Edinburgh, UNITED KINGDOM10, University of Edinburgh, Edinburgh, UNITED KINGDOM11, University of Edinburgh, Edinburgh, UNITED KINGDOM12 Background: Brain iron deposits (IDs) are associated with cognitive decline, cerebrovascular and neurodegenerative diseases. We examine whether the effect of iron deposits is mediated by or inde-pendent of brain tissue damage represented by hyperintensities in the white matter and subcortical grey matter visible on FLAIR and T2-weighted structural MR scans (WMH). Methods: We analysed data from 662 community-dwelling older individuals of a birth cohort mean age 73 years old, with MMSE scores > 24, who underwent multimodality brain MRI. We used validated methods devel-oped in-house to extract volumes of IDs in the basal ganglia, white matter, thalamus, brain stem and cortex, brain tissue and WMH. To determine the effect of the total burden of IDs on cognitive abil-ity, and whether it was independent or not from the burden of WMH on brain tissue, we used Tobit regressions calculated in MPlus 6.1, controlling for age and gender. Results: Overall, 72.8% of the sample had IDs. The median total volume of IDs was 40 mm3. Basal ganglia IDs, with median vol-ume of 35 mm3, were found in 70.6% of the sample. IDs in the brain stem were found in 12.9% of the sample, in the cortex in 1.9%, in the white matter in 6.1% and in the thalamus in 1.0%. Regres-sion analysis showed that IDs have a small but significant negative effect on cognitive ability (stan-dardized β=-0.09, p<0.01) and a significant positive effect on WMH (std β=0.09, p=0.03). The bur-den of WMH has a significant negative effect on cognitive ability, independent of IDs (std β=-0.16, p<0.01). However, the effect of IDs in cognition is partially mediated by the volume of WMH (std β=-0.02, p<0.01). Conclusion: Brain iron deposits have a negative effect on cognitive ability in the elderly, partially mediated by the presence of white matter hyperintensities. IDs might be an indica-tor of small vessel disease that predisposes to white matter damage, affecting the neuronal networks underlying higher cognitive functioning.


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