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Mitsuhiro Yoshita, Evan Fletcher,

Extent and Distribution of White Matter Hyperintensities in Normal Aging, Mild Cognitive Impairment and Alzheimer’s Disease. Department of Neurology and Center for Neuroscience University of California at Davis. Mitsuhiro Yoshita, Evan Fletcher,

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Mitsuhiro Yoshita, Evan Fletcher,

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  1. Extent and Distribution ofWhite Matter Hyperintensities in Normal Aging, Mild Cognitive Impairment and Alzheimer’s Disease Department of Neurology and Center for Neuroscience University of California at Davis Mitsuhiro Yoshita, Evan Fletcher, Oliver Martinez, Mario Ortega, Bruce Reed, Dan Mungas and Charles DeCarli

  2. Object & Background Mild Cognitive Impairment (MCI) Normal Aging Alzheimer’s Disease (NA) (AD) White Matter Hyperintensites (WMH) How different in Extent and Distribution

  3. AD MCI NA Number (F/M) 26 (16/10) 29 (12/17) 33 (23/10) Age (y) 79.6 ± 6.8* 74.6 ± 8.1 73.4 ± 8.1 range 63-93 60-88 61-91 Education (y) 11.7 ± 5.2 12.6 ± 5.4 10.9 ± 5.8 range 0-18 0-21 0-20 MMSE 19.5 ± 6.8a 26.6 ± 2.3 27.9 ± 2.7 range 0-27 20-30 19-30 Vascular risk score range Brain volume (%) 77.3 ± 4.2b 80.7 ± 4.2 83.3 ± 4.3 WMH volume (%) 1.33 ±1.30c 0.92 ±0.93 0.56 ±0.67 Data represented as mean ± standard deviation. * p < 0.01 between AD and NA, ap < 0.001 between AD and others. bp < 0.01 between AD and others, cp < 0.001 between AD and NA. Subject Demographics

  4. DeCarli C, et al. Stroke2005. A P Composite image A P Methods Image Analysis Schema for WMH segmentation and nonlinear transformation for mapping

  5. Pb Pp Pp Pb Pa Po Po Pa Cs Cg Cg (B) (A) Cs ROI on 3-D WMH maps ROI volume (mm3) : Cg: 263, Cs: 205, Pa: 1325, Pb: 3190, Pp: 2385, Po: 983. Abbreviations: Cg: genu of corpus callosum, Cs: splenium of corpus callosum, Pa: anterior periventricular region, Pb: body of periventricular region, Pp: posterior periventricular region, Po: occipital periventricular region. We computed the number of voxel of WMH in each ROI, and calculated percentage of voxel which have WMH in each ROI of each subject.

  6. Statistical Analysis • 1. Groups were compared using analysis of variance (ANOVA) or Kruskal-Wallis test as appropriate according to the distribution of the data, with post hoc analysis. • 2. Correlations were evaluated by Spearman’s ranks correlation test. • 3. Results are expressed as mean values ± standard deviation. • A p value less than 0.05 was considered significant. • 5. Data were analyzed using the Statistical Package for Social Sciences (SPSS for Windows, version 12.0; SPSS Inc, Chicago, IL).

  7. 40 20 0 -20 -40 -60 -80 -100 40 20 0 -20 -40 -60 -80 -100 60 60 (A-2) (A-1) X= 2 X= 21 80 80 60 60 40 40 20 20 0 0 -20 -20 -60 -20 0 20 40 -40 60 -60 -20 0 20 40 -40 60 (B-1) (B-2) Z= 28 Z= 22 40 40 20 20 0 0 -20 -20 -40 -40 -60 -60 -80 -80 -60 -40 -20 0 20 40 60 -60 -40 -20 0 20 40 60 80 Y= -26 (C-2) (C-1) 80 Y= -4 60 60 40 40 20 20 0 0 -20 -20 -40 (D) P A WMH frequency maps in all subjects

  8. (B) (C) (A) Three-dimensional reconstruction of the WMH (orange) and ventricular (grey) maps. Orange color indicate the frequency of voxels containing the WMH more than 10%. (A): group of NA (B): group of MCI (C): group of AD 3-D WMH frequency maps in each group

  9. (A) : Periventricular region (%) * ** 80 * 70 60 50 40 30 20 10 0 Anterior Body Posterior Occipital : Corpus callosum region (B) * ** (%) 70 * 60 50 : AD 40 30 : MCI 20 10 : NA 0 Genu Splenium *p < 0.05, **p < 0.01. Error bars indicate standard deviation of the mean. Group difference of WMH severity in each ROI

  10. Pa Pb Pp Po Cg Cs Age AD 0.060 0.068 0.202 0.350 0.120 0.276 0.237 0.355 0.477*0.553** 0.319 0.055 0.220 0.298 0.411*0.394* 0.159 0.164 MCI NA MMSE AD 0.355 0.149 0.078 -0.042 0.085 0.032 -0.054 0.018 -0.116 -0.160 0.252 -0.003 0.084 -0.085 -0.051 0.316 0.198 0.192 MCI NA *p < 0.05, ** p < 0.01 corrected. Abbreviations: Pa: anterior periventricular region Pb: body of periventricular region Pp: posterior periventricular region Po: occipital periventricular region Cg: genu of corpus callosum Cs: splenium of corpus callosum Correlations between age, MMSE and WMH severity in each ROI

  11. Conclusion We believe the methods developed here conclusively show the difference of WMH distribution of each cognitive stage. These observations also support the notion of both a common ischemic etiology and Wallerian degeneration as a mechanism of WMH in each cognitive stage. Our study shows that measurements of the extent and distribution of WMH in both corpus callosum and periventricular area are suitable for assessment for NA, MCI and AD.

  12. Thanks Student: Ryan Berthold, Chris Davies, Alex Early, Marty Greenia, Evan Lloyd Staff: Lauren Cibattari, Krista Garcia, Oliver Martinez, Mario Ortega, Baljeet Singh, Laura Whiteside, Sky Raptentsetsang

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