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March 05, 2013; 80 (10) Article

Thrombogenic microvesicles and white matter hyperintensities in postmenopausal women

Limor Raz, M. Jayachandran, Nirubol Tosakulwong, Timothy G. Lesnick, Samantha M. Wille, Matthew C. Murphy, Matthew L. Senjem, Jeffrey L. Gunter, Prashanthi Vemuri, Clifford R. Jack, Virginia M. Miller, Kejal Kantarci
First published February 13, 2013, DOI: https://doi.org/10.1212/WNL.0b013e3182840c9f
Limor Raz
From the Departments of Physiology and Biomedical Engineering (L.R., M.J., V.M.M.), Health Sciences Research (N.T., T.G.L.), Radiology (S.M.W., M.C.M., M.L.S., J.L.G., P.V., C.R.J., K.K.), and Surgery (V.M.M.), Mayo Clinic, Rochester, MN.
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M. Jayachandran
From the Departments of Physiology and Biomedical Engineering (L.R., M.J., V.M.M.), Health Sciences Research (N.T., T.G.L.), Radiology (S.M.W., M.C.M., M.L.S., J.L.G., P.V., C.R.J., K.K.), and Surgery (V.M.M.), Mayo Clinic, Rochester, MN.
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Nirubol Tosakulwong
From the Departments of Physiology and Biomedical Engineering (L.R., M.J., V.M.M.), Health Sciences Research (N.T., T.G.L.), Radiology (S.M.W., M.C.M., M.L.S., J.L.G., P.V., C.R.J., K.K.), and Surgery (V.M.M.), Mayo Clinic, Rochester, MN.
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Timothy G. Lesnick
From the Departments of Physiology and Biomedical Engineering (L.R., M.J., V.M.M.), Health Sciences Research (N.T., T.G.L.), Radiology (S.M.W., M.C.M., M.L.S., J.L.G., P.V., C.R.J., K.K.), and Surgery (V.M.M.), Mayo Clinic, Rochester, MN.
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Samantha M. Wille
From the Departments of Physiology and Biomedical Engineering (L.R., M.J., V.M.M.), Health Sciences Research (N.T., T.G.L.), Radiology (S.M.W., M.C.M., M.L.S., J.L.G., P.V., C.R.J., K.K.), and Surgery (V.M.M.), Mayo Clinic, Rochester, MN.
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Matthew C. Murphy
From the Departments of Physiology and Biomedical Engineering (L.R., M.J., V.M.M.), Health Sciences Research (N.T., T.G.L.), Radiology (S.M.W., M.C.M., M.L.S., J.L.G., P.V., C.R.J., K.K.), and Surgery (V.M.M.), Mayo Clinic, Rochester, MN.
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Matthew L. Senjem
From the Departments of Physiology and Biomedical Engineering (L.R., M.J., V.M.M.), Health Sciences Research (N.T., T.G.L.), Radiology (S.M.W., M.C.M., M.L.S., J.L.G., P.V., C.R.J., K.K.), and Surgery (V.M.M.), Mayo Clinic, Rochester, MN.
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Jeffrey L. Gunter
From the Departments of Physiology and Biomedical Engineering (L.R., M.J., V.M.M.), Health Sciences Research (N.T., T.G.L.), Radiology (S.M.W., M.C.M., M.L.S., J.L.G., P.V., C.R.J., K.K.), and Surgery (V.M.M.), Mayo Clinic, Rochester, MN.
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Prashanthi Vemuri
From the Departments of Physiology and Biomedical Engineering (L.R., M.J., V.M.M.), Health Sciences Research (N.T., T.G.L.), Radiology (S.M.W., M.C.M., M.L.S., J.L.G., P.V., C.R.J., K.K.), and Surgery (V.M.M.), Mayo Clinic, Rochester, MN.
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Clifford R. Jack Jr
From the Departments of Physiology and Biomedical Engineering (L.R., M.J., V.M.M.), Health Sciences Research (N.T., T.G.L.), Radiology (S.M.W., M.C.M., M.L.S., J.L.G., P.V., C.R.J., K.K.), and Surgery (V.M.M.), Mayo Clinic, Rochester, MN.
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Virginia M. Miller
From the Departments of Physiology and Biomedical Engineering (L.R., M.J., V.M.M.), Health Sciences Research (N.T., T.G.L.), Radiology (S.M.W., M.C.M., M.L.S., J.L.G., P.V., C.R.J., K.K.), and Surgery (V.M.M.), Mayo Clinic, Rochester, MN.
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Kejal Kantarci
From the Departments of Physiology and Biomedical Engineering (L.R., M.J., V.M.M.), Health Sciences Research (N.T., T.G.L.), Radiology (S.M.W., M.C.M., M.L.S., J.L.G., P.V., C.R.J., K.K.), and Surgery (V.M.M.), Mayo Clinic, Rochester, MN.
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Citation
Thrombogenic microvesicles and white matter hyperintensities in postmenopausal women
Limor Raz, M. Jayachandran, Nirubol Tosakulwong, Timothy G. Lesnick, Samantha M. Wille, Matthew C. Murphy, Matthew L. Senjem, Jeffrey L. Gunter, Prashanthi Vemuri, Clifford R. Jack, Virginia M. Miller, Kejal Kantarci
Neurology Mar 2013, 80 (10) 911-918; DOI: 10.1212/WNL.0b013e3182840c9f

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Abstract

Objective: To determine the association of conventional cardiovascular risk factors, markers of platelet activation, and thrombogenic blood-borne microvesicles with white matter hyperintensity (WMH) load and progression in recently menopausal women.

Methods: Women (n = 95) enrolled in the Mayo Clinic Kronos Early Estrogen Prevention Study underwent MRI at baseline and at 18, 36, and 48 months after randomization to hormone treatments. Conventional cardiovascular risk factors, carotid intima-medial thickness, coronary arterial calcification, plasma lipids, markers of platelet activation, and thrombogenic microvesicles were measured at baseline. WMH volumes were calculated using a semiautomated segmentation algorithm based on fluid-attenuated inversion recovery MRI. Correlations of those parameters with baseline WMH and longitudinal change in WMH were adjusted for age, months past menopause, and APOE ε4 status in linear regression analysis.

Results: At baseline, WMH were present in all women. The WMH to white matter volume fraction at baseline was 0.88% (0.69%, 1.16%). WMH volume increased by 122.1 mm3 (95% confidence interval: −164.3, 539.5) at 36 months (p = 0.003) and 155.4 mm3 (95% confidence interval: −92.13, 599.4) at 48 months (p < 0.001). These increases correlated with numbers of platelet-derived and total thrombogenic microvesicles at baseline (p = 0.03).

Conclusion: Associations of platelet-derived, thrombogenic microvesicles at baseline and increases in WMH suggest that in vivo platelet activation may contribute to a cascade of events leading to development of WMH in recently menopausal women.

GLOSSARY

BMI=
body mass index;
CAC=
coronary arterial calcification;
CIMT=
carotid intima-medial thickness;
FLAIR=
fluid-attenuated inversion recovery;
KEEPS=
Kronos Early Estrogen Prevention Study;
LDL=
low-density lipoprotein;
MPRAGE=
magnetization-prepared rapid acquisition gradient echo;
TPM=
time past menopause;
WM=
white matter;
WMH=
white matter hyperintensity

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Supplemental data at www.neurology.org

  • Received August 21, 2012.
  • Accepted November 21, 2012.
  • © 2013 American Academy of Neurology
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