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February 06, 2018; 90 (6) Article

Sex differences in cerebrovascular pathologies on FLAIR in cognitively unimpaired elderly

Farzan Fatemi, Kejal Kantarci, Jonathan Graff-Radford, Gregory M. Preboske, Stephen D. Weigand, Scott A. Przybelski, David S. Knopman, Mary M. Machulda, Rosebud O. Roberts, Michelle M. Mielke, Ronald C. Petersen, Clifford R. Jack, Prashanthi Vemuri
First published January 17, 2018, DOI: https://doi.org/10.1212/WNL.0000000000004913
Farzan Fatemi
From the Departments of Radiology (F.F., K.K., G.M.P., C.R.J., P.V.), Health Sciences Research (S.D.W., S.A.P., R.O.R., M.M. Mielke), Neurology (J.G.-R., D.S.K., R.O.R., M.M. Mielke, R.C.P.), and Psychology (M.M. Machulda), Mayo Clinic Rochester; and School of Medicine (F.F.), University of Minnesota, Minneapolis.
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Kejal Kantarci
From the Departments of Radiology (F.F., K.K., G.M.P., C.R.J., P.V.), Health Sciences Research (S.D.W., S.A.P., R.O.R., M.M. Mielke), Neurology (J.G.-R., D.S.K., R.O.R., M.M. Mielke, R.C.P.), and Psychology (M.M. Machulda), Mayo Clinic Rochester; and School of Medicine (F.F.), University of Minnesota, Minneapolis.
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Jonathan Graff-Radford
From the Departments of Radiology (F.F., K.K., G.M.P., C.R.J., P.V.), Health Sciences Research (S.D.W., S.A.P., R.O.R., M.M. Mielke), Neurology (J.G.-R., D.S.K., R.O.R., M.M. Mielke, R.C.P.), and Psychology (M.M. Machulda), Mayo Clinic Rochester; and School of Medicine (F.F.), University of Minnesota, Minneapolis.
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Gregory M. Preboske
From the Departments of Radiology (F.F., K.K., G.M.P., C.R.J., P.V.), Health Sciences Research (S.D.W., S.A.P., R.O.R., M.M. Mielke), Neurology (J.G.-R., D.S.K., R.O.R., M.M. Mielke, R.C.P.), and Psychology (M.M. Machulda), Mayo Clinic Rochester; and School of Medicine (F.F.), University of Minnesota, Minneapolis.
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Stephen D. Weigand
From the Departments of Radiology (F.F., K.K., G.M.P., C.R.J., P.V.), Health Sciences Research (S.D.W., S.A.P., R.O.R., M.M. Mielke), Neurology (J.G.-R., D.S.K., R.O.R., M.M. Mielke, R.C.P.), and Psychology (M.M. Machulda), Mayo Clinic Rochester; and School of Medicine (F.F.), University of Minnesota, Minneapolis.
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Scott A. Przybelski
From the Departments of Radiology (F.F., K.K., G.M.P., C.R.J., P.V.), Health Sciences Research (S.D.W., S.A.P., R.O.R., M.M. Mielke), Neurology (J.G.-R., D.S.K., R.O.R., M.M. Mielke, R.C.P.), and Psychology (M.M. Machulda), Mayo Clinic Rochester; and School of Medicine (F.F.), University of Minnesota, Minneapolis.
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David S. Knopman
From the Departments of Radiology (F.F., K.K., G.M.P., C.R.J., P.V.), Health Sciences Research (S.D.W., S.A.P., R.O.R., M.M. Mielke), Neurology (J.G.-R., D.S.K., R.O.R., M.M. Mielke, R.C.P.), and Psychology (M.M. Machulda), Mayo Clinic Rochester; and School of Medicine (F.F.), University of Minnesota, Minneapolis.
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Mary M. Machulda
From the Departments of Radiology (F.F., K.K., G.M.P., C.R.J., P.V.), Health Sciences Research (S.D.W., S.A.P., R.O.R., M.M. Mielke), Neurology (J.G.-R., D.S.K., R.O.R., M.M. Mielke, R.C.P.), and Psychology (M.M. Machulda), Mayo Clinic Rochester; and School of Medicine (F.F.), University of Minnesota, Minneapolis.
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Rosebud O. Roberts
From the Departments of Radiology (F.F., K.K., G.M.P., C.R.J., P.V.), Health Sciences Research (S.D.W., S.A.P., R.O.R., M.M. Mielke), Neurology (J.G.-R., D.S.K., R.O.R., M.M. Mielke, R.C.P.), and Psychology (M.M. Machulda), Mayo Clinic Rochester; and School of Medicine (F.F.), University of Minnesota, Minneapolis.
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Michelle M. Mielke
From the Departments of Radiology (F.F., K.K., G.M.P., C.R.J., P.V.), Health Sciences Research (S.D.W., S.A.P., R.O.R., M.M. Mielke), Neurology (J.G.-R., D.S.K., R.O.R., M.M. Mielke, R.C.P.), and Psychology (M.M. Machulda), Mayo Clinic Rochester; and School of Medicine (F.F.), University of Minnesota, Minneapolis.
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Ronald C. Petersen
From the Departments of Radiology (F.F., K.K., G.M.P., C.R.J., P.V.), Health Sciences Research (S.D.W., S.A.P., R.O.R., M.M. Mielke), Neurology (J.G.-R., D.S.K., R.O.R., M.M. Mielke, R.C.P.), and Psychology (M.M. Machulda), Mayo Clinic Rochester; and School of Medicine (F.F.), University of Minnesota, Minneapolis.
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Clifford R. Jack Jr
From the Departments of Radiology (F.F., K.K., G.M.P., C.R.J., P.V.), Health Sciences Research (S.D.W., S.A.P., R.O.R., M.M. Mielke), Neurology (J.G.-R., D.S.K., R.O.R., M.M. Mielke, R.C.P.), and Psychology (M.M. Machulda), Mayo Clinic Rochester; and School of Medicine (F.F.), University of Minnesota, Minneapolis.
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Prashanthi Vemuri
From the Departments of Radiology (F.F., K.K., G.M.P., C.R.J., P.V.), Health Sciences Research (S.D.W., S.A.P., R.O.R., M.M. Mielke), Neurology (J.G.-R., D.S.K., R.O.R., M.M. Mielke, R.C.P.), and Psychology (M.M. Machulda), Mayo Clinic Rochester; and School of Medicine (F.F.), University of Minnesota, Minneapolis.
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Citation
Sex differences in cerebrovascular pathologies on FLAIR in cognitively unimpaired elderly
Farzan Fatemi, Kejal Kantarci, Jonathan Graff-Radford, Gregory M. Preboske, Stephen D. Weigand, Scott A. Przybelski, David S. Knopman, Mary M. Machulda, Rosebud O. Roberts, Michelle M. Mielke, Ronald C. Petersen, Clifford R. Jack, Prashanthi Vemuri
Neurology Feb 2018, 90 (6) e466-e473; DOI: 10.1212/WNL.0000000000004913

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Abstract

Objective To examine sex differences in cerebrovascular pathologies (CVPs) as seen on fluid-attenuated inversion recovery (FLAIR) MRI and in cardiovascular and metabolic risk factors in a population-based cognitively unimpaired cohort and to examine whether sex is independently associated with FLAIR findings after accounting for differences in important midlife risk factors.

Methods We identified 1,301 cognitively normal participants (663 men and 638 women) enrolled in the Mayo Clinic Study of Aging (age ≥70 years) who had FLAIR MRI and ascertained total burden of white matter (WM) hyperintensities (WMH), subcortical infarctions, and cortical infarctions. We compared CVPs and midlife and late-life vascular risk factors between men and women. We fit regression models with each CVP as an outcome, treating age, sex, and midlife risk factors as predictors.

Results Women had significantly greater WMH volume relative to their WM volume compared to men (2.8% vs 2.4% of WM, p < 0.001), while men had a greater frequency of cortical infarctions compared to women (9% vs 4%, p < 0.001). Subcortical infarctions were equally common in men and women (20%). In regression modeling after adjustment for WM volume, the mean WMH volume difference between men and women was of the same magnitude as a 7-year difference in age. In contrast, men had 2.2-greater relative odds of having a cortical infarction compared to women. These sex differences persisted even after adjustment for midlife vascular risk factors.

Conclusions There were important sex differences in CVP findings on FLAIR in cognitively unimpaired elderly. Understanding these sex differences could aid in the development of sex-specific preventive strategies.

Glossary

CI=
confidence interval;
CVP=
cerebrovascular pathology;
FLAIR=
fluid-attenuated inversion recovery;
ICD-9=
International Classification of Diseases, 9th revision;
MCSA=
Mayo Clinic Study of Aging;
OR=
odds ratio;
REP=
Rochester Epidemiology Project;
WM=
white matter;
WMH=
white matter hyperintensities

Footnotes

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

  • Received February 26, 2017.
  • Accepted in final form October 27, 2017.
  • © 2018 American Academy of Neurology
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