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Abstract

Background and Objectives

The menopause transition is increasingly recognized as a time of importance for women's brain health. A growing body of work indicates that the classic menopausal symptom, vasomotor symptom (VMS), may be associated with poorer cardiovascular health. Other work links VMS to poorer cognition. We investigate whether VMS, when rigorously assessed using physiologic measures, are associated with greater white matter hyperintensity volume (WMHV) among midlife women. We consider a range of potential explanatory factors in these associations and explore whether VMS are associated with the spatial distribution of WMHV.

Methods

Women aged 45–67 years and free of hormone therapy underwent 24 hours of physiologic VMS monitoring (sternal skin conductance), actigraphy assessment of sleep, physical measures, phlebotomy, and 3 Tesla neuroimaging. Associations between VMS (24-hour, wake, and sleep VMS, with wake and sleep intervals defined by actigraphy) and whole brain WMHV were considered in linear regression models adjusted for age, race, education, smoking, body mass index, blood pressure, insulin resistance, and lipids. Secondary models considered WMHV in specific brain regions (deep, periventricular, frontal, temporal, parietal, and occipital) and additional covariates including sleep.

Results

The study sample included 226 women. Physiologically assessed VMS were associated with greater whole brain WMHV in multivariable models, with the strongest associations observed for sleep VMS (24-hour VMS, B[SE] = 0.095 [0.045], p = 0.032; Wake VMS, B[SE] = 0.078 [0.046], p = 0.089, Sleep VMS, B[SE] = 0.173 [0.060], p = 0.004). Associations were not accounted for by additional covariates including actigraphy-assessed sleep (wake after sleep onset). When considering the spatial distribution of WMHV, sleep VMS were associated with both deep WMHV, periventricular WMHV, and frontal lobe WMHV.

Discussion

VMS, particularly VMS occurring during sleep, were associated with greater WMHV. Identification of female-specific midlife markers of poor brain health later in life is critical to identify women who warrant early intervention and prevention. VMS have the potential to serve as female-specific midlife markers of brain health in women.

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Information & Authors

Information

Published In

Neurology®
Volume 100Number 2January 10, 2023
Pages: e133-e141
PubMed: 36224031

Publication History

Received: March 18, 2022
Accepted: August 30, 2022
Published online: October 12, 2022
Published in print: January 10, 2023

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Disclosure

R.C. Thurston is a consultant for Astellas, Bayer, Happify Health, Hello Therapeutics, and Vira Health. H.J. Aizenstein is an advisor to Eisai. P. Maki is a consultant for AbbVie, Balchem, and Pfizer and Advisor to Astellas, Bayer, and Johnson&Johnson. M. Wu, Y. Chang, C.A. Derby, and E.A. Barinas-Mitchell have no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.

Study Funding

This research was supported by the NIH (NIH), National Institute on Aging (RF1AG053504 and R01AG053504 to Thurston & Maki), and the NIH Heart Lung and Blood Institute (R01HL105647 and 2K24HL123565 to Thurston). This work was also supported by the University of Pittsburgh Clinical and Translational Science Institute (NIH Grant UL1TR000005) and the University of Pittsburgh Small Molecule Biomarker Core (NIH Grant S10RR023461 to Poloyac).

Authors

Affiliations & Disclosures

Rebecca C. Thurston, PhD https://orcid.org/0000-0001-6580-1202
From the Department of Psychiatry (R.C.T., M.W., H.J.A.), Epidemiology (R.C.T., E.A.B.-M.), Psychology (R.C.T.), and Neurosurgery (Y.-F.C.), University of Pittsburgh, PA; Department of Neurology and Epidemiology and Population Health (C.A.D.), Albert Einstein College of Medicine, Bronx, NY; and Department of Psychiatry (P.M.), University of Illinois at Chicago, IL.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Minjie Wu, PhD
From the Department of Psychiatry (R.C.T., M.W., H.J.A.), Epidemiology (R.C.T., E.A.B.-M.), Psychology (R.C.T.), and Neurosurgery (Y.-F.C.), University of Pittsburgh, PA; Department of Neurology and Epidemiology and Population Health (C.A.D.), Albert Einstein College of Medicine, Bronx, NY; and Department of Psychiatry (P.M.), University of Illinois at Chicago, IL.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Yue-Fang Chang, PhD
From the Department of Psychiatry (R.C.T., M.W., H.J.A.), Epidemiology (R.C.T., E.A.B.-M.), Psychology (R.C.T.), and Neurosurgery (Y.-F.C.), University of Pittsburgh, PA; Department of Neurology and Epidemiology and Population Health (C.A.D.), Albert Einstein College of Medicine, Bronx, NY; and Department of Psychiatry (P.M.), University of Illinois at Chicago, IL.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
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1.
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Howard J. Aizenstein, MD, PhD https://orcid.org/0000-0003-4897-6582
From the Department of Psychiatry (R.C.T., M.W., H.J.A.), Epidemiology (R.C.T., E.A.B.-M.), Psychology (R.C.T.), and Neurosurgery (Y.-F.C.), University of Pittsburgh, PA; Department of Neurology and Epidemiology and Population Health (C.A.D.), Albert Einstein College of Medicine, Bronx, NY; and Department of Psychiatry (P.M.), University of Illinois at Chicago, IL.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
From the Department of Psychiatry (R.C.T., M.W., H.J.A.), Epidemiology (R.C.T., E.A.B.-M.), Psychology (R.C.T.), and Neurosurgery (Y.-F.C.), University of Pittsburgh, PA; Department of Neurology and Epidemiology and Population Health (C.A.D.), Albert Einstein College of Medicine, Bronx, NY; and Department of Psychiatry (P.M.), University of Illinois at Chicago, IL.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Emma A. Barinas-Mitchell, PhD https://orcid.org/0000-0002-7280-7781
From the Department of Psychiatry (R.C.T., M.W., H.J.A.), Epidemiology (R.C.T., E.A.B.-M.), Psychology (R.C.T.), and Neurosurgery (Y.-F.C.), University of Pittsburgh, PA; Department of Neurology and Epidemiology and Population Health (C.A.D.), Albert Einstein College of Medicine, Bronx, NY; and Department of Psychiatry (P.M.), University of Illinois at Chicago, IL.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE
Pauline Maki, PhD
From the Department of Psychiatry (R.C.T., M.W., H.J.A.), Epidemiology (R.C.T., E.A.B.-M.), Psychology (R.C.T.), and Neurosurgery (Y.-F.C.), University of Pittsburgh, PA; Department of Neurology and Epidemiology and Population Health (C.A.D.), Albert Einstein College of Medicine, Bronx, NY; and Department of Psychiatry (P.M.), University of Illinois at Chicago, IL.
Disclosure
Scientific Advisory Boards:
1.
NONE
Gifts:
1.
NONE
Funding for Travel or Speaker Honoraria:
1.
NONE
Editorial Boards:
1.
NONE
Patents:
1.
NONE
Publishing Royalties:
1.
NONE
Employment, Commercial Entity:
1.
NONE
Consultancies:
1.
NONE
Speakers' Bureaus:
1.
NONE
Other Activities:
1.
NONE
Clinical Procedures or Imaging Studies:
1.
NONE
Research Support, Commercial Entities:
1.
NONE
Research Support, Government Entities:
1.
NONE
Research Support, Academic Entities:
1.
NONE
Research Support, Foundations and Societies:
1.
NONE
Stock/stock Options/board of Directors Compensation:
1.
NONE
License Fee Payments, Technology or Inventions:
1.
NONE
Royalty Payments, Technology or Inventions:
1.
NONE
Stock/stock Options, Research Sponsor:
1.
NONE
Stock/stock Options, Medical Equipment & Materials:
1.
NONE
Legal Proceedings:
1.
NONE

Notes

Correspondence Dr. Thurston [email protected]
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.
Submitted and externally peer reviewed. The handling editor was José Merino, MD, MPhil, FAAN.

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