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Viewpoint
July 8, 2020

Sex Differences in Disorders of the Brain and Heart—A Global Crisis of Multimorbidity and Novel Opportunity

Author Affiliations
  • 1Massachusetts General Hospital, Department of Psychiatry, Harvard Medical School, Boston
  • 2Massachusetts General Hospital, Department of Obstetrics and Gynecology, Harvard Medical School, Boston
  • 3Women and Health Initiative, Harvard T. H. Chan School of Public Health, Boston, Massachusetts
  • 4Innovation Center on Sex Differences in Medicine, MGH Research Institute, Massachusetts General Hospital, Boston
  • 5WomenAgainstAlzheimer’s/USAgainstAlzheimer’s, Policy and Advocacy Organization, Washington, DC
JAMA Psychiatry. 2021;78(1):7-8. doi:10.1001/jamapsychiatry.2020.1944

The coronavirus disease 2019 (COVID-19) crisis has led to an increasing recognition of the critical associations of sex (eg, immunity differences) and gender (eg, health care utilization differences) with disease outcomes and lack of data reported by sex. While this is commendable, the issues are not new. There is no better example than the global crisis of sex/gender differences in the co-occurrence (or multimorbidity) of the 3 major chronic diseases of our time (major depressive disorder [MDD], cardiovascular disease [CVD], and Alzheimer disease [AD]), interconnected disorders of the brain and heart, that are critical preexisting conditions into which the COVID-19 infectious crisis has interacted. Over a century, medical progress markedly extended longevity by approximately 30 years. However, this resulted in a high prevalence of these chronic diseases creating substantial adverse effects on health care and economic systems globally.

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    1 Comment for this article
    EXPAND ALL
    Physical exercise – a link to gender equality and chronic disease prevention”
    David Byfield, BSc, MPhil, PhD (cand) | Neurovascular Research Laboratory, Faculty of Life Sciences and Education, University of South Wales, UK
    We read the recent Viewpoint by Goldstein et al. 1 with interest highlighting the global crisis related to sex differences in three major chronic diseases and corresponding interconnections with disorders of the heart and brain. Herein, we take the opportunity to justify why low back pain (LBP) may represent a hitherto unexplored albeit, potentially important risk factor, that may contribute, at least in part, to the underlying phenotypic variation reported by the authors. 1

    In support, females of all ages are less physically active compared to their male counterparts. LBP is the leading cause of years
    lived with disability across the globe and both the age-standardised prevalence and disability years is higher in females relative to males.2 Furthermore, LBP has been independently associated with cardiovascular disease risk factors including type 2 diabetes, obesity and moderate cognitive decline contributing indirectly to premature mortality. While the mechanistic bases underlying neurodegenerative diseases are clearly complex and multifactorial, we propose an integrated hypothesis unified by LBP/physical inactivity-induced vascular endothelial dysfunction.3

    First, the musculoskeletal degeneration and disability associated with LBP may further compound physical inactivity due to the mechanical/physical restrictions it imposes. Second, chronic systemic oxidative-inflammatory-nitrosative stress, either as a cause or consequence of LBP, can interfere with immunological processes of the brain and promote dementia progression subsequent to vascular endothelial impairment and microglia activation. 4

    What can be done to simultaneously tackle disorders of the back, heart and brain? Physical activity may prove the unifying preventative panacea that brings optimism amidst the current lack of curative treatments. Indeed, the basic act of becoming fit has been associated with a 40–50% reduced risk of incident dementia, 30–40% reduced risk of dementia-related mortality and reduced prevalence of LBP. 5

    Accordingly, there is a strong public health message that improving cardio/cerebrovascular respiratory fitness through physical activity can reduce the risk of mortality. This is especially important for women who are less physically active compared to their male counterparts across the lifespan. Policies that directly address the challenges associated with this ‘sex gap’ and include exercise as a vascular protective intervention need to be prioritised.
    References
    1. Goldstein JM, Langer A, Lesser JA. Sex differences in disorders of the brain and heart-A global crisis of multimorbidity and novel opportunity. JAMA Psychiatry. 2021;78(5):7-8.
    2. Wu A, March L, Zheng X et al. Global low back pain prevalence and years lived with disability from 1990 to 2017: estimates from the Global Burden of Disease Study 2017. Ann Trans Med. 2020;8(6);299 http://dx.doi.org/10.21037/atm.2020.02.175.
    3. Bailey DM, Byfield D, du Rose A, Corkill R. From bad backs to bad brains; chronic pain, physical inactivity and the link to dementia. Lancet. 2018; 392;2018
    4. Heneka MT, Carson MJ, El Khoury J, et al. Neuroinflammation in Alzheimer's disease. Lancet Neurol 2015; 14(4): 388-405.
    5. Tari AR, Nauman J, Zisko N, et al. Temporal changes in cardiorespiratory fitness and risk of dementia incidence and mortality: a population-based prospective cohort study. Lancet Public Health 2019; 4(11): e565-e74.
    CONFLICT OF INTEREST: None Reported
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