Enhancing brain health in the global south through a sex and gender lens
Medina-Hernández, E., Fernández-Gómez, M. J. & Barrera-Mellado, I. Gender inequality in Latin America: a multidimensional analysis based on ECLAC indicators. Sustainability 13, 13140 (2021).
Google Scholar
Yu, S. Uncovering the hidden impacts of inequality on mental health: a global study. Transl. Psychiatry 8, 98 (2018).
Google Scholar
Zugman, A. et al. Country-level gender inequality is associated with structural differences in the brains of women and men. Proc. Natl Acad. Sci. USA 120, e2218782120 (2023).
Google Scholar
Barth, C. & de Lange, A. G. Towards an understanding of women’s brain aging: the immunology of pregnancy and menopause. Front. Neuroendocrinol. 58, 100850 (2020).
Google Scholar
Caldwell, J. Z. K. & Isenberg, N. The aging brain: risk factors and interventions for long term brain health in women. Curr. Opin. Obstet. Gynecol. 35, 169–175 (2023).
Google Scholar
Mielke, M. M. et al. Consideration of sex and gender in Alzheimer’s disease and related disorders from a global perspective. Alzheimers Dement. 18, 2707–2724 (2022).
Google Scholar
Yu, S., Qian, L. & Ma, J. The influence of gender and wealth inequality on Alzheimer’s disease among the elderly: a global study. Heliyon 9, e14677 (2023).
Google Scholar
Ibanez, A. & Zimmer, E. R. Time to synergize mental health with brain health. Nat. Ment. Health 1, 441–443 (2023).
Google Scholar
Eyre, H. A. et al. Brain health is a determinant of mental health. Am. J. Geriatr. Psychiatry 31, 379–381 (2023).
Google Scholar
Craske, M., Herzallah, M., Nusslock, R. & Patel, V. From neural circuits to communities: an integrative multidisciplinary roadmap for global mental health. Nat. Ment. Health 1, 12–24 (2023).
Google Scholar
The Global Gender Gap Report 2023 (World Economic Forum, 2023).
Ruano, A. L., Rodriguez, D., Rossi, P. G. & Maceira, D. Understanding inequities in health and health systems in Latin America and the Caribbean: a thematic series. Int. J. Equity Health 20, 94 (2021).
Google Scholar
Costa, J. C. et al. Inequalities in the health, nutrition and wellbeing of Afrodescendant women and children: a cross-sectional analysis of ten Latin American and Caribbean countries. Lancet Reg. Health Am. 15, 100345 (2022).
Google Scholar
Ibanez, A., Legaz, A. & Ruiz-Adame, M. Addressing the gaps between socioeconomic disparities and biological models of dementia. Brain 146, 3561–3564 (2023).
Google Scholar
Forging a Path Beyond Borders: The Global South (United Nations Conference on Trade and Development (UNCTAD), 2018).
Ibanez, A. et al. Neuroecological links of the exposome and One Health. Neuron 112, 1905–1910 (2024).
Google Scholar
Babulal, G. M. et al. Perspectives on ethnic and racial disparities in Alzheimer’s disease and related dementias: update and areas of immediate need. Alzheimers Dement. 15, 292–312 (2019).
Google Scholar
Baez, S., Alladi, S. & Ibanez, A. Global South research is critical for understanding brain health, ageing and dementia. Clin. Transl. Med 13, e1486 (2023).
Google Scholar
Chancel, L., Piketty, T., Saez, E. & Zucman, G. World Inequality Report 2022 (World Inequality Lab, 2022).
Heise, L. et al. Gender inequality and restrictive gender norms: framing the challenges to health. Lancet 393, 2440–2454 (2019).
Google Scholar
Santamaria-Garcia, H. et al. Factors associated with healthy aging in Latin American populations. Nat. Med. 29, 2248–2258 (2023).
Google Scholar
GBD 2021 Nervous System Disorders Collaborators. Global, regional and national burden of disorders affecting the nervous system, 1990-2021: a systematic analysis for the Global Burden of Disease Study 2021. Lancet Neurol. 23, 344–381 (2024).
Google Scholar
O’Neil, A., Scovelle, A. J., Milner, A. J. & Kavanagh, A. Gender/sex as a social determinant of cardiovascular risk. Circulation 137, 854–864 (2018).
Google Scholar
The World Bank. World Development Indicators; (accessed 19 November 2023).
Hay, K. et al. Disrupting gender norms in health systems: making the case for change. Lancet 393, 2535–2549 (2019).
Google Scholar
Mujica, O. J. et al. Recent trends in maternal and child health inequalities in Latin America and the Caribbean: analysis of repeated national surveys. Int. J. Equity Health 22, 125 (2023).
Google Scholar
Ortigoza, A. et al. Women’s empowerment and infant mortality in Latin America: evidence from 286 cities. Cities Health 7, 93–101 (2023).
Google Scholar
Emmerick, I. C., Luiza, V. L., Camacho, L. A., Vialle-Valentin, C. & Ross-Degnan, D. Barriers in household access to medicines for chronic conditions in three Latin American countries. Int. J. Equity Health 14, 115 (2015).
Google Scholar
Carbone, J. T. Allostatic load and mental health: a latent class analysis of physiological dysregulation. Stress 24, 394–403 (2021).
Google Scholar
McEwen, B. S. Protection and damage from acute and chronic stress: allostasis and allostatic overload and relevance to the pathophysiology of psychiatric disorders. Ann. N. Y. Acad. Sci. 1032, 1–7 (2004).
Google Scholar
Lenart-Bugla, M. et al. The association between allostatic load and brain: a systematic review. Psychoneuroendocrinology 145, 105917 (2022).
Google Scholar
Migeot, J. A., Duran-Aniotz, C. A., Signorelli, C. M., Piguet, O. & Ibanez, A. A predictive coding framework of allostatic-interoceptive overload in frontotemporal dementia. Trends Neurosci. 45, 838–853 (2022).
Google Scholar
Ziemka-Nalecz, M., Pawelec, P., Ziabska, K. & Zalewska, T. Sex differences in brain disorders. Int. J. Mol. Sci. 24, 14571 (2023).
Google Scholar
Krieger, N. Genders, sexes and health: what are the connections—and why does it matter? Int. J. Epidemiol. 32, 652–657 (2003).
Google Scholar
Puri, T. A., Richard, J. E. & Galea, L. A. M. Beyond sex differences: short- and long-term effects of pregnancy on the brain. Trends Neurosci. 46, 459–471 (2023).
Google Scholar
de Lange, A. G. et al. Population-based neuroimaging reveals traces of childbirth in the maternal brain. Proc. Natl Acad. Sci. USA 116, 22341–22346 (2019).
Google Scholar
Orchard, E. R. et al. Relationship between parenthood and cortical thickness in late adulthood. PLoS ONE 15, e0236031 (2020).
Google Scholar
Chechko, N. et al. The expectant brain-pregnancy leads to changes in brain morphology in the early postpartum period. Cereb. Cortex 32, 4025–4038 (2022).
Google Scholar
Bae, J. B. et al. Does parity matter in women’s risk of dementia? A COSMIC collaboration cohort study. BMC Med. 18, 210 (2020).
Google Scholar
Wu, Y., De Asis-Cruz, J. & Limperopoulos, C. Brain structural and functional outcomes in the offspring of women experiencing psychological distress during pregnancy. Mol. Psychiatry 29, 2223–2240 (2024).
Google Scholar
Jiang, L. et al. A global view of hypertensive disorders and diabetes mellitus during pregnancy. Nat. Rev. Endocrinol. 18, 760–775 (2022).
Google Scholar
Mielke, M. M. et al. Impaired cognition and brain atrophy decades after hypertensive pregnancy disorders. Circ. Cardiovasc. Qual. Outcomes 9, S70–S76 (2016).
Google Scholar
Rocca, W. A. et al. Association of premenopausal bilateral oophorectomy with cognitive performance and risk of mild cognitive impairment. JAMA Netw. Open 4, e2131448 (2021).
Google Scholar
Sochocka, M. et al. Cognitive decline in early and premature menopause. Int. J. Mol. Sci. 24, 6566 (2023).
Google Scholar
Lopez-Lee, C., Kodama, L. & Gan, L. Sex differences in neurodegeneration: the role of the immune system in humans. Biol. Psychiatry 91, 72–80 (2022).
Google Scholar
Snyder, H. M. et al. Sex biology contributions to vulnerability to Alzheimer’s disease: a think tank convened by the Women’s Alzheimer’s Research Initiative. Alzheimers Dement. 12, 1186–1196 (2016).
Google Scholar
Koran, M. E. I., Wagener, M., Hohman, T. J. & Alzheimer’s Neuroimaging, I. Sex differences in the association between AD biomarkers and cognitive decline. Brain Imaging Behav. 11, 205–213 (2017).
Google Scholar
Moguilner, S. et al. Brain clocks capture diversity and disparities in aging and dementia across geographically diverse populations. Nat. Med. (2024).
Epperson, C. N., Sammel, M. D. & Freeman, E. W. Menopause effects on verbal memory: findings from a longitudinal community cohort. J. Clin. Endocrinol. Metab. 98, 3829–3838 (2013).
Google Scholar
Mosconi, L. et al. Sex differences in Alzheimer risk: brain imaging of endocrine vs chronologic aging. Neurology 89, 1382–1390 (2017).
Google Scholar
Storsve, A. B. et al. Differential longitudinal changes in cortical thickness, surface area and volume across the adult life span: regions of accelerating and decelerating change. J. Neurosci. 34, 8488–8498 (2014).
Google Scholar
Mosconi, L. et al. Increased Alzheimer’s risk during the menopause transition: a 3-year longitudinal brain imaging study. PLoS ONE 13, e0207885 (2018).
Google Scholar
Mosconi, L. et al. Menopause impacts human brain structure, connectivity, energy metabolism and amyloid-beta deposition. Sci. Rep. 11, 10867 (2021).
Google Scholar
Nebel, R. A. et al. Understanding the impact of sex and gender in Alzheimer’s disease: a call to action. Alzheimers Dement. 14, 1171–1183 (2018).
Google Scholar
Altmann, A., Tian, L., Henderson, V. W., Greicius, M. D. & Alzheimer’s Disease Neuroimaging Initiative. Sex modifies the APOE-related risk of developing Alzheimer disease. Ann. Neurol. 75, 563–573 (2014).
Google Scholar
Naslavsky, M. S. et al. Global and local ancestry modulate APOE association with Alzheimer’s neuropathology and cognitive outcomes in an admixed sample. Mol. Psychiatry 27, 4800–4808 (2022).
Google Scholar
Hanamsagar, R. & Bilbo, S. D. Sex differences in neurodevelopmental and neurodegenerative disorders: focus on microglial function and neuroinflammation during development. J. Steroid Biochem. Mol. Biol. 160, 127–133 (2016).
Google Scholar
Forsyth, K. S., Jiwrajka, N., Lovell, C. D., Toothacre, N. E. & Anguera, M. C. The conneXion between sex and immune responses. Nat. Rev. Immunol. 24, 487–502 (2024).
Google Scholar
Casaletto, K. B. et al. Sex-specific effects of microglial activation on Alzheimer’s disease proteinopathy in older adults. Brain 145, 3536–3545 (2022).
Google Scholar
Congdon, E. E. Sex differences in autophagy contribute to female vulnerability in Alzheimer’s disease. Front. Neurosci. 12, 372 (2018).
Google Scholar
Xiang, J. et al. How does estrogen work on autophagy? Autophagy 15, 197–211 (2019).
Google Scholar
Lopez-Lee, C., Torres, E. R. S., Carling, G. & Gan, L. Mechanisms of sex differences in Alzheimer’s disease. Neuron 112, 1208–1221 (2024).
Google Scholar
Bolte, S. et al. Sex and gender in neurodevelopmental conditions. Nat. Rev. Neurol. 19, 136–159 (2023).
Google Scholar
Sandin, S. et al. Examining sex differences in autism heritability. JAMA Psychiatry 81, 673–680 (2024).
Google Scholar
Solomon, M. B. & Herman, J. P. Sex differences in psychopathology: of gonads, adrenals and mental illness. Physiol. Behav. 97, 250–258 (2009).
Google Scholar
Orben, A., Meier, A., Dalgleish, T. & Blakemore, S.-J. Mechanisms linking social media use to adolescent mental health vulnerability. Nat. Rev. Psychol. 3, 407–423 (2024).
Google Scholar
Office, I. L. World Employment Social Outlook 2017: Trends for Women (International Labour Organization, 2017).
Campos-Serna, J., Ronda-Perez, E., Artazcoz, L., Moen, B. E. & Benavides, F. G. Gender inequalities in occupational health related to the unequal distribution of working and employment conditions: a systematic review. Int. J. Equity Health 12, 57 (2013).
Google Scholar
Qiu, C. et al. Lifetime principal occupation and risk of Alzheimer’s disease in the Kungsholmen project. Am. J. Ind. Med. 43, 204–211 (2003).
Google Scholar
Gordon, S. B. et al. Respiratory risks from household air pollution in low and middle income countries. Lancet Respir. Med. 2, 823–860 (2014).
Google Scholar
UNICEF. Safely Managed Drinking Water—Thematic Report on Drinking Water (World Health Organization, 2017).
Crotti, R., Pal, K., Ratcheva, V. & Zahidi, S. Global Gender Gap Report 2021 (World Economic Forum, 2021).
Ibanez, A. et al. Dementia caregiving across Latin America and the Caribbean and brain health diplomacy. Lancet Healthy Longev. 2, e222–e231 (2021).
Google Scholar
Adedeji, I. A., Ogunniyi, A., Henderson, D. C. & Sam-Agudu, N. A. Experiences and practices of caregiving for older persons living with dementia in African countries: a qualitative scoping review. Dementia (London) 21, 995–1011 (2022).
Google Scholar
Xiong, C. et al. Sex and gender differences in caregiving burden experienced by family caregivers of persons with dementia: a systematic review. PLoS ONE 15, e0231848 (2020).
Google Scholar
Asuquo, E. F., Etowa, J. & Akpaan, M. Assessing women caregiving role to people living with HIV/AIDS in Nigeria, West Africa. Sage Open 10.1177/21582440176920 (2017).
Livingston, G. et al. Dementia prevention, intervention and care: 2020 report of the Lancet Commission. Lancet 396, 413–446 (2020).
Google Scholar
Blumberg, R. L. Gender Bias Textbooks: A Hidden Obstacle on the Road to Gender Equality in Education 1–54 (United Nations Educational, Scientific and Cultural Organization (UNESCO), 2007).
Islam, K. M. M. & Asadullah, M. N. Gender stereotypes and education: a comparative content analysis of Malaysian, Indonesian, Pakistani and Bangladeshi school textbooks. PLoS ONE 13, e0190807 (2018).
Google Scholar
Ragonese, C., Shand, T. & Barker, G. Masculine Norms and Men’s Health: Making the Connections (Promundo, 2018).
Rock, K., Valle, C. & Grabman, G. Physical inactivity among adolescents in Managua, Nicaragua: a cross-sectional study and legal analysis. J. Sport Dev. 1, 48–59 (2013).
Berkhout, S. G., Hashmi, S. & Pikula, A. Understanding gender inequity in brain health outcomes: missed stroke as a case study for intersectionality. Front. Glob. Womens Health 5, 1350294 (2024).
Google Scholar
Castro, A., Savage, V. & Kaufman, H. Assessing equitable care for Indigenous and Afrodescendant women in Latin America. Rev. Panam. Salud Publica 38, 96–109 (2015).
Google Scholar
Lanham, M. et al. ‘We’re going to leave you for last, because of how you are’: transgender women’s experiences of gender-based violence in healthcare, education and police encounters in Latin America and the Caribbean. Violence Gend. 6, 37–46 (2019).
Google Scholar
Muller, A. et al. Experience of and factors associated with violence against sexual and gender minorities in nine African countries: a cross-sectional study. BMC Public Health 21, 357 (2021).
Google Scholar
Metheny, N., Mkhize, S. P., Scott, D. & Hatcher, A. Violence victimization and depressive symptoms among a sub-sample of sexual and gender minority adults in a population-based South African study. J. Interpers. Violence 10.1177/08862605241243348 (2024).
Parekh, A., Fadiran, E. O., Uhl, K. & Throckmorton, D. C. Adverse effects in women: implications for drug development and regulatory policies. Expert Rev. Clin. Pharmacol. 4, 453–466 (2011).
Google Scholar
Beery, A. K. & Zucker, I. Sex bias in neuroscience and biomedical research. Neurosci. Biobehav. Rev. 35, 565–572 (2011).
Google Scholar
Mortberg, M. A., Vallabh, S. M. & Minikel, E. V. Disease stages and therapeutic hypotheses in two decades of neurodegenerative disease clinical trials. Sci. Rep. 12, 17708 (2022).
Google Scholar
Huque, H. et al. Could country-level factors explain sex differences in dementia incidence and prevalence? A systematic review and meta-analysis. J. Alzheimers Dis. 91, 1231–1241 (2023).
Google Scholar
Gonzalez-Gomez, R. et al. Educational disparities in brain health and dementia across Latin America and the United States. Alzheimers Dement. (2024).
Google Scholar
Frederiksen, H. et al. Sex-specific estrogen levels and reference intervals from infancy to late adulthood determined by LC-MS/MS. J. Clin. Endocrinol. Metab. 105, 754–768 (2020).
Google Scholar
Gill, D. et al. Age at menarche and time spent in education: a Mendelian randomization study. Behav. Genet. 45, 480–485 (2017).
Google Scholar
Cavanagh, S. E., Riegle-Crumb, C. & Crosnoe, R. Puberty and the education of girls. Soc. Psychol. Q 70, 186–198 (2007).
Google Scholar
Torvik, F. A. et al. Early puberty is associated with higher academic achievement in boys and girls and partially explains academic sex differences. J. Adolesc. Health 69, 503–510 (2021).
Google Scholar
Goering, M., Albright, M. G. & Mrug, S. The effects of pubertal timing on academic performance in adolescence and career success in adulthood: evidence from a 16-year longitudinal study. J. Youth Adolesc. 52, 1769–1787 (2023).
Google Scholar
Schmitt, M. L. et al. ‘It always gets pushed aside’: qualitative perspectives on puberty and menstruation education in U.S.A. schools. Front. Reprod. Health 4, 1018217 (2022).
Google Scholar
Patwardhan, V. et al. Differences across the lifespan between females and males in the top 20 causes of disease burden globally: a systematic analysis of the Global Burden of Disease Study 2021. Lancet Public Health 9, e282–e294 (2024).
Google Scholar
Livingston, J. M. et al. Influence of metabolic syndrome on cerebral perfusion and cognition. Neurobiol. Dis. 137, 104756 (2020).
Google Scholar
Mendoza-Caamal, E. C. et al. Metabolic syndrome in indigenous communities in Mexico: a descriptive and cross-sectional study. BMC Public Health 20, 339 (2020).
Google Scholar
Marquez-Sandoval, F. et al. The prevalence of metabolic syndrome in Latin America: a systematic review. Public Health Nutr. 14, 1702–1713 (2011).
Google Scholar
Bowo-Ngandji, A. et al. Prevalence of the metabolic syndrome in African populations: a systematic review and meta-analysis. PLoS ONE 18, e0289155 (2023).
Google Scholar
Santilli, F., D’Ardes, D., Guagnano, M. T. & Davi, G. Metabolic syndrome: sex-related cardiovascular risk and therapeutic approach. Curr. Med. Chem. 24, 2602–2627 (2017).
Google Scholar
George-Carey, R. et al. An estimate of the prevalence of dementia in Africa: a systematic analysis. J. Glob. Health 2, 020401 (2012).
Google Scholar
Jia, L. et al. Prevalence, risk factors, and management of dementia and mild cognitive impairment in adults aged 60 years or older in China: a cross-sectional study. Lancet Public Health 5, e661–e671 (2020).
Google Scholar
Connelly, P. J., Currie, G. & Delles, C. Sex differences in the prevalence, outcomes and management of hypertension. Curr. Hypertens. Rep. 24, 185–192 (2022).
Google Scholar
Azizi, Z., Alipour, P., Raparelli, V., Norris, C. M. & Pilote, L. The role of sex and gender in hypertension. J. Hum. Hypertens. 37, 589–595 (2023).
Google Scholar
Mukadam, N., Sommerlad, A., Huntley, J. & Livingston, G. Population attributable fractions for risk factors for dementia in low-income and middle-income countries: an analysis using cross-sectional survey data. Lancet Glob. Health 7, e596–e603 (2019).
Google Scholar
Kivipelto, M. et al. World-Wide FINGERS Network: a global approach to risk reduction and prevention of dementia. Alzheimers Dement. 16, 1078–1094 (2020).
Google Scholar
Arumugam, A. et al. Patient and public involvement in research: a review of practical resources for young investigators. BMC Rheumatol. 7, 2 (2023).
Google Scholar
Sanhueza, A. et al. The Every Woman Every Child initiative: supporting countries in Latin America and the Caribbean to reduce social inequalities in health. Int. J. Equity Health 21, 83 (2022).
Google Scholar
Heller, C. et al. The ENIGMA-Neuroendocrinology working group to bridge gaps in female mental health research. Nat. Mental Health 2, 348–350 (2024).
Google Scholar
Kelly, C. et al. Intersectionality, health equity and EDI: what’s the difference for health researchers? Int. J. Equity Health 21, 182 (2022).
Google Scholar
Alegria, M. & Cheng, M. Intersectional approaches are essential to identify the multiple sources of oppression. J. Psychopathol. Clin. Sci. 132, 590–593 (2023).
Google Scholar
Aguzzoli Peres, F. et al. Walking the talk for dementia: a unique immersive, embodied and multi-experiential initiative. Alzheimers Dement. 20, 2309–2322 (2024).
Google Scholar
Pape, M. et al. Sex contextualism in laboratory research: enhancing rigor and precision in the study of sex-related variables. Cell 187, 1316–1326 (2024).
Google Scholar
Mauvais-Jarvis, F. et al. Sex and gender: modifiers of health, disease and medicine. Lancet 396, 565–582 (2020).
Google Scholar
Scheim, A. I. et al. Health status of transgender people globally: a systematic review of research on disease burden and correlates. PLoS ONE 19, e0299373 (2024).
Google Scholar
Wang, Y. et al. A national transgender health survey from China assessing gender identity conversion practice, mental health, substance use and suicidality. Nat. Mental Health 1, 254–265 (2023).
Google Scholar
Tebbe, E. A. & Budge, S. L. Factors that drive mental health disparities and promote well-being in transgender and nonbinary people. Nat. Rev. Psychol. 1, 694–707 (2022).
Google Scholar
Toral-Rios, D. et al. SORL1 polymorphisms in Mexican patients with Alzheimeras disease. Genes 13, 587 (2022).
Google Scholar
Arboleda-Velasquez, J. F. et al. Resistance to autosomal dominant Alzheimer’s disease in an APOE3 Christchurch homozygote: a case report. Nat. Med. 25, 1680–1683 (2019).
Google Scholar
link