Structural inequality linked to brain volume and network dynamics in aging and dementia across the Americas
Open accessAbstract
Structural inequality, the uneven distribution of resources and opportunities, influences health outcomes. However, the biological embedding of structural inequality in aging and dementia, especially among underrepresented populations, is unclear. We examined the association between structural inequality (country-level and state-level Gini indices) and brain volume and connectivity in 2,135 healthy controls, and individuals with Alzheimer's disease and frontotemporal lobe degeneration from Latin America and the United States. Greater structural inequality was linked to reduced brain volume and connectivity, with stronger effects in Latin America, especially in the temporo-cerebellar, fronto-thalamic and hippocampal regions. In the United States, milder effects were observed in the insular-cingular and temporal areas. Results were more pronounced in Alzheimer's disease and were independent of age, sex, education, cognition and other confounding factors. The findings highlight the critical role of structural inequality in aging and dementia, emphasizing the biological embedding of macrosocial factors and the need for targeted interventions in underserved populations.
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Resilience is understudied in the majority world, including low-, middle-, and upper-middle-income countries, where socioeconomic inequities, environmental stressors, high disease burdens, and limited healthcare access create distinct health trajectories.
“While extensively studied in high-income countries, resilience remains underexplored in the majority world, including low-, middleand upper-middle-income countries—where socioeconomic inequities, environmental stressors, large burdens of infectious and noncommunicable diseases and limited healthcare access shape unique health trajectories6–15.”
From Resilience and brain health in global populations (2025) · cites this paper as [14]
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Experimental — accuracy not yet measuredWhen multiple disparity-related measures are included as predictors, smaller sex differences are observed.
“When multiple disparity-related measures are included as predictors, smaller sex differences are observed20,34.”
From The exposome of healthy and accelerated aging across 40 countries (2025) · cites this paper as [20]
Structural and environmental determinants have a substantial influence on aging beyond individual conditions.
“suggesting that structural and environmental determinants have a substantial influence on aging beyond individual conditions20,34.”
From The exposome of healthy and accelerated aging across 40 countries (2025) · cites this paper as [20]
Classical exposomal factors, including air pollution, structural socioeconomic inequality, gender inequalities, and migration, are associated with accelerated aging.
“Classical exposomal factors, including physical(air pollution) and social factors (structural socioeconomic inequality20,26,34, gender inequalities27, and migration33) are known to impact brain health and aging, which we demonstrate to also be associated with accelerated aging.”
From The exposome of healthy and accelerated aging across 40 countries (2025) · cites this paper as [20]
Aggregate-level metrics are not without bias from data sources, especially those of national relevance.
“As in other works2,20, aggregate-level metrics are not without bias from data sources, especially those of national relevance.”
From The exposome of healthy and accelerated aging across 40 countries (2025) · cites this paper as [20]
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- Authors
- Legaz, A., Altschuler, F., Gonzalez-Gomez, R., Hernández, H., Baez, S., Migeot, J., Fittipaldi, S., Medel, V., Maito, M. A., Godoy, M. E., Moguilner, S., Cruzat, J., Coronel-Oliveros, C., Tagliazuchi, E., Santamaria Garcia, H., Farina, F. R., Reyes, P., Javandel, S., García, A. M., Deleglise, Á., Matallana, D. L., Avila-Funes, J. A., Slachevsky, A., Behrens, M. I., Custodio, N., Trujillo-Llano, C., Cardona, J. F., Barttfeld, P., Brusco, I. L., Bruno, M. A., Sosa Ortiz, A. L., Pina-Escudero, S. D., Takada, L. T., França Resende, E. D. P., Possin, K. L., Okada de Oliveira, M., Hu, K., Lopera, F., Lawlor, B., Valcour, V., Yokoyama, J. S., Miller, B., & Ibañez, A.
- Affiliations
- Adolfo Ibáñez University (CL)
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- Trinity College Dublin (IE)
- University of California, San Francisco (US)
- University of San Andrés (AR)
- Harvard University (US)
- Pontificia Universidad Javeriana (CO)
- Universidad de Santiago de Chile (CL)
- Universidad del Desarrollo (CL)
- Instituto Peruano de Neurociencias (PE)
- Universidad del Valle (CO)
- Universidad de Buenos Aires (AR)
- Universidade de São Paulo (BR)
- Universidad de Antioquia (CO)
- ORCID
- Legaz, Agustina
- Altschuler, Florencia
- Gonzalez-Gomez, Raul
- Hernández, Hernán
- Migeot, Joaquín
- Fittipaldi, Sol
- Medel, Vicente
- Maito, Marcelo Adrián
- Moguilner, Sebastián
- Cruzat, Josephine
- Farina, Francesca R.
- Reyes, Pablo
- García, Adolfo M.
- Deleglise, Álvaro
- Matallana, Diana L.
- Slachevsky, Andrea
- Behrens, María I.
- Custodio, Nilton
- Cardona, Juan F.
- Barttfeld, Pablo
- Sosa Ortiz, Ana L.
- Pina-Escudero, Stefanie D.
- Takada, Leonel T.
- Possin, Katherine L.
- Hu, Kun
- Lopera, Francisco
- Lawlor, Brian
- Valcour, Victor
- Yokoyama, Jennifer S.
- Miller, Bruce
- Ibañez, Agustin
- Venue
- Nature Aging
- Published
- 2024-12-27
- Volume
- 5
- Issue
- 2
- Pages
- 259-274
- ISSN
- 2662-8465 (ISSN-L)
- PMC
- PMC12010405
- OpenAlex
- W4405829122
- Cited by
- 36
- References
- 48
- Citations by year
- 2026: 12 · 2025: 23 · 2024: 1
- FWCI
- 10.54
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature Aging (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Conicet (submittedVersion, cc-by-nc-sa)
- Funders
- Alzheimer's Association (20-725707, SG-20- 725707)
- Agencia Nacional de Investigación y Desarrollo (15150012, ANID/FONDAP/15150012, 1210195, 1210176, 1220995)
- National Institutes of Health (15150012)
- National Institute on Aging (AG057234, R01 AG21051, 1210176, 1210195, R01AG057234, P01AG019724, R01AG082056, R01AG075775, R01AG083799)
- Fogarty International Center
- Fondo de Financiamiento de Centros de Investigación en Áreas Prioritarias (15150012)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Social Sciences › Health › Health disparities and outcomes
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- structural inequality, economic inequality, Gini coefficient, brain volume, brain connectivity, Alzheimer's disease, frontotemporal lobar degeneration, dementia, aging, hippocampus, Latin America, United States
- MeSH terms
- Aged, Aged, 80 and over, Aging, Alzheimer Disease, Brain, Dementia, Female, Humans, Latin America, Magnetic Resonance Imaging, Male, Middle Aged, Organ Size, Socioeconomic Factors, United States
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