Resilience and brain health in global populations

Abstract

Resilience is a multifaceted concept that spans biological, psychological and social domains, and is critical for population health—particularly brain health. While most existing research originates from the global north, there is an urgent need to explore resilience in the majority world settings, where unique biological, exposomal, economic and sociocultural factors shape health. In this Review, we highlight resilience as a key modifier of brain health outcomes. We explore the biological correlates of resilience and the influence of the exposome. We propose future synergistic integrations of exposome, cultural reserve, community resilience, allostasis and whole-body health principles to promote an inclusive perspective in diverse settings. This approach is particularly relevant for majority world contexts, where resource constraints and cultural diversity demand adaptive, scalable and context-sensitive strategies. We discuss measurement approaches and operationalization strategies and, finally, we identify key priorities for future research and policy strategies, with an emphasis on local relevance, equity and sustainability.

Introduction

Resilience is the dynamic ability to adapt and thrive in adversity, encompassing biological, psychological and social dimensions. In the context of lifespan and brain health, resilience has a critical role in mitigating the impacts of aging, stress and disease, promoting cognitive vitality throughout life^1–5. 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 trajectories^6–15.

Resilience in the majority world is often framed through culturally grounded concepts. In African cultures, ‘ukuphumelela’—meaning to flourish or ‘become victorious’ in the face of adversity—reflects the Ubuntu philosophy, emphasizing collective resilience, mutual support and shared responsibility over individual success¹⁶. In Latin America, the concept of familismo (family cohesion) highlights the protective role of strong familial bonds¹⁷, and similarly in South Asia, communal coping strategies serve as integral mechanisms for navigating adversity¹⁸. These cultural expressions of resilience denote the significance of social connectedness, intergenerational knowledge transfer and collective well-being as essential components of adaptive capacity.

Beyond individuals and communities, resilience also extends to systemic and societal levels. The World Health Organization (WHO) and the United Nations Sustainable Development Goals highlight system-level resilience—the ability of societies to absorb, adapt and transform in response to crises such as economic downturns, pandemics and environmental challenges¹⁹. The Ebola outbreak in West Africa exemplified how resilient health systems are critical for reducing inequities and sustaining essential functions. In such resource-limited settings, strengthening healthcare infrastructure and social safety nets is imperative to withstand intersecting challenges such as poverty, inequality and disease burdens²⁰.

Despite gaps in the current literature, the majority world offers innovative resilience models, including ecological approaches to brain and whole-body health²¹, frameworks encompassing the exposome (the cumulative physical and social exposures interacting with biological systems^13,21–23), participatory budgeting²⁴ and community-led cooperative finance models^25,26—many of which remain underrepresented in global discourse. The urgency to bridge this gap is further intensified by rising neurological and psychiatric disorders, climate-related stressors and the lingering effects of COVID-19, which disproportionately impact lower-resource environments^27,28. Addressing these challenges demands an inclusive approach integrating diverse cultural, environmental and biological factors into resilience frameworks.

In this narrative Review, we explore resilience as a critical determinant of brain health, particularly in the majority world. We integrate concepts of cognitive reserve, brain reserve and resilience, while examining biological mechanisms of stress response, adaptation and cultural variations. Special attention is given to the influence of sex, gender, age and race/ethnicity in shaping resilience across the lifespan, considering both sociocultural expectations and biological differences. Additionally, we address challenges in measuring resilience globally, advocating for culturally sensitive tools and methodologies to more accurately capture its complexity. Drawing on the existing literature and our collective expertise, we highlight strategies for boosting resilience that show promise in terms of outcomes, sustainability and scalability. We argue for the crucial need to systematically evaluate resilience across diverse populations by incorporating environmental, biological, cognitive, psychological and social dimensions (Fig. 1). Finally, we outline future research priorities and policy directions, advocating for precision health strategies and culturally grounded interventions to promote resilience globally.

Fig. 1.

Resilience model and factors. a, Resilience is divided into four domains— biological, cognitive, psychological and social—surrounded by an environmental component. The Biological domain addresses brain reserve, multi-omics, and genetics and epigenetics, reflecting the underlying physical basis for adaptation. The Cognitive domain includes cognitive stimulation, occupational complexity and educational attainment, highlighting factors that enhance learning, problem-solving and neural plasticity. The Psychological domain focuses on emotional self-regulation, coping strategies, self-awareness and metacognition, emphasizing mental and emotional fortitude. The Social domain underscores social connection, intergenerational knowledge and family bonds, offering support and collective resources to reinforce resilience. The Environmental component incorporates exposome elements like climate change, pollution, economic factors and community living arrangements, shaping aggregate and individual-level resilience. This model illustrates how each domain interacts with contextual influences, underscoring the multidimensional nature of resilience. b, Resilience unfolds across the lifespan, from early-life factors (top) like genes, learning, socialization and nutrition being most influential in childhood. Certain processes such as self-regulation remain relevant throughout the life course. Later-life factors (bottom) like brain reserve, cognitive health and social activity gain importance over time, reflecting the cumulative and shifting nature of resilience. c, The three spider plots illustrate how resilience emerges from diverse sources. Each example depicts how resilience can arise from various domains, forming a cumulative defense against adversity to maintain well-being across the lifespan. Figure partially created with BioRender.com.

Defining resilience across levels

Partial scientific consensus exists on the definitions and applications of resilience in global brain health research³. For this Review, we build on the notion that resilience in brain health²⁹ is shaped by multiple interrelated constructs including biological (brain plasticity, compensation, allostasis) psychological (cognitive reserve, emotional self-regulation) and social (familial, socioeconomic and cultural protective factors) levels^3,30,31. These levels are interdependent, and their interactions help explain individual differences in aging and neurological outcomes.

At the biological level, resilience is the capacity of the brain to adapt to aging and pathology through mechanisms such as neuroplasticity, compensation, reserve and allostasis, allowing sustained function despite biological challenges. In the context of aging⁴, it refers to the brain’s capacity to cope with aging-related changes and pathological processes through interconnected mechanisms³². These integrative and dynamic processes buffer against decline by leveraging neural reserve, brain reserve and allostasis mechanisms (the body’s process of maintaining stability via adaptive physiological and behavioral responses to stress³³; see below for more details). Within this framework, compensation involves recruiting alternative neural pathways, while neuroplasticity enables the brain to reorganize and adapt. The principle of degeneracy—different structures performing the same function—is widespread through diverse neural pathways³⁴. Brain maintenance also extends these concepts by emphasizing mechanisms that prevent or delay pathology onset through environmental influences³⁵.

At the psychological level, resilience refers to an individual’s ability to maintain or regain emotional and cognitive stability in the face of adversity. Emotional resilience is supported by the brain’s affective systems and involves traits such as optimism, emotional self-regulation, metacognition and adaptability; and it is also shaped by cultural constructs¹⁷. Cognitive resilience depends on cognitive reserve³² to cope with damage through preexisting strategies influenced by factors such as education, occupational complexity and cognitively stimulating activities^3,10,30,36.

At the social level, resilience involves the capacity of communities and social networks to support individuals in overcoming adversity through shared resources, cultural practices and mutual support systems. Resilience can emerge from strong community networks, where community-driven and culturally anchored practices foster collective well-being through shared resources to bolster reserve even without formal education^17,18. For instance, community-driven initiatives such as cooperative health insurance models serve as ‘social reserves’, mitigating economic and health-related adversities³⁷, and illustrate the interplay between communal support and individual resilience. Studies in the global north often emphasize individual traits and adaptability³⁸. Although resilience research in the global south is limited, the region’s collectivist ethos offers a unique opportunity to explore how community-driven resources shape resilience. Culturally embedded strengths, such as strong kinship ties, traditional knowledge systems and community-led social protection programs³⁹, offer resilience resources. Many indigenous communities conceptualize health holistically, integrating physical, mental, emotional and spiritual well-being^2,40. Economic constraints in lowand middle-income countries (LMICs) often give rise to adaptive strategies rooted in resourcefulness, creativity and traditional knowledge, which collectively serve as mechanisms of resilience. Examples include participatory budgeting initiatives in Brazil, which empower communities to influence public resource allocation, ensuring equitable access to essential social services⁴¹, as well as community-based health insurance schemes in Sub-Saharan Africa, which pool risks to enhance healthcare accessibility⁴².

Studying resilience across these levels allows us to understand the interactions across multiple protective factors and risk factors. For instance, pollution, migration, urbanization and structural inequalities can induce accelerated aging²³ and disrupt reserve-building processes in many regions. Adverse exposomes²³, such as poor nutrition, pollution and infectious disease burden, further exacerbate biological vulnerabilities. Severe environmental stressors, including droughts, floods and climate-driven displacement, also threaten community resilience by escalating biological and psychological vulnerability. Limited healthcare and technological resources can restrict the scalability and sustainability of interventions, and entrenched socioeconomic inequities may overwhelm community-driven efforts despite their inherent strength. Understanding the biological, psychological and social foundations of resilience in diverse contexts is essential to fully realize its potential in promoting brain health.

The foundational mechanisms of resilience

This section explores the mechanisms that underlie resilience, from genetic and epigenetic regulation to neuroplasticity, allostatic interoception and nutrition. It also highlights how these processes are influenced by multiple factors such as protective genetic variants, environmental stressors and cultural practices (Fig. 1a and Box 1), offering a multidimensional perspective on the foundations of resilience.

BOX 1. Examples of genetic, environmental and community-based resilience Genetic resilience in Alzheimer’s disease.

Rare genetic mutations can confer extraordinary resilience, such as a Colombian man carrying the PSEN1-p.Glu280Ala mutation—typically associated with dementia by the mid-40s—who remained cognitively unimpaired until age ⁶⁷ years¹⁵⁸. Despite exhibiting a high amyloid plaque burden, his brain showed remarkably low tau pathology. He was found to carry a rare RELN variant (p.His3447Arg, ‘COLBOS’) that enhances Reelin–DAB1 signaling and reduces tau phosphorylation, mitigating downstream neurodegeneration. Another similar case homozygous for the APOE3 ‘Christchurch’ variant (p.Arg136Ser), enables genetic resilience by alleviating the effects of PSEN1-p.Glu280Ala, a mutation strongly linked to early-onset Alzheimer’s disease. Carriers exhibit delayed cognitive decline, likely due to reduced APOE binding to heparan sulfate proteoglycans, limiting tau pathology and enhancing vascular integrity¹⁵⁹. Together, these cases illustrate how specific protective alleles can counteract Alzheimer’s pathology at the molecular level, highlighting the potential of genetic resilience mechanisms.

Exposome and resilience in delayed aging. Resilience can emerge from supportive environments. A global analysis of over 160,000 adults introduced an aging clock that integrates behavioral and biological measures to estimate protective factors and risk factors for dementia²³. Individuals exposed to less adverse exposomes— characterized by cleaner air, higher educational access, stronger democratic institutions and lower social and gender inequality— consistently showed delayed biological and behavioral aging compared with their chronological age. These factors synergistically promoted resilience. In contrast, accelerated aging was observed in people from regions marked by political instability, economic disparity and poor public health infrastructure. Environmental changes aimed at reducing chronic stress and pollution may promote healthier behaviors and enhance cognitive reserve through education and equity—collectively slowing biological and behavioral decline.

Community resilience in the context of pathological aging. Brain Resilience Kenya (https://www.aku.edu/bmi/research/Pages/brk.aspx/) is a just-launched study that may provide valuable insights from older adults facing chronic stressors in socioeconomically diverse regions within Kenya, East Africa. Through an ethnographic study of informal settlements (Kibera and Mathare) and an urban area (Parklands), the project will explore how individuals adapt to financial pressure, interpersonal conflicts, caregiving burdens, work–life balance challenges and marital strain, all recognized as accelerants of pathological aging. These assessments will be combined with multi-omics, neuroimaging and continuous behavioral sensing with wearable devices. Preliminary findings (unpublished) highlight that resilience is strongly mediated by family support, social connections and religious or spiritual engagement. These social and cultural resources promoted coping, emotional recovery and psychological resilience. However, systemic challenges threaten the sustainability of these resilience strategies. The BRK study highlights the urgent need for culturally adapted resilience measures and interventions that leverage existing community strengths while addressing broader structural vulnerabilities to promote healthy brain aging in African contexts. Together, these cases underscore complementary pathways highlighting the multidimensional nature of resilience.

Biological and exposome contributions

Resilience is influenced by genetic and environmental interactions shaping neural development, stress regulation and neuroplasticity. Genome-wide association studies have identified multiple genetic loci associated with resilience, suggesting a polygenic basis⁴³. Key genetic variants such as the Val66Met polymorphism in the BDNF gene affect neuroplasticity, with Val carriers showing greater adaptability under stress, while Met carriers exhibit reduced plasticity and heightened vulnerability⁴⁴. Examples of mutations that confer protection against dementia and Alzheimer’s disease are described in Box 1. Other resilience-related polymorphisms include 5-HTTLPR (a polymorphism in the promoter region of the SLC6A4 gene), which influences serotonin regulation, with the long allele linked to improved emotional regulation⁴⁵. The FKBP5 protein modulates hypothalamic–pituitary–adrenal (HPA) axis sensitivity, influencing cortisol release in response to stress. Specific FKBP5 variants promote adaptive stress responses, characterized by proportional cortisol secretion and efficient downregulation after exposure, preventing excessive HPA axis activation^46,47. Gene–environment interactions, which are crucial to the development of therapies and interventions, are the subject of extensive research in the global south⁴⁸. For instance, low-activity MAOA-L variants (the low-activity allele of a promoter polymorphism in the MAOA gene) of the monoamine oxidase A enzyme increase stress vulnerability⁴⁹, although supportive environments can mitigate these effects.

Epigenomics explores how environmental factors, for example, trauma, diet and social interactions, influence gene expression via mechanisms like DNA methylation, histone modification and chromatin remodeling⁵⁰. NR3C1 methylation affects glucocorticoid receptor expression, alters HPA axis regulation and increases stress susceptibility during early developmental stages⁵¹. Epigenetic aging clocks, such as DNA methylation-based measures, indicate that early-life adversity accelerates aging, leading to poorer long-term health⁵². Evidence from the CARDIA study links childhood adversity to accelerated epigenetic aging and increased cardiovascular and cognitive risks in midlife⁵³. Further insights come from downstream transcriptomics, proteomics and metabolomics, which reveal resilience-related molecular pathways. Transcriptomics studies show that resilience involves distinct gene expression patterns, such as increased BDNF mRNA expression following stress exposure, enhancing neuroplasticity⁴⁴. Proteomics identifies increased levels of stress-recovery proteins, including heat shock proteins and synapsin I, in resilient individuals⁵⁴. Metabolomics highlights the role of neurotransmitter metabolites such as glutamate, GABA (γ-aminobutyric acid) and dopamine derivatives in stress adaptation⁵⁵; for example, increased glutamate turnover is linked to neuroplasticity, whereas balanced GABAergic signaling aids stress recovery^55,56.

Biological mechanisms are embedded in the exposome^21–23. Positive exposures such as supportive relationships, education, enrichment activities and proper nutrition enhance resilience through adaptive epigenetic modifications and physiological responses^57–62. They bolster cognitive and brain reserves, strengthen allostatic interoception and facilitate effective stress regulation, manifesting as improved self-regulation, adaptive coping and emotional stability⁶². Conversely, adverse conditions such as pollution, heatwaves or social isolation contribute to maladaptive epigenetic changes, increased allostatic load, cognitive decline and diminished resilience^{21,22,63–67}. This results in heightened stress reactivity, reduced coping capacity and emotional dysregulation, amplifying health risks and vulnerability across the lifespan.

Allostatic interoception and adaptation to environmental demands

Allostasis³³ is linked to interoception, which is the brain’s ability to sense and regulate internal bodily states^63–67. Allostatic interoception (Fig. 2a) is the brain’s ability to anticipate and regulate bodily responses to environmental demands and involves neural, neuroendocrine and immune mechanisms that enable adaptation^63–68. Chronic stress exposure leads to allostatic load. In this state, chronic stress overwhelms the body’s adaptive capacity, causing wear and tear on physiological systems and increasing the risk of cardiovascular disease, metabolic disorders and cognitive decline^60,69,70. Socioeconomic hardships, pollution and psychosocial stressors elevate allostatic load, highlighting the interaction between environmental and biological stress regulation. Allostatic interoception efficiently fosters resilience by dynamically adjusting physiological parameters such as heart rate, hormone secretion and metabolism, thereby optimizing responses to stress⁶⁰. For example, chronic HPA axis activation impairs memory, yet adaptive coping strategies and social support modulate stress responses, reducing allostatic load and enhancing resilience^30,63,64. The interplay between multimodal resilience and allostatic interoception offers a new framework for understanding brain health (Fig. 2b,c). When adaptive, this process fosters resilience by efficiently managing stress. However, maladaptive interoception may result in increased allostatic load and subsequent health deterioration. These concepts have been applied to aging research^65–67,71. Alzheimer’s disease biomarkers, including abnormal amyloid-β protein (1–42) levels and increased levels of cortisol (indicative of disrupted allostasis) predicted faster clinical progression to Alzheimer’s disease⁶⁰. However, high cognitive and brain reserve proxies—such as education and larger intracranial volume—modified this risk by delaying symptom onset despite biomarker abnormalities^3,30. This underscores the protective role of reserve in stress response regulation.

Fig. 2.

The allostatic interoceptive system and brain–body–environment loops. a, Key allostatic interoceptive brain regions—including the insula, amygdala, hippocampus, thalamus and cingulate cortex—generate predictions about bodily needs and adjust responses through descending pathways to multiple organ systems. These predictions modulate parameters such as heart rate, respiratory rate, metabolic activity and muscle tone. Prediction error signal mismatches between expected and actual states, requiring energy expenditure to restore balance. b, Favorable social exposome and determinants of health (SDHs)—such as financial security, access to green areas, safety and supportive relationships—facilitate mild stress exposure and promote adaptive responses (top). These conditions allow for efficient stress regulation and energy allocation, preserving physiological homeostasis (middle). Stress responses remain within a healthy range, with cumulative hormetic effects that enhance resilience across time. The energy expended on the stress response closely matches the adaptive energy expenditure needed to cope with stressors (bottom), ensuring metabolic efficiency. c, Adverse social exposome and SDHs—including financial stress, pollution, insecurity and violence—lead to chronic stress exposure and allostatic overload (top). Persistent stressor accumulation results in dysregulated physiological responses (middle), increased baseline stress response and increased energy expenditure. This leads to two maladaptive trajectories (bottom): type 1 allostatic overload (hyperactivation of stress systems) and type 2 allostatic overload (blunted reactivity and reduced baseline functioning). Both patterns reflect a breakdown into efficient prediction and regulation. Figure partially created with BioRender.com

Excessive reliance on physiological resilience mechanisms can lead to allostatic overload. Unlike static models like the diathesis– stress framework, which views resilience as a fixed trait triggered by stressors⁷², allostasis emphasizes the flexibility and context-dependent nature of physiological responses. This dynamic perspective makes allostasis particularly relevant in diverse settings where environmental stressors vary widely. For example, individuals with well-balanced cortisol responses to stress demonstrate greater resilience as their physiological systems return to baseline efficiently. However, in cultural contexts where resilience may be centered on adaptation and coping, the emphasis on enduring adversity may create social expectations that drive emotional suppression, potentially leading to chronic stress⁷³. Systemic inequalities, food insecurity and poverty can lead to type 1 allostatic load (where energy demands exceed reserves)³³ or type 2 allostatic load (where excessive energy intake disrupts homeostasis)³³ (Fig. 2c), both of which contribute to cardiovascular disease, metabolic disorders and mental health conditions^31,60,69,70. In this light, allostasis emerges as a comprehensive model for assessing resilience, as it integrates physiological, psychological and environmental factors.

Hormesis and cultural patterns of resilience

A crucial component of allostasis is hormesis, a biphasic response where mild stress exposure enhances physiological defenses, fostering resilience^74,75. This form of adaptive priming, potentially mediated by allostatic interoception, primes the body to manage future stressors more effectively. However, excessive or chronic stress exposure disrupts this balance, leading to allostatic overload and negative health outcomes^76,77. Patterns of hormetic priming differ between regions. In the global north, hormetic priming is often intentional, achieved through structured activities such as exercise, intermittent fasting and controlled cold exposure, designed to proactively enhance resilience^78–80. In the global south, hormetic priming is often embedded in daily life, with high physical activity from manual labor, agricultural work and natural fasting (due to food scarcity) mirroring hormetic adaptations that promote resilience^81,82. However, urbanization and Westernized lifestyles (for example, changes in diet and increased sedentary behavior) are eroding these protective behaviors, contributing to rising chronic disease burdens^83,84.

Even if hormesis may foster resilience, chronic environmental stressors in low-resource settings, such as poverty, pollution and healthcare inaccessibility, may disrupt allostatic interoception (Fig. 2c,d). However, culturally ingrained coping mechanisms, such as strong social networks and community-driven social protection systems, often mitigate these effects^85,86. In many African, Latin American and South Asian societies, communal living and strong social networks offer emotional and practical support, potentially enhancing resilience. Traditional practices, including intergenerational households and collective caregiving, further promote community-driven social protection, buffering against chronic stress.

The impact of malnutrition on brain health

Multisystem biomarkers of allostatic load including cortisol (neuroendocrine system), blood pressure (cardiovascular), hemoglobin A1c (metabolic) and C-reactive protein (immune) offer insights into the physiological cost of resilience, particularly in communities where resilience is pushed to its limits. A key example is malnutrition, which has a substantial impact on brain function, neuroplasticity and stress regulation⁸⁷. Prevalent in LMICs, nutrient deficiencies can exacerbate allostatic overload by heightening cortisol levels, impairing cognitive function and increasing stress vulnerability⁸⁸. For instance, maternal undernutrition induces epigenetic modifications that perpetuate intergenerational cycles of adversity. Methylation of the NR3C1 gene, which encodes the glucocorticoid receptor, has been linked to impaired stress regulation, increasing susceptibility to chronic stress in individuals and their offspring^89,90.

Additionally, fetal growth has a more enduring effect on late-life brain structure than changes occurring later in life, highlighting the critical role of prenatal and perinatal health in shaping brain reserve⁹¹. Thus, reducing teratogenic exposures, such as those related to maternal malnutrition, infections and environmental toxins, and addressing perinatal health disparities, can improve brain reserve across the lifespan. Low birth weight, often a consequence of maternal malnutrition, is associated with reduced cortical surface area and brain volume in offspring development⁹², reinforcing the importance of prenatal and perinatal care in promoting resilience⁹¹. These unique aspects of resilience in majority world contexts, that is, nutritional deficiencies and food insecurity, underscore the complex interplay of genetic, environmental and dietary influences.

Nutrient-sensing pathways (for example, mTOR and AMPK) have a critical role in regulating resilience under chronic stress and malnutrition⁹³. mTOR, which integrates nutrient signals like amino acids and glucose, is crucial for synaptic growth and adaptive plasticity; its suppression in undernourished populations limits the brain’s capacity to adapt⁹⁴. Additionally, polymorphisms in FADS2 (encoding fatty acid desaturase 2) influence omega-3 fatty acid metabolism, impacting synaptic plasticity and stress response mechanisms⁹⁵. Populations with genetic variations in FADS2 may require higher dietary intake of omega-3 fatty acids to maintain adequate levels of eicosapentaenoic acid and docosahexaenoic acid, which are critical for neurodevelopment and resilience under chronic stress⁹⁶. Similarly, polymorphisms in MTHFR, which affect folate metabolism, influence neural development and psychological resilience⁹⁷. Adequate folate intake through fortification or supplementation can mitigate these risks, emphasizing the need to integrate genetic insights into nutritional strategies. Adequate nutrition is essential for optimal brain development, function and resilience, yet malnutrition remains a major challenge in many LMICs due to poverty, food insecurity and limited diet diversity. Micronutrient deficiencies in omega-3 fatty acids, iron, zinc, iodine and vitamins A, B12 and D are linked to reduced brain volume, impaired myelination and reduced neuroplasticity, leading to learning difficulties, lower IQ scores and decreased cognitive resilience⁹⁸. Poor nutritional status also disrupts the HPA axis, resulting in heightened cortisol production, increased allostatic load and diminished resilience to stress⁶⁰. To mitigate these effects, targeted nutritional interventions, perinatal care improvements and culturally informed stress-reduction strategies are crucial in reducing allostatic load and enhancing resilience in vulnerable populations. Addressing these challenges requires a multisystemic approach that integrates public health, nutrition and precision medicine to improve outcomes for individuals in the majority world settings.

The role of sex, gender, ethnicity and age

Sex, gender, ethnicity, and age all shape resilience via their influence on responses to stress^7,99–106. A future precision brain health¹⁰⁷ agenda must account for these dynamics to develop tailored interventions that enhance resilience across diverse populations^104–106. Biological sex plays a crucial role in neurological susceptibility and resilience. The X chromosome, which represents 5% of the genome, is highly expressed in the brain. Females, in comparison with males, benefit more from additional expression of genes escaping X-inactivation¹⁰⁸, associated with slower cognitive decline and lower mortality rates across species^108–110. However, despite this protective effect, women face a higher lifetime risk of Alzheimer’s disease¹¹¹. Hormonal variations further shape resilience. Estrogen enhances synaptic plasticity and neuronal survival99, while sex-specific genetic factors influence stress adaptation and resilience. For example, the FKBP51 gene modulates stress responses differently in male and female neurons, impacting resilience¹⁰³. Additionally, hypertensive disorders of pregnancy—such as preeclampsia—increase the risk of later-life brain atrophy and cognitive decline^104,112,113, with disparities in incidence across global regions. The highest rates are observed in South Asia and sub-Saharan Africa, and the lowest in Australasia, Oceania and Central Europe¹¹⁴.

Beyond biology, gender roles influence resilience strategies, although research on gender identity and brain health remains scarce. Due to disproportionate exposure to social inequalities and caregiving roles, women are at increased risk of chronic stress¹¹⁵; however, caregiving can also enhance resilience in some contexts, through the development of strong social support networks and engagement in collective practices¹¹⁶. Communal activities, shared caregiving responsibilities and social cohesion can provide emotional support and practical assistance, buffering stress-related risks¹⁰⁰. Conversely, men often face cultural pressures to be providers and protectors, potentially limiting their willingness to seek help and negatively affecting resilience mechanisms. Transgender and gender-diverse individuals face distinct brain health challenges, especially in low-resource settings due to stigma, discrimination and limited access to care, which can increase allostatic load⁷. Yet, research on their resilience remains limited. Inclusive, culturally sensitive approaches are needed to address these gaps and move beyond binary frameworks in resilience research. Race, often misconstrued as a biological construct,¹¹⁷ has nuanced implications on resilience, as it intersects with gender and social determinants of health. Disparities in education, healthcare access and nutrition impact cognitive outcomes, while structural inequities and chronic discrimination contribute to increased allostatic load and cognitive decline in marginalized populations¹¹⁸. Despite these challenges, cultural strengths within racial and ethnic groups foster resilience. African and Afro-diasporic communities (also in Latinos and Asian groups) benefit from multigenerational living arrangements and communal caregiving models that support cognitive well-being². Addressing gendered and racial factors is critical for designing effective interventions that build on cultural strengths while challenging harmful norms.

Resilience varies across the lifespan¹¹⁹ (Fig. 1b), shaped by developmental transitions, environmental exposures and sociocultural contexts. In early life, the developing brain is particularly susceptible to environmental influences¹²⁰. Adverse experiences such as poverty, malnutrition and violence can alter stress regulation and increase allostatic load, leading to long-term cognitive and mental health risks^{101,121–124}. However, early interventions, such as enriched learning environments and strong caregiving, can foster cognitive reserve and resilience. Culturally appropriate programs that engage families and communities have effectively promoted brain health¹⁰². Work-related stress, caregiving responsibilities and social roles shape resilience during adulthood. Gender and cultural expectations continue to influence resilience, underscoring the need for interventions considering these contextual factors. For older adults, aging is associated with reduced neuroplasticity and increased vulnerability to neurodegeneration. However, lifestyle factors such as physical activity, cognitive engagement and social participation promote resilience⁹⁸. Cultural perceptions of aging also play a role. For instance, older people in some societies hold respected positions that provide purpose and support, reinforcing their psychological and cognitive resilience.

An intersectional approach is critical for tailoring future interventions that address both the challenges and strengths associated with diverse identities. Embedding culturally grounded elements such as storytelling, intergenerational caregiving or language-specific learning in early childhood education may help build cognitive reserve in underserved communities. In adulthood, physical activity and dietary strategies that align with traditional practices (for example, community walking groups or culturally familiar foods) may promote engagement and resilience. Programs for older adults can enhance purpose and social integration by respecting conventional roles, such as elder mentorship. Future research should explore how intersecting factors like sex, gender, race, age and culture interact to shape resilience, guiding equity-informed brain health interventions.

Measuring and operationalizing resilience in global settings

Assessing resilience across diverse cultural contexts requires reliable, culturally appropriate measurement tools. We present a comparative overview of existing frameworks (summarized in Table 1), including traditional resilience scales, the WHO intrinsic capacity framework, culturally adapted tools, computational biological models and wearable technologies.

Table 1:

Comparison of different frameworks for assessing resilience

Framework	Domains	Cultural Adaptability	Methodology	Applicability in Majority World Settings	Advantages	Limitations
Traditional Resilience Scales (i.e.,136)	Psychological traits such as personal competence, acceptance of change, and secure relationships.	Limited, often based on Western individualistic concepts.	Self-report questionnaires with standardized items.	Low applicability without adaptation.	Easy to administer; well-validated in specific contexts.	May not capture culturally specific expressions of resilience; potential language barriers.
WHO’s Intrinsic Capacity Framework (i.e.,135)	Physical and mental capacities, including cognition, mobility, vitality, sensory functions, and psychological wellbeing.	High, focuses on functional abilities over culturally specific behaviors.	Holistic assessment combining physical exams, cognitive tests, and self-reports.	High applicability with contextualization.	Comprehensive; adaptable to various cultural contexts; emphasizes functionality.	Requires resources for comprehensive assessment; may need adaptation for specific settings.
Culturally Adapted Tools (i.e.,138)	Context-specific factors like community support, spiritual beliefs, family cohesion, and cultural practices.	High, designed, or adapted for specific cultural contexts.	Mixed methods including interviews, focus groups, and culturally relevant questionnaires.	High applicability when adequately adapted.	Captures local expressions of resilience; increases relevance and accuracy.	Time-consuming to develop and validate; may lack standardization across contexts.
Computational Biological Frameworks (i.e., 69,72,116)	Biological aging markers, physiological responses to stress, systemic adaptation mechanisms.	Moderate, biological processes are exposomedependent.	Biomarker analysis, physiological measurements, computational modeling.	Moderate/Variable applicability depending on resources.	Provides objective data; can detect physiological signs of resilience or vulnerability.	Requires technical expertise and equipment; may not be accessible in low-resource settings.
Wearable Technologies (i.e.,155)	Real-time physiological parameters such as heart rate variability, sleep patterns, activity levels.	Moderate, technology use may vary culturally; data interpretation requires context.	Use of wearable devices to collect continuous physiological data.	Increasing applicability with mobile technology proliferation.	Offers real-time monitoring; potential for early intervention.	Privacy concerns; data security issues; require user engagement and technological infrastructure.

Traditional resilience scales

These tools assess psychological traits such as personal competence, acceptance of change and secure relationships¹²⁵. While they are easy to administer and validate in specific contexts, their applicability in majority world settings is limited. Traditional scales, such as the Connor–Davidson resilience scale¹²⁶, were developed in high-income countries and emphasize Western constructs like self-efficacy and individual coping¹²⁵. Direct translations may not convey the intended meaning of items, and some concepts may lack equivalents in other languages (for example, ‘bouncing back’ after stress). Assessments can yield unreliable or invalid results without careful adaptation and validation, leading to misinterpretations of resilience levels in different populations. Developing culturally responsive resilience measures involves translation, back-translation, stakeholder engagement, and validation across diverse sociodemographic and clinical populations¹²⁷.

WHO’s intrinsic capacity framework

This framework¹²⁸ considers resilience through five domains: cognition (memory, attention, problem-solving), mobility (movement and balance), vitality (energy levels, nutrition), sensory function (vision, hearing) and psychological well-being (emotional and mental health)¹²⁸. Its focus on functional abilities rather than culturally bound behaviors makes it highly adaptable across diverse contexts. Although implementation requires substantial resources, it provides a comprehensive and holistic view of resilience that is particularly useful when properly contextualized. Efforts to develop more culturally responsive measures are underway. Combined intrinsic capacity domains predict resilience in older adults¹²⁹, are associated with survival in older individuals with cancer¹³⁰ and are mediated by multilevel resilience¹³¹. A recent blood-based epigenetic clock has been developed to measure intrinsic capacity; this test predicted mortality and showed strong associations with clinical, immunological and lifestyle factors¹³².

Culturally adapted approaches

Culturally adapted resilience measurement tools integrate locally relevant dimensions such as community support, spiritual beliefs, family cohesion and traditional practices^133–135. Designed or tailored for specific cultural settings, they offer high relevance and validity in majority world contexts. For instance, social interaction and community engagement contribute to emotional self-regulation and psychological resilience^133,134,136. The child, youth and adult resilience measures incorporate family support, social belonging and community support^137,138. The South Asian assessments integrate resilience measures across social dynamics in families, communities and schools¹⁰⁰. In Latin America, resilience assessments reflect ‘familismo’ (family cohesion)¹⁷, offering insights into Hispanic populations. Indigenous knowledge systems and traditional practices^2,40 provide cultural-sensitive resilience assessments in African rural communities. Collectivist cultures prioritize communal coping and interdependence¹³⁵. However, research on this topic from the global south often remains small in scope and lacks the robust, longitudinal designs typically seen in the global north.

Computational biological frameworks

Computational frameworks rely on biological markers of aging, stress physiology and systemic adaptation mechanisms to infer resilience¹³². Regular exercise has been shown to enhance neuroplasticity and resilience^139,140. Tools such as brain and organ clocks and epigenetic clocks estimate biological age, offering insights into physiological resilience⁵². Additionally, biophysical modeling can integrate responses to environmental demands in neural dynamics¹⁴¹. Although these methods provide objective data, their application in resource-limited settings is constrained by technical expertise and infrastructure requirements. While offering objective, quantifiable data, their cultural adaptability is moderate, as the exposome shapes biological processes. Their utility in global settings is variable due to the need for technical expertise and access to advanced equipment.

Wearable technologies

Wearable devices offer real-time monitoring and continuous data collection of physiological resilience markers such as heart rate variability, sleep patterns and activity levels, which are beneficial for early detection and dynamic monitoring of stress recovery. Embedded and embodied measures of cognition in natural, real-world settings¹⁴² (wearable devices and ecological assessments, real-time monitoring of physiological resilience and allostatic interoception) can better capture the dynamic interactions between individual variability and environmental exposures. For instance, physiological metrics collected from wearable devices had predictive ability in identifying resilience states¹⁴³. Passive wearable sensors and ecological momentary assessment identified associations between sleeping behavior, heart rate and resilience¹⁴⁴. Pulse rate wearables and entropy-based metrics can identify individuals who show signs of cognitive resilience equivalent to being up to 3 years younger¹⁴⁵. Deep phenotyping of wearable sensor data identifies markers of longevity, stress and resilience¹⁴⁶. Unlike fragmented cognitive processes studied in traditional neuroscience, these approaches offer a holistic, context-aware assessment of real-life resilience. The increasing availability of mobile technology makes wearable solutions more accessible, although cultural considerations, privacy concerns, equitable access and data security remain key challenges.

Toward more integrated frameworks

Current resilience assessment must evolve toward integrative models combining classical assessments and intrinsic capacity with cultural, biological and real-world data. Each framework presents advantages and limitations (Table 1) that require interdisciplinary collaboration and codeveloping tools with communities to capture resilience in a personal, biological and socioecological capacity. Integrating data from multiple sources via computational modeling^141,147 can help with this integration. The Brain Resilience Kenya Study (Box 1) is the first to explore brain resilience in African populations, combining classical and cultural resiliency measures, multi-omics, neuroimaging and continuous behavioral sensing with wearable devices. Initiatives such as the Yaoundé Declaration¹⁴⁸ (a formal commitment to promote equitable, locally led strategies for brain health across the continent), Africa-FINGERS¹⁴⁹ and LatAm-FINGERS¹⁵⁰ projects (initiatives aimed at preventing cognitive decline and dementia through local multidomain lifestyle interventions) can support the effectiveness of integrating traditional knowledge with evidence-based solutions. Advancing resilience assessment globally and across metrics can help enhance understanding, improve interventions and support brain health across diverse populations.

Future directions

Despite growing recognition of the multidimensional nature of brain health and resilience, substantial research and policy gaps remain. Addressing these requires an integrated approach that includes research and policy translation, and more synergistic approaches. Future developments need to recognize the dynamic interplay between micro-level (individual), meso-level (community) and macro-level (national, global) influences, providing a robust foundation for designing contextually relevant, effective and sustainable interventions.

Most of the research on resilience has been divided across fields. Biological resilience^1,3 leverages neurobiological mechanisms, integrating genetic, metabolic and biomarker data to identify vulnerabilities and enhance cognitive and psychological resilience through early interventions. Social and cultural resilience^2,4,5 emphasizes the protective role of intergenerational support, collective identity and social cohesion in mitigating adversity and strengthening cognitive health. Environmental resilience accounts for exposomes²³ such as economic disparities and climate stressors, advocating for equity-driven policies that promote systemic adaptability. However, a more holistic and less siloed view can help overcome the fragmentation of traditional approaches by bridging scientific precision with culturally grounded strategies¹⁰⁷, while prioritizing inclusivity and equity.

Research priorities

Future efforts should focus on integrating cultural relevance and biological embedding of exposome and structural effects²¹. Priority must be given to longitudinal studies that track cognitive and brain resilience across the lifespan, uncovering how context-specific exposures—ranging from poverty to pollution—interact with biological systems to shape neurodevelopmental trajectories. Identifying critical intervention windows and biological markers, such as allostatic load, brain clocks and epigenetic aging, is essential for tailoring scalable interventions.

To ensure validity and equity, resilience research must embed community-driven approaches^125,133,134. Studies involving biospecimens or digital technologies must be governed by frameworks that protect autonomy and data sovereignty. Transparent protocols are urgently needed to address the sociopolitical implications of genetic and epigenetic findings, particularly in marginalized populations. Future measurement strategies should combine culturally adapted tools with biological indicators such as cardiometabolic markers, stress and multi-omics profiles. Conventional psychological scales fail to capture the complex, multimodal nature of resilience. Research must focus on developing and validating integrative tools that reflect the lived realities of diverse populations.

Technological innovations—including wearable sensors, mobile cognitive tools and environmental monitors—offer new possibilities for context-aware resilience tracking. Yet digital inequality, limited infrastructure and data governance remain critical barriers. Machine learning approaches capable of synthesizing biological, environmental and psychological inputs must be codesigned with local systems to ensure relevance and utility. Finally, global collaboration must shift from replicative models toward locally oriented scientific discovery and capacity-building partnerships. Infrastructure for biobanking, neuroimaging and digital phenotyping remains scarce in many low-resource settings. Supporting global and south-led data repositories, training in bioinformatics and locally anchored governance models is essential. A global resilience science must enable reciprocal north–south and south–south exchange, driving inclusive innovations in brain health.

Future policy priorities

There are multiple avenues to improve the translational findings into actionable frameworks (Box 2). Governments must move beyond anecdotal inclusion of resilience into public health frameworks and pursue deep structural alignment with local realities. This means positioning resilience not as a reactive concept, but as a measurable, upstream determinant of brain health—embedded within health systems, educational strategies and economic reform. Health policy should incorporate indicators of adaptive stress regulation, ecological exposure and social buffering capacity into routine surveillance. Aligning these metrics with system-level interventions, such as community-based mental health services and culturally grounded care models, can shift resilience from theory to sustained impact.

BOX 2. Policy roadmap for promoting brain health and resilience.

Integrate resilient cultural practices into health strategies

• Recognize and incorporate cultural concepts into resilience programs.

• Support community-based initiatives that leverage traditional practices.

• Encourage the inclusion of native and local perspectives on holistic well-being in healthcare.

Enhance education access to build cognitive and brain reserves

• Invest in equitable early childhood education, particularly in marginalized and rural areas, to stimulate cognitive development and neuroplasticity.

• Promote lifelong learning opportunities and vocational training considering local languages and cultural contexts.

Address poverty and socioeconomic inequalities as part of a core brain health agenda

• Implement social protection policies that reduce poverty-related stressors, such as universal basic income or targeted subsidies for essential goods.

• Develop infrastructure projects that improve access to clean water, sanitation and safe housing to reduce environmental stressors impacting allostatic load.

Improve nutrition and dietary practices

• Establish nutrition programs focusing on maternal and child health.

• Support local agriculture and sustainable food systems and promote diets rich in essential nutrients.

• Launch community education campaigns about the importance of nutrition for brain health.

Tailor precision health approaches to local contexts

• Conduct community-engaged research to understand local biological and exposome diversity.

• Develop tailored interventions that address local environmental toxins or stressors.

• Ensure precision health initiatives are conducted ethically, with informed consent, community engagement and cultural sensitivity.

Implement interventions throughout the life course

• Design programs that address the needs at different life stages, such as parenting workshops for new parents.

• Integrate mental health services into primary care.

• Provide support for adolescents through skill-building programs that enhance emotional regulation and social skills.

• Design specific interventions for resilience in older adults and patients with health-related diseases.

Foster multisectoral collaboration and policy integration

• Establish interdepartmental committees involving health, education, environment and social services to coordinate resilience initiatives.

• Align national policies with global frameworks to standardize efforts.

• Encourage public–private partnerships to leverage resources and expertise.

Education must be reframed as a core component of resilience infrastructure^10,30,36. Lifelong cognitive reserve is shaped not only by access to schooling but also by engagement with uncertainty and complex exposomes. Poverty, often treated as contextual background, must be recognized as a critical neurobiological disruptor. Policies such as conditional cash transfers, basic income experiments or community wealth-sharing models should be directly linked to indicators of brain health and mental well-being. Similarly, nutrition policy must account for neurodevelopmental timing, micronutrient needs and the epigenetic impact of food insecurity. Empowering communities to govern food systems could enhance biological and collective resilience.

Resilience strategies and related interventions should not target individuals in isolation¹⁵¹. Interventions must engage population-based approaches, kinship networks, social institutions and ecological systems. A multiscale policy framework—connecting molecular health to planetary health—is essential for addressing the systemic drivers of adversity. In the future, resilience should become a capacity to be structurally enabled through integrated, equity-driven and culturally responsive public policy.

A holistic path forward combining research and policy

Unlike reductionist models that isolate specific factors, a synergistic approach^141,147 highlights broader determinants of resilience, including biological underpinnings, economic inequality and sociocultural dynamics. Enhancing resilience and addressing allostatic interoceptive overload in low-resource settings requires multidimensional methods, multicomponent interventions and translational efforts.

A prime example of such synergy and future applicability lies in nutrition-based strategies such as food security initiatives that promote sustainable agriculture and equitable food distribution. The ‘planeterranean’ diet¹⁵² proposed by the UNESCO Chair on Health Education and Sustainable Development, adapts the nutritional principles of the Mediterranean diet to regional contexts, offering a globally adaptable model. By integrating locally sourced vegetables, fruits, cereals and unsaturated fats, it creates culturally tailored diets that address nutritional deficiencies, while preserving traditional food practices¹⁵². Comprehensive nutrition strategies, including culturally adapted education, maternal counseling and the inclusion of nutrient-dense local foods, have the potential to strengthen neurocognitive resilience, particularly in vulnerable populations. Emerging microbiome-targeted interventions complement these strategies by mitigating the long-term effects of childhood undernutrition on brain development and stress adaptation^153,154. Traditional diets rich in whole grains, legumes and antioxidant-rich foods can reduce neuroinflammation and support biological resilience¹⁵⁵. Complementary programs focused on early development are equally vital. The Nurturing Care Framework, developed by the WHO, UNICEF and the World Bank Group¹⁵⁶, emphasizes safety, responsive caregiving and early learning. These are key components for fostering lifelong brain health and psychological reserve. A multimodal, synergetic approach to resilience—combining biological, cognitive, psychological, social and environmental strategies—is both practical and scalable. An integrated, context-sensitive approach, centered on nutrition, early development and community systems exemplifies a scalable pathway to strengthen cognitive and social resilience.

Conclusions

Resilience should be viewed as a dynamic balance rather than an unyielding trait. Although protective, relying too heavily on individual coping can ultimately lead to allostatic overload, underscoring the need to address systemic inequities¹⁵¹. Integrating insights from genomics, multi-omics and exposomics^141,147 can help to understand resilience as not solely genetically predetermined but shaped by biopsychosocial– environmental interactions. Precision health strategies integrating individual variability, environmental exposures and cultural contexts offer promising pathways to enhance resilience and guide targeted interventions and policy reforms.