Aging is a multifaceted process that encompasses physical, cognitive, and emotional changes. As the global population continues to age, understanding the factors that influence cognitive health in later life has become a critical area of research. Increasing evidence highlights the significant role of social exposures, such as social engagement, socioeconomic status (SES), social support, and social networks, in shaping cognitive trajectories during aging [1, 2]. For an example, studies have consistently shown that social engagement is protective against cognitive decline, with older adults who maintain active social lives exhibiting better cognitive performance and a reduced risk of dementia [1, 3]. Conversely, social isolation and loneliness have been linked to an increased risk of cognitive impairment and dementia [3, 4]. In a longitudinal study, Wilson and colleagues found that individuals with higher levels of social activity were less likely to develop Alzheimer’s disease, suggesting that cognitive stimulation from social interactions may help preserve brain function in aging [5]. The association between social networks and cognitive health is further supported by studies showing individuals with broader and more supportive social ties to experience slower rates of cognitive decline [2, 6]. In the coming decades, older adults are expected to make up a third of Canada’s population, and cognitive impairments can have profound negative impacts on an older adult’s life [7]. One cohort study showed associations between mid-life marital status and later cognitive functions, where being divorced or widowed were both associated with greater odds of later cognitive impairments [8]. Another cohort study showed social isolation and loneliness in older adults are both associated with lower cognitive scores [9]. SES also plays a critical role in cognitive health during aging. Low SES, characterized by limited access to resources, education, and healthcare, has been consistently associated with worse cognitive outcomes and a higher risk of dementia [3]. The impact of SES on cognitive aging is postulated to be mediated through various pathways, including chronic stress, limited access to healthcare, and less cognitive stimulation throughout life [10]. These findings underscore the importance of social environments and experiences in shaping cognitive trajectories during aging, pointing to the need for integrated approaches that consider both individual and social factors. However, despite the wealth of evidence supporting the link between social exposures and cognitive outcomes in older adults, the mechanisms that underlie these associations remain unclear.

The biopsychosocial model of health, which was first proposed by Engel in 1977, emphasizes the interaction between biological, psychological, and social factors in influencing health outcomes [11, 12]. In the context of cognitive aging, this model provides a comprehensive framework for understanding how social exposures contribute to cognitive function. Social factors, such as social support and engagement, interact with psychological and biological processes to influence cognitive outcomes. For instance, psychological factors like stress, coping strategies, and mental health are known to interact with social support to affect cognitive health [1, 13]. Chronic stress, often exacerbated by adverse social environments, has been implicated in cognitive decline through its effects on the hypothalamic-pituitary-adrenal (HPA) axis, leading to elevated levels of cortisol that can negatively impact brain regions such as the hippocampus, which is crucial for memory and learning [14]. Moreover, social engagement may buffer against the negative effects of stress by promoting positive psychological states, such as a sense of belonging and self-worth, which, in turn, may protect against cognitive decline [15, 16]. At the biological level, several mechanisms have been proposed to explain how social exposures may influence cognitive aging. One of the most studied mechanisms is the role of inflammation. Chronic stress and social adversity have been shown to increase inflammatory markers, which in turn may contribute to neurodegenerative processes and cognitive decline [17, 18]. Inflammatory responses, particularly the activation of microglia and the release of proinflammatory cytokines, have been linked to brain aging and Alzheimer’s disease pathology [19]. Another potential biological pathway is neurotrophic support. Social engagement has been shown to enhance the release of brain-derived neurotrophic factor (BDNF), a protein crucial for neuronal survival and plasticity, thereby promoting cognitive resilience in the face of aging [20]. Another potential mechanism linking social exposures to cognitive health in older age is through epigenetics [21, 22]. Studies over the last decade have shown that age-related epigenetic changes quantified in epigenome-wide association studies or those characterizing the epigenetic clock are linked to cognitive health in older age and may be modified by social exposures. Other mechanisms that have been explored include increased allostatic load, which is defined as the “wear and tear” the body experiences when repeated neural or neuroendocrine responses are activated during stressful situations, as well as telomere shortening [14, 23–25].

This scoping review aims to summarize the existing evidence on the association between measures of social adversity and neurocognitive outcomes in adults and describe potential the underlying biological processes and pathways. Specifically, we will summarize evidence on diverse but interconnected biological mechanisms including inflammation, allostatic load, and genetic and epigenetic markers as potential mediators for the association often seen between social adversity and cognition. By mapping the existing evidence and identifying key research areas, we hope to contribute to a deeper understanding of how social, psychological, and biological factors converge to influence cognitive outcomes in later life. This knowledge is crucial not only for advancing the science of cognitive aging but also for developing targeted interventions that address the social determinants of cognitive health and that promote healthy aging.

This manuscript was developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) Checklist [26]. A review protocol can be accessed on OSF registries (DOI 10.17605/OSF.IO/2DFWM).

This scoping review sought to investigate the biological mechanisms through which social adversity may impact cognitive outcomes during aging. Collectively, the findings indicate that various forms of social adversity—including low socioeconomic status (SES), loneliness, and psychosocial stress—are associated with negative cognitive outcomes, particularly in older adults. Importantly, biological mechanisms such as inflammation, allostatic load, and genetic/epigenetic markers were identified as potential mediators in these relationships, though the strength and consistency of these associations varied across studies. Inflammation appeared to play a prominent role, with several studies demonstrating that higher levels of inflammatory markers, such as CRP and interleukin-6, were linked to both social adversity and cognitive decline [30, 35]. However, other studies did not find inflammation to mediate the relationship between social adversity and cognition, highlighting the complexity of these interactions [33]. These mixed findings suggest that while inflammation is a plausible biological pathway, it may not be universally relevant for all individuals or social contexts, and further research is needed to better delineate its role in cognitive aging.

Allostatic load, a measure of the cumulative physiological wear and tear resulting from chronic stress, was another biological mechanism identified in the reviewed studies. Four studies explored this concept in the context of social adversity and cognitive outcomes. For instance, research by Fazeli et al. [39] demonstrated that allostatic load mediated the relationship between SES and neurocognitive function in older adults living with HIV, supporting the notion that prolonged exposure to social adversity may lead to physiological dysregulation, which in turn exacerbates cognitive decline [39]. Similarly, Krishnadas et al. [32] found that socioeconomic deprivation was associated with cortical structural changes, particularly in the Wernicke’s area, and that inflammatory markers mediated this relationship [32]. Conversely, Akrivos et al. [29] and De Looze et al. [37] reported that while social adversity was associated with poorer cognitive performance, allostatic load explained only partly explained the proportion of this variance, suggesting that other mechanisms may be more central to these associations [29, 37]. These findings point to the need for a more nuanced understanding of how allostatic load contributes to cognitive aging, particularly when considered alongside other factors such as inflammation and genetic predispositions, and importantly social and environmental exposures in early-life and across the life course [41, 42].

The role of genetics, epigenetics, and genetic aging markers in mediating the relationship between social adversity and cognitive outcomes emerged as another important area of interest. Several studies investigated telomere length (LTL), DNA methylation, and epigenetic aging as potential biological mediators. Huang et al. [31] found that shorter LTL mediated the relationship between low SES and cognitive decline, providing support for the hypothesis that social adversity accelerates biological aging. However, other studies, such as De Looze et al. [37], did not find LTL to mediate the association between perceived stress and cognitive outcomes, suggesting that epigenetic mechanisms may be context-dependent. Notably, studies examining DNA methylation, including those by Lynch et al. [38] and Liang et al. [16], found that specific epigenetic changes, such as those linked to loneliness and social isolation, were associated with poorer cognitive outcomes. For example, Lynch et al. [38] demonstrated that epigenetic aging, as measured by GrimAge, mediated the relationship between loneliness and cognitive decline. These findings suggest that epigenetic alterations could represent a critical biological pathway through which social adversity influences cognitive health, though more research is needed to establish causal links and to identify which epigenetic markers are most predictive of cognitive outcomes.

Overall, the differing findings from some reviewed studies likely reflect heterogeneity in study populations as well as the differences in types of social adversities assessed. For instance, some studies used objective indicators of SES, while others relied on subjective measures like perceived stress or loneliness, which may engage different biological pathways. Some studies also measured only one specific cognitive domain as opposed to overall cognition. These differences underscore the importance of further future studies with standardized measurement approaches to better capture the influence of biological mediators on this association between social adversity and cognitive aging.

Notably, while inflammation, allostatic load, and epigenetics represent promising biological pathways linking social adversity to cognitive decline, the reviewed studies also highlight the need for more comprehensive models that integrate multiple biological, psychological, and social factors. Many of the studies included in this review focused on a single biological mechanism or social factor, often in isolation, and did not consider the potential for complex interactions between these variables. For instance, while inflammation was a common mediator in the studies examining social isolation, its effect was not always consistent across different cognitive domains or social contexts [30, 35]. Similarly, while allostatic load and SES were found to be associated with cognitive outcomes, the magnitude of the relationship was often modest and varied depending on the individual’s specific life circumstances [29]. This suggests that future research should adopt a more integrative, multidimensional approach that considers the dynamic interplay between genetic, physiological, and social factors in shaping cognitive health [43]. Longitudinal studies with larger and more diverse populations are particularly needed to establish causal relationships and to explore how these pathways evolve over time, especially in light of the aging process. By advancing our understanding of the complex mechanisms through which social adversity affects cognitive aging, researchers can help inform interventions aimed at mitigating the impact of social inequalities on cognitive health in older adults.

As well, this study did not explore if similar biological mediators exist for the well-known association between early-life adversity, such as low SES, childhood trauma, chronic stress, and effects on cognitive function in later adulthood [44, 45]. Adverse childhood experiences (ACEs), such as poverty, neglect, or family instability, have been associated with lasting alterations in stress regulation, inflammation, and brain development, which may predispose individuals to accelerated cognitive aging. For instance, studies have shown that early-life socioeconomic disadvantage is linked to altered HPA axis functioning and pro-inflammatory phenotypes, which have been implicated in later-life cognitive impairment [46, 47]. For future studies, it would be important to apply a life course perspective and consider how accumulation of adversity influences cognitive aging trajectories. Additionally, the role of intersectional factors such as gender and race was only mentioned in one study by Fazeli et al. Incorporating life course epidemiology and intersectionality into future research is essential for identifying sensitive periods for intervention and better understanding disparities in cognitive aging outcomes. As well, future studies should stratify analyses or test for effect modification to identify populations most vulnerable to biologically mediated effects of social adversity on cognition, taking into consideration factors such as sex, ethnicity, and ACEs.

There are several strengths to our study. Our search strategy was developed in collaboration with a trained research librarian to identify the optimal data sources and search terms for a comprehensive review. Quality assessment showed that all the studies included in our review achieved over seven points on the nine-point NOS scale. This is largely since most studies employed pre-existing, large-scale, nationally representative data, minimizing selection bias in participants and confirmation bias in data analysis. Our study also has some limitations including the modest number of studies that were eligible for inclusion; we had also excluded studies in languages other than English. Also, the heterogeneity in the studies included in terms of social adversity, cognitive domains, and biological factors may have limited the ability to compare the included studies. The included studies are predominantly cross-sectional studies, which limits the ability to infer causal or temporal relationships, and future research that focuses on longitudinal cohort designs would be meaningful for establishing causality. Lastly, given that our scoping review has chosen to focus on the aforementioned biological mediators of inflammation, allostatic load, and genetics factors, we have not explored other plausible pathways, such as neurotrophic factors including brain-derived neurotrophic factor, oxidative stress, and microbiome-gut-brain axis, which should be investigated in future reviews [48–50].