Clinical Manifestations

Chronic pain (CP) and depression frequently co-occur in the elderly, severely impacting individuals with Alzheimer's disease (AD). Their overlapping neurobiological pathways exacerbate each other, accelerating functional decline and worsening cognitive deficits. Untreated CP and depression may even contribute to dementia progression, while adverse social determinants of health (SDH) further compound their effects. However, the triadic relationship between CP, depression, and AD remains poorly understood, particularly in Latin American (LA) populations, where health disparities and environmental factors may shape outcomes. This study explores their interplay in this underrepresented context.

A cohort of 320 older adults, including 146 individuals with AD and 174 healthy controls (HC), was recruited from Chile, Argentina, Mexico, and Peru. The sample was sex-balanced, and all participants provided informed consent in accordance with the Declaration of Helsinki. Recruitment was facilitated through the Multicenter Consortium to Expand Dementia Research in Latin America (ReDLat), utilizing standardized protocols across all sites. Data collection encompassed neuropsychological assessments, CP and depression evaluations, SDH measures, and demographic factors. CP was assessed through indicators such as pain frequency, intensity, and symptom severity, while depression was evaluated using validated scales.

Structural equation modeling (SEM) revealed that depression significantly mediated the relationship between CP and AD. A marginally significant positive association was identified between depression and CP (p = 0.050), and a strong association was observed between depression and AD (p = 0.001). CP, as represented by pain frequency, intensity, and symptom severity, demonstrated high explanatory power (R² = 97.6%). Depression also showed a strong association with dementia risk (R² = 96.4%). Furthermore, unfavorable SDH were positively correlated with higher CP and depression scores.

These findings underscore the critical role of depression as a mediator in the CP-AD relationship, which is further exacerbated by adverse SDH in older adults from LA. Addressing social disparities and improving access to mental health and pain management services are essential for mitigating dementia risk and improving overall health outcomes in this vulnerable population.