A dual-pathway model of depression's mediation between chronic pain and dementia

Exp Gerontol. 2026 Feb 10:113068. doi: 10.1016/j.exger.2026.113068. Online ahead of print.

ABSTRACT

BACKGROUND: Although chronic pain is a recognized risk factor for cognitive decline and dementia, often mediated by depression, it remains unclear whether depression plays a differential mediating role across chronic pain duration in the pathway to dementia.

METHODS: We conducted a cross-sectional analysis of data from 1096 adults aged ≥45 years, obtained from the Inpatient Comprehensive Assessment Database (2020-2023) of the Department of Geriatrics at The First Affiliated Hospital of Chongqing Medical University. Chronic pain was defined as self-reported pain persisting for over three months. Based on chronic pain duration, participants were categorized as: chronic pain-free, 3-24 months, or > 24 months. Dementia was diagnosed using education-stratified cutoff scores on the Mini-Mental State Examination (MMSE), and depression was assessed with the Patient Health Questionnaire-9 (PHQ-9). Data were analyzed using chi-square tests, binary logistic regression, and mediation analysis (PROCESS macro).

RESULTS: After adjusting for potential confounders, multivariable logistic regression models revealed that the prevalence of dementia was significantly higher in individuals with chronic pain than in those without. Furthermore, a longer pain duration (>24 months) was associated with a significantly increased risk of dementia compared to a shorter duration (3-24 months) (OR = 2.60, p < 0.05; OR = 1.78, p < 0.05). Mediation analysis indicated that depression fully mediated the association in the chronic pain (3-24 months) group, but only partially in the >24 months group.

CONCLUSIONS: Chronic pain duration is significantly associated with dementia, with depression playing a differential mediating role across chronic pain durations.

PMID:41679614 | DOI:10.1016/j.exger.2026.113068