High-impact pain predicts subjective cognitive decline and interacts with APOE4 genotype in the development of objective cognitive impairment

Abstract

Chronic pain is the most common health challenge for older adults and a significant risk factor for cognitive impairments and dementia. This study examined the relationship of high-impact pain (i.e., pain that limits daily activities) with subjective cognitive decline (SCD) and objective cognitive impairment in 13,763 adults aged 50 and older from the Health and Retirement Study (2004–2020). High-impact pain was associated with a higher prevalence (32.4%) and incidence of SCD compared to no pain (18.0%) and low-impact pain (21.3%). High-impact pain also predicted an increased risk of objective cognitive impairment, particularly in individuals without the APOE4 allele. The adjusted hazard ratio (aHR) for incident SCD in high-impact pain versus no pain was 1.31 (95% CI: 1.31, 1.42). The aHR for objective cognitive impairment compared to no or low-impact pain was 1.21 (95% CI: 1.07, 1.36) in APOE4-negative individuals, controlling for SCD and relevant biopsychosocial factors. Our findings suggest that high-impact pain is a stronger predictor of future cognitive impairments than SCD alone in most of the population who do not carry the APOE4 allele. Interventions targeting high-impact pain, starting in middle age, may help mitigate the risk of cognitive decline and dementia. Future research is needed to understand potential mechanisms whereby pain either directly or indirectly impacts cognition to develop preventive and effective therapeutic strategies.

Perspective

This study highlights high-impact pain as a predictor of subjective and objective cognitive decline in older adults. High-impact pain may contribute to cognitive impairment, especially in individuals without the high-risk APOE4 allele, and may represent a modifiable target for early interventions to reduce the risk of dementia.