Association of Cognitive Reserve and Chronic Disease Comorbidity with the Risk of Progression from Subjective Cognitive Decline to Objective Cognitive Impairment: A Cohort Study Among Chinese Community-Dwelling Older Adults

Background: Although cognitive reserve (CR) and chronic disease comorbidity (CDC) are closely related to cognitive trajectories, their independent and combined effects on objective cognitive impairment (OCI) in subjective cognitive decline (SCD) remain insufficiently evidenced. Objective: This study aimed to investigate the independent effects and interactions between CR and CDC on the risk of OCI in community-dwelling older adults with SCD. Methods: This prospective cohort study included 605 community-dwelling SCD patients aged ≥ 60 years from Wuxi City in 2022, with a 3-year follow-up to assess progression to OCI (mild cognitive impairment or dementia). Cox proportional hazards (Cox PH) regression models were used to analyze the associations and interactions between CR, CDC, and OCI risk. Kaplan-Meier curves were employed to compare the probability of remaining free from OCI across different combinations of CR and CDC. Results: During follow-up, 195 SCD patients progressed to OCI. Cox PH regression identified low CR (LCR) and high CDC (HCDC) as factors independently associated with elevated OCI risk in SCD patients. Compared with the LCR group, the high CR (HCR) group had a significantly lower risk of cognitive progression (HR = 0.473, 95% CI: 0.350– 0.640, P < 0.001); in contrast, the HCDC group had a higher risk than the low CDC (LCDC) group (HR = 5.286, 95% CI: 3.772– 7.409, P < 0.001). A significant positive additive interaction was observed between CR and CDC. Survival analysis revealed that patients with HCDC combined with LCR exhibited the highest risk of progression, while those with LCDC and HCR demonstrated the highest probability of maintaining normal cognition. Conclusion: HCR was associated with lower risk of OCI among community-dwelling older adults with SCD, whereas LCR and HCDC showed synergistic association with elevated cognitive progression risk. Moreover, HCR remained independently associated with reduced risk even under HCDC exposure.