The neural correlates underlying late-life depressive symptoms and cognitive deterioration are largely unclear, and little is known about the role of chronic physical conditions in such association. This research explores both concurrent and longitudinal associations between late-life depressive symptoms and cognitive functions, with examining the neural substrate and chronic vascular diseases (CVDs) in these associations.

A total of 4109 participants (mean age = 65.4, 63.0% females) were evaluated for cognitive functions through various neuropsychological assessments. Depressive symptoms were assessed by the Geriatric Depression Scale and CVDs were self-reported. T1-weighted magnetic resonance imaging (MRI), diffusion tensor imaging, and functional MRI (fMRI) data were acquired in a subsample (n = 791).

Cognitively, higher depressive symptoms were correlated with poor performance across all cognitive domains, with the strongest association with episodic memory (r = ‒0.138, p < 0.001). Regarding brain structure, depressive symptoms were negatively correlated with thalamic volume and white matter integrity. Further, white matter integrity was found to mediate the longitudinal association between depressive symptoms and episodic memory (indirect effect = −0.017, 95% CI −0.045 to −0.002) and this mediation was only significant for those with severe CVDs (β = −0.177, p = 0.008).

This study is one of the first to provide neural evidence elucidating the longitudinal associations between late-life depressive symptoms and cognitive dysfunction. Additionally, the severity of CVDs strengthened these associations, which enlightens the potential of managing CVDs as an intervention target for preventing depressive symptoms-related cognitive decline.