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Background Both an elevated homocysteine (Hcy) level and depression are risk factors for cognitive impairment in the general population, but no study has analyzed whether the coexistence of an elevated Hcy level and late‐life depression (LLD) is associated with worse cognitive performance. Objective We aimed to investigate the relationship between Hcy levels and cognitive function in individuals with LLD and whether the coexistence of an elevated Hcy level and LLD is associated with worse cognitive performance. Methods A total of 113 LLD patients and 89 normal controls underwent a standardized clinical interview and comprehensive neuropsychological assessment battery. Plasma concentrations of Hcy were detected. Factorial analyses were performed to examine the impact of the coexistence of an elevated Hcy level and LLD on cognitive performance. Results Plasma Hcy levels in patients with LLD were significantly higher than that in normal controls. Only for LLD patients, Hcy level was negatively correlated with global cognition, executive function, attention, and visual space. The factorial analysis showed that there was a significant interactive effect of Hcy level (normal and elevated levels) and LLD (with and without LLD) on global cognition. In post hoc comparisons, the elderly individuals with both elevated Hcy levels and LLD tended to have the worst global cognitive function compared with those with LLD or elevated Hcy levels alone. Conclusions The coexistence of an elevated Hcy level and LLD was associated with worse cognitive performance. Early intervention should be initiated to protect cognition in LLD patients with elevated Hcy levels.

Background Late-life depression is a risk factor of dementia. It may increase the risk of reliable cognitive decline in the short term, and its associated risk factors remain unclear. Cortisol level may be one of the important predictors. Objectives To estimate whether patients with late-life depression are at an increased risk for reliable global cognitive declines in 1 year, and explore associated risk factors predicting cognitive declines. Methods This prospective 1-year follow-up study involved 148 participants (67 with late-life depression and 81 normal elderly). Global cognitive function was assessed by the Mini-Mental State Examination (MMSE). The reliable global cognitive decline was defined by the reliable change index (RCI) of the MMSE. Factors related to cognitive function (e.g., age, gender, education, duration of depression and severity of depression) were obtained. Serum cortisol levels were measured at baseline. Results At the 1-year follow-up assessment, 19 patients with late-life depression (28.4%) showed reliable global cognitive declines, a risk that was 6.4 times (95% CIs = 1.3–31.1, p = 0.021) higher than that of normal elderly. Elevated serum cortisol levels and older age were associated with the risk of cognitive decline that was 1.6- and 1.2-times higher (95% CIs = 1.07–2.5, p = 0.02, and 95% CIs = 1.04–1.4, p = 0.01 respectively). Limitations Serum cortisol levels were measured only in the morning. Conclusions Late-life depression is associated with a greatly increased risk of reliable cognitive decline in short term. Cortisol dysregulation may contribute to the pathology of cognitive decline.