Background It is uncertain whether depression might affect cognitive function in Alzheimer’s disease (AD). Most of studies on the effect of depression treatment on cognitive function in AD were briefly evaluated by Mini-Mental State Examination (MMSE). MMSE is poor sensitive to detect cognitive change. This study examined the cognitive response to depression treatment in AD via multi-domain assessment. In addition, we explored whether effect of depression treatment in AD is different those of late-life depression (LLD). Methods This study include AD patients with depression (AD + D) and without depression (AD − D), LLD patients (LLD), and healthy controls (HC). The patients were treated according to their diagnosis for 16 weeks: acetylcholinesterase inhibitors (AChEIs) and selective serotonin reuptake inhibitors (SSRIs) for AD + D, AChEIs for AD − D, and SSRIs for LLD. The cognitive changes from pre- to post-treatment were compared between AD + D and AD − D or LLD and HC. An independent sample t test was performed to compare the degree of change between the groups. Paired t tests were used to determine cognitive function changes in each depression treatment responder group. Results At baseline, AD + D had more impairment in language function compared to AD − D, and LLD had greater deficit in executive function than HC. After depression treatment, more impaired cognitive domains at baseline were improved in AD + D and LLD, respectively. Moreover, AD + D showed an improvement in the global cognitive function (MMSE). Conclusions Results indicated that language function was influenced by depression in AD, which is first evidence for specific cognitive domain related to depression in AD. Our finding indicates that depression could negatively impact cognitive function, and depression treatment may have beneficial cognitive effect in both AD and LLD. This study suggests the importance of early detection and treatment of depression in AD and LLD. Trial registration Clinical Research Information Service, CRIS, ID#: KCT0004041, Registered 5 June 2019, retrospectively registered after first patient enrollment date (4 March 2014) https:// cris. nih. go. kr/ cris/ search/ detai lSear ch. do? seq= 14140 & status= 5& seq_ group= 14140 & search_ page=M.
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