Recurrent depression has persistent effects on cognition but this does not appear to be mediated by neuroinflammation

Abstract

Background: Later-life depression appears to be different to depression in younger adults. The underlying pathology may also differ. Depression is linked to dementia but whether it is a risk factor or an early sign of a developing dementia remains unclear. Neuroinflammation is increasingly recognised in both depression and Alzheimer's Disease.

Aims: To investigate the link between depression, inflammation and dementia. We hypothesised that recurrent depression has adverse effects on performance in cognitive tests in middle to older age and that this effect is modified by anti-inflammatory medication.

Methods: We identified UK based cohort studies which included individuals aged >50, had medical information, results from detailed cognitive testing and had used reliable measures to assess depression. Individuals with recurrent depression had ≥ 2 episodes of depression. Controls had no history of depression. The presence/absence of inflammatory illness was assessed using a standardised list of inflammatory conditions. Individuals with dementia, chronic neurological and psychotic conditions were excluded. Logistic and linear regression were used to examine the effect of depression on cognitive test performance and the mediating effect of chronic inflammation.

Results: Unexpectedly in both studies there was evidence that those with recurrent depression performed better in some cognitive tasks (e.g Mill Hill vocabulary) but worse in others (e.g. reaction time). In UK Biobank there was no evidence that anti-inflammatories moderated this effect.

Limitations: Cross-sectional assessment of cognition.

Conclusions: Although previous recurrent depression has small effects on cognitive test performance this does not appear to be mediated by chronic inflammatory disease.

Keywords: Alzheimer's Disease; Cognition; Depression; Depressive disorders; Inflammation.