Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

A large-scale analysis of two UK datasets has shown that recurrent depression affects performance in several tests of thinking skills. However, this difference was not altered by taking anti-inflammatory medications such as Ibuprofen, suggesting that neuroinflammation may not be the underlying process driving depression’s effect on cognition.

A cognitive test showing numbers and coloured dots

Depression was established as a potentially modifiable risk factor of dementia by the Lancet commission in 2017. Separately, inflammation – especially inflammation occurring in the brain, termed neuroinflammation – is emerging as a probable mechanism involved in dementia, particularly in accelerating its progression.

Previous studies investigating the link between depression, inflammation and dementia have mostly involved small samples of fewer than 100 participants. A research team led by Dr Lindsey Sinclair, a Clinical Research Fellow at Bristol Medical School, conducted a large-scale study in the DPUK Data Portal examining data from participants in the UK Biobank and Generation Scotland cohorts. The research team included DPUK’s Director, Professor John Gallacher, and Senior Scientist and Data Manager, Dr Sarah Bauermeister.

The study is published in the Journal of Affective Disorders

Dr Sinclair said: ‘We aimed to find out whether depression has effects on performance in cognitive tests, even after the depression is over. We also wanted to find out whether inflammation might be why this happens by looking at whether people with depression taking anti-inflammatory medication were less severely affected. In two large UK-based cohorts we found that depression does have effects on cognition, but no evidence that inflammation is involved.’

UK Biobank

Participants in UK Biobank completed cognitive tests including a pairing memory test, a verbal reasoning test, and an online version of the card game ‘snap’ to test their reaction times. When the researchers analysed these test scores in people over 50 with and without depression, they found slower mean reaction times in people with recurrent depression. Interestingly, those with depression scored higher in both the verbal reasoning and the pairs test. This demonstrates that the way depression influences cognition is nuanced.

Generation Scotland

Participants in the Generation Scotland cohort completed several established cognitive tests including the Mill Hill vocabulary scale, the digit symbol substitution test (where participants must remember and match corresponding symbols and numbers), and the three-letter verbal fluency test. In the verbal fluency test, people are given three letters and must think of as many words beginning with these letters as they can within a given time limit.

Again, only people over the age of 50 were studied, and those with recurrent depression scored lower in the digit symbol substitution test. This cognitive task assesses multiple aspects of cognition, demonstrating that multiple cognitive functions are affected by depression. However, these participants scored higher than control participants without depression on the Mill Hill vocabulary test and on the verbal fluency task.

Although the results from both UK Biobank and Generation Scotland showed that depression influences cognition, there was no evidence in either cohort that taking anti-inflammatory drugs affected this relationship. This implies that the effect of recurrent depression on cognition is unlikely to be caused by neuroinflammation. Despite this, the researchers did find in both cohorts that chronic inflammation negatively impacted cognition, irrespective of the presence of depression.

Dr Sinclair said: ‘We have shown in one-off testing that depression has adverse effects on cognition, but the important next step is to see what happens over time to this effect.’

The researchers now propose further examination of the effect of depression and anti-inflammatory medications on cognition over an extended period.