Bi‐directional interaction between hypoglycaemia and cognitive impairment in elderly patients treated with glucose‐lowering agents: a systematic review and meta‐analysis

Aims To examine the bi‐directional relationship, whereby hypoglycaemia is a risk factor for dementia, and where dementia increases risk of hypoglycaemia in older patients with diabetes mellitus treated with glucose‐lowering agents. Methods We searched MEDLINE and EMBASE over a 10‐year span from 2005 to 2015 (with automated PubMed updates to A ugust 2015) for observational studies of the association between hypoglycaemia and cognitive impairment or dementia in participants aged >55 years. Assessment of study validity was based on ascertainment of hypoglycaemia, dementia and risk of confounding. We conducted random effects inverse variance meta‐analyses, and assessed heterogeneity using the I 2 statistic. Results We screened 1177 citations, and selected 12 studies, of which nine were suitable for meta‐analysis. There were a total of 1 439 818 participants, with a mean age of 75 years. Meta‐analysis of five studies showed a significantly increased risk of dementia in patients who had hypoglycaemic episodes: pooled odds ratio 1.68 95% confidence interval ( CI ) 1.45, 1.95. We also found a significantly increased risk of hypoglycaemia in patients with dementia: pooled odds ratio from five studies 1.61 (95% CI 1.25, 2.06). Limitations of the study were heterogeneity in the meta‐analysis, and uncertain ascertainment of dementia and hypoglycaemic outcomes and temporal relationships. Publication bias may have favoured the reporting of more significant findings. Conclusions Our meta‐analysis shows a bi‐directional relationship between cognitive impairment and hypoglycaemia in older patients. Glucose‐lowering therapy should be carefully tailored and monitored in older patients who are susceptible to cognitive decline.