title: Bi-directional interaction between hypoglycaemia and cognitive impairment in elderly patients treated with glucose-lowering agents: a systematic review and meta-analysis.
abstract: OBJECTIVE
  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 August 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.
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich, UK.
authors.forename: K
authors.initials: K
authors.lastname: Mattishent
authors.affiliation: Norwich Medical School, University of East Anglia, Norwich, UK.
authors.forename: Y K
authors.initials: YK
authors.lastname: Loke
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D003072:Cognition Disorders / Q000150:complications / Q000453:epidemiology / Q000209:etiology* / Q000517:prevention & control; D000066492:Cognitive Aging; D017281:Cost of Illness; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000523:psychology; D016903:Drug Monitoring; D019317:Evidence-Based Medicine; D006801:Humans; D006943:Hyperglycemia / Q000517:prevention & control; D007003:Hypoglycemia / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D064887:Observational Studies as Topic; D015203:Reproducibility of Results; D012307:Risk Factors
chemical_list: D007004:Hypoglycemic Agents
keywords: diabetes mellitus; hypoglycaemia; meta-analysis; systematic review