Diabetes mellitus and risks of cognitive impairment and dementia: A systematic review and meta-analysis of 144 prospective studies

Uncertainties persist about the associations of diabetes with risk of cognitive impairment and dementia. We aimed to illuminate these associations from various aspects.We identified relevant prospective studies by searching PubMed up to Jun 2019. Summary relative risks (RR) were estimated using random-effects models. Credibility of each meta-analysis was assessed. Meta-regression and subgroup analyses were conducted.Of 28,082 identified literatures, 144 were eligible for inclusion in the systematic review, among which 122 were included in the meta-analysis. Diabetes conferred a 1.25- to 1.91-fold excess risk for cognitive disorders (cognitive impairment and dementia). Subjects with prediabetes also had higher risk for dementia. As for diabetes-related biochemical indicators, fasting plasma glucose (FPG) was non-linearly related to cognitive disorders; the elevated levels of 2 -h postload glucose (2h-PG), glycosylated hemoglobin (HbA1c), low and high levels of fasting plasma insulin (FPI) were associated with an increased risk of dementia. Encouragingly, the use of pioglitazone exhibited a 47% reduced risk of dementia in diabetic population.Diabetes, even prediabetes and changes of diabetes-related biochemical indicators, predicted increased incidence of cognitive impairment and dementia. The protective effects of pioglitazone warrant further investigation in randomized trials.