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

Background: : Uncertainties persist about the associations of diabetes with risk of cognitive impairment and dementia. We aimed to illuminate these associations from various aspects. Methods: : 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. Results: : 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. Conclusions: : 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.