Risk of incident Alzheimer's disease in diabetic patients: a systematic review of prospective trials.

Diabetes mellitus is an established risk factor of cognitive decline. This excess risk has frequently been attributed to cerebrovascular disease. The contribution of diabetes mellitus to the risk of Alzheimer's disease is less clear. We performed a systematic literature review based on prospective studies that examined the risk of incident Alzheimer's disease in diabetic patients. Fourteen studies in eleven different populations fulfilled the entry criteria. Only one study per population was included by pre-defined criteria, leaving eleven studies for analysis. All studies reported risk ratios greater than one (median 1.59, range 1.15-2.7). In four studies, this excess risk was statistically significant (median 1.73, range 1.59-1.9); in seven studies the lower border of the 95% confidence interval was below 1.0. Factors associated with significant results were a sample size of 600 or more diabetic subjects, inclusion of patients with mild glycemic dysregulation as assessed by oral glucose tolerance test, and a high proportion of diagnoses of Alzheimer's disease verified by autopsy or magnetic resonance imaging. Diabetes mellitus is likely to increase the risk of Alzheimer's disease. The association of Alzheimer's disease and diabetes mellitus is more clear-cut, if mild cases of diabetes mellitus are included in the analysis.