AIMS/HYPOTHESIS: Diabetes has been related to Alzheimer's disease with inconsistent findings. We aimed to clarify the association of diabetes with different dementing disorders taking into account glycaemic control, and to explore the link between glucose dysregulation and neurodegeneration.

METHODS: A dementia-free cohort (n = 1,248) aged >or=75 years was longitudinally examined to detect dementia, Alzheimer's disease and vascular dementia (VaD) cases (Diagnostic and Statistical Manual of Mental Disorders, revised third edition [DSM-III-R] criteria). The Alzheimer's disease diagnoses were subdivided into Alzheimer's disease with stroke and Alzheimer's disease without hypertension, heart disease and stroke. Diabetes was ascertained based on medical history, or hypoglycaemic medication use, or a random blood glucose level >or=11.0 mmol/l, which included undiagnosed diabetes when neither a history of diabetes nor hypoglycaemic drugs use was present. Uncontrolled diabetes was classified as a random blood glucose level >or=11.0 mmol/l in diabetic patients. Borderline diabetes was defined as a random blood glucose level of 7.8-11.0 mmol/l in diabetes-free individuals. Cox models were used to estimate HRs.

RESULTS: During the 9 year follow-up, 420 individuals developed dementia, including 47 with VaD and 320 with Alzheimer's disease (of the 320 Alzheimer's disease cases, 78 had previous, temporally unrelated stroke, and 137 had no major vascular comorbidities). Overall diabetes was only related to VaD (HR 3.21, 95% CI 1.20-8.63). Undiagnosed diabetes led to an HR of 3.29 (95% CI 1.20-9.01) for Alzheimer's disease. Diabetic patients with random blood glucose levels <7.8 mmol/l showed no increased dementia risk. Uncontrolled and borderline diabetes were further associated with Alzheimer's disease without vascular comorbidities.

CONCLUSIONS/INTERPRETATION: Uncontrolled diabetes increases the risk of Alzheimer's disease and VaD. Our findings suggest a direct link between glucose dysregulation and neurodegeneration.