For a study, researchers sought to evaluate the direct and indirect connection between prediabetes with dementia risk, as well as to investigate the age of diabetes development and eventual dementia risk. At baseline (1990-1992), prediabetes was defined as an HbA1C level of 5.7-6.4% among adults without a history of diagnosed diabetes or diabetic medication use; diabetes was defined as a self-reported physician diagnosis, diabetes medication use, or an HbA1C level of 6.5% or above. During the follow-up, the incidence of diabetes with the same criteria was added as a time-varying variable. Surveillance, interviews, and adjudication were used to determine incident dementia. The time scale for survival analysis was age, with an origin at 50 and left and right censoring. Sex, race, education, APOE, BMI, smoking status, alcohol usage, physical activity, total cholesterol, HDL cholesterol, and hypertension were all considered in the adjustment models.

At baseline, 2,314 (17.3%) of the 13,388 individuals had prediabetes, and 1798 (13.4%) had diabetes. In the fully adjusted model, the adjusted hazard ratios for dementia were 2.35 (95% CI: 1.99, 2.76) and 1.13 (95% CI: 1.02, 1.25) for diabetes and prediabetes compared to no diabetes. The extra risk of dementia for prediabetes was reduced by half if incident diabetes was included, and the link was not significant. For diabetes with age beginning at 60, 60-69, 70-79, and 80-93, the relative risks of dementia were 3.16 (95% CI: 2.15, 4.66), 1.64 (95% CI: 1.36, 1.97), 1.29 (95% CI: 1.14, 1.47), and 1.06 (95% CI: 0.89, 1.28), respectively.

Diabetes and prediabetes in middle age were linked to an increased risk of dementia and mortality. Diabetes development at a younger age was associated with a stronger dosage response and a higher risk of dementia. The intervening occurrence of clinical diabetes explained most of the risk of dementia in pre-diabetes. Preventing or delaying the development of prediabetes to diabetes might assist dementia preventive initiatives.