Increased dementia risk predominantly in diabetes mellitus rather than in hypertension or hyperlipidemia: a population-based cohort study

Background: The pathophysiology of insulin resistance-induced hypertension and hyperlipidemia might entail differences in dementia risk in cases with hypertension and hyperlipidemia without prior diabetes mellitus (DM). This study investigated whether incident hypertension, incident hyperlipidemia, or both, increased the dementia risk in patients with and without DM. Methods: A nationwide retrospective cohort study was conducted. The study sample was obtained from the National Health Insurance Research Database. We enrolled 10,316 patients with a new diagnosis of DM between 2000 and 2002 in the DM cohort. For the same period, we randomly selected 41,264 patients without DM in the non-DM cohort (matched by age and sex at a 1: 4 ratio with the DM cohort). Both cohorts were then separately divided into four groups on the basis of incident hypertension or incident hyperlipidemia status. Results: In total, 51,580 patients aged between 20 and 99 years were enrolled. The dementia risk was higher in the DM cohort than in the non-DM cohort (adjusted hazard ratio (HR) = 1.47, 95% confidence interval (CI) = 1.30-1.67, p < 0.001). In the DM cohort, the dementia risk in patients with both hypertension and hyperlipidemia did not significantly increase compared with that in those without hypertension and hyperlipidemia (p = 0.529). Similar results were observed in those with either hypertension (p = 0.341) or hyperlipidemia (p = 0.189). In the non-DM cohort, patients with both hypertension and hyperlipidemia had a higher dementia risk (adjusted HR = 1.33, 95% CI = 1.09-1.63, p = 0.006). The results remained largely unchanged in patients with only hypertension (adjusted HR = 1.22, 95% CI = 1.05-1.40, p = 0.008). However, the dementia risk did not increase significantly in patients with only hyperlipidemia (p = 0.187). Conclusions: The development of hypertension, hyperlipidemia, or both, following a diagnosis of incident diabetes is secondary to diabetes onset and likely mediated through insulin resistance associated with diabetes, which does not further accentuate dementia risk. DM itself (i.e., the systemic influence of hyperglycemia) might be the main driver of increased dementia risk.