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

Abstract

BackgroundThe 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.MethodsA 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.ResultsIn 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).ConclusionsThe 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.

Weight loss from 20 years of age is associated with cognitive impairment in middle-aged and elderly individuals

“…BMI and long-term weight changes were divided into quintiles. We first checked the association between the demographic variables of sex, age, education level, and histories of stroke and diabetes [ 20 ] (basic determinants of MMSE-assessed cognitive impairment) and prevalence of cognitive impairment, and then ORs calculated according to potential predictors were adjusted for covariates, including sex, age, education level, and histories of stroke and diabetes. P for trend was calculated by logistic regression analysis.…”

Association of Late Life Depression, (Non-) Modifiable Risk and Protective Factors with Dementia and Alzheimer’s Disease: Literature Review on Current Evidences, Preventive Interventions and Possible Future Trends in Prevention and Treatment of Dementia

“…Diabetes mellitus is a metabolic disorder characterized by insulin resistance or insulin deficiency. During diabetes variations in plasma osmotic pressure and oxidative stress levels may result in cognitive changes in the brain, that is, the imbalance between oxidants and antioxidants initiates neurodegeneration through the excessive deposition of Aβ peptide and the release of free radicals, and, correspondingly, they can lead to dementia [ 80 , 81 ]. The preliminary results of recent clinical trial studies have indicated that intranasal insulin therapy may help improve verbal memory, especially, the story recall performance of the APOE genotype [ 82 ].…”

“…We remind the reader that, for instance, midlife obesity is often associated with hypertension and diabetes mellitus. These three possibly modifiable risk factors can cause an accumulation of neurotoxic peptides and oxidative stress level changes in the brain that in time may result in cognitive impairment and dementia [ 78 , 81 , 89 ]. Similarly, the higher risk of dementia in the elderly individuals with various comorbid cardiometabolic diseases such as diabetes mellitus or stroke can be moderated by social engagement and physical activities [ 131 ].…”

[P1–566]: Is There an Association Between Cancer and Dementia in Cohorts With and Without T2dm? A National Observational Study

“…In a recent retrospective cohort study using the National Insurance Research Database of about 10,000 patients with diabetes and 50,000 age and sex matched non-diabetic patients, researchers found that dementia risk was higher in diabetics and the risk did not significantly increase in the presence of hypertension and hyperlipidemia. However, in the non-diabetes cohort, patients who had both hypertension and hyperlipidemia had a higher risk of dementia compared to those without (Fan Y-C et al, 2017). This study sheds light on the complexity of vascular risk factors and whether they are perhaps meditated through one main mechanism (ex: insulin resistance) without really having an independent effect on dementia risk.…”