Insulin resistance drives cognitive impairment in hypertensive pre-diabetic frail elders: the CENTENNIAL study

Aims: Pre-diabetes is a condition that confers an increased cardiovascular risk. Frailty is very common in hypertensive patients, and insulin resistance has been linked to frailty in older adults with diabetes. On these grounds, our aim was to evaluate the association between insulin resistance and cognitive impairment in hypertensive and pre-diabetic and frail older adults. Methods and results: We studied consecutive pre-diabetic and hypertensive elders with frailty presenting at the Avellino local health authority of the Italian Ministry of Health (ASL AV) from March 2021 to March 2022. All of them fulfilled the following inclusion criteria: a previous diagnosis of hypertension with no clinical or laboratory evidence of secondary causes, a confirmed diagnosis of pre-diabetes, age >65 years, Montreal Cognitive Assessment (MoCA) Score <26, and frailty. We enrolled 178 frail patients, of which 141 successfully completed the study. We observed a strong inverse correlation (r = -0.807; P < 0.001) between MoCA Score and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR). The results were confirmed by a linear regression analysis using MoCA Score as dependent variable, after adjusting for several potential confounders. Conclusion: Taken together, our data highlight for the first time the association between insulin resistance and global cognitive function in frail elders with hypertension and pre-diabetes.