Glycemic dysregulation and cognitive impairment in aging adults: a cross-sectional study with amyloid biomarker correlation.

<h4>Background</h4>Type 2 Diabetes Mellitus (T2DM) is a rising health concern, particularly affecting the elderly population. Beyond its well-established metabolic consequences, growing evidence suggests a strong association between type 2 diabetes mellitus and cognitive decline. The core features of diabetes, viz., chronic hyperglycemia and insulin resistance (IR), not only contribute to the neurodegenerative changes in the brain but also promote the generation and accumulation of amyloid-β (a hallmark feature in Alzheimer's disease). These molecular changes triggered by T2DM play a pivotal role in the onset of cognitive damage. In this study, we have explored the interplay between glycemic status, cognitive performance, and plasma amyloid-β (Aβ) levels in an ageing population.<h4>Methodology</h4>A cross-sectional study was conducted among 396 individuals aged 51-80 years. Based on their HbA1c levels, the study participants were categorized into four glycemic groups: individuals without diabetes, individuals with prediabetes, individuals with diabetes, and individuals with uncontrolled diabetes. Cognitive function was evaluated using the Modified Mini-Mental State Examination (3MSE). Fasting glucose, insulin, Homeostatic Model Assessment (HOMA)-IR, lipid profiles, and plasma Aβ 1-40 and Aβ 1-42 were measured. Statistical analyses were carried out using Chi-square tests, logistic regression, Spearman correlation, and Receiver Operating Characteristic (ROC) curve analysis.<h4>Results</h4>A comparative assessment in the study revealed the prevalence of cognitive impairment across all glycemic groups, with 40.15% of participants overall affected. It was observed that the prevalence increased with the glycemic index, with 26.97% of individuals without diabetes affected, 35.92% of individuals with prediabetes, 55.03% of individuals with diabetes under control, and 70.91% of individuals with uncontrolled diabetes (p < 0.001). Logistic regression indicated progressively higher odds of cognitive impairment with worsening glycemic control (OR for individuals with uncontrolled diabetes ≈6.87, p < 0.001). Age and HbA1c were significantly inversely correlated with 3MS scores. Plasma Aβ 1-40 and Aβ 1-42 levels were elevated in individuals with diabetes groups, while the Aβ 1-42/Aβ 1-40 ratio was positively associated with cognitive performance. The ROC curve analysis of the logistic regression indicated an Area Under Curve (AUC) of 0.76, suggesting good predictive capability.<h4>Conclusion</h4>Impaired glycemic status was found to be strongly associated with increased cognitive decline, alongside altered amyloid biomarker profiles, in elderly populations. These findings suggest the heightened importance of metabolic homeostasis and also underscore the critical need for early metabolic interventions and cognitive screening in the individuals with diabetes to mitigate the risk of early neurodegeneration.