Association of Insulin Resistance and Metabolic Syndrome with Cognitive Impairment in Nonobese, Nondiabetic Older Adults: A Cross-Sectional Study

Background/Objectives: Insulin resistance (IR) and metabolic Syndrome (MSy) have been linked to cognitive decline, but their presence in mild cognitive impairment (MCI) and Alzheimer disease (AD) remains unclear. We evaluated MSy and IR in nonobese, nondiabetic older adults with cognitive dysfunction. Methods: The cross-sectional study included 143 participants aged 65–90 years: 62 with AD, 41 with MCI, and 40 cognitively preserved controls. Anthropometric measures, blood pressure, fasting glucose, insulin, and lipid levels were assessed. Diabetes was excluded by oral glucose tolerance testing. IR was estimated using HOMA-IR, and MSy was diagnosed according to International Diabetes Federation (IDF) criteria. Group differences and associations with cognitive impairment were assessed using analysis of variance and regression analyses. Results: Fasting insulin increased from controls to MCI and AD (7.18 ± 4.32, 13.76 ± 6.89, and 18.58 ± 8.19 mU/L), as did HOMA-IR (1.49 ± 0.98, 3.35 ± 1.72, and 4.59 ± 2.19, p < 0.05). Compared with controls, both cognitively impaired groups had higher fasting glucose, TCh, LDL-ch and lower HDL-ch (all p < 0.05), whereas triglycerides did not differ (p = 0.266). MSy prevalence was 22.5% in controls, 46.3% in MCI, and 35.5% in AD; however, the overall difference was not statistically significant (p = 0.079). In binary logistic regression analysis, sex, age, LDL-ch, and HOMA-IR were independently associated with cognitive impairment (all p < 0.05). Conclusions: Increased IR was more consistently associated with cognitive impairment than the presence of MSy, with the highest degree of IR observed in AD. These findings support an association between metabolic dysfunction and cognitive impairment and suggest that IR may represent a potential target for preventive and therapeutic strategies.