The Role of Inflammatory Markers in Linking Metabolic Syndrome to Cognitive Decline in Middle-Aged Women: A Focus on TNF-α and IL-6

Background: Metabolic syndrome (MetS) and related disorders, such as insulin resistance, pose significant health risks in middle-aged women, including cognitive decline. Chronic inflammation, characterized by elevated levels of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha), has been identified as a key mechanism linking metabolic disturbances to neurodegenerative processes. Methods: This study aimed to examine the associations between metabolic disorders, inflammatory markers, and cognitive function among middle-aged women. A cross-sectional study was conducted on 179 non-smoking perimenopausal and postmenopausal women aged 43-73 years. Anthropometric, metabolic, and cognitive parameters were assessed, including body mass index (BMI), waist-to-height ratio (WHtR), fasting glucose (GLU), triglycerides (TG), IL-6, TNF-alpha, and Mini-Mental State Examination (MMSE) scores. Logistic regression models were applied to evaluate the relationships between inflammation, MetS components, and cognitive impairments. Results: Women with insulin resistance showed significantly worse metabolic profiles and lower MMSE scores (23.98 vs. 24.91, p = 0.032). IL-6 levels were strongly associated with hypertriglyceridemia (OR = 1.096, 95% CI: 1.044-1.151, p < 0.001) and insulin resistance (OR = 1.068, 95% CI: 1.030-1.107, p < 0.001), while TNF-alpha correlated with abdominal obesity (WHtR OR = 1.429, 95% CI: 1.005-2.031, p = 0.047). Moreover, TNF-alpha was a significant predictor of cognitive impairments (OR = 1.362, 95% CI: 1.153-1.610, p < 0.001), whereas IL-6 showed no significant association. Conclusions: These findings highlight that TNF-alpha may be a key inflammatory marker associated with metabolic disturbances and cognitive decline in middle-aged women. IL-6 appears to be more specifically linked to lipid abnormalities and insulin resistance. Targeted interventions to reduce inflammation may moderate metabolic and cognitive risks in this population.