Cardiometabolic Risk Factors and Domain-Specific Cognitive Function in Prediabetes and Type 2 Diabetes

Abstract

Background: Cardiometabolic risk factors are increasingly recognised as contributors to cognitive decline, yet their associations with domain-specific cognitive performance in adults with prediabetes or well-controlled type 2 diabetes (T2DM) remain poorly characterised. Methods: This cross-sectional study included 49 adults with prediabetes or well-controlled T2DM (managed by diet or metformin alone; HbA1c < 8%). Cognitive function was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB), Trail Making Tests (TMTs) parts A and B, Stroop, and Digit Symbol Substitution Test (DSST). Multivariable linear regression examined associations between cardiometabolic predictors (adiposity [DXA], glycaemic indices [OGTT], and serum lipids) and cognitive outcomes, adjusting for age, BMI, and education. Results: Higher HbA1c was independently associated with increased false alarms on the rapid visual processing task (RVPPFA; β = 0.04 [95% CI 0.01, 0.07]; p = 0.015); fasting and 2 h glucose were not associated with any cognitive measure. Higher triglycerides were associated with lower sustained attention accuracy (RVPA; β = −0.02 [95% CI −0.04, −0.004]; p = 0.016) and lower DSST scores (β = −4.61 [95% CI −8.81, −0.40]; p = 0.033). Higher HDL cholesterol was independently associated with better sustained attention (RVPA; β = 0.08 [95% CI 0.02, 0.15]; p = 0.017). No consistent associations were found between adiposity measures and any cognitive outcome, with no effect modification by sex or diabetes status (all Pinteraction > 0.05). Conclusions: In cognitively healthy adults with prediabetes or well-controlled T2DM, higher HbA1c and triglycerides and lower HDL were associated with poorer domain-specific cognitive performance in the absence of overt cognitive impairment. Larger longitudinal studies are needed to establish whether these associations represent early cognitive changes and to determine whether reducing cardiometabolic risk can preserve cognitive function.