The Association of Fasting Glucose and Total Cholesterol with Cognitive Performance in a Primary Care Population: A Cross-Sectional Study

Objectives: This cross-sectional study aimed to evaluate the associations between fundamental metabolic markers, specifically fasting glucose and total cholesterol, and cognitive performance in a primary care population, continuing previous analyses focused on subclinical vascular parameters. Methods: The study included 137 primary care patients who completed neuropsychological assessments (Addenbrooke’s Cognitive Examination-III (ACE-III) and Mini-Mental State Examination (MMSE)) and a clinical interview. Fasting glucose and total cholesterol levels were extracted from their medical records. Results: Based on the MMSE, 26 participants (19.0%) had mild cognitive impairment (MCI), and 8 (5.8%) had neurocognitive disorders. Univariate regression analysis revealed that fasting glucose was significantly and inversely associated with the total ACE-III score (B = 0.277; 95% CI: −0.441 to −0.113; p = 0.001) and the M-ACE subscale score (B = 0.175; 95% CI: −0.342 to −0.008; p = 0.046). Conversely, total cholesterol showed a positive association with both the overall ACE-III score (B = 0.173; 95% CI: 0.006 to 0.340; p = 0.046) and the M-ACE score (B = 0.219; 95% CI: 0.053 to 0.385; p = 0.011). A potential clinical paradox was observed, as among patients with established cardiovascular disease, lower total cholesterol (177.39 vs. 201.58 mg/dL, p = 0.047) co-occurred with poorer cognitive outcomes (mean ACE-III: 81.47 vs. 87.62, p = 0.003), possibly reflecting a confounding effect of statin therapy. Standard MMSE scores did not correlate significantly with any evaluated metabolic parameters. Conclusions: Fasting glucose and total cholesterol are cross-sectionally associated with cognitive performance in this primary care cohort, whereas standard MMSE scores did not exhibit significant metabolic correlations. Given the exploratory, cross-sectional design, these findings are strictly hypothesis-generating and do not establish clinical screening utility or causality. The disparate patterns of association between the ACE-III and MMSE suggest that these screening tools may capture metabolism-related cognitive variations differently, highlighting the need for prospective longitudinal research.