Longitudinal Associations Between Glycemic Status and Cognitive Function in Older Participants at High Risk of Cardiovascular Disease: Two-Year Follow-Up in the PREDIMED-Plus Study

Abstract BACKGROUND: Type 2 diabetes was related with larger cognitive decline. However, other glycemic dysregulations showed inconsistent results. Our aim was to examine longitudinal associations between diabetes/glycemic status and cognitive function in older adults with metabolic syndrome. METHODS: We conducted a 2-year prospective cohort study (n=6,874) within the framework of the PREDIMED-Plus study. The participants (with overweight/obesity and metabolic syndrome; mean age 64.9 years; 48.5% women) completed a battery of 8 cognitive tests, and a global cognitive function Z-score (GCF) was estimated. Participants were categorized by diabetes status (no-diabetes, prediabetes, and <5 or ≥5-year diabetes duration), and control. At baseline, insulin resistance (HOMA-IR) and glycated hemoglobin (HbA1c) levels were measured and antidiabetic medications were recorded. Linear and logistic regression models, adjusted by potential confounders, were fitted to assess associations between glycemic status and changes in cognitive function. RESULTS: Prediabetes status was unrelated to cognitive decline. However, compared to participants without diabetes, those with ≥5-year diabetes duration had greater reductions in the GCF (β=-0.11 [95%CI -0.16;-0.06]), processing speed and executive function measurements. Inverse associations were observed between baseline HOMA-IR and changes in the GCF (β=-0.0094 [95%CI -0.0164;-0.0023]), but also between HbA1c levels and changes in the GCF (β=-0.0610 [95%CI -0.0889;-0.0331]), the Mini-Mental test, and other executive function tests. Poor diabetes control was inversely associated with phonologic fluency. Sulfonylureas, but especially insulin use, were related to cognitive decline.CONCLUSIONS: Insulin resistance, diabetes status, longer diabetes duration, poor glycemic control, and insulin treatment were associated with worsening cognitive function at short-term in a population at high cardiovascular risk.TRIAL REGISTRATION: ISRCTN, ISRCTN89898870. Registered 28 May 2014 - Retrospectively registered, http://www.isrctn.com/ISRCTN89898870