To study to what extent differences in cognitive performance between individuals with different glucose metabolism status are potentially attributable to hyperglycemia, insulin resistance, and blood pressure–related variables.
We used cross-sectional data from 2,531 participants from the Maastricht Study (mean age ± SD, 60 ± 8 years; 52% men; n = 666 with type 2 diabetes), all of whom completed a neuropsychological test battery. Hyperglycemia was assessed by a composite index of fasting glucose, postload glucose, glycated hemoglobin (HbA1c), and tissue advanced glycation end products; insulin resistance by the HOMA of insulin resistance index; and blood pressure–related variables included 24-h ambulatory pressures, their weighted SDs, and the use of antihypertensive medication. Linear regression analyses were used to estimate mediating effects.
After adjustment for age, sex, and education, individuals with type 2 diabetes, compared with those with normal glucose metabolism, performed worse in all cognitive domains (mean differences in composite z scores for memory –0.087, processing speed –0.196, executive function and attention –0.182; P values <0.032), whereas individuals with prediabetes did not. Diabetes-associated differences in processing speed and executive function and attention were largely explained by hyperglycemia (mediating effect 79.6% [bootstrapped 95% CI 36.6; 123.4] and 50.3% [0.6; 101.2], respectively) and, for processing speed, to a lesser extent by blood pressure–related variables (17.7% [5.6; 30.1]), but not by insulin resistance. None of the factors explained the differences in memory function.
Our cross-sectional data suggest that early glycemic and blood pressure control, perhaps even in the prediabetic stage, may be promising therapeutic targets for the prevention of diabetes-associated decrements in cognitive performance.
