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. 2017 Nov;40(11):1537-1547.
doi: 10.2337/dc17-0330. Epub 2017 Aug 25.

The Role of Hyperglycemia, Insulin Resistance, and Blood Pressure in Diabetes-Associated Differences in Cognitive Performance-The Maastricht Study

Stefan L C Geijselaers  1   2   3 , Simone J S Sep  1   2 , Danny Claessens  1 , Miranda T Schram  1   2 , Martin P J van Boxtel  4 , Ronald M A Henry  1   2 , Frans R J Verhey  4 , Abraham A Kroon  1   2 , Pieter C Dagnelie  2   5   6 , Casper G Schalkwijk  1   2 , Carla J H van der Kallen  1   2 , Geert Jan Biessels  3 , Coen D A Stehouwer  7   2
Affiliations

The Role of Hyperglycemia, Insulin Resistance, and Blood Pressure in Diabetes-Associated Differences in Cognitive Performance-The Maastricht Study

Stefan L C Geijselaers et al. Diabetes Care. 2017 Nov.

Abstract

Objective: 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.

Research design and methods: 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.

Results: 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.

Conclusions: 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.

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