Stefan L C Geijselaers1,2,3, Simone J S Sep1,2, Danny Claessens1, Miranda T Schram1,2, Martin P J van Boxtel4, Ronald M A Henry1,2, Frans R J Verhey4, Abraham A Kroon1,2, Pieter C Dagnelie2,5,6, Casper G Schalkwijk1,2, Carla J H van der Kallen1,2, Geert Jan Biessels3, Coen D A Stehouwer7,2. 1. Department of Internal Medicine, Maastricht University Medical Centre+, Maastricht, the Netherlands. 2. School for Cardiovascular Diseases (CARIM), Maastricht University, Maastricht, the Netherlands. 3. Department of Neurology, Brain Centre Rudolf Magnus, University Medical Centre Utrecht, Utrecht, the Netherlands. 4. Department of Psychiatry and Neuropsychology and School for Mental Health and Neuroscience, Maastricht University Medical Centre+, Maastricht, the Netherlands. 5. School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, the Netherlands. 6. Department of Epidemiology, Maastricht University, Maastricht, the Netherlands. 7. Department of Internal Medicine, Maastricht University Medical Centre+, Maastricht, the Netherlands cda.stehouwer@mumc.nl.
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.
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.
Authors: Leonard H Epstein; Rocco A Paluch; Jeff S Stein; Alexandra M Mellis; Teresa Quattrin; Lucy D Mastrandrea; Kyle A Bree; Mark H Greenawald; Warren K Bickel Journal: J Behav Med Date: 2019-03-22
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