Abstract
Slower psychomotor speed is very common in patients with type 1 diabetes mellitus (T1D), but the underlying mechanisms are not clear. We propose that hyperglycemia is associated with slower psychomotor speed via disruption of brain activation. Eighty-five adults (48% women, mean age: 49.0 years, mean duration: 40.8) with childhood onset T1D were recruited for this cross-sectional study. Median response time in seconds (longer = worse performance) and brain activation were measured while performing a psychomotor speed task. Exposure to hyperglycemia, measured as glycosylated hemoglobin A1c, was associated with longer response time and with higher activation in the inferior frontal gyrus and primary sensorimotor and dorsal cingulate cortex. Higher activation in inferior frontal gyrus, primary sensorimotor cortex, thalamus, and cuneus was related to longer response times; in contrast, higher activation in the superior parietal lobe was associated with shorter response times. Associations were independent of small vessel disease in the brain or other organs. In this group of middle-aged adults with T1D, the pathway linking chronic hyperglycemia with slower processing speed appears to include increased brain activation, but not small vessel disease. Activation in the superior parietal lobe may compensate for dysregulation in brain activation in the presence of hyperglycemia.
Highlights
Compared to aged nondiabetic adults, persons with type 1 diabetes (T1D) are more likely to exhibit cognitive deficits, especially localized within the psychomotor and information processing domains [1,2,3,4,5]
We found that chronic hyperglycemia was related to higher activation in selected brain regions that were engaged in performing the Digit Symbol Substitution Tests (DSST) and to worse task performance
Consistent with the literature in adults with T1D, we found that chronic hyperglycemia was associated with poorer performance of a task of psychomotor speed while in the scanner, and this association was robust to adjustment for other covariates
Summary
Compared to aged nondiabetic adults, persons with type 1 diabetes (T1D) are more likely to exhibit cognitive deficits, especially localized within the psychomotor and information processing domains [1,2,3,4,5]. Slower psychomotor speed is associated with several negative health outcomes, in persons both with [6,7,8] and without diabetes [9, 10]. With the rising number of persons with T1D surviving into older age [14], it is increasingly important to characterize the predictors of slower psychomotor speed to design interventions that reduce its negative impact on health outcomes. Chronic hyperglycemia has been implicated in cognitive complications in several studies of T1D, including ours [15,16,17,18]. Small vessel diseases, including brain white matter hyperintensities and retinopathy, have been associated
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