title: Brain Activation and Psychomotor Speed in Middle-Aged Patients with Type 1 Diabetes: Relationships with Hyperglycemia and Brain Small Vessel Disease.
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.
authors.affiliation: Department of Radiology, University of Pittsburgh, 3600 Forbes Avenue, Plaza Level, Pittsburgh, PA 15213, USA.
authors.forename: Misun
authors.initials: M
authors.lastname: Hwang
authors.affiliation: Department of Internal Medicine, Department of Psychiatry, and Department of Biostatistics, University of Pittsburgh, 200 Meyran Avenue, Suite 326, Pittsburgh, PA 15213, USA.
authors.forename: Dana L
authors.initials: DL
authors.lastname: Tudorascu
authors.affiliation: Department of Epidemiology, University of Pittsburgh, 130 N. Bellefield Avenue, Suite 443, Pittsburgh, PA 15213, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Nunley
authors.affiliation: Department of Bioengineering, University of Pittsburgh, 253 Sterling Plaza, Pittsburgh, PA 15213, USA.
authors.forename: Helmet
authors.initials: H
authors.lastname: Karim
authors.affiliation: Department of Psychiatry, University of Pittsburgh, 3811 O'Hara Street, Pittsburgh, PA 15213, USA.
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Aizenstein
authors.affiliation: Department of Epidemiology, University of Pittsburgh, 3512 Fifth Avenue, Pittsburgh, PA 15213, USA.
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Orchard
authors.affiliation: Department of Epidemiology, University of Pittsburgh, 130 N. Bellefield Avenue, Suite 467, Pittsburgh, PA 15213, USA.
authors.forename: Caterina
authors.initials: C
authors.lastname: Rosano
mesh_terms: D000367:Age Factors; D000375:Aging / Q000523:psychology*; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D001921:Brain / Q000503:physiopathology*; D001931:Brain Mapping / Q000379:methods; D059345:Cerebral Small Vessel Diseases / Q000097:blood / Q000209:etiology* / Q000503:physiopathology / Q000523:psychology; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000150:complications* / Q000503:physiopathology / Q000523:psychology; D003925:Diabetic Angiopathies / Q000097:blood / Q000209:etiology* / Q000503:physiopathology / Q000523:psychology; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D011597:Psychomotor Performance; D011930:Reaction Time; D013997:Time Factors
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human