title: Impaired macromolecular protein pools in fronto-striato-thalamic circuits in type 2 diabetes revealed by magnetization transfer imaging.
abstract: Previous research has shown that type 2 diabetes mellitus (T2DM) is associated with white matter microstructural changes, cognitive impairment, and decreased resting-state functional connectivity and spontaneous brain activity. This study used magnetization transfer imaging to examine, for the first time, the integrity of macromolecular protein pools in fronto-striato-thalamic circuits and its clinical and cognitive correlates in patients with T2DM. T2DM patients without mood disorders (n = 20, aged 65.05 ± 11.95 years) and healthy control subjects (HCs; n = 26, aged 62.92 ± 12.71 years) were recruited. Nodes of fronto-striato-thalamic circuits-head of the caudate nucleus (hCaud), putamen, globus pallidus, thalamus-and four cortical regions-rostral and dorsal anterior cingulate cortex, dorsolateral prefrontal cortex, and lateral orbitofrontal cortex-were examined. Compared with HCs, patients with T2DM had significantly lower magnetization transfer ratio (MTR) in bilateral anterior cingulate and hCaud. Reduced MTRs in the above regions showed correlations with T2DM-related clinical measures, including hemoglobin A1c level and vascular risk factors, and neuropsychological task performance in the domains of learning and memory, executive function, and attention and information processing. The impaired biophysical integrity of brain macromolecular protein pools and their local microenvironments in T2DM patients may provide insights into the neurological pathophysiology underlying diabetes-associated clinical and cognitive deficits.
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, Chicago, IL Department of Radiology, University of Illinois at Chicago, Chicago, IL Department of Bioengineering, University of Illinois at Chicago, Chicago, IL syang@psych.uic.edu akumar@psych.uic.edu.
authors.forename: Shaolin
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, Chicago, IL.
authors.forename: Olusola
authors.initials: O
authors.lastname: Ajilore
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, Chicago, IL.
authors.forename: Minjie
authors.initials: M
authors.lastname: Wu
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, Chicago, IL.
authors.forename: Melissa
authors.initials: M
authors.lastname: Lamar
authors.affiliation: Department of Psychiatry, University of Illinois at Chicago, Chicago, IL syang@psych.uic.edu akumar@psych.uic.edu.
authors.forename: Anand
authors.initials: A
authors.lastname: Kumar
mesh_terms: D000368:Aged; D001284:Atrophy / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D002560:Cerebrovascular Circulation; D003072:Cognition Disorders / Q000378:metabolism / Q000473:pathology; D003342:Corpus Striatum / Q000378:metabolism / Q000473:pathology; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism / Q000473:pathology; D006801:Humans; D046911:Macromolecular Substances / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000378:metabolism / Q000473:pathology; D009483:Neuropsychological Tests; D013788:Thalamus / Q000378:metabolism / Q000473:pathology
chemical_list: D046911:Macromolecular Substances
references.citation: Magn Reson Med. 1989 Apr;10(1):135-44
references.pmid: 2547135
references.citation: Arch Neurol. 2008 Nov;65(11):1454-9
references.pmid: 19001163
references.citation: Diabetes. 2014 Feb;63(2):728-38
references.pmid: 24203723
references.citation: Endocrinol Metab Clin North Am. 1996 Jun;25(2):325-59
references.pmid: 8799703
references.citation: Br J Soc Clin Psychol. 1967 Dec;6(4):278-96
references.pmid: 6080235
references.citation: Magn Reson Med. 2006 Oct;56(4):866-75
references.pmid: 16964602
references.citation: Diabetologia. 2010 Dec;53(12):2480-6
references.pmid: 20711716
references.citation: Diabetes Care. 2009 Jan;32(1):48-50
references.pmid: 18835947
references.citation: Arch Gen Psychiatry. 2003 Aug;60(8):779-88
references.pmid: 12912761
references.citation: Arthritis Res Ther. 2006;8(2):R38
references.pmid: 16469116
references.citation: Neuroimage. 2012 Jan 16;59(2):1098-105
references.pmid: 21967726
references.citation: Annu Rev Neurosci. 1986;9:357-81
references.pmid: 3085570
references.citation: Arch Neurol. 2007 Apr;64(4):570-5
references.pmid: 17420320
references.citation: Ann Neurol. 1999 Nov;46(5):747-54
references.pmid: 10553992
references.citation: J Psychiatr Res. 1975 Nov;12(3):189-98
references.pmid: 1202204
references.citation: Diabetes Care. 2013 Jan;36 Suppl 1:S11-66
references.pmid: 23264422
references.citation: Proc Natl Acad Sci U S A. 2002 Apr 16;99(8):5649-54
references.pmid: 11960018
references.citation: Psychiatry Res. 2010 Nov 30;184(2):63-70
references.pmid: 20832254
references.citation: Neuropsychopharmacology. 2013 Jul;38(8):1451-9
references.pmid: 23389692
references.citation: Diabetes. 2012 Sep;61(9):2375-9
references.pmid: 22664957
references.citation: J Am Geriatr Soc. 1968 May;16(5):622-6
references.pmid: 5646906
references.citation: Arch Gen Psychiatry. 2009 Mar;66(3):324-30
references.pmid: 19255382
references.citation: Lancet Neurol. 2006 Jan;5(1):64-74
references.pmid: 16361024
references.citation: Bipolar Disord. 2012 Sep;14(6):597-606
references.pmid: 22882719
references.citation: J Neurol Sci. 2010 Dec 15;299(1-2):126-30
references.pmid: 20869085
references.citation: Stroke. 1994 Jan;25(1):40-3
references.pmid: 8266381
references.citation: Diabetes. 2014 Feb;63(2):749-60
references.pmid: 24353185
references.citation: Neuropsychopharmacology. 2007 Jun;32(6):1224-31
references.pmid: 17180124
references.citation: Psychosom Med. 2001 Jul-Aug;63(4):619-30
references.pmid: 11485116
references.citation: Mult Scler. 2007 May;13(4):483-9
references.pmid: 17463071
references.citation: Schizophr Res. 2009 Apr;109(1-3):159-66
references.pmid: 19272755
references.citation: J Magn Reson Imaging. 2008 Jan;27(1):14-9
references.pmid: 18050330
references.citation: Mol Psychiatry. 2014 Jun;19(6):710-6
references.pmid: 23877833
references.citation: Ann Neurol. 2004 Sep;56(3):407-15
references.pmid: 15349868