PMID- 31295719 OWN - NLM STAT- MEDLINE DCOM- 20200423 LR - 20240214 IS - 1872-8952 (Electronic) IS - 1388-2457 (Print) IS - 1388-2457 (Linking) VI - 130 IP - 9 DP - 2019 Sep TI - Diabetes and the link between neuroplasticity and glutamate in the aging human motor cortex. PG - 1502-1510 LID - S1388-2457(19)30894-6 [pii] LID - 10.1016/j.clinph.2019.04.721 [doi] AB - OBJECTIVES: In older adults, type-2 diabetes mellitus (T2DM) impacts cognition and increases dementia risk. Prior studies suggest that impaired neuroplasticity may contribute to the cognitive decline in T2DM, but the underlying mechanisms of altered neuroplasticity are unclear. We investigated the relationship of the concentration of glutamatergic metabolites with measures of cortical plasticity in older adults across the spectrum of glucose intolerance/insulin resistance. METHODS: Forty adults (50-87 years: 17-T2DM, 14-pre-diabetes, 9-controls) underwent magnetic resonance spectroscopy to quantify glutamate and other key metabolites within a 2 cm(3) region around the hand knob of the left primary motor cortex. Thirty-six also underwent a separate transcranial magnetic stimulation (TMS) assessment of cortical excitability and plasticity using single-pulse TMS and intermittent theta-burst stimulation targeting the same brain region. RESULTS: Group differences were observed in relative concentrations of glutamine (p = .028), glucose (p = .008), total cholines (p = .048), and the glutamine/glutamate ratio (p = .024). Cortical plasticity was reduced in both T2DM and pre-diabetes groups relative to controls (p-values < .05). Only the T2DM group showed a significant positive association between glutamate concentration and plasticity (r = .56, p = .030). CONCLUSIONS: Neuroplastic mechanisms are already impaired in pre-diabetes. In T2DM, reduced cortico-motor plasticity is associated with lower cortical glutamate concentration. SIGNIFICANCE: Impaired plasticity in T2DM is associated with low glutamatergic metabolite levels. The glutamatergic neurotransmission system constitutes a potential therapeutic target for cognitive problems linked to plasticity-related deficiencies in T2DM. CI - Copyright (c) 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved. FAU - Fried, Peter J AU - Fried PJ AD - Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Cognitive Neurology, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. Electronic address: pfried@bidmc.harvard.edu. FAU - Pascual-Leone, Alvaro AU - Pascual-Leone A AD - Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Cognitive Neurology, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA; Institut Guttman, Universitat Autonoma de Barcelona, Badalona, Barcelona, Spain. FAU - Bolo, Nicolas R AU - Bolo NR AD - Spectroscopy, Psychiatry and Imaging Neuroscience Laboratory, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. LA - eng GR - R21 NS085491/NS/NINDS NIH HHS/United States GR - R21 NS082870/NS/NINDS NIH HHS/United States GR - R01 NS073601/NS/NINDS NIH HHS/United States GR - R21 MH099196/MH/NIMH NIH HHS/United States GR - R01 HD069776/HD/NICHD NIH HHS/United States GR - UL1 RR025758/RR/NCRR NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20190621 PL - Netherlands TA - Clin Neurophysiol JT - Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology JID - 100883319 RN - 020IUV4N33 (Phosphocreatine) RN - 0RH81L854J (Glutamine) RN - 107-73-3 (Phosphorylcholine) RN - 30KYC7MIAI (Aspartic Acid) RN - 3KX376GY7L (Glutamic Acid) RN - 4L6452S749 (Inositol) RN - 60M22SGW66 (Glycerylphosphorylcholine) RN - 997-55-7 (N-acetylaspartate) RN - GAN16C9B8O (Glutathione) RN - IY9XDZ35W2 (Glucose) RN - MU72812GK0 (Creatine) SB - IM MH - Aged MH - Aged, 80 and over MH - Aging/metabolism/physiology MH - Aspartic Acid/analogs & derivatives/metabolism MH - Creatine/metabolism MH - Diabetes Mellitus, Type 2/metabolism/*physiopathology MH - Female MH - Glucose/metabolism MH - Glucose Intolerance MH - Glutamic Acid/*metabolism MH - Glutamine/metabolism MH - Glutathione/metabolism MH - Glycerylphosphorylcholine/metabolism MH - Humans MH - Inositol/metabolism MH - Insulin Resistance MH - Magnetic Resonance Spectroscopy MH - Male MH - Middle Aged MH - Motor Cortex/metabolism/*physiology MH - *Neuronal Plasticity MH - Phosphocreatine/metabolism MH - Phosphorylcholine/metabolism MH - Prediabetic State/metabolism/*physiopathology MH - Theta Rhythm/physiology MH - Transcranial Magnetic Stimulation/methods PMC - PMC6684252 MID - NIHMS1534170 OTO - NOTNLM OT - Aging OT - Cortical plasticity OT - Glutamate OT - Impaired glucose tolerance OT - Insulin resistance OT - Magnetic resonance spectroscopy OT - Transcranial magnetic stimulation OT - Type-2 diabetes mellitus COIS- Conflict of Interest Statement Dr. Pascual-Leone serves on the scientific advisory boards for Starlab Neuroscience, Neuroelectrics, Neosync, NovaVision, and Cognito; and is listed as an inventor on several issued and pending patents on the real-time integration of transcranial magnetic stimulation with electroencephalography and magnetic resonance imaging. The authors declare no competing interests. EDAT- 2019/07/12 06:00 MHDA- 2020/04/24 06:00 PMCR- 2020/09/01 CRDT- 2019/07/12 06:00 PHST- 2018/10/22 00:00 [received] PHST- 2019/03/15 00:00 [revised] PHST- 2019/04/22 00:00 [accepted] PHST- 2019/07/12 06:00 [pubmed] PHST- 2020/04/24 06:00 [medline] PHST- 2019/07/12 06:00 [entrez] PHST- 2020/09/01 00:00 [pmc-release] AID - S1388-2457(19)30894-6 [pii] AID - 10.1016/j.clinph.2019.04.721 [doi] PST - ppublish SO - Clin Neurophysiol. 2019 Sep;130(9):1502-1510. doi: 10.1016/j.clinph.2019.04.721. Epub 2019 Jun 21.