PMID- 27636847 OWN - NLM STAT- MEDLINE DCOM- 20180215 LR - 20220408 IS - 1875-8908 (Electronic) IS - 1387-2877 (Print) IS - 1387-2877 (Linking) VI - 55 IP - 1 DP - 2017 TI - Humans with Type-2 Diabetes Show Abnormal Long-Term Potentiation-Like Cortical Plasticity Associated with Verbal Learning Deficits. PG - 89-100 AB - BACKGROUND: Type-2 diabetes mellitus (T2DM) accelerates cognitive aging and increases risk of Alzheimer's disease. Rodent models of T2DM show altered synaptic plasticity associated with reduced learning and memory. Humans with T2DM also show cognitive deficits, including reduced learning and memory, but the relationship of these impairments to the efficacy of neuroplastic mechanisms has never been assessed. OBJECTIVE: Our primary objective was to compare mechanisms of cortical plasticity in humans with and without T2DM. Our secondary objective was to relate plasticity measures to standard measures of cognition. METHODS: A prospective cross-sectional cohort study was conducted on 21 adults with T2DM and 15 demographically-similar non-diabetic controls. Long-term potentiation-like plasticity was assessed in primary motor cortex by comparing the amplitude of motor evoked potentials (MEPs) from single-pulse transcranial magnetic stimulation before and after intermittent theta-burst stimulation (iTBS). Plasticity measures were compared between groups and related to neuropsychological scores. RESULTS: In T2DM, iTBS-induced modulation of MEPs was significantly less than controls, even after controlling for potential confounds. Furthermore, in T2DM, modulation of MEPs 10-min post-iTBS was significantly correlated with Rey Auditory Verbal Learning Task (RAVLT) performance. CONCLUSION: Humans with T2DM show abnormal cortico-motor plasticity that is correlated with reduced verbal learning. Since iTBS after-effects and the RAVLT are both NMDA receptor-dependent measures, their relationship in T2DM may reflect brain-wide alterations in the efficacy of NMDA receptors. These findings offer novel mechanistic insights into the brain consequences of T2DM and provide a reliable means to monitor brain health and evaluate the efficacy of clinical interventions. FAU - Fried, Peter J AU - Fried PJ AD - Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Interventional Cognitive Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. FAU - Schilberg, Lukas AU - Schilberg L AD - Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Interventional Cognitive Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. AD - Department of Cognitive Neuroscience, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, The Netherlands. FAU - Brem, Anna-Katharine AU - Brem AK AD - Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Interventional Cognitive Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. AD - Department of Experimental Psychology, University of Oxford, Oxford, UK. FAU - Saxena, Sadhvi AU - Saxena S AD - Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Interventional Cognitive Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. AD - Department of Psychiatry and Behavioral Sciences, Johns Hopkins Medical School, Baltimore, MD, USA. FAU - Wong, Bonnie AU - Wong B AD - Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Interventional Cognitive Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. AD - Frontotemporal Dementia Unit, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA. FAU - Cypess, Aaron M AU - Cypess AM AD - Diabetes, Endocrinology, and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD, USA. AD - Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA. FAU - Horton, Edward S AU - Horton ES AD - Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA. FAU - Pascual-Leone, Alvaro AU - Pascual-Leone A AD - Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Interventional Cognitive Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA. LA - eng GR - R21 AG051846/AG/NIA NIH HHS/United States 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 - Observational Study PL - Netherlands TA - J Alzheimers Dis JT - Journal of Alzheimer's disease : JAD JID - 9814863 SB - IM MH - Aged MH - Aged, 80 and over MH - Cognition MH - Cross-Sectional Studies MH - Diabetes Mellitus, Type 2/*physiopathology/psychology MH - Electromyography MH - Evoked Potentials, Motor/physiology MH - Humans MH - Learning Disabilities/etiology/*physiopathology MH - Magnetic Resonance Imaging MH - Middle Aged MH - Motor Cortex/diagnostic imaging/*physiopathology MH - Muscle, Skeletal/physiopathology MH - *Neuronal Plasticity/physiology MH - Neuropsychological Tests MH - Prospective Studies MH - *Speech Perception MH - Transcranial Magnetic Stimulation PMC - PMC5193103 MID - NIHMS835993 OTO - NOTNLM OT - Cognitive aging OT - neuroplasticity OT - transcranial magnetic stimulation OT - type 2 diabetes mellitus OT - verbal learning EDAT- 2016/09/17 06:00 MHDA- 2018/02/16 06:00 PMCR- 2017/01/01 CRDT- 2016/09/17 06:00 PHST- 2016/09/17 06:00 [pubmed] PHST- 2018/02/16 06:00 [medline] PHST- 2016/09/17 06:00 [entrez] PHST- 2017/01/01 00:00 [pmc-release] AID - JAD160505 [pii] AID - 10.3233/JAD-160505 [doi] PST - ppublish SO - J Alzheimers Dis. 2017;55(1):89-100. doi: 10.3233/JAD-160505.