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      BDNF Val66Met polymorphism is associated with altered activity-dependent modulation of short-interval intracortical inhibition in bilateral M1

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          Abstract

          The BDNF Val66Met polymorphism is associated with impaired short-term plasticity in the motor cortex, short-term motor learning, and intermanual transfer of a procedural motor skill. Here, we investigated the impact of the Val66Met polymorphism on the modulation of cortical excitability and interhemispheric inhibition through sensorimotor practice of simple dynamic skills with the right and left first dorsal interosseous (FDI) muscles. To that end, we compared motor evoked potentials (MEP) amplitudes and short-interval intracortical inhibition (SICI) in the bilateral representations of the FDI muscle in the primary motor cortex (M1), and interhemispheric inhibition (IHI) from the left to right M1, before and after right and left FDI muscle training in an alternated sequence. Val66Met participants did not differ from their Val66Val counterparts on motor performance at baseline and following motor training, or on measures of MEP amplitude and IHI. However, while the Val66Val group displayed significant SICI reduction in the bilateral M1 in response to motor training, SICI remained unchanged in the Val66Met group. Further, Val66Val group’s SICI decrease in the left M1, which was also observed following unimanual training with the right hand in the Control Right group, was correlated with motor improvement with the left hand. The potential interaction between left and right M1 activity during bimanual training and the implications of altered activity-dependent cortical excitability on short-term motor learning in Val66Met carriers are discussed.

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          Vitamin E and donepezil for the treatment of mild cognitive impairment.

          Mild cognitive impairment is a transitional state between the cognitive changes of normal aging and early Alzheimer's disease. In a double-blind study, we evaluated subjects with the amnestic subtype of mild cognitive impairment. Subjects were randomly assigned to receive 2000 IU of vitamin E daily, 10 mg of donepezil daily, or placebo for three years. The primary outcome was clinically possible or probable Alzheimer's disease; secondary outcomes were cognition and function. A total of 769 subjects were enrolled, and possible or probable Alzheimer's disease developed in 212. The overall rate of progression from mild cognitive impairment to Alzheimer's disease was 16 percent per year. As compared with the placebo group, there were no significant differences in the probability of progression to Alzheimer's disease in the vitamin E group (hazard ratio, 1.02; 95 percent confidence interval, 0.74 to 1.41; P=0.91) or the donepezil group (hazard ratio, 0.80; 95 percent confidence interval, 0.57 to 1.13; P=0.42) during the three years of treatment. Prespecified analyses of the treatment effects at 6-month intervals showed that as compared with the placebo group, the donepezil group had a reduced likelihood of progression to Alzheimer's disease during the first 12 months of the study (P=0.04), a finding supported by the secondary outcome measures. Among carriers of one or more apolipoprotein E epsilon4 alleles, the benefit of donepezil was evident throughout the three-year follow-up. There were no significant differences in the rate of progression to Alzheimer's disease between the vitamin E and placebo groups at any point, either among all patients or among apolipoprotein E epsilon4 carriers. Vitamin E had no benefit in patients with mild cognitive impairment. Although donepezil therapy was associated with a lower rate of progression to Alzheimer's disease during the first 12 months of treatment, the rate of progression to Alzheimer's disease after three years was not lower among patients treated with donepezil than among those given placebo. Copyright 2005 Massachusetts Medical Society.
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              Developing criteria for establishing interrater reliability of specific items: applications to assessment of adaptive behavior.

              A set of criteria based upon biostatistical considerations for determining the interrater reliability of specific adaptive behavior items in a given setting was presented. The advantages and limitations of extant statistical assessment procedures were discussed. Also, a set of guidelines for differentiating type of adaptive behavior that are statistically reliable from those that are reliable in a clinical or practical sense was delineated. Data sets were presented throughout in order to illustrate the advantages of recommended statistical procedures over other available ones.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SoftwareRole: SupervisionRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: Investigation
                Role: Data curationRole: Formal analysisRole: Investigation
                Role: ConceptualizationRole: Funding acquisitionRole: ResourcesRole: SupervisionRole: ValidationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                1 June 2018
                2018
                : 13
                : 6
                : e0197505
                Affiliations
                [1 ] Université de Montréal, Montréal, Canada
                [2 ] Hôpital Sainte-Justine Research Center, Montréal, Canada
                University of Ottawa, CANADA
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0001-7307-480X
                Article
                PONE-D-17-41793
                10.1371/journal.pone.0197505
                5983496
                29856758
                209f7248-d5c8-4c46-bd01-6e760789bfae
                © 2018 Morin-Moncet et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 27 November 2017
                : 3 May 2018
                Page count
                Figures: 7, Tables: 0, Pages: 21
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100000038, Natural Sciences and Engineering Research Council of Canada;
                Award ID: RGPIN-2016-05079
                Award Recipient :
                This work was supported by grant from the Natural Sciences and Engineering Research of Canada, RGPIN-2016-05079 ( http://www.nserc-crsng.gc.ca/index_eng.asp) to HT. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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