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      Age-related iron accumulation and demyelination in the basal ganglia are closely related to verbal memory and executive functioning

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          Abstract

          Age-related cognitive decline has been linked to alterations of the dopaminergic system and its subcortical trajectories. Recent work suggests a critical role of iron accumulation within the basal ganglia (BG) in verbal memory performance, and increased iron levels have been related to demyelination. However, the specificity of age-related iron increases with respect to cognitive functions remains unclear. Therefore, we investigated the interplay of age, cognitive performance, and structural integrity of the BG. In total, 79 healthy older participants underwent a broad cognitive assessment (fluid and crystallized intelligence, verbal and numeric memory, processing speed, executive functions) and structural MRI. As expected, performance in most cognitive tests had a negative relationship with age. Moreover, BG grey matter volume and magnetization transfer (MT, indicative of myelin) decreased, and R2* (indicative of iron) increased with age. Importantly, R2* and demyelination negatively correlated with verbal memory and executive functions. Within the SN/VTA, age correlated negatively with MT, but there was no clear evidence in favor of a relationship between behavior and R2* or MT. Our results suggest that age-related increases in iron and demyelination within the BG, which are part of a fronto-striatal network, not only impact on verbal memory but also executive functions.

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          Most cited references114

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          The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment.

          To develop a 10-minute cognitive screening tool (Montreal Cognitive Assessment, MoCA) to assist first-line physicians in detection of mild cognitive impairment (MCI), a clinical state that often progresses to dementia. Validation study. A community clinic and an academic center. Ninety-four patients meeting MCI clinical criteria supported by psychometric measures, 93 patients with mild Alzheimer's disease (AD) (Mini-Mental State Examination (MMSE) score > or =17), and 90 healthy elderly controls (NC). The MoCA and MMSE were administered to all participants, and sensitivity and specificity of both measures were assessed for detection of MCI and mild AD. Using a cutoff score 26, the MMSE had a sensitivity of 18% to detect MCI, whereas the MoCA detected 90% of MCI subjects. In the mild AD group, the MMSE had a sensitivity of 78%, whereas the MoCA detected 100%. Specificity was excellent for both MMSE and MoCA (100% and 87%, respectively). MCI as an entity is evolving and somewhat controversial. The MoCA is a brief cognitive screening tool with high sensitivity and specificity for detecting MCI as currently conceptualized in patients performing in the normal range on the MMSE.
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            Executive Functions

            Executive functions (EFs) make possible mentally playing with ideas; taking the time to think before acting; meeting novel, unanticipated challenges; resisting temptations; and staying focused. Core EFs are inhibition [response inhibition (self-control—resisting temptations and resisting acting impulsively) and interference control (selective attention and cognitive inhibition)], working memory, and cognitive flexibility (including creatively thinking “outside the box,” seeing anything from different perspectives, and quickly and flexibly adapting to changed circumstances). The developmental progression and representative measures of each are discussed. Controversies are addressed (e.g., the relation between EFs and fluid intelligence, self-regulation, executive attention, and effortful control, and the relation between working memory and inhibition and attention). The importance of social, emotional, and physical health for cognitive health is discussed because stress, lack of sleep, loneliness, or lack of exercise each impair EFs. That EFs are trainable and can be improved with practice is addressed, including diverse methods tried thus far.
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              FSL.

              FSL (the FMRIB Software Library) is a comprehensive library of analysis tools for functional, structural and diffusion MRI brain imaging data, written mainly by members of the Analysis Group, FMRIB, Oxford. For this NeuroImage special issue on "20 years of fMRI" we have been asked to write about the history, developments and current status of FSL. We also include some descriptions of parts of FSL that are not well covered in the existing literature. We hope that some of this content might be of interest to users of FSL, and also maybe to new research groups considering creating, releasing and supporting new software packages for brain image analysis. Copyright © 2011 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                davina.biel@med.uni-muenchen.de
                nico.bunzeck@uni-luebeck.de
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                3 May 2021
                3 May 2021
                2021
                : 11
                : 9438
                Affiliations
                [1 ]GRID grid.4562.5, ISNI 0000 0001 0057 2672, Department of Psychology, , University of Lübeck, ; 23562 Lübeck, Germany
                [2 ]GRID grid.5252.0, ISNI 0000 0004 1936 973X, Institute for Stroke and Dementia Research (ISD), , University Hospital, LMU Munich, ; 81377 Munich, Germany
                [3 ]GRID grid.4562.5, ISNI 0000 0001 0057 2672, Center of Brain, Behavior and Metabolism (CBBM), , University of Lübeck, ; Ratzeburger Allee 160, 23562 Lübeck, Germany
                Author information
                https://orcid.org/0000-0002-2597-1992
                https://orcid.org/0000-0001-8834-450X
                Article
                88840
                10.1038/s41598-021-88840-1
                8093241
                33941809
                8a06feb2-b74a-467c-96a2-4bfc40e79714
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 17 June 2020
                : 13 April 2021
                Funding
                Funded by: University of Lübeck, Germany
                Funded by: Universität zu Lübeck (3165)
                Categories
                Article
                Custom metadata
                © The Author(s) 2021

                Uncategorized
                cognitive ageing,cognitive neuroscience,neural ageing,biomarkers
                Uncategorized
                cognitive ageing, cognitive neuroscience, neural ageing, biomarkers

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