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      Predicting conversion to Alzheimer’s disease in individuals with Mild Cognitive Impairment using clinically transferable features

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          Abstract

          Patients with Mild Cognitive Impairment (MCI) have an increased risk of Alzheimer’s disease (AD). Early identification of underlying neurodegenerative processes is essential to provide treatment before the disease is well established in the brain. Here we used longitudinal data from the ADNI database to investigate prediction of a trajectory towards AD in a group of patients defined as MCI at a baseline examination. One group remained stable over time (sMCI, n = 357) and one converted to AD (cAD, n = 321). By running two independent classification methods within a machine learning framework, with cognitive function, hippocampal volume and genetic APOE status as features, we obtained a cross-validation classification accuracy of about 70%. This level of accuracy was confirmed across different classification methods and validation procedures. Moreover, the sets of misclassified subjects had a large overlap between the two models. Impaired memory function was consistently found to be one of the core symptoms of MCI patients on a trajectory towards AD. The prediction above chance level shown in the present study should inspire further work to develop tools that can aid clinicians in making prognostic decisions.

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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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              Neuropathological stageing of Alzheimer-related changes

              Eighty-three brains obtained at autopsy from nondemented and demented individuals were examined for extracellular amyloid deposits and intraneuronal neurofibrillary changes. The distribution pattern and packing density of amyloid deposits turned out to be of limited significance for differentiation of neuropathological stages. Neurofibrillary changes occurred in the form of neuritic plaques, neurofibrillary tangles and neuropil threads. The distribution of neuritic plaques varied widely not only within architectonic units but also from one individual to another. Neurofibrillary tangles and neuropil threads, in contrast, exhibited a characteristic distribution pattern permitting the differentiation of six stages. The first two stages were characterized by an either mild or severe alteration of the transentorhinal layer Pre-alpha (transentorhinal stages I-II). The two forms of limbic stages (stages III-IV) were marked by a conspicuous affection of layer Pre-alpha in both transentorhinal region and proper entorhinal cortex. In addition, there was mild involvement of the first Ammon's horn sector. The hallmark of the two isocortical stages (stages V-VI) was the destruction of virtually all isocortical association areas. The investigation showed that recognition of the six stages required qualitative evaluation of only a few key preparations.
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                Author and article information

                Contributors
                astri.lundervold@uib.no
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                16 September 2022
                16 September 2022
                2022
                : 12
                : 15566
                Affiliations
                [1 ]GRID grid.7914.b, ISNI 0000 0004 1936 7443, Department of Biological and Medical Psychology, , University of Bergen, ; Bergen, Norway
                [2 ]GRID grid.412008.f, ISNI 0000 0000 9753 1393, Mohn Medical Imaging and Visualization Centre (MMIV), Department of Radiology, , Haukeland University Hospital, ; Bergen, Norway
                [3 ]GRID grid.7914.b, ISNI 0000 0004 1936 7443, Department of Biomedicine, , University of Bergen, ; Bergen, Norway
                [4 ]GRID grid.412284.9, ISNI 0000 0004 0620 0652, Institute of Electronics, , Lodz University of Technology, ; Lodz, Poland
                [5 ]GRID grid.477239.c, ISNI 0000 0004 1754 9964, Department of Computer Science, Electrical Engineering, and Mathematical Sciences, , Western Norway University of Applied Sciences, ; Bergen, Norway
                Article
                18805
                10.1038/s41598-022-18805-5
                9481567
                36114257
                91d68c30-7a90-4f9a-91ef-10a19044532f
                © The Author(s) 2022

                Open AccessThis 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
                : 24 February 2022
                : 19 August 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004257, Helse Vest;
                Award ID: F-12534
                Award Recipient :
                Funded by: Trond Mohn stiftelse
                Award ID: BFS2018TMT07
                Funded by: University of Bergen (incl Haukeland University Hospital)
                Categories
                Article
                Custom metadata
                © The Author(s) 2022

                Uncategorized
                dementia,alzheimer's disease,human behaviour
                Uncategorized
                dementia, alzheimer's disease, human behaviour

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