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      Age-Dependent Association Between Cognitive Reserve Proxy and Longitudinal White Matter Microstructure in Older Adults

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          Abstract

          Objective

          This study examined the association of lifetime experiences, measured by a cognitive reserve (CR) composite score composed of years of education, literacy, and vocabulary measures, to level and rate of change in white matter microstructure, as assessed by diffusion tensor imaging (DTI) measures. We also examined whether the relationship between the proxy CR composite score and white matter microstructure was modified by participant age, APOE-ε4 genetic status, and level of vascular risk.

          Methods

          A sample of 192 non-demented ( n = 166 cognitively normal, n = 26 mild cognitive impairment) older adults [mean age = 70.17 (SD = 8.5) years] from the BIOCARD study underwent longitudinal DTI (mean follow-up = 2.5 years, max = 4.7 years). White matter microstructure was quantified by fractional anisotropy (FA) and radial diffusivity (RD) values in global white matter tracts and medial temporal lobe (MTL) white matter tracts.

          Results

          Using longitudinal linear mixed effect models, we found that FA decreased over time and RD increased over time in both the global and MTL DTI composites, but the rate of change in these DTI measures was not related to level of CR. However, there were significant interactions between the CR composite score and age for global RD in the full sample, and for global FA, global RD, and MTL RD among those with normal cognition. These interactions indicated that among participants with a lower baseline age, higher CR composite scores were associated with higher FA and lower RD values, while among participants with higher age at baseline, higher CR composite scores were associated with lower FA and higher RD values. Furthermore, these relationships were not modified by APOE-ε4 genotype or level of vascular risk.

          Conclusion

          The association between level of CR and DTI measures differs by age, suggesting a possible neuroprotective effect of CR among late middle-aged adults that shifts to a compensatory effect among older adults.

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          Most cited references74

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          The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

          The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of revising the 1984 criteria for Alzheimer's disease (AD) dementia. The workgroup sought to ensure that the revised criteria would be flexible enough to be used by both general healthcare providers without access to neuropsychological testing, advanced imaging, and cerebrospinal fluid measures, and specialized investigators involved in research or in clinical trial studies who would have these tools available. We present criteria for all-cause dementia and for AD dementia. We retained the general framework of probable AD dementia from the 1984 criteria. On the basis of the past 27 years of experience, we made several changes in the clinical criteria for the diagnosis. We also retained the term possible AD dementia, but redefined it in a manner more focused than before. Biomarker evidence was also integrated into the diagnostic formulations for probable and possible AD dementia for use in research settings. The core clinical criteria for AD dementia will continue to be the cornerstone of the diagnosis in clinical practice, but biomarker evidence is expected to enhance the pathophysiological specificity of the diagnosis of AD dementia. Much work lies ahead for validating the biomarker diagnosis of AD dementia. Copyright © 2011. Published by Elsevier Inc.
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            “Mini-mental state”

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              The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease

              The National Institute on Aging and the Alzheimer's Association charged a workgroup with the task of developing criteria for the symptomatic predementia phase of Alzheimer's disease (AD), referred to in this article as mild cognitive impairment due to AD. The workgroup developed the following two sets of criteria: (1) core clinical criteria that could be used by healthcare providers without access to advanced imaging techniques or cerebrospinal fluid analysis, and (2) research criteria that could be used in clinical research settings, including clinical trials. The second set of criteria incorporate the use of biomarkers based on imaging and cerebrospinal fluid measures. The final set of criteria for mild cognitive impairment due to AD has four levels of certainty, depending on the presence and nature of the biomarker findings. Considerable work is needed to validate the criteria that use biomarkers and to standardize biomarker analysis for use in community settings. Copyright © 2011 The Alzheimer's Association. All rights reserved.
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                Author and article information

                Contributors
                Journal
                Front Psychol
                Front Psychol
                Front. Psychol.
                Frontiers in Psychology
                Frontiers Media S.A.
                1664-1078
                10 June 2022
                2022
                : 13
                : 859826
                Affiliations
                [1] 1Department of Neurology, School of Medicine, Johns Hopkins University , Baltimore, MD, United States
                [2] 2Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University , Baltimore, MD, United States
                [3] 3Department of Radiology, School of Medicine, Johns Hopkins University , Baltimore, MD, United States
                Author notes

                Edited by: Rochele Paz Fonseca, Pontifical Catholic University of Rio Grande do Sul, Brazil

                Reviewed by: Derek Archer, Vanderbilt University Medical Center, United States; Lissett Gonzalez-Burgos, University of La Laguna, Spain

                *Correspondence: Corinne Pettigrew, cpettigrew@ 123456jhmi.edu

                This article was submitted to Cognition, a section of the journal Frontiers in Psychology

                Article
                10.3389/fpsyg.2022.859826
                9226781
                35756247
                e8909201-f01a-4f44-94b9-b686ec3d54b3
                Copyright © 2022 Brichko, Soldan, Zhu, Wang, Faria, Albert, Pettigrew and The BIOCARD Research Team.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 21 January 2022
                : 12 May 2022
                Page count
                Figures: 2, Tables: 2, Equations: 0, References: 74, Pages: 12, Words: 9765
                Funding
                Funded by: National Institutes of Health , doi 10.13039/100000002;
                Award ID: U19-AG033655
                Award ID: P30-AG066507
                Categories
                Psychology
                Original Research

                Clinical Psychology & Psychiatry
                diffusion tensor imaging,cognitive reserve,brain maintenance,aging,white matter microstructure,vascular risk,apoe

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