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      A machine learning-based linguistic battery for diagnosing mild cognitive impairment due to Alzheimer’s disease

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          Abstract

          There is a limited evaluation of an independent linguistic battery for early diagnosis of Mild Cognitive Impairment due to Alzheimer’s disease (MCI-AD). We hypothesized that an independent linguistic battery comprising of only the language components or subtests of popular test batteries could give a better clinical diagnosis for MCI-AD compared to using an exhaustive battery of tests. As such, we combined multiple clinical datasets and performed Exploratory Factor Analysis (EFA) to extract the underlying linguistic constructs from a combination of the Consortium to Establish a Registry for Alzheimer’s disease (CERAD), Wechsler Memory Scale (WMS) Logical Memory (LM) I and II, and the Boston Naming Test. Furthermore, we trained a machine-learning algorithm that validates the clinical relevance of the independent linguistic battery for differentiating between patients with MCI-AD and cognitive healthy control individuals. Our EFA identified ten linguistic variables with distinct underlying linguistic constructs that show Cronbach’s alpha of 0.74 on the MCI-AD group and 0.87 on the healthy control group. Our machine learning evaluation showed a robust AUC of 0.97 when controlled for age, sex, race, and education, and a clinically reliable AUC of 0.88 without controlling for age, sex, race, and education. Overall, the linguistic battery showed a better diagnostic result compared to the Mini-Mental State Examination (MMSE), Clinical Dementia Rating Scale (CDR), and a combination of MMSE and CDR.

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          Most cited references26

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          Clinical dementia rating: a reliable and valid diagnostic and staging measure for dementia of the Alzheimer type.

          J Morris (1997)
          Global staging measures for dementia of the Alzheimer type (DAT) assess the influence of cognitive loss on the ability to conduct everyday activities and represent the "ultimate test" of efficacy for antidementia drug trials. They provide information about clinically meaningful function and behavior and are less affected by the "floor" and "ceiling" effects commonly associated with psychometric tests. The Washington University Clinical Dementia Rating (CDR) is a global scale developed to clinically denote the presence of DAT and stage its severity. The clinical protocol incorporates semistructured interviews with the patient and informant to obtain information necessary to rate the subject's cognitive performance in six domains: memory, orientation, judgment and problem solving, community affairs, home and hobbies, and personal care. The CDR has been standardized for multicenter use, including the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) and the Alzheimer's Disease Cooperative Study, and interrater reliability has been established. Criterion validity for both the global CDR and scores on individual domains has been demonstrated, and the CDR also has been validated neuropathologically, particularly for the presence or absence of dementia. Standardized training protocols are available. Although not well suited as a brief screening tool for population surveys of dementia because the protocol depends on sufficient time to conduct interviews, the CDR has become widely accepted in the clinical setting as a reliable and valid global assessment measure for DAT.
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            The proportion of missing data should not be used to guide decisions on multiple imputation

            Objectives Researchers are concerned whether multiple imputation (MI) or complete case analysis should be used when a large proportion of data are missing. We aimed to provide guidance for drawing conclusions from data with a large proportion of missingness. Study Design and Setting Via simulations, we investigated how the proportion of missing data, the fraction of missing information (FMI), and availability of auxiliary variables affected MI performance. Outcome data were missing completely at random or missing at random (MAR). Results Provided sufficient auxiliary information was available; MI was beneficial in terms of bias and never detrimental in terms of efficiency. Models with similar FMI values, but differing proportions of missing data, also had similar precision for effect estimates. In the absence of bias, the FMI was a better guide to the efficiency gains using MI than the proportion of missing data. Conclusion We provide evidence that for MAR data, valid MI reduces bias even when the proportion of missingness is large. We advise researchers to use FMI to guide choice of auxiliary variables for efficiency gain in imputation analyses, and that sensitivity analyses including different imputation models may be needed if the number of complete cases is small.
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              Comparing the Pearson and Spearman correlation coefficients across distributions and sample sizes: A tutorial using simulations and empirical data.

              The Pearson product–moment correlation coefficient (rp) and the Spearman rank correlation coefficient (rs) are widely used in psychological research. We compare rp and rs on 3 criteria: variability, bias with respect to the population value, and robustness to an outlier. Using simulations across low (N = 5) to high (N = 1,000) sample sizes we show that, for normally distributed variables, rp and rs have similar expected values but rs is more variable, especially when the correlation is strong. However, when the variables have high kurtosis, rp is more variable than rs. Next, we conducted a sampling study of a psychometric dataset featuring symmetrically distributed data with light tails, and of 2 Likert-type survey datasets, 1 with light-tailed and the other with heavy-tailed distributions. Consistent with the simulations, rp had lower variability than rs in the psychometric dataset. In the survey datasets with heavy-tailed variables in particular, rs had lower variability than rp, and often corresponded more accurately to the population Pearson correlation coefficient (Rp) than rp did. The simulations and the sampling studies showed that variability in terms of standard deviations can be reduced by about 20% by choosing rs instead of rp. In comparison, increasing the sample size by a factor of 2 results in a 41% reduction of the standard deviations of rs and rp. In conclusion, rp is suitable for light-tailed distributions, whereas rs is preferable when variables feature heavy-tailed distributions or when outliers are present, as is often the case in psychological research.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SoftwareRole: Writing – original draft
                Role: InvestigationRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing – review & editing
                Role: Project administrationRole: Writing – review & editing
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                2020
                5 March 2020
                : 15
                : 3
                : e0229460
                Affiliations
                [1 ] Department of Health Services Management and Policy, College of Public Health, East Tennessee State University, Johnson City, TN, United States of America
                [2 ] Psychiatry Research Division, Department of Psychiatry and Behavioral Sciences, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, United States of America
                Nathan S Kline Institute, UNITED STATES
                Author notes

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

                Author information
                http://orcid.org/0000-0001-7678-8680
                Article
                PONE-D-19-26354
                10.1371/journal.pone.0229460
                7058300
                32134942
                0ca2c205-e058-4159-b030-3a5322a6a9c0
                © 2020 Orimaye 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
                : 19 September 2019
                : 6 February 2020
                Page count
                Figures: 2, Tables: 8, Pages: 18
                Funding
                This study was funded in part by the Department of Psychiatry and Behavioral Sciences, James H. Quillen College of Medicine, East Tennessee State University. No additional external funding was received for this study.
                Categories
                Research Article
                Biology and Life Sciences
                Neuroscience
                Cognitive Science
                Cognitive Neuroscience
                Cognitive Neurology
                Cognitive Impairment
                Biology and Life Sciences
                Neuroscience
                Cognitive Neuroscience
                Cognitive Neurology
                Cognitive Impairment
                Medicine and Health Sciences
                Neurology
                Cognitive Neurology
                Cognitive Impairment
                Social Sciences
                Linguistics
                Cognitive Linguistics
                Medicine and Health Sciences
                Mental Health and Psychiatry
                Dementia
                Alzheimer's Disease
                Medicine and Health Sciences
                Neurology
                Dementia
                Alzheimer's Disease
                Medicine and Health Sciences
                Neurology
                Neurodegenerative Diseases
                Alzheimer's Disease
                Computer and Information Sciences
                Artificial Intelligence
                Machine Learning
                Biology and Life Sciences
                Neuroscience
                Cognitive Science
                Cognition
                Memory
                Biology and Life Sciences
                Neuroscience
                Learning and Memory
                Memory
                Social Sciences
                Linguistics
                Sociolinguistics
                Physical Sciences
                Mathematics
                Applied Mathematics
                Algorithms
                Machine Learning Algorithms
                Research and Analysis Methods
                Simulation and Modeling
                Algorithms
                Machine Learning Algorithms
                Computer and Information Sciences
                Artificial Intelligence
                Machine Learning
                Machine Learning Algorithms
                Medicine and Health Sciences
                Diagnostic Medicine
                Custom metadata
                All data files are available from the Layton Aging and Alzheimer’s Disease Center and the Oregon Center for Aging and Technology Research Repository ( http://www.ohsu.edu/xd/research/centers-institutes/orcatech/index.cfm), and the National Alzheimer’s Coordinating Center(NACC) Uniform Data sets version 3.0 (UDS 3.0)( https://www.alz.washington.edu/WEB/data_descript.html).

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