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      Declines in Connected Language Are Associated with Very Early Mild Cognitive Impairment: Results from the Wisconsin Registry for Alzheimer’s Prevention

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          Abstract

          Changes to everyday spoken language (“connected language”) are evident in persons with AD dementia, yet little is known about when these changes are first detectable on the continuum of cognitive decline. The aim of this study was to determine if participants with very early, subclinical memory declines were also showing declines in connected language. We analyzed connected language samples obtained from a simple picture description task at two time points in 264 participants from the Wisconsin Registry for Alzheimer’s Prevention (WRAP). In parallel, participants were classified as either “Cognitively Healthy” or “Early Mild Cognitive Impairment” based on longitudinal neuropsychological test performance. Linear mixed effects models were used to analyze language parameters that were extracted from the connected language samples using automated feature extraction. Participants with eMCI status declined faster in features of speech fluency and semantic content than those who were cognitively stable. Measures of lexical diversity and grammatical complexity were not associated with eMCI status in this group. These findings provide novel insights about the relationship between cognitive decline and everyday language, using a quick, inexpensive, and performance-based method.

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          Most cited references61

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          Executive function and the frontal lobes: a meta-analytic review.

          Currently, there is debate among scholars regarding how to operationalize and measure executive functions. These functions generally are referred to as "supervisory" cognitive processes because they involve higher level organization and execution of complex thoughts and behavior. Although conceptualizations vary regarding what mental processes actually constitute the "executive function" construct, there has been a historical linkage of these "higher-level" processes with the frontal lobes. In fact, many investigators have used the term "frontal functions" synonymously with "executive functions" despite evidence that contradicts this synonymous usage. The current review provides a critical analysis of lesion and neuroimaging studies using three popular executive function measures (Wisconsin Card Sorting Test, Phonemic Verbal Fluency, and Stroop Color Word Interference Test) in order to examine the validity of the executive function construct in terms of its relation to activation and damage to the frontal lobes. Empirical lesion data are examined via meta-analysis procedures along with formula derivatives. Results reveal mixed evidence that does not support a one-to-one relationship between executive functions and frontal lobe activity. The paper concludes with a discussion of the implications of construing the validity of these neuropsychological tests in anatomical, rather than cognitive and behavioral, terms.
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            Innovative diagnostic tools for early detection of Alzheimer's disease.

            Current state-of-the-art diagnostic measures of Alzheimer's disease (AD) are invasive (cerebrospinal fluid analysis), expensive (neuroimaging) and time-consuming (neuropsychological assessment) and thus have limited accessibility as frontline screening and diagnostic tools for AD. Thus, there is an increasing need for additional noninvasive and/or cost-effective tools, allowing identification of subjects in the preclinical or early clinical stages of AD who could be suitable for further cognitive evaluation and dementia diagnostics. Implementation of such tests may facilitate early and potentially more effective therapeutic and preventative strategies for AD. Before applying them in clinical practice, these tools should be examined in ongoing large clinical trials. This review will summarize and highlight the most promising screening tools including neuropsychometric, clinical, blood, and neurophysiological tests.
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              Linguistic ability in early life and cognitive function and Alzheimer's disease in late life. Findings from the Nun Study.

              To determine if linguistic ability in early life is associated with cognitive function and Alzheimer's disease in late life. Two measures of linguistic ability in early life, idea density and grammatical complexity, were derived from autobiographies written at a mean age of 22 years. Approximately 58 years later, the women who wrote these autobiographies participated in an assessment of cognitive function, and those who subsequently died were evaluated neuropathologically. Convents in the United States participating in the Nun Study; primarily convents in the Milwaukee, Wis, area. Cognitive function was investigated in 93 participants who were aged 75 to 95 years at the time of their assessments, and Alzheimer's disease was investigated in the 14 participants who died at 79 to 96 years of age. Seven neuropsychological tests and neuropathologically confirmed Alzheimer's disease. Low idea density and low grammatical complexity in autobiographies written in early life were associated with low cognitive test scores in late life. Low idea density in early life had stronger and more consistent associations with poor cognitive function than did low grammatical complexity. Among the 14 sisters who died, neuropathologically confirmed Alzheimer's disease was present in all of those with low idea density in early life and in none of those with high idea density. Low linguistic ability in early life was a strong predictor of poor cognitive function and Alzheimer's disease in late life.
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                Author and article information

                Contributors
                Journal
                Front Aging Neurosci
                Front Aging Neurosci
                Front. Aging Neurosci.
                Frontiers in Aging Neuroscience
                Frontiers Media S.A.
                1663-4365
                09 January 2018
                2017
                : 9
                : 437
                Affiliations
                [1] 1Wisconsin Alzheimer’s Institute, University of Wisconsin School of Medicine and Public Health , Madison, WI, United States
                [2] 2Department of Neurology, University of Wisconsin School of Medicine and Public Health , Madison, WI, United States
                [3] 3Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital , Madison, WI, United States
                [4] 4Wisconsin Alzheimer’s Disease Research Center, University of Wisconsin School of Medicine and Public Health , Madison, WI, United States
                [5] 5Department of Communication Sciences and Disorders, University of Wisconsin–Madison , Madison, WI, United States
                [6] 6Neuroscience Training Program and Department of Surgery, University of Wisconsin–Madison , Madison, WI, United States
                Author notes

                Edited by: Lutz Jäncke, University of Zurich, Switzerland

                Reviewed by: Jed A. Meltzer, Baycrest Hospital, Canada; Guido Gainotti, Fondazione Policlinico Universitario A. Gemelli – Università Cattolica del Sacro Cuore, Italy

                *Correspondence: Kimberly D. Mueller, kdmueller@ 123456wisc.edu
                Article
                10.3389/fnagi.2017.00437
                5767238
                29375365
                406bc596-6542-4faa-8d0e-0359f1a08803
                Copyright © 2018 Mueller, Koscik, Hermann, Johnson and Turkstra.

                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) or licensor 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
                : 20 October 2017
                : 18 December 2017
                Page count
                Figures: 3, Tables: 5, Equations: 0, References: 75, Pages: 14, Words: 0
                Funding
                Funded by: National Institutes of Health 10.13039/100000002
                Award ID: R01 AG027161
                Categories
                Neuroscience
                Original Research

                Neurosciences
                alzheimer’s disease (ad),mild cognitive impairment (mci),language,speech,connected speech,discourse analysis,picture description,verbal fluency

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