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Association of Antineuronal Antibody Levels with Cognitive Impairment in Older Cuban Adults

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      Abstract

      ABSTRACT INTRODUCTION Alzheimer disease is the main cause of dementia associated with aging in Cuba and the world. Development of methods for early diagnosis is vital to increasing intervention effectiveness and improving patient quality of life. Recent studies have shown associations between alterations in serum levels of antineuronal antibodies and Alzheimer disease pathology. However, the specific relationship between such antineuronal antibodies and Alzheimer pathogenesis remains unclear because of the great variety of antibodies identified and their heterogeneity among patients and nondemented controls. OBJECTIVE Assess the association between serum levels of antibodies against neuronal antigens (total brain protein, aldolase and amyloid beta protein) and cognitive performance in older Cuban adults. METHODS A cross-sectional pilot study was conducted of adults aged ≥65 years living in Havana’s Playa Municipality and Artemisa Province (southwest of Havana). A sociodemographic and risk factor questionnaire was administered, neuropsychological assessment conducted, and physical and neurological examinations performed. A relative or caregiver was also interviewed. Laboratory tests included: complete blood count, glycemia, lipid panel, and apolipoprotein E genotype. Of 143 individuals studied, 33 were cognitively normal, 52 had mild cognitive impairment, and 58, probable Alzheimer disease. Serum antibody levels were determined by ELISA and compared using covariance analysis with a significance level of 0.05. ELISA specificity, sensitivity and predictive value were assessed by analyzing their respective diagnostic performance curves. RESULTS Patients with probable Alzheimer disease performed least well on the mini mental state examination (cognitively normal 28.8, SD 1.2; mild cognitive impairment 27.4, SD 2.2; probable Alzheimer disease 12.9, SD 6.5; ANOVA p <0.001). The percentage of Apo E4 carriers was seven times greater in the group with probable Alzheimer disease than in the cognitively normal group. Among the antibodies studied, only those against amyloid beta peptide had levels significantly higher in the Alzheimer disease group than in the cognitively normal group (p = 0.007) and the group with mild cognitive impairment (p = 0.002). CONCLUSIONS Results support the presence of an autoimmune component in Alzheimer disease and suggest that serum anti–amyloid-beta could be used for its diagnosis.

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      Most cited references 60

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      The Clinical Dementia Rating (CDR): current version and scoring rules.

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        Mild cognitive impairment as a diagnostic entity.

        The concept of cognitive impairment intervening between normal ageing and very early dementia has been in the literature for many years. Recently, the construct of mild cognitive impairment (MCI) has been proposed to designate an early, but abnormal, state of cognitive impairment. MCI has generated a great deal of research from both clinical and research perspectives. Numerous epidemiological studies have documented the accelerated rate of progression to dementia and Alzheimer's disease (AD) in MCI subjects and certain predictor variables appear valid. However, there has been controversy regarding the precise definition of the concept and its implementation in various clinical settings. Clinical subtypes of MCI have been proposed to broaden the concept and include prodromal forms of a variety of dementias. It is suggested that the diagnosis of MCI can be made in a fashion similar to the clinical diagnoses of dementia and AD. An algorithm is presented to assist the clinician in identifying subjects and subclassifying them into the various types of MCI. By refining the criteria for MCI, clinical trials can be designed with appropriate inclusion and exclusion restrictions to allow for the investigation of therapeutics tailored for specific targets and populations.
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          A method of comparing the areas under receiver operating characteristic curves derived from the same cases.

          Receiver operating characteristic (ROC) curves are used to describe and compare the performance of diagnostic technology and diagnostic algorithms. This paper refines the statistical comparison of the areas under two ROC curves derived from the same set of patients by taking into account the correlation between the areas that is induced by the paired nature of the data. The correspondence between the area under an ROC curve and the Wilcoxon statistic is used and underlying Gaussian distributions (binormal) are assumed to provide a table that converts the observed correlations in paired ratings of images into a correlation between the two ROC areas. This between-area correlation can be used to reduce the standard error (uncertainty) about the observed difference in areas. This correction for pairing, analogous to that used in the paired t-test, can produce a considerable increase in the statistical sensitivity (power) of the comparison. For studies involving multiple readers, this method provides a measure of a component of the sampling variation that is otherwise difficult to obtain.
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            Author and article information

            Affiliations
            orgnameCuban Neuroscience Center Cuba
            orgnameCuban Neuroscience Center Cuba
            orgnameIván Portuondo General Teaching Hospital Cuba
            orgnameCuban Neuroscience Center Cuba
            orgnameCuban Neuroscience Center Cuba
            orgnameIván Portuondo General Teaching Hospital Cuba
            orgnameCuban Neuroscience Center Cuba
            orgnameIván Portuondo General Teaching Hospital Cuba
            orgnameCuban Neuroscience Center Cuba
            orgnameIván Portuondo General Teaching Hospital Cuba
            orgnameCuban Neuroscience Center Cuba
            orgnameIván Portuondo General Teaching Hospital Cuba
            orgnameCuban Neuroscience Center Cuba
            Contributors
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            Journal
            medicc
            MEDICC Review
            MEDICC rev.
            Medical Education Cooperation with Cuba (Oakland, California, United States )
            1555-7960
            July 2017
            : 19
            : 2-3
            : 32-39
            S1555-79602017000200032
            10.1590/medicc.2017.1902030007

            This work is licensed under a Creative Commons Attribution-NonCommercial 3.0 International License.

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            Figures: 0, Tables: 0, Equations: 0, References: 60, Pages: 8
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            Product Information: SciELO Public Health

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