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      Incident Subjective Cognitive Decline Does Not Predict Mortality in the Elderly – Results from the Longitudinal German Study on Ageing, Cognition, and Dementia (AgeCoDe)

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          Abstract

          Objective

          Subjective cognitive decline (SCD) might represent the first symptomatic representation of Alzheimer’s disease (AD), which is associated with increased mortality. Only few studies, however, have analyzed the association of SCD and mortality, and if so, based on prevalent cases. Thus, we investigated incident SCD in memory and mortality.

          Methods

          Data were derived from the German AgeCoDe study, a prospective longitudinal study on the epidemiology of mild cognitive impairment (MCI) and dementia in primary care patients over 75 years covering an observation period of 7.5 years. We used univariate and multivariate Cox regression analyses to examine the relationship of SCD and mortality. Further, we estimated survival times by the Kaplan Meier method and case-fatality rates with regard to SCD.

          Results

          Among 971 individuals without objective cognitive impairment, 233 (24.0%) incidentally expressed SCD at follow-up I. Incident SCD was not significantly associated with increased mortality in the univariate (HR = 1.0, 95% confidence interval = 0.8–1.3, p = .90) as well as in the multivariate analysis (HR = 0.9, 95% confidence interval = 0.7–1.2, p = .40). The same applied for SCD in relation to concerns. Mean survival time with SCD was 8.0 years ( SD = 0.1) after onset.

          Conclusion

          Incident SCD in memory in individuals with unimpaired cognitive performance does not predict mortality. The main reason might be that SCD does not ultimately lead into future cognitive decline in any case. However, as prevalence studies suggest, subjectively perceived decline in non-memory cognitive domains might be associated with increased mortality. Future studies may address mortality in such other cognitive domains of SCD in incident cases.

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          Most cited references20

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          Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI.

          We have used restriction isotyping (restriction enzyme isoform genotyping) for rapid typing of common apolipoprotein E isoforms (E2, E3, E4). ApoE restriction isotyping used oligonucleotides to amplify apolipoprotein E gene sequences containing amino acid positions 112 and 158. The amplification products were digested with HhaI and subjected to electrophoresis on polyacrylamide gels. Each of the isoforms was distinguished by a unique combination of HhaI fragment sizes that enabled unambiguous typing of all homozygotic and heterozygotic combinations. HhaI cleaves at GCGC encoding 112arg (E4) and 158arg (E3, E4), but does not cut at GTGC encoding 112cys (E2, E3) and 158cys (E2).
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            A network dysfunction perspective on neurodegenerative diseases.

            Patients with Alzheimer's disease or other neurodegenerative disorders show remarkable fluctuations in neurological functions, even during the same day. These fluctuations cannot be caused by sudden loss or gain of nerve cells. Instead, it is likely that they reflect variations in the activity of neural networks and, perhaps, chronic intoxication by abnormal proteins that the brain is temporarily able to overcome. These ideas have far-reaching therapeutic implications.
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              World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects.

              (2015)
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                14 January 2016
                2016
                : 11
                : 1
                : e0147050
                Affiliations
                [1 ]Institute of Social Medicine, Occupational Health and Public Health (ISAP), University of Leipzig, Leipzig, Germany
                [2 ]LIFE–Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany
                [3 ]Department of Psychiatry, University of Bonn, Bonn, Germany
                [4 ]Institute of General Practice, Medical Faculty, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
                [5 ]Department of Primary Medical Care, Center for Psychosocial Medicine, University Medical Center Hamburg-Eppendorf, Hamburg-Eppendorf, Germany
                [6 ]Work Group Medical Statistics and IT-Infrastructure, Institute for General Practice, Hannover Medical School, Hannover, Germany
                [7 ]Central Institute of Mental Health, Medical Faculty, Mannheim/Heidelberg University, Mannheim, Germany
                [8 ]Department of Psychiatry, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
                [9 ]Department of Health Economics and Health Services Research, Hamburg Center for Health Economics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
                [10 ]German Center for Neurodegenerative Diseases, DZNE, Bonn, Germany
                [11 ]Department of Psychiatry, University of Cologne, Cologne, Germany
                University of Naples Federico II, ITALY
                Author notes

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

                Conceived and designed the experiments: HB MP SW HHK WM MS FJ SRH. Performed the experiments: HB MP SW HHK WM MS FJ SRH. Analyzed the data: SR TL BW. Contributed reagents/materials/analysis tools: BW JP. Wrote the paper: SR TL FJ SRH. Acquisition of data: TL KH AF AE JW CL EM. Revised the manuscript critically for important contents: KH AF AE BW JW HB CB AK MP CL JP SW EM HHK WM MS.

                ¶ Membership of the AgeCoDe Study Group is listed in the Acknowledgments.

                Article
                PONE-D-15-40739
                10.1371/journal.pone.0147050
                4713115
                26766555
                ec1a99fc-fe05-405c-9de4-88a71caeaa50
                © 2016 Roehr 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
                : 15 September 2015
                : 28 December 2015
                Page count
                Figures: 1, Tables: 3, Pages: 16
                Funding
                This publication is part of the German Research Network on Dementia (KND), the German Research Network on Degenerative Dementia (KNDD), and the Study on Needs, Health Service Use, Costs and Health-related Quality of Life in a large Sample of Oldest-old Primary Care Patients (85+) (AgeQualiDe) and was funded by the German Federal Ministry of Education and Research (grants KND 01GI0102, 01GI0420, 01GI0422, 01GI0423, 01GI0429, 01GI0431, 01GI0433 and 01GI0434; grants KNDD 01GI0710, 01GI0711, 01GI0712, 01GI0713, 01GI0714, 01GI0715, 01GI0716 and 01ET1006B; and grants AgeQualiDe 01GY1322A, 01GY1322B, 01GY1322C, 01GY1322D, 01GY1322E, 01GY1322F, 01GY1322G).
                Categories
                Research Article
                Custom metadata
                Due to restrictions that protect participant privacy, data are available upon request. Legal restrictions in form of data guidelines require the central data center to be involved in any handling and distribution of all data. The data will be available upon request to all interested researchers. Interested parties may contact the Working Group Medical Statistics and IT-Infrastructure (contact information: Birgitt Wiese, wiese.birgitt@ 123456mh-hannover.de , +49 511 532-4414).

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