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      Herpesvirus infections, antiviral treatment, and the risk of dementia—a registry‐based cohort study in Sweden

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          Abstract

          Introduction

          Herpesviruses, including Herpes simplex virus type 1 (HSV1) and varicella zoster‐virus (VZV), have been implicated in Alzheimer's disease (AD) development. Likewise, antiviral treatment has been suggested to protect against dementia development in herpes‐infected individuals.

          Methods

          The study enrolled 265,172 subjects aged ≥ 50 years, with diagnoses of VZV or HSV, or prescribed antiviral drugs between 31 December 2005 and 31 December 2017. Controls were matched in a 1:1 ratio by sex and birth year.

          Results

          Antiviral treatment was associated with decreased risk of dementia (adjusted hazard ratio [HR] 0.89, 95% confidence interval [CI] 0.86 to 0.92), while herpes infection without antiviral drugs increased the risk of dementia (adjusted HR 1.50, 95% CI 1.29 to 1.74).

          Discussion

          Antiviral treatment was associated with a reduced long‐term risk of dementia among individuals with overt signs of herpes infection. This is consistent with earlier findings indicating that herpesviruses are involved in the pathogenesis of AD.

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          External review and validation of the Swedish national inpatient register

          Jonas F. Ludvigsson, Eva Andersson, Anders Ekbom … (2011)
          Background The Swedish National Inpatient Register (IPR), also called the Hospital Discharge Register, is a principal source of data for numerous research projects. The IPR is part of the National Patient Register. The Swedish IPR was launched in 1964 (psychiatric diagnoses from 1973) but complete coverage did not begin until 1987. Currently, more than 99% of all somatic (including surgery) and psychiatric hospital discharges are registered in the IPR. A previous validation of the IPR by the National Board of Health and Welfare showed that 85-95% of all diagnoses in the IPR are valid. The current paper describes the history, structure, coverage and quality of the Swedish IPR. Methods and results In January 2010, we searched the medical databases, Medline and HighWire, using the search algorithm "validat* (inpatient or hospital discharge) Sweden". We also contacted 218 members of the Swedish Society of Epidemiology and an additional 201 medical researchers to identify papers that had validated the IPR. In total, 132 papers were reviewed. The positive predictive value (PPV) was found to differ between diagnoses in the IPR, but is generally 85-95%. Conclusions In conclusion, the validity of the Swedish IPR is high for many but not all diagnoses. The long follow-up makes the register particularly suitable for large-scale population-based research, but for certain research areas the use of other health registers, such as the Swedish Cancer Register, may be more suitable.
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            The new Swedish Prescribed Drug Register--opportunities for pharmacoepidemiological research and experience from the first six months.

            Bjorn Wettermark, Niklas Hammar, Carl Michael Fored … (2007)
            To describe the content and potentials of the new Swedish national register on prescribed and dispensed medicines. The Swedish Prescribed Drug Register contains information about age, sex and unique identifier of the patient as well as the prescriber's profession and practice. Information regarding drug utilization and expenditures for prescribed drugs in the entire Swedish population was extracted from the first six months July-December 2005 and compared with total drug sales in the country including OTC and hospital use. The total quantity of drugs sold in Sweden was 2666 million DDDs, corresponding to 1608 DDD/1000 inhabitants daily. The total expenditures were 1.6 billion Euro. The prescribed drugs, included in the register, accounted for 84% of the total utilization and 77% of the total expenditures. About half of all men and two-thirds of all women in the country purchased drugs. The proportion increased by age. The most common drugs for chronic treatment were diuretics among women (8.8% of the population) and antithrombotic agents among men (7.6%). Psychotropic drugs, corticosteroids and analgesics were more common among women, while men used antithrombotic agents, antidiabetic drugs, lipid lowering agents and ACE inhibitors to a greater extent. The new register provides valuable data on exposure to drugs and is useful to study patterns of drug utilization. The possibilities for record linkage to other health registers gives from an international perspective good opportunities to explore drug and disease associations and the risks, benefits, effectiveness and health economical effects of drug use.
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              Multiscale Analysis of Independent Alzheimer’s Cohorts Finds Disruption of Molecular, Genetic, and Clinical Networks by Human Herpesvirus

              Eric E. Schadt, Joel T Dudley, Sam Gandy … (2018)
              Investigators have long suspected that pathogenic microbes might contribute to the onset and progression of Alzheimer’s disease (AD) although definitive evidence has not been presented. Whether such findings represent a causal contribution, or reflect opportunistic passengers of neurodegeneration is also difficult to resolve. We constructed multiscale networks of the late onset AD-associated virome, integrating genomic, transcriptomic, proteomic, and histopathological data across four brain regions from human postmortem tissue. We observed increased human herpesvirus 6A (HHV-6A) and human herpesvirus 7 (HHV-7) from subjects with AD compared with controls. These results were replicated in two additional, independent and geographically dispersed cohorts. We observed regulatory relationships linking viral abundance and modulators of APP metabolism, including induction of APBB2 , APPBP2 , BIN1 , BACE1 , CLU , PICALM , and PSEN1 by HHV-6A. This study elucidates networks linking molecular, clinical, and neuropathological features with viral activity and is consistent with viral activity constituting a general feature of AD. Readhead et al. construct multiscale networks of the late onset Alzheimer’s disease (AD) associated virome, and observe pathogenic regulation of molecular, clinical and neuropathological networks by several common viruses, particularly human herpesvirus 6A and human herpesvirus 7.
              Article 0 comments Cited 169 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Karin Lopatko Lindman: karin.lopatko.lindman@umu.se
                Journal
                Journal ID (nlm-ta): Alzheimers Dement (N Y)
                Journal ID (iso-abbrev): Alzheimers Dement (N Y)
                Journal ID (doi): 10.1002/(ISSN)2352-8737
                Journal ID (publisher-id): TRC2
                Title: Alzheimer's & Dementia : Translational Research & Clinical Interventions
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Electronic): 2352-8737
                Publication date (Electronic): 14 February 2021
                Publication date Collection: 2021
                Volume: 7
                Issue: 1 ( doiID: 10.1002/trc2.v7.1 )
                Electronic Location Identifier: e12119
                Affiliations
                [ 1 ] Department of Community Medicine and Rehabilitation, Geriatric Medicine Umeå University Umeå Sweden
                [ 2 ] Department of Public Health and Caring Sciences, Geriatric Medicine Uppsala University Uppsala Sweden
                [ 3 ] Centre for Demographic and Ageing Research Umeå University Umeå Sweden
                [ 4 ] Department of Clinical Microbiology, Virology Umeå University Umeå Sweden
                [ 5 ] Wallenberg Centre for Molecular Medicine (WCMM) Umeå University Umeå Sweden
                Author notes
                [*] [* ] Correspondence

                Karin Lopatko Lindman, Department of Community Medicine and Rehabilitation, Geriatric Medicine, Umeå University, SE‐901 85 Umeå, Sweden.

                Email: karin.lopatko.lindman@ 123456umu.se

                Article
                Publisher ID: TRC212119
                DOI: 10.1002/trc2.12119
                PMC ID: 7882534
                PubMed ID: 33614892
                SO-VID: be8b6374-af50-4ad3-b974-109fa1afcbde
                Copyright © © 2020 The Authors. Alzheimer's & Dementia: Translational Research & Clinical Interventions published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association.
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                Date received : 16 October 2020
                Date accepted : 04 November 2020
                Page count
                Figures: 1, Tables: 2, Pages: 8, Words: 5338
                Categories
                Subject: Research Article
                Subject: Research Articles
                Custom metadata
                source-schema-version-number 2.0
                cover-date 2021
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.7 mode:remove_FC converted:14.02.2021

                Keywords: alzheimer's disease,antiviral agents,dementia,herpes simplex,herpes zoster,retrospective cohort study,varicella zoster
                Data availability:
                Keywords: alzheimer's disease, antiviral agents, dementia, herpes simplex, herpes zoster, retrospective cohort study, varicella zoster

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