| 1. |
- Hemmingsson, Eva-Stina, et al.
(författare)
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Antiviral treatment associated with reduced risk of clinical Alzheimer's disease : A nested case-control study
- 2021
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Ingår i: Alzheimer’s & Dementia. - : John Wiley & Sons. - 2352-8737. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In this nested case-control study, we investigated if antiviral treatment given prior to onset of Alzheimer's disease (AD) could influence incident AD.Methods: From a large population-based cohort study in northern Sweden, 262 individuals that later developed AD were compared to a non-AD matched control group with respect to prescriptions of herpes antiviral treatment. All included subjects were herpes simplex virus 1 (HSV1) carriers and the matching criteria were age, sex, apolipoprotein E genotype (ε4 allele carriership), and study sample start year.Results: Among those who developed AD, 6 prescriptions of antivirals were found, compared to 20 among matched controls. Adjusted for length of follow-up, a conditional logistic regression indicated a difference in the risk for AD development between groups (odds ratio for AD with an antiviral prescription 0.287, P = .018).Discussion: Antiviral treatment might possibly reduce the risk for later development of HSV1-associated AD.
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| 2. |
- Lindman, Karin Lopatko, et al.
(författare)
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A genetic signature including apolipoprotein E epsilon 4 potentiates the risk of herpes simplex-associated Alzheimer's disease
- 2019
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Ingår i: Alzheimer’s & Dementia. - : Wiley. - 2352-8737. ; 5:1, s. 697-704
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Tidskriftsartikel (refereegranskat)abstract
- IntroductionHerpes simplex virus type 1 (HSV1) in combination with genetic susceptibility has previously been implicated in Alzheimer's disease (AD) pathogenesis. MethodsPlasma from 360 AD cases, obtained on average 9.6years before diagnosis, and their age- and sex-matched controls, were analyzed for anti-HSV1 immunoglobulin (Ig) G with enzyme-linked immunosorbent assays (ELISAs). APOE genotype and nine other selected risk genes for AD were extracted from a genome-wide association study analysis by deCODE genetics, Reykjavik, Iceland. ResultsThe interaction between APOE epsilon 4 heterozygosity (APOE epsilon 2/epsilon 4 or epsilon 3/epsilon 4) and anti-HSV1 IgG carriage increased the risk of AD (OR 4.55, P=.02). A genetic risk score based on the nine AD risk genes also interacted with anti-HSV1 IgG for the risk of developing AD (OR 2.35, P=.01). DiscussionThe present findings suggest that the APOE epsilon 4 allele and other AD genetic risk factors might potentiate the risk of HSV1-associated AD.
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| 3. |
- Lopatko Lindman, Karin, et al.
(författare)
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Herpesvirus infections, antiviral treatment, and the risk ofdementia : a registry-based cohort study in Sweden
- 2021
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Ingår i: Alzheimer’s & Dementia. - : John Wiley & Sons. - 2352-8737. ; 7:1
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Weidung, Bodil, et al.
(författare)
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VALZ-Pilot : High-dose valacyclovir treatment in patients with early-stage Alzheimer's disease
- 2022
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Ingår i: Alzheimer’s & Dementia. - : John Wiley & Sons. - 2352-8737. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: Herpes simplex virus (HSV) may be involved in Alzheimer's disease (AD) pathophysiology. The antiviral valacyclovir inhibits HSV replication.Methods: This phase-II pilot trial involved valacyclovir administration (thrice daily, 500 mg week 1, 1000 mg weeks 2–4) to persons aged ≥ 65 years with early-stage AD, anti-HSV immunoglobulin G, and apolipoprotein E ε4. Intervention safety, tolerability, feasibility, and effects on Mini-Mental State Examination (MMSE) scores and cerebrospinal fluid (CSF) biomarkers were evaluated.Results: Thirty-two of 33 subjects completed the trial on full dosage. Eighteen percent experienced likely intervention-related mild, temporary adverse events. CSF acyclovir concentrations were mean 5.29 ± 2.31 μmol/L. CSF total tau and neurofilament light concentrations were unchanged; MMSE score and CSF soluble triggering receptor expressed on myeloid cells 2 concentrations increased (P = .02 and .03).Discussion: Four weeks of high-dose valacyclovir treatment was safe, tolerable, and feasible in early-stage AD. Our findings may guide future trial design.
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