Abstract

AbstractBackgroundConsidering the potential implication of Herpes viruses in the development of dementia, anti‐herpetic drugs (AHD) may represent a new means of prevention.MethodUsing a medico‐administrative database, we assessed the association between the intake of systemic AHD and the incidence of i) dementia, ii) Alzheimer’s disease (AD) and iii) vascular dementia (VaD) among 68 291 participants over 65 followed between 2009 and 2017. Cox models using systemic AHD as time‐dependent variable were adjusted for age, sex, being beneficiary of a complementary health insurance scheme for low‐income people, the presence of several co‐morbidities (hypertension, diabetes, hypercholesterolemia, stroke, heart diseases), the intake of anti‐inflammatory drugs, the number of consultations, and the number of different medications the year before inclusion.Result9.7% of the participants (n=6642) had at least one intake of systemic AHD and 8883 incident dementia were identified. The intake of at least one systemic AHD was significantly associated to a decreased risk of AD (aHR 0.85 95% confidence interval [0.75‐0.96], p=0.009) and, to a lesser extent regarding p‐values, to both dementia any cause (aHR 0.90 [0.82‐0.99], p=0.03) and VaD (aHR 0.80 [0.65‐0.995], p=0.045). As the percentage of participants with a regular intake was very low (among those with at least one intake of systemic AHD, the median number of deliveries per year of follow‐up was 0.12), the efficacy of regular intake of AHD could not be evaluated.ConclusionTaking at least one systemic AHD during follow‐up was significantly associated to a risk reduced by 15% of developing AD. Despite the low percentage of participants with a regular intake during the follow‐up, this association may reflect a protective impact of systemic AHD on the prevention of dementia in particular considering the possibility of more regular treatment in the period preceding the inclusion. It also highlights the limitations of medico‐administrative databases to assess the efficacy of a regular intake of systemic AHD given their current use in clinical practice. Thus, given the growing body of evidence supporting the infectious hypothesis, preventive clinical trials with prolonged treatment by systemic AHD are urgently needed.

Highlights

  • Considering the growing body of evidence suggesting a potential implication of herpesviruses in the development of dementia, several authors have questioned a protective effect of antiherpetic drugs (AHDs) which may represent a new means of prevention, well tolerated and accessible

  • Data source The “Echantillon Généraliste des Bénéficiaires” (EGB) is a 1/97th random sample of affiliates to the French Health Insurance System [34, 35]. It is representative of the national population in terms of sex and age and contains in particular information relating to (i) sociodemographic data including information of health insurance complementary coverage for low-income people; (ii) “long-term diseases” (LTDs), a group of chronic diseases for which all medical expenses are fully reimbursed; (iii) outpatient healthcare expenditures reimbursements; (iv) outpatient drug reimbursements identified by their Anatomical Therapeutic Chemical (ATC) code and the prescriber specialty [36]; (v) information on hospitalizations with the primary, related, and associate diagnoses coded according to the International Classification of Diseases 10th revision (ICD10); and (vi) dates of death

  • First, taking at least one systemic AHD during followup was significantly associated with a 15% reduced risk of developing Alzheimer’s disease (AD), even after taking into account several potential methodological biases

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Summary

Introduction

Considering the growing body of evidence suggesting a potential implication of herpesviruses in the development of dementia, several authors have questioned a protective effect of antiherpetic drugs (AHDs) which may represent a new means of prevention, well tolerated and accessible. Among the suspected pathogens (which include in particular different herpesviruses [5,6,7]), herpes simplex virus type 1 (HSV-1) is the most studied candidate [8], and numerous studies in vitro, in animals and in humans provide arguments in favor of its involvement in AD. It is a neurotropic virus with a particular tropism for the temporal lobe. The existence of susceptibility factors (whether genetic, environmental, or related to the virus) may explain why—despite an HSV-1 seroprevalence of around 80% in the elderly [10], some infected subjects remain healthy carriers while others develop neurological complications of the infection

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