Abstract
BackgroundConsidering 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 easily accessible. Subsequently, several epidemiological studies have shown a reduction in the risk of dementia in subjects treated with AHDs, but the biological plausibility of this association and the impact of potential methodological biases need to be discussed in more depth.MethodsUsing a French medico-administrative database, we assessed the association between the intake of systemic AHDs and the incidence of (i) dementia, (ii) Alzheimer’s disease (AD), and (iii) vascular dementia in 68,291 subjects over 65 who were followed between 2009 and 2017. Regarding potential methodological biases, Cox models were adjusted for numerous potential confounding factors (including proxies of sociodemographic status, comorbidities, and use of healthcare) and sensitivity analyses were performed in an attempt to limit the risk of indication and reverse causality biases.Results9.7% of subjects (n=6642) had at least one intake of systemic AHD, and 8883 incident cases of dementia were identified. Intake of at least one systemic AHD during follow-up was significantly associated with a decreased risk of AD (aHR 0.85 95% confidence interval [0.75–0.96], p=0.009) and, to a lesser extent with respect to p values, to both dementia from any cause and vascular dementia. The association with AD remained significant in sensitivity analyses. The number of subjects with a regular intake was low and prevented us from studying its association with dementia.ConclusionsTaking at least one systemic AHD during follow-up was significantly associated with a 15% reduced risk of developing AD, even after taking into account several potential methodological biases. Nevertheless, the low frequency of subjects with a regular intake questions the biological plausibility of this association and highlights the limits of epidemiological data to evaluate a potential protective effect of a regular treatment by systemic AHDs on the incidence of dementia
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
Summary
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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