Background 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 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. Methods Using 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. Results 9.7% 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. Conclusions Taking 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
ObjectiveTo estimate the risk of ischaemic stroke associated with antidopaminergic antiemetic (ADA) use.DesignCase-time-control study.SettingData from the nationwide French reimbursement healthcare system database Système National des Données de Santé (SNDS).ParticipantsEligible participants were ≥18 years with a first ischaemic stroke between 2012 and 2016 and at least one reimbursement for any ADA in the 70 days before stroke. Frequencies of ADA reimbursements were compared for a risk period (days -14 to -1 before stroke) and three matched reference periods (days -70 to -57, -56 to -43, and -42 to -29) for each patient. Time trend of ADA use was controlled by using a control group of 21 859 randomly selected people free of the event who were individually matched to patients with stroke according to age, sex, and risk factors of ischaemic stroke.Main outcome measuresAssociation between ADA use and risk of ischaemic stroke was assessed by estimating the ratio of the odds ratios of exposure evaluated in patients with stroke and in controls. Analyses were adjusted for time varying confounders (anticoagulants, antiplatelets, and prothrombotic or vasoconstrictive drugs).ResultsAmong the 2612 patients identified with incident stroke, 1250 received an ADA in the risk period and 1060 in the reference periods. The comparison with the 5128 and 13 165 controls who received an ADA in the same periods yielded a ratio of adjusted odds ratios of 3.12 (95% confidence interval 2.85 to 3.42). Analyses stratified by age, sex, and history of dementia showed similar results. Ratio of adjusted odds ratios for analyses stratified by ADA was 2.51 (2.18 to 2.88) for domperidone, 3.62 (3.11 to 4.23) for metopimazine, and 3.53 (2.62 to 4.76) for metoclopramide. Sensitivity analyses suggested the risk would be higher in the first days of use.ConclusionsUsing French nationwide exhaustive reimbursement data, this self-controlled study reported an increased risk of ischaemic stroke with recent ADA use. The highest increase was found for metopimazine and metoclopramide.
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