Association between the use of anti-herpetic drugs and subsequent initiation of Alzheimer's disease drug treatment: Dutch population-based inception cohort study.

内容摘要

To examine whether exposure to anti-herpetic drugs (AHDs: acyclovir, valacyclovir, famciclovir) is associated with reduced risk of Alzheimer's disease (AD) treatment initiation. Population-based retrospective matched cohort study. University Groningen community pharmacy database IADB.nl, covering approximately 125 Dutch pharmacies (1994-2024). 262&#x2009;757 adults aged 50-80 years without prior dementia or AD treatment. Exposed individuals with antiherpetic prescriptions (n=23&#x2009;887) were matched 1:10 to unexposed controls (n=238&#x2009;870) by age, sex and calendar time. AHDs: acyclovir, valacyclovir, famciclovir. Initiation of AD drug treatment, defined as at least two prescriptions for rivastigmine, donepezil, galantamine or memantine within 1 year. Cox proportional hazards models estimated HRs with 95% CIs, adjusted for comorbidities and medications. Analyses were stratified by period (1994-2018&#x2009;vs 2019-2024)&#x2009;and drug type. During follow-up, 2495 participants initiated AD treatment. The age of the participants was 65 (SD 9), and 59% were female. Any AHD exposure was associated with 90% reduced hazard of AD treatment (HR 0.09, 95%&#x2009;CI 0.07 to 0.13, p<0.001). Similar association was found in both periods: HR 0.14 (95% CI 0.09 to 0.20) in period one and HR 0.05 (95% CI 0.03 to 0.10) in period 2. All three AHDs were associated with a lower likelihood of future AD drug prescription: valacyclovir HR 0.10, acyclovir HR 0.09, famciclovir HR 0.07. The incidence rate of AD treatment initiation was substantially lower among AHD users compared with unexposed individuals overall (0.69/1000 person-years (py) vs 4.96/1000 py, p<0.001), with this association evident in both period 1 (0.65/1000 py vs 3.74/1000 py, p<0.001) and period 2 (0.81/1000 py vs 8.22/1000 py, p<0.001). AHD exposure was consistently associated with markedly lower risk of AD treatment initiation, with similar findings observed in recent years. These findings support the hypothesis that herpesvirus reactivation may contribute to AD pathogenesis and suggest antiviral therapy could have preventive implications. Confirmation through prospective studies and randomised trials is needed.