Valacyclovir Treatment of Early Symptomatic Alzheimer Disease

作者：D. P. Devanand, Thomas Wısnıewskı, Qolamreza Razlighi, Min Qian, Renjie Wei, Howard Andrews, Edward P. Acosta, Karen L. Bell, Gregory H. Pelton, Deborah A. Deliyannides, Allison C. Perrin, Elise Caccappolo, Anne A. Gershon, Konasale M. Prasad, William Charles Kreisl, Akiva Mintz, Edward D. Huey · 发表于：JAMA · 年份：2025 · DOI：10.1001/jama.2025.21738 · 被引用次数：13 · 研究领域：Hepatitis C virus research、Alzheimer's disease research and treatments、Cytomegalovirus and herpesvirus research

Importance: Neuroscientific, epidemiological, and electronic health record studies implicate herpes simplex virus (HSV) as potentially etiological for Alzheimer disease (AD). Objective: To compare the efficacy and adverse effects of valacyclovir vs placebo in participants with early symptomatic AD and HSV seropositivity (HSV-1 or HSV-2). Design, Setting, and Participants: This randomized clinical trial included adults with a clinical diagnosis of probable AD or a clinical diagnosis of mild cognitive impairment with positive biomarkers for AD, a positive serum antibody test (IgG or IgM) for HSV-1 or HSV-2, and a Mini-Mental State Examination score of 18 to 28. The trial was conducted at 3 US outpatient clinics specializing in memory disorders. Recruitment occurred from January 2018 to May 2022; the last follow-up occurred in September 2024. Intervention: Either 4 g/d of valacyclovir (n = 60) or matching placebo (n = 60). Main Outcomes and Measures: The primary outcome was least-squares mean (LSM) change at 78 weeks in the 11-item Alzheimer's Disease Assessment Scale Cognitive (ADAS-Cognitive) Subscale score (range, 0-70; higher scores indicate greater impairment). The secondary outcomes were LSM change in the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) Scale score; LSM change in the 18F-florbetapir amyloid positron emission tomography (PET) standardized uptake value ratio (SUVR; higher scores indicate higher amyloid levels) for 6 brain regions (...