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Updated: May 31, 2026

A Machine Learning Approach to Design an Efficient Selective Screening of Mild Cognitive Impairment
Published on: January 11, 2020
Valacyclovir Treatment in Mild Cognitive Impairment: The VALMCI Randomized Clinical Trial
Davangere P Devanand1,2, Edward D Huey3, Min Qian4
1Department of Psychiatry, New York State Psychiatric Institute.
Background:
Evidence from neuroscience, epidemiology, and electronic health records studies implicates herpes simplex viruses (HSV) as potentially etiologic for Alzheimer disease (AD).
Methods:
The VALMCI study was conducted in a research outpatient clinic specializing in memory disorders. The efficacy and side effects of valacyclovir 4 g/day were compared with placebo in a 12-month pilot, randomized, double-blind trial of participants with mild cognitive impairment (MCI), seropositivity to HSV1 or HSV2, and positive 18 F-florbetapir PET scan.
Results:
Totally, 42 of 50 participants (84%) completed the trial. In linear mixed-effects model analyses with age, sex, and apolipoprotein E e4 genotype as covariates, change in the primary outcome of 18 F-florbetapir PET mean SUVR was not significant with least-squares mean difference -0.01 (95% CI: -0.12 to 0.10; P =0.82). For secondary cognitive and functional outcomes, PACC composite z -score showed the least square mean difference 0.16 (95% CI: -0.17 to 0.49; P =0.32), and ADCS-ADL-PI score showed the least square mean difference 1.96 (95% CI: -0.43 to 4.34; P =0.11).
Conclusion:
The results do not support the use of valacyclovir in the treatment of individuals with MCI with HSV seropositivity and PET amyloid positivity.
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