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Intercurrent illnesses or medication changes (including addition of sedating medications or unavailability of regular symptomatic AD medications): This estimand will be analysed in participants who undergo follow-up RBANS assessment at 180 days (+0, 10 days) and who have taken at least 80% of the study medication, and where there have been no intercurrent events blindly adjudicated as affecting cognition (principal stratum strategy) Secondary estimand epigenetic change 1

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Buprenorphine is administered in a formulation with naloxone because the latter efficiently blocks the addictive effects of buprenorphine to prevent misuse [39]