The use of memantine for prevention of Alzheimer's disease: Pilot feasibility study rationale and protocol.

BACKGROUND: Alzheimer's disease (AD) affects over 6 million older adults in the Untiled States. Evidence suggests the neuropathology leading to the disorder begins decades earlier, calling for a preventative treatment that can be administered to at risk individuals. Memantine hydrochloride, an NMDA receptor antagonist, is a possible candidate for prophylactic treatment by diminishing excessive NMDA receptor activity. METHODS: This is a 2-year, double-blind, randomized, placebo-controlled trial of memantine hydrochloride (1:1 randomization allocation using randomly permutated blocks of unequal size). Participants are APOε4 carriers slightly under the average age of AD symptom onset (50-65 years of age) with a positive family history of a first degree relative with AD. Amyloid PET scans are performed pre and post treatment. Cognitive assessments and physical and neurological examinations are completed at regular intervals throughout the feasibility trial. DISCUSSION: This study will assess the feasibility of the use of memantine hydrochloride for prevention of AD. The primary aim is to determine feasibility of participants who a) enrolled among those found eligible, and b) completed the study among those randomized to a study arm. Exploratory aims include examination of cognitive and safety assessments. Although not powered to determine efficacy, the study will provide direction on design elements needed for a Phase III clinical trial. No formal hypotheses are included in this feasibility trial. TRIAL REGISTRATION: Clinical Trials NCT05063851.