Efficacy results from the unique long‐term randomised controlled double‐blind LipiDiDiet trial with a multinutrient intervention in prodromal AD/MCI_AD

Abstract

AbstractBackgroundLifestyle factors such as nutrition and diet are modifiable risk factors for the progression of mild cognitive impairment (MCI) to Alzheimer’s disease (AD). A small number of interventions recently showed cognitive and functional benefits. It is unclear however how long these benefits will last, requiring long‐term studies.LipiDiDiet was the first AD double‐blind, placebo‐controlled trial clinical trial to show a significant and sustainable benefit, including a 45% reduction in decline on CDR‐SB performance in a prodromal study population evaluating a multinutrient formulation (Soininen Lancet Neurology 2017; Soininen Alz&Dem 2021). We now extended the analysis from 3 years to up to 6 years of active intervention to investigate long‐term effects.MethodLipiDiDiet is a 6‐year randomised, double‐blind, placebo‐controlled trial, investigating the effects of a nutritional intervention in individuals with prodromal AD/MCIAD. 311 individuals with prodromal AD (IWG‐1) were randomized to active (125ml once‐a‐day drink; Fortasyn Connect [Souvenaid]) or a calorie‐matched control. Following the first 2 years of intervention, participants could opt‐in for annual extensions up to a maximum of 6‐year double‐blind intervention. Individual participants progressing to mild dementia were provided AD medication and/or open‐label active product and could continue in the trial. Main outcomes included Neuropsychological Test Battery (NTB) composites on cognition and memory, and the Clinical Dementia Rating‐Sum of Boxes (CDR‐SB). Modified intention‐to‐treat analyses were performed over 4‐6 years of intervention using a joint model combining longitudinal and survival data.ResultAdding data from all participants who completed the 4‐year visit while still on double‐blind treatment (n = 38) to the previously performed joint model analyses on the 3‐year data showed that the initially observed benefits on cognition, memory, and CDR‐SB appear to have continued beyond 3 years. These and other ongoing analyses are addressing the statistical challenges specific to long‐term AD trials including non‐random patterns of missing data.ConclusionIn addition to the already demonstrated sustainable benefits of Fortasyn Connect in individuals with prodromal AD/MCIAD, combined with feasibility of its long‐term use without indications for health concerns, we now report first results indicating that benefits on cognition, memory, and CDR‐SB are sustained over 4 years.