The impact of a nutritional intervention in prodromal Alzheimer’s disease: The LipiDiDiet clinical trial

Abstract

AbstractBackgroundDiet and nutrition are important modifiable risk factors for Alzheimer’s disease (AD). For the last two decades, the LipiDiDiet consortium has been investigating the role of nutrients and their synergistic action on key AD pathological features. Based on preclinical results, 11 nutrients were selected which, when applied in this specific combination, gave the best results in rodent AD models: i.e. the omega‐3 fatty acids DHA and EPA, phospholipids, vitamins B6, B12, folic acid, C and E, choline, selenium, and UMP. The LipiDiDiet trial1 is a 6‐year, double‐blind, parallel‐group, multi‐centre, randomised controlled clinical trial, designed to investigate effects of the specific multinutrient combination Fortasyn Connect on cognition and related measures in prodromal AD. Initial 24 month results showed significant benefit on clinical dementia rating‐sum of boxes (CDR‐SB) and hippocampal and ventricular volumes in the modified intention‐to‐treat population. Here we report previously specified primary and secondary outcomes over 36 months of intervention.MethodProdromal AD participants (n=311) were randomised to receive either active product (125 mL drink containing Fortasyn Connect) or a calorie‐matched placebo control once daily.Result162 participants completed the 36‐month period. With increasing treatment duration, the benefit of the active group over the control group exceeded what had been observed for the first 24 months (Soininen et al., Lancet Neurology 2017). For the 5‐item neuropsychological test battery (NTB) on cognition, a significant between‐group difference was observed in estimated mean change from baseline over 36 months favouring active intervention (0.212 [95% CI 0.044 to 0.380]; p=0.014; 60% reduction in decline). In addition, significant benefits were found on CDR‐SB, NTB memory, and hippocampal, ventricular, and whole brain volumes on MRI. Self‐reported compliance to the study product was high and there was no indication of safety concern.ConclusionWe observed significantly slower decline in cognition including memory, CDR‐SB measuring cognition and function, and brain structural measures. Importantly, prolonged intervention with this specific combination of nutrients resulted in a broader range of endpoints showing statistically significant differences. Sustainable benefits lasting for 3 or more years have not been reported before in prodromal AD. Dutch Trial Register: NTR1705. 1EUFP7 N°211696 LipiDiDiet.