Gut-brain health effects of PREbiotics in older adults with suspected COgnitive DEcline: design of the PRECODE randomised placebo-controlled trial

Global lifespan is rising, alongside increasing age-related conditions. Cognitive disorders such as dementia, are projected to triple in number by 2050. Currently, no cure is available for Alzheimer's disease (AD), the most common form of dementia, and the need for preventative strategies is paramount. Subjective cognitive decline plus (SCD+) lies on the AD continuum, with increased risk of accelerated cognitive decline, providing an ideal target group for early intervention. The microbiota-gut-brain axis (MGBA) is an emerging avenue for prevention, as dietary fibres may beneficially modulate microbiota and microbial metabolites, such as short chain fatty acids and tryptophan-indoles, resulting in improved gastrointestinal and cognitive functioning. PRECODE is a four-armed, randomised, double-blinded, placebo-controlled trial in 164 older adults (60-79 years) with SCD+ and additional "LIfestyle for BRAin Health" (LIBRA) risk factors. The study aims to investigate 26 weeks of supplementation with chicory inulin, resistant dextrin, and seaweed polysaccharide compared to placebo (maltodextrin) on the MGBA. The primary outcome is effects on neurocognition, assessed by brain activation during working memory load measured with blood-oxygen level dependant functional magnetic resonance imaging (BOLD fMRI) and performance during 2-back task. The secondary outcomes include cognition by neuropsychological test battery, brain and intestinal health parameters, and immune and metabolic markers. Findings may guide new preventative modalities in preclinical AD and provide mechanistic insights into the MGBA in individuals at risk for cognitive decline. Clinical trial registration: https://clinicaltrials.gov/study/NCT06433037.