The primary objective of PRECODE is to investigate the effect of 26 weeks of supplementation with three different dietary fibres (chicory inulin, resistant dextrin, and seaweed polysaccharide) compared to a placebo (maltodextrin) on microbiota gut-brain health effects in 164 older adults (aged 60-79) with Subjective Cognitive Decline Plus (SCD+) by assessing changes in brain function and working memory by blood oxygen level dependant (BOLD) signal activity and task accuracy during n-back task functional magnetic resonance imaging (fMRI) assessment. This is a randomised, double-blinded, placebo-controlled intervention study with parallel design and four arms (n=41 each). The secondary objectives are the following parameters related to potential gut-brain pathways: (1) neuropsychological test battery scoring, (2) other relevant brain health parameters (amyloid-beta biomarkers, tryptophan metabolites, BDNF measures), (3) relevant intestinal health parameters (intestinal barrier function, microbiota composition, SCFA/BCFA analyses), and (4) immune and metabolic parameters (inflammatory marker panel, fasting glucose and insulin, HbA1c, lipogram). Tertiary outcomes relate to physiological parameters as determined by wearable smartwatches (heart rate, physical activity, mood).
PRECODE is the first study in its kind in which prebiotics are tested for improvement of cognitive functioning in older adults at risk of conversion to Alzheimer’s disease. SCD+ is a predecessor stage of AD, but at which stage the cognitive deficits can still be reversed. Thereby a substantial health benefit can still be gained. The partners within the project who deliver the dietary fibres will gain a wealth of knowledge concerning their product in terms of effectiveness (for brain health), potential repurposed use, digestibility, potential side effects and palatability.

Currently, no cure is available for Alzheimer’s disease. Various symptomatic and a few disease-modifying treatments are available, but these treatments only have very limited or mild clinical effects and are often accompanied by severe side effects. Clinical follow-up studies to evaluate the effect of dietary fibre in older adults with suspected cognitive decline are required, but are still lacking to date (knowledge gap). This study thus will significantly contribute to the mission put forward by the Knowledge and Innovation Agenda (KIA; 2020-2023) from the Dutch Ministry of Health, Wellbeing and Sports, to (mission 1) decrease the burden as a consequence of an unhealthy lifestyle by 30% in 2040, to (mission 3) increase by 25% the number of people with chronic severe illnesses to take part in society by 2030, and, finally, to (mission 4) increase the quality of life of people suffering from dementia with 25% by 2030. In general, this PPP falls under mission D, “Valued, healthy and safe food”. Under this mission, one of the main Multi-Year Mission-Driven Innovation Programs (MMIP), is D2: “The consumer, sustainable and healthy food, in a green living environment”. Our proposal fits perfectly under this MMIP D2, since it relates to deciphering the relationship between nutrition and health, with a primary focus on healthy ageing. One of the priorities, and, the particular subprogram about ‘nutrition and health’, of this MMIP, literally state (translated, rephrased and shortened): “Gaining valuable insights into the role, effectiveness and health effects of nutrition/specific food groups for the maintenance of cognition, quality of live, stimulation of microbiota-gut-brain health, and, prevention of age-related diseases, accompanied with the development of standardized measurement methods to monitor health”.

PRECODE wants to decipher whether prebiotic supplementation may maintain or improve cognitive functioning with ageing, especially in older adults already suffering from suspected cognitive decline. This is by acting upon the microbiota-gut-brain axis. Our project aligns with the ToC of the MMIP D2, by targeting cognitive health in older adults, and thus potentially reducing the burden of cognitive decline and associated healthcare costs. PRECODE also wants to promote preventative healthcare solutions. Furthermore, MMIP D2 focuses on promoting healthy aging and a healthy lifestyle (gezond kunnen opgroeien en gezond ouder worden), and we aim with PRECODE to enhance cognitive functioning in older adults, which is a key aspect of maintaining independence and quality of life as people age .

Primary Deliverables D1 (Q1 2024 & Q2 2025):
-D1.1: METC approval for the trial (Q1 2024; originally thought: Q3 2023)
-D1.2: Recruitment completion (Q1-2 2025; originally thought: Q3-4 2024)
-D1.3: Biobank storage (-80°C) of all samples (Q1-2 2025; originally thought: Q4 2024)
-D1.4: Comprehensive analysis of the gut-brain health effects of prebiotics in older adults with SCD+, focusing on changes in brain function and working memory assessed through blood oxygen level dependent (BOLD) signal activity and task accuracy during n-back task functional magnetic resonance imaging (fMRI) assessment after 26 weeks of supplementation with chicory inulin, resistant dextrin, seaweed polysaccharide, and placebo (maltodextrin) (Q2 2025).

Secondary Deliverables D2 (Q3-4 2025):
-D2.1: Detailed evaluation of neuropsychological test battery scoring to assess cognitive function improvements (Q3 2025).
-D2.2: Analysis of other relevant brain health parameters including plasma amyloid-beta biomarkers, plasma/fecal tryptophan metabolites, and plasma Brain-Derived Neurotrophic Factor (BDNF) measures (Q4 2025).
-D2.3: Assessment of intestinal health parameters such as plasma/fecal intestinal barrier function, microbiota composition, and short-chain fatty acid (SCFA) and branched-chain fatty acid (BCFA) analyses (Q4 2025).
-D2.4: Examination of immune and metabolic parameters including an inflammatory marker panel, fasting glucose and insulin levels, HbA1c, and lipogram (Q4 2025).

Tertiary Deliverables D3 (Q3 2025):
-D3.1: Analysis of physiological parameters measured by wearable smartwatches, including heart rate, physical activity levels, and mood changes throughout the intervention period.

Overall Deliverables D4 (from Q4 2025 onwards and following):
-D4.1: In person meeting with all partners and three-monthly online follow-up meetings
-D4.2: Comprehensive final report summarizing findings from all primary, secondary, and tertiary outcomes, providing insights into the efficacy and mechanisms of action of different dietary fibers on gut-brain health in older adults with SCD+.
-D4.3: Manuscripts for publication in peer-reviewed journals to disseminate research findings and contribute to the scientific understanding of the gut-brain axis and cognitive health in aging populations.
-D4.4: Presentations at (inter)national scientific conferences to share results with the research community and key stakeholders, potentially informing future interventions and policies aimed at promoting cognitive health in older adults.