Gut-brain health effects of PREbiotics in older adults with suspected COgnitive Decline: the PRECODE study

Due to the greying of society, a triplication of the number of people worldwide suffering from dementia, with Alzheimer’s disease (AD) as the commonest form, is expected by 2050. Emerging evidence points towards a crucial role of intestinal health, with the microbiota composition in the colon receiving more attention. The role of prebiotics/prebiotic supplements in alleviating cognitive impairments in older adults with suspected cognitive decline by acting on the overall gut-brain axis, is a topic that merits further scrutiny.

The first in its kind

So far, a handful of preclinical mouse studies and in vivo studies in human volunteers have alluded to various sources of dietary fiber for their capacity to improve cognitive functioning, general mood, diabetes, overweight, glycaemia, physical activity, sleep quality, immunogenicity, and, to inhibit tau phosphorylation, the latter which is a hallmark in AD brain. In this regard, clinical follow-up studies in older adults with suspected cognitive decline are required, but are still lacking. Therefore, this granted TKI-PPP (private-public partnership) project in collaboration with three private partners (Sensus, Roquette-Frères, Oceanium ltd.) and one other academic institute (TU/e) will be the first human intervention trial in its kind, investigating the cognitive and behavioral effects of prebiotics over the course of 6 months in older adults with Subjective Cognitive Decline Plus (SCD+) aged 60-75, who are at an increased risk of further conversion to mild cognitive impairment or AD.

From microbiota to gut to brain

We plan to investigate the gut and brain health effects of three (potential) prebiotic fiber supplements in particular, more specifically, chicory inulin-type fructans, resistant dextrin, and, seaweed-extracted β-glucans. These three prebiotic supplements are preferred because of their previously revealed beneficial effects on human gut physiology and mental health. Both standardized clinical assessment scales of cognitive and behavioral functioning, as well as the analysis of a variety of gut- and brain health markers, such as microbiota composition, microbiota-derived metabolite production (including short-chain fatty acids), (neuro)inflammatory markers, tryptophan-related indole metabolites, cortisol, amyloid-beta(Aβ)1-42/Aβ1-40 ratio (AD biomarkers), the apolipoprotein E genotype, and, markers of intestinal permeability, will be performed on samples collected at baseline, at week 13 (in part), and, at completion of the trial (week 26). Moreover, we will implement e-wearable technology via smartwatches during a confined period of the trial, which will provide additional valuable information on mood, sleep, physical activity and cardiovascular function, all of which can be linked with the analyzed metabolites and AD-related biomarkers on the one hand (secondary outcome measures), and, potentially, improved cognitive functioning and change in microbiota composition and activity on the other hand (primary outcome measures). Finally, participants will undergo BOLD fMRI imaging to unveil whether working memory performance has improved over the 26-week period of prebiotic supplementation.

Overall, this project may significantly add to the evidence of implementing prebiotics as part of the daily diet of older adults, serving as one valuable approach in reducing dementia and promote healthy ageing by 2030 as part of the National Dementia Strategy.