JMIR Publications

ABSTRACT

Background:

Studies of multidomain lifestyle interventions show mixed results on preventing or delaying cognitive decline in ageing. A better understanding of the mechanisms underlying these interventions could help explain these mixed findings.

Objective:

The HELI study aims to investigate the brain and peripheral mechanisms of a multidomain lifestyle intervention in older adults at risk of cognitive decline.

Methods:

The HELI study is a 6-month multicentre, randomized, controlled multidomain lifestyle intervention trial powered to include 104 Dutch older adults at risk of cognitive decline. Individuals were deemed at risk when scoring ≥2 points on a lifestyle-modifiable risk factor scale (e.g. overweight, physical inactivity, hypertension, hypercholesterolemia). The multidomain lifestyle intervention consisted of five domains (diet, physical activity, stress management/mindfulness, cognitive training, and sleep) and participants were randomized in one of two intervention groups: (1) a high-intensity coaching group consisting of weekly supervised online and on-site group meetings, exercises and learning materials from lifestyle-specific course modules, and (2) a low-intensity coaching group consisting of general lifestyle-related health information sent through e-mail every two weeks. The primary study outcomes are changes between baseline and 6-month follow-up in (1) brain activation in dorsolateral prefrontal cortex (dlPFC) and hippocampus and task accuracy during an fMRI working memory task (2) ASL-quantified cerebral blood flow in dlPFC and hippocampus, (3) systemic inflammation from blood plasma (IL-6, TNF-α, hs-CRP) and (4) microbiota profile from faeces (gut microbiome diversity (Shannon and phylogenetic diversity) and richness (Chao1)). In addition, we will investigate intervention-induced gut-immune-brain links by assessing the relation between the effects found in the aforementioned primary brain and gut outcome measures. Secondary study outcomes include (1) structural and neurochemical MRI, (2) anthropometric measurements, (3) neuropsychological test battery scores, (4) lifestyle-domain related measures from questionnaire scores and a smartwatch, and an array of peripheral measures from (5) faecal analysis, (6) blood analysis, and (7) breath analysis.

Results:

Between April 2022 and October 2023 we have successfully included n = 102 older Dutch adults (mean age: 66.6 (SD: 4.3) years; 65.7% female) with ≥2 lifestyle-modifiable risk factors of cognitive ageing (median risk: 3 (IQR: 2, 3)). The most common self-reported lifestyle-modifiable risk factors of cognitive ageing at baseline were overweight or obesity (74.5%), followed by hypertension (56.9%), hypercholesterolemia (55.9%), and physical inactivity (55.9%).

Conclusions:

The HELI study aims to enhance our understanding of working mechanisms of multidomain lifestyle interventions through its comprehensive characterization of central and peripheral markers. We intend to achieve this aim by assessing lifestyle intervention-induced changes in functional and structural MRI brain measures, as well as peripheral measures of the gut-immune-brain axis involved in cognitive ageing. Clinical Trial: ClinicalTrials.gov ID NCT05777863 ToetsingOnline.nl filenumber NL78263.091.21