The Effects of a Multidomain Lifestyle Intervention on Brain Function and Its Relation With Immunometabolic Markers and Intestinal Health in Older Adults at Risk of Cognitive Decline: Study Design and Baseline Characteristics of the HELI Randomized Controlled Trial
Bibliographic record
Abstract
Background: Studies of multidomain lifestyle interventions show mixed results on preventing or delaying cognitive decline in aging. A better understanding of central and peripheral mechanisms underlying these interventions could help explain these mixed findings. Objective: The HELI (Hersenfuncties na LeefstijlInterventie) 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 multicenter, 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 (eg, overweight, physical inactivity, hypertension, and hypercholesterolemia). The intervention consisted of 5 domains (diet, physical activity, stress management and mindfulness, cognitive training, and sleep) and participants were randomized to one of two groups: (1) a high-intensity coaching group with weekly supervised online and on-site group meetings, exercises, and lifestyle-specific course materials, and (2) a low-intensity coaching group receiving general lifestyle health information sent through email every 2 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 a functional magnetic resonance imaging (fMRI) working memory task, (2) arterial spin labeling-quantified cerebral blood flow in dlPFC and hippocampus, (3) systemic inflammation from blood plasma (interleukin-6, tumor necrosis factor-α, high-sensitivity C-reactive protein) and (4) microbiota profile from feces (gut microbiome diversity [Shannon and phylogenetic diversity] and richness [Chao1]). In addition, we will investigate intervention-induced gut-immune-brain links by assessing relations between effects in primary brain and gut outcomes. Secondary study outcomes include (1) structural and neurochemical magnetic resonance imaging (MRI), (2) anthropometric measurements, (3) neuropsychological test battery scores, (4) lifestyle-related questionnaire and smartwatch measures, and peripheral measures from (5) fecal, (6) blood, and (7) breath analyses. Results: This work was supported by a Crossover grant (Maintaining Optimal Cognitive Functioning In Aging [MOCIA] 17611) of the Dutch Research Council (NWO), granted in December 2019. The MOCIA program is a public-private partnership. Between April 2022 and October 2023, we successfully included 102 older Dutch adults (mean age 66.6, SD 4.3 years; 67/102, 65.7% female) with ≥2 lifestyle-modifiable risk factors of cognitive aging (median risk 3, IQR 2-3). The most common self-reported lifestyle-modifiable risk factors at baseline were overweight or obesity (76/102, 74.5%), followed by hypertension (58/102, 56.9%), hypercholesterolemia (57/102, 55.9%), and physical inactivity (57/102, 55.9%). Conclusions: The HELI study aims to enhance our understanding of the 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 aging.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.006 | 0.008 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.006 | 0.005 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".