The Effects of a Multidomain Lifestyle Intervention on Brain Functioning and Its Relation With Immunometabolic Markers in Ageing (HELI)

The Effects of a Multidomain Lifestyle Intervention on Brain Functioning and Its Relation With Immunometabolic Markers in Ageing: the HELI Study

HELI is a multicenter, randomised controlled trial in two Dutch research centres (Donders Centre for Cognitive Neuroimaging, Nijmegen, and the department of Human Nutrition & Health at Wageningen University) among 104 older adults aged 60-75 years who are at risk for cognitive decline with an intervention duration of 26 weeks (roughly 6 months). Participants are randomized in a 1:1 ratio to a multidomain lifestyle intervention characterized by group-sessions and guidance (high-intensity intervention group) versus online access to general lifestyle-related health information in the form of biweekly leaflets (low-intensity intervention group).

Study Overview

• Status: Completed
• Conditions: Aging; Cognitive Decline; Risk Reduction; Life Style
• Intervention / Treatment: Behavioral: Multidomain lifestyle intervention

• Study Type: Interventional
• Enrollment (Actual): 102
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands
      • Donders Centre for Cognitive Neuroimaging
    • Wageningen, Gelderland, Netherlands
      • Wageningen University & Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Written informed consent;
• Age between 60-75 years (at pre-screening);
• Fluency in Dutch (speaking, reading and writing);
• Lives near study centres in Nijmegen and Wageningen (max. 50 kilometers of travelling, to ensure study centre visits are possible without excessive travel burden);
• Presence of ≥2 self-reported risk factors for cognitive decline (BMI of 30 or higher, physical inactivity according to World Health Organization guidelines, hypertension [not using hypertensive drugs counts as an additional risk factor], hypercholesterolemia, diabetes type-II, non-symptomatic cardiovascular disease).

Exclusion Criteria:

• Concurrent participation in other intervention trials;
• Technologically illiterate (complete incompetence in working with computers, apps, online questionnaires, etc.);
• No internet access from home;
• Clinical diagnosis of ≥1 of the following: vascular event (CVA), neurological pathology (e.g. mild cognitive impairment, dementia, multiple sclerosis, Parkinson's, epilepsy), current malignant disease(s) (with or without current treatment), current psychiatric disorder(s) (e.g. depression, psychosis, bipolar episodes), symptomatic cardiovascular disease (e.g. stroke, angina pectoris, heart failure, myocardial infarction), revascularisation surgery in the last 12 months at pre-screening, inflammatory bowel disease (characterised with diarrhoea), visual impairment (e.g. blindness), hearing or communicative impairment;
• Unable to undergo MRI (e.g. metal objects in upper body, past brain surgery, active implants, claustrophobic);
• Cognitive impairment as determined by the Telephone Interview for Cognitive Status (TICS-M1), performed during pre-screening before inclusion.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High-intensity group; The high-intensity group receives a supervised multidomain lifestyle intervention consisting of weekly group meetings. During the weekly group meetings, information and exercises are provided, and participants are able to exchange experiences and advice with other group members.	Behavioral: Multidomain lifestyle intervention; A multidomain lifestyle intervention including the following lifestyle domains: (1) diet, (2) physical activity, (3) sleep, (4) stress/mindfulness, and (5) cognitive training.
No Intervention: Low-intensity group; The low-intensity group only receives access to general lifestyle-related health information through biweekly leaflets, which are provided through e-mail.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in brain activity during working memory	Blood-oxygen level dependent activity during N-back (2-back) fMRI task	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in working memory performance	Task accuracy during N-back (2-back) fMRI task	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in cerebral perfusion levels	Cerebral perfusion measured using arterial spin labelling (ASL)	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in microbiota profile	16S rRNA based profile of gut microbiota in faeces	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in inflammatory profile in blood plasma: hs-CRP	Blood plasma inflammatory profile analysis to measure hs-CRP level	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in inflammatory profile in blood plasma: IL-6	Blood plasma inflammatory profile analysis to measure IL-6 level	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in inflammatory profile in blood plasma: TNF-α	Blood plasma inflammatory profile analysis to measure TNF-α level	Change between Baseline (T0) and Follow-up after 6 months (T1)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Body mass index	Measured in kg/m^2	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Waist circumference	Measured in cm	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Hip circumference	Measured in cm	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Blood pressure	Measured by blood pressure monitor. Scores range from approximately (for diastolic) 60-120 and (for systolic) 100-180 mmHg, with higher scores indicating higher blood pressure.	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Abdominal fat distribution (neuroimaging)	Visceral adipose tissue(VAT)/subcutaneous adipose tissue (SAT) ratio measured by abdominal T1-weighted MRI scan	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Brain structure volume profile (neuroimaging)	Brain structure volumes (grey matter, white matter, brain vesicles), measured by MP2RAGE structural sequence	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Brain myo-inositol levels (neuroimaging)	Brain myo-inositol levels reflecting local neuroinflammation in dorsolateral prefrontal cortex and hippocampus, measured by magnetic resonance spectroscopy (MRS)	Change between Baseline (T0) and Follow-up after 6 months (T1)
Intracranial iron deposition (neuroimaging)	Local aggregation of iron deposition within the brain, measured by quantitative susceptibility mapping (QSM)	Baseline (T0)
Change in Neuropsychological test battery scoring	Z-scoring of cognitive assessments targeting cognitive domains predominantly affected by cognitive ageing: executive function (incl. working memory), episodic memory and processing speed	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Trail Making Test A (TMT-A) Numbers : trial time (cognitive assessment)	Discrete number; score 0 - no maximum (seconds to assessment completion). Lower score indicates a better outcome	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Trail Making Test A (TMT-A) Numbers: errors (cognitive assessment)	Discrete number; score 0 - no maximum (amount of errors). Lower score indicates a better outcome	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Trail Making Test B (TMT-B) Numbers and Letters : trial time (cognitive assessment)	Discrete number; score 0 - no maximum (seconds to assessment completion). Lower score indicates a better outcome	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Trail Making Test B (TMT-B) Numbers and Letters: errors (cognitive assessment)	Discrete number; score 0 - no maximum (amount of errors). Lower score indicates a better outcome	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Verbal Fluency Test (VFT) (cognitive assessment)	Word count in one minute; score 0 - no maximum. Higher score indicates a better outcome	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Rey Auditory Verbal Learning Test (RAVLT): learning trials (cognitive assessment)	Discrete number; score 0 - 15 (amount of words remembered during learning trial 1 to 5). Higher score indicates a better score	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Rey Auditory Verbal Learning Test (RAVLT): delayed recall (cognitive assessment)	Discrete number; score 0 - 15 (amount of words remembered during delayed recall). Higher score indicates a better score	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Digit Symbol Substitution Test (DSST) (cognitive assessment)	Discrete number; score 0 - 90 (amount of symbols correctly substituted). Higher score indicates better outcome	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Wechsler Adult Intelligence Scale (WAIS) digit span (cognitive assessment)	Discrete number; score 0 - 90 (amount of digit spans correctly repeated). Higher score indicates better outcome	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Five Facet Mindfulness Questionnaire (questionnaire)	Self-assessment of mindfulness; score 24 - 120. Higher score indicate more mindfulness	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Sedentary Behaviour Questionnaire (questionnaire)	Average hours and minutes of sedentary behavior a day; score 0 - 24 hours. Higher score (more hours) indicates more sedentary behavior	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Eetscore food questionnaire (questionnaire)	Dutch Healthy Diet Index 2015; score 0 - 160. Higher score indicates a better outcome	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Perceived Stress Scale (questionnaire)	Stress perception; score 0 - 40. Higher score indicate more perceived stress	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Pittsburgh Sleep Quality Index (PSQI) (questionnaire)	Sleep quality; score 0 - 21. Higher score (referred to as global or total score) indicates worse sleep quality	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in SQUASH (questionnaire)	Physical activity. METs derived from the Ainsworth's compendium of physical activity will be used to classify physical activity intensity (<1.5METs- sedentary, 1.6-2.9 METs- light, 3.0-5.9METs- moderate, >6.0- vigorous physical activity)	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Cognitive Failures Questionnaire (questionnaire)	Subjective cognitive functioning; score 0 - 100. A higher score indicates more subjective cognitive failure	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Memory Self-Efficacy MIA (questionnaire)	Self-evaluation and confidence of memory. Sum of Part 1 + Part 2A and B. Part 1: Strategy (scores 10 - 50, higher scores indicate more use of strategies), Part 2A: Subjective memory functioning (score 23 - 115, higher score indicates better memory self-efficacy) and Part 2B: Locus (score 7 - 35, higher scores indicate better perceived personal control over remembering abilities)	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in total amount of bacteria, fungi and specific bacterial strains (faeces)	Total amount of bacteria, fungi and specific bacterial strains are quantified using digital droplet PCR in faecal samples	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in individual short-chain fatty acids (SCFAs) profile (faeces)	GC-MS and LC-MS measurements to assess profile of individual SCFAs in faecal samples (acetic acid, formic acid, propionic acid, isobutyric acid, butyric acid, isovaleric acid, valeric acid, 4-methyl valeric acid, hexanoic acid, heptanoic acid)	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in microbiome-derived bioactive compounds (faeces)	Amount of microbiome-derived bioactive compounds is measured by untargeted LC-MS microbiota-derived metabolite analysis in faecal samples	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in intestinal inflammation profile (faeces)	Assay-based profile of intestinal inflammation measured in faecal samples	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Gut transit time	Gut transit time measured by blue muffin consumption and appearance in faeces	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in metabolic profile (blood)	Assay-based profile of (energy) metabolism measured in plasma samples	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in inflammation profile (blood)	Assay-based profile of systemic inflammation measured in plasma samples	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in intestinal integrity profile (blood)	Assay-based profile of intestinal integrity measured in plasma samples	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in brain health profile (blood)	Assay-based profile of brain health measured in plasma samples	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in white blood cell count (blood)	White blood cell count measured via finger prick analysis	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in small intestinal bacterial overgrowth (SIBO) (breath)	Measurement of total exhaled hydrogen gas after glucose consumption in breath samples	Change between Baseline (T0) and Follow-up after 6 months (T1)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Baseline Demographics and medical history (questionnaire)	Demographic information, medical history and medication use - qualitative assessment	Baseline (T0)
Montreal Cognitive Assessment (MOCA) (cognitive assessment)	Discrete number; score 0 - 30. Higher score indicates better cognitive performance (≥26 indicates normal cognitive functioning)	Baseline (T0)
Change in 4DKL (questionnaire)	(Psychosocial) complaints in daily life; separate scores for distress (>10 moderate, >20 severe), depression (>2 moderate, >5 severe), anxiety (>3 moderate, >9 severe) and somatisation (>10 moderate, >20 severe)	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in EQ-5D-5L (questionnaire)	Quality of life; score 0 - 100. Higher score indicate better quality of life	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in LIBRA (questionnaire)	Modifiable dementia risk using lifestyle for brain health; score -5.9 - +12.7. Higher score indicates a worse outcome (higher dementia risk)	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Lubben Social Network Scale (questionnaire)	Social contact and perceived social support; score 0 - 30. Higher score indicates a better outcome (higher level of perceived social support)	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in SARC-F Sarcopenia questionnaire (questionnaire)	Sarcopenia; score 0 - 10 (i.e. 0-2 points for each component; 0 = best to 10 = worst)	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Cognitive Emotions Regulation Questionnaire (questionnaire)	Cognitive coping strategies. Answers are scored on a 7-point Likert-type scale ranging from 1 (strongly disagree) to 7 (strongly agree). The scoring takes the average of all the scores in each subscale of cognitive reappraisal and expressive suppression	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Hospital Anxiety and Depression Scale (questionnaire)	Anxiety and depression; separate scores for anxiety (0 - 21) and depression (0 - 21). For each domain, a score >8 indicates psychiatric condition of anxiety or depression	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Starkstein Apathy Scale (questionnaire)	Screen and measure apathetic symptoms. A higher total score (range 0-42) indicates more severe apathy, with a score greater than 14 or greater is indicative of clinical apathy	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in COVID status (questionnaire)	Vaccination status, COVID history - qualitative assessment	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Gastrointestinal symptoms questionnaire (questionnaire)	Gastrointestinal symptoms, qualitative assessment	Change between Baseline (T0) and Follow-up after 6 months (T1)
Change in Bristol stool chart (questionnaire)	Classification of faeces type, qualitative assessment	Change between Baseline (T0) and Follow-up after 6 months (T1)

Collaborators and Investigators

• Sponsor: Donders Centre for Cognitive Neuroimaging
• Collaborators: Wageningen University and Research
• Investigators: Principal Investigator: Esther Aarts, PhD, Donders Centre for Cognitive Neuroimaging

Study record dates

Study Major Dates

• Study Start (Actual): May 10, 2022
• Primary Completion (Actual): May 23, 2024
• Study Completion (Actual): May 23, 2024

Study Registration Dates

• First Submitted: September 27, 2022
• First Submitted That Met QC Criteria: March 8, 2023
• First Posted (Actual): March 21, 2023

Study Record Updates

• Last Update Posted (Actual): June 21, 2024
• Last Update Submitted That Met QC Criteria: June 19, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: 3033003.01

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No