MedPath

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

Not Applicable
Completed
Conditions
Life Style
Risk Reduction
Cognitive Decline
Aging
Interventions
Behavioral: Multidomain lifestyle intervention
Registration Number
NCT05777863
Lead Sponsor
Donders Centre for Cognitive Neuroimaging
Brief Summary

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).

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
102
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
High-intensity groupMultidomain lifestyle interventionThe 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.
Primary Outcome Measures
NameTimeMethod
Change in working memory performanceChange between Baseline (T0) and Follow-up after 6 months (T1)

Task accuracy during N-back (2-back) fMRI task

Change in brain activity during working memoryChange between Baseline (T0) and Follow-up after 6 months (T1)

Blood-oxygen level dependent activity during N-back (2-back) fMRI task

Change in inflammatory profile in blood plasma: TNF-αChange between Baseline (T0) and Follow-up after 6 months (T1)

Blood plasma inflammatory profile analysis to measure TNF-α level

Change in cerebral perfusion levelsChange between Baseline (T0) and Follow-up after 6 months (T1)

Cerebral perfusion measured using arterial spin labelling (ASL)

Change in inflammatory profile in blood plasma: IL-6Change between Baseline (T0) and Follow-up after 6 months (T1)

Blood plasma inflammatory profile analysis to measure IL-6 level

Change in inflammatory profile in blood plasma: hs-CRPChange between Baseline (T0) and Follow-up after 6 months (T1)

Blood plasma inflammatory profile analysis to measure hs-CRP level

Change in microbiota profileChange between Baseline (T0) and Follow-up after 6 months (T1)

16S rRNA based profile of gut microbiota in faeces

Secondary Outcome Measures
NameTimeMethod
Change in Waist circumferenceChange between Baseline (T0) and Follow-up after 6 months (T1)

Measured in cm

Intracranial iron deposition (neuroimaging)Baseline (T0)

Local aggregation of iron deposition within the brain, measured by quantitative susceptibility mapping (QSM)

Change in Digit Symbol Substitution Test (DSST) (cognitive assessment)Change between Baseline (T0) and Follow-up after 6 months (T1)

Discrete number; score 0 - 90 (amount of symbols correctly substituted). Higher score indicates better outcome

Change in Sedentary Behaviour Questionnaire (questionnaire)Change between Baseline (T0) and Follow-up after 6 months (T1)

Average hours and minutes of sedentary behavior a day; score 0 - 24 hours. Higher score (more hours) indicates more sedentary behavior

Change in Body mass indexChange between Baseline (T0) and Follow-up after 6 months (T1)

Measured in kg/m\^2

Change in Trail Making Test A (TMT-A) Numbers : trial time (cognitive assessment)Change between Baseline (T0) and Follow-up after 6 months (T1)

Discrete number; score 0 - no maximum (seconds to assessment completion). Lower score indicates a better outcome

Change in Blood pressureChange between Baseline (T0) and Follow-up after 6 months (T1)

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 in Abdominal fat distribution (neuroimaging)Change between Baseline (T0) and Follow-up after 6 months (T1)

Visceral adipose tissue(VAT)/subcutaneous adipose tissue (SAT) ratio measured by abdominal T1-weighted MRI scan

Change in Brain myo-inositol levels (neuroimaging)Change between Baseline (T0) and Follow-up after 6 months (T1)

Brain myo-inositol levels reflecting local neuroinflammation in dorsolateral prefrontal cortex and hippocampus, measured by magnetic resonance spectroscopy (MRS)

Change in Trail Making Test B (TMT-B) Numbers and Letters: errors (cognitive assessment)Change between Baseline (T0) and Follow-up after 6 months (T1)

Discrete number; score 0 - no maximum (amount of errors). Lower score indicates a better outcome

Change in Hip circumferenceChange between Baseline (T0) and Follow-up after 6 months (T1)

Measured in cm

Change in Brain structure volume profile (neuroimaging)Change between Baseline (T0) and Follow-up after 6 months (T1)

Brain structure volumes (grey matter, white matter, brain vesicles), measured by MP2RAGE structural sequence

Change in Rey Auditory Verbal Learning Test (RAVLT): learning trials (cognitive assessment)Change between Baseline (T0) and Follow-up after 6 months (T1)

Discrete number; score 0 - 15 (amount of words remembered during learning trial 1 to 5). Higher score indicates a better score

Change in Eetscore food questionnaire (questionnaire)Change between Baseline (T0) and Follow-up after 6 months (T1)

Dutch Healthy Diet Index 2015; score 0 - 160. Higher score indicates a better outcome

Change in Pittsburgh Sleep Quality Index (PSQI) (questionnaire)Change between Baseline (T0) and Follow-up after 6 months (T1)

Sleep quality; score 0 - 21. Higher score (referred to as global or total score) indicates worse sleep quality

Change in SQUASH (questionnaire)Change between Baseline (T0) and Follow-up after 6 months (T1)

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 in Cognitive Failures Questionnaire (questionnaire)Change between Baseline (T0) and Follow-up after 6 months (T1)

Subjective cognitive functioning; score 0 - 100. A higher score indicates more subjective cognitive failure

Change in Memory Self-Efficacy MIA (questionnaire)Change between Baseline (T0) and Follow-up after 6 months (T1)

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 in Neuropsychological test battery scoringChange between Baseline (T0) and Follow-up after 6 months (T1)

Z-scoring of cognitive assessments targeting cognitive domains predominantly affected by cognitive ageing: executive function (incl. working memory), episodic memory and processing speed

Change in Trail Making Test A (TMT-A) Numbers: errors (cognitive assessment)Change between Baseline (T0) and Follow-up after 6 months (T1)

Discrete number; score 0 - no maximum (amount of errors). Lower score indicates a better outcome

Change in Trail Making Test B (TMT-B) Numbers and Letters : trial time (cognitive assessment)Change between Baseline (T0) and Follow-up after 6 months (T1)

Discrete number; score 0 - no maximum (seconds to assessment completion). Lower score indicates a better outcome

Change in Rey Auditory Verbal Learning Test (RAVLT): delayed recall (cognitive assessment)Change between Baseline (T0) and Follow-up after 6 months (T1)

Discrete number; score 0 - 15 (amount of words remembered during delayed recall). Higher score indicates a better score

Change in individual short-chain fatty acids (SCFAs) profile (faeces)Change between Baseline (T0) and Follow-up after 6 months (T1)

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 in Verbal Fluency Test (VFT) (cognitive assessment)Change between Baseline (T0) and Follow-up after 6 months (T1)

Word count in one minute; score 0 - no maximum. Higher score indicates a better outcome

Change in total amount of bacteria, fungi and specific bacterial strains (faeces)Change between Baseline (T0) and Follow-up after 6 months (T1)

Total amount of bacteria, fungi and specific bacterial strains are quantified using digital droplet PCR in faecal samples

Change in Wechsler Adult Intelligence Scale (WAIS) digit span (cognitive assessment)Change between Baseline (T0) and Follow-up after 6 months (T1)

Discrete number; score 0 - 90 (amount of digit spans correctly repeated). Higher score indicates better outcome

Change in Five Facet Mindfulness Questionnaire (questionnaire)Change between Baseline (T0) and Follow-up after 6 months (T1)

Self-assessment of mindfulness; score 24 - 120. Higher score indicate more mindfulness

Change in Perceived Stress Scale (questionnaire)Change between Baseline (T0) and Follow-up after 6 months (T1)

Stress perception; score 0 - 40. Higher score indicate more perceived stress

Change in intestinal inflammation profile (faeces)Change between Baseline (T0) and Follow-up after 6 months (T1)

Assay-based profile of intestinal inflammation measured in faecal samples

Change in small intestinal bacterial overgrowth (SIBO) (breath)Change between Baseline (T0) and Follow-up after 6 months (T1)

Measurement of total exhaled hydrogen gas after glucose consumption in breath samples

Change in microbiome-derived bioactive compounds (faeces)Change between Baseline (T0) and Follow-up after 6 months (T1)

Amount of microbiome-derived bioactive compounds is measured by untargeted LC-MS microbiota-derived metabolite analysis in faecal samples

Change in Gut transit timeChange between Baseline (T0) and Follow-up after 6 months (T1)

Gut transit time measured by blue muffin consumption and appearance in faeces

Change in inflammation profile (blood)Change between Baseline (T0) and Follow-up after 6 months (T1)

Assay-based profile of systemic inflammation measured in plasma samples

Change in metabolic profile (blood)Change between Baseline (T0) and Follow-up after 6 months (T1)

Assay-based profile of (energy) metabolism measured in plasma samples

Change in intestinal integrity profile (blood)Change between Baseline (T0) and Follow-up after 6 months (T1)

Assay-based profile of intestinal integrity measured in plasma samples

Change in brain health profile (blood)Change between Baseline (T0) and Follow-up after 6 months (T1)

Assay-based profile of brain health measured in plasma samples

Change in white blood cell count (blood)Change between Baseline (T0) and Follow-up after 6 months (T1)

White blood cell count measured via finger prick analysis

Trial Locations

Locations (2)

Donders Centre for Cognitive Neuroimaging

🇳🇱

Nijmegen, Gelderland, Netherlands

Wageningen University & Research

🇳🇱

Wageningen, Gelderland, Netherlands

© Copyright 2025. All Rights Reserved by MedPath