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

Aging Clinical Trial

— HELI  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05777863
• Other study ID #: 3033003.01
• Status: Active, not recruiting
• Phase: N/A
• Start date: May 10, 2022
• Est. completion date: May 23, 2024

Study information

• Verified date: April 2024
• Source: Donders Centre for Cognitive Neuroimaging
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 102
• Est. completion date: May 23, 2024
• Est. primary completion date: May 23, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Aging
• Cognitive Decline
• Cognitive Dysfunction
• Life Style
• Risk Reduction

Intervention

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.

Locations

Country	Name	City	State
Netherlands	Donders Centre for Cognitive Neuroimaging	Nijmegen	Gelderland
Netherlands	Wageningen University & Research	Wageningen	Gelderland

Sponsors (2)

Lead Sponsor	Collaborator
Donders Centre for Cognitive Neuroimaging	Wageningen University and Research

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Montreal Cognitive Assessment (MOCA) (cognitive assessment)	Discrete number; score 0 - 30. Higher score indicates better cognitive performance (=26 indicates normal cognitive functioning)	Baseline (T0)
Other	Baseline Demographics and medical history (questionnaire)	Demographic information, medical history and medication use - qualitative assessment	Baseline (T0)
Other	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)
Other	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)
Other	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)
Other	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)
Other	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)
Other	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)
Other	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)
Other	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)
Other	Change in COVID status (questionnaire)	Vaccination status, COVID history - qualitative assessment	Change between Baseline (T0) and Follow-up after 6 months (T1)
Other	Change in Gastrointestinal symptoms questionnaire (questionnaire)	Gastrointestinal symptoms, qualitative assessment	Change between Baseline (T0) and Follow-up after 6 months (T1)
Other	Change in Bristol stool chart (questionnaire)	Classification of faeces type, qualitative assessment	Change between Baseline (T0) and Follow-up after 6 months (T1)
Primary	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)
Primary	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)
Primary	Change in cerebral perfusion levels	Cerebral perfusion measured using arterial spin labelling (ASL)	Change between Baseline (T0) and Follow-up after 6 months (T1)
Primary	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)
Primary	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)
Primary	Change in inflammatory profile in blood plasma: TNF-a	Blood plasma inflammatory profile analysis to measure TNF-a level	Change between Baseline (T0) and Follow-up after 6 months (T1)
Primary	Change in microbiota profile	16S rRNA based profile of gut microbiota in faeces	Change between Baseline (T0) and Follow-up after 6 months (T1)
Secondary	Change in Body mass index	Measured in kg/m^2	Change between Baseline (T0) and Follow-up after 6 months (T1)
Secondary	Change in Waist circumference	Measured in cm	Change between Baseline (T0) and Follow-up after 6 months (T1)
Secondary	Change in Hip circumference	Measured in cm	Change between Baseline (T0) and Follow-up after 6 months (T1)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	Intracranial iron deposition (neuroimaging)	Local aggregation of iron deposition within the brain, measured by quantitative susceptibility mapping (QSM)	Baseline (T0)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)