The primary objective of this study is divided into two steps:Step 1. To investigate the effect of a 26-week (around 6 months) multidomain lifestyle intervention on brain function (working memory, cerebral perfusion) and peripheral immunometabolic…
ID
Source
Brief title
Condition
- Other condition
- Age related factors
Synonym
Health condition
risicofactoren voor cognitief functioneren (cognitieve veroudering)
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Our primary study objectives, with the forthcoming primary study outcomes, are:
Step 1.
a) Brain activity during working memory:
BOLD activity and task-accuracy during N-back fMRI task.
b) Cerebral perfusion levels:
MRI-ASL levels.
c) Peripheral immunometabolic markers:
Inflammation markers (IL-6, TNF-α, hs-CRP; from blood plasma) & gut microbiome
composition (diversity and richness; from faeces).
Step 2.
To investigate intervention-induced immunometabolic-brain links by analysing
the relations between the sign-effects of step 1 (see a, b, and c).
Secondary outcome
Our secondary study objectives, with the forthcoming secondary study outcomes,
are:
a) To identify baseline predictors for cognitive ageing and intervention
efficacy:
Structural MRI (e.g. grey/white matter volume, ventricular enlargement,
abdominal adipose T1 assessment, etc.), neurochemical MR assessments (MRS;
myo-inositol, QSM; iron accumulation), and participant demographics at baseline
(e.g. age, sex, education level, etc.).
b) To investigate the effect of a 26-week multidomain lifestyle intervention on
neuropsychological test battery scoring (cognitive functioning):
Z-scoring on cognitive domains predominantly affected by cognitive ageing:
executive function, working memory and processing speed.
c) To investigate which specific lifestyle domains bring about effects on
specific measures:
Relations between improvement in domain-related questionnaire scores and
primary outcome measures.
d) To investigate the effect of a 26-week multidomain lifestyle intervention on
a broad array of other immunometabolic brain markers relevant for cognitive
ageing:
Fecal analysis (microbiota quantification of composition; e.g. functional
microbiota analysis, analysis for metabolites), plasma analysis (e.g. markers
of intestinal integrity, further inflammatory condition assessment, nutritional
status, (early) Alzheimer markers, microbiota-derived bioactive compounds),
urine analysis (microbiota-derived bioactive compounds), and breath analysis
(SIBO; small intestinal bacterial overgrowth).
e) To perform a manipulation check to test whether our multidomain lifestyle
intervention-induced changes in brain functioning and perfusion in the
hippocampus and dl-PFC (regions of interest) predict improved cognitive
performance:
Relations between changes in the hippocampus and dl-PFC (BOLD-responses and
perfusion) and changes in the working memory (fMRI task) and cognitive domain
performance score (neuropsychological tests) following the intervention.
Background summary
Population ageing brings significant challenges to our society. With increasing
age, the prevalence of incurable neurodegenerative diseases, like Alzheimer*s
Disease (AD) - the most common form of dementia - increases likewise. In 2018,
50 million people worldwide were living with dementia and it has been estimated
that this number will reach 132 million in 2050. Curative approaches have so
far been unsuccessful due to the multiple (irreversible) biological pathways
involved and are also hampered by the large individual differences in treatment
effects. Therefore, preventing or delaying the onset of dementia has utmost
priority.
Previous lifestyle intervention studies have been conducted that propose
effects of lifestyle factors on mechanisms such as cognitive performance,
functional brain responses, cerebral blood flow, and peripheral markers (e.g.
immune-inflammation, gut microbiome composition). Additionally, it is becoming
increasingly clear that peripheral immuno-metabolic markers and the gut
microbiome could influence central mechanisms in the brain. However, many of
these studies are lifestyle intervention studies focusing on one domain, whilst
multiple studies have indicated that multidomain (>=2 domains) interventions
show a greater effect on cognitive decline in ageing. It is unclear how
multidomain lifestyle interventions influence the brain and the periphery, and
additionally, the correlational links between the brain and periphery remain to
be further elucidated. We hypothesize that multidomain lifestyle interventions
affect multiple peripheral and central mechanisms simultaneously, as well as
the interrelated connections between these mechanisms.
To test this hypothesis, we will employ a multidomain lifestyle intervention in
older adults with cardiovascular risk: the HELI study. The HELI-study (derived
from the Dutch 'Hersenfuncties na Leefstijlinterventie', meaning: 'Brain
function after lifestyle intervention') is designed as a multidomain lifestyle
intervention that uses five different lifestyle domains (diet, physical
activity, sleep, stress/mindfulness, cognitive training) to improve cognitive
and immunometabolic outcomes. We will assess its effects on multiple structural
and functional MRI-related brain measures as well as peripheral measures in
blood (immune-related), faeces and urine (gut microbiome-related), as well as
their connections. Additionally, we would like to mechanistically explain
individual differences in treatment response by assessing the neurocognitive
and immunometabolic (primary) outcome measures.
Study objective
The primary objective of this study is divided into two steps:
Step 1. To investigate the effect of a 26-week (around 6 months) multidomain
lifestyle intervention on brain function (working memory, cerebral perfusion)
and peripheral immunometabolic markers (IL-6, TNF-α, hs-CRP, composition and
richness of the gut microbiome).
Step 2. To investigate intervention-induced immunometabolic-brain links by
analysing the relations between the intervention-induced effects of the
immunometabolic and brain measures.
Working memory is measured by BOLD activity and task-accuracy during a N-back
fMRI task, and cerebral perfusion is measured by MRI-ASL. The immuno-metabolic
markers of IL-6, TNF-α en hs-CRP are measured by performing blood plasma
analyses, and the gut microbiome composition and richness are analysed by
taking faecal samples.
The secondary objectives are (1) to identify baseline predictors for
intervention efficacy, (2) to investigate the effect of a 26-week multidomain
lifestyle intervention on neuropsychological test battery scoring (cognitive
functioning), (3) to investigate which specific lifestyle domains bring about
effects on specific outcomes, (4) to investigate the effect of a 26-week
multidomain intervention on a broad array of other immunometabolic-brain
markers relevant for cognitive ageing, (5) and to perform a manipulation check
to test whether our multidomain lifestyle intervention-induced changes in brain
functioning and perfusion in the hippocampus and dl-PFC (regions of interest)
predict improved cognitive performance.
Study design
HELI is a multicenter, randomised, controlled, multidomain lifestyle
intervention study of 26 weeks (around 6 months) with 104 Dutch elderly at risk
of cognitive decline (based on established risk factors). Participants are
randomised in a 1:1 ratio to either one of two groups of the multidomain
lifestyle intervention: high-intensity or low-intensity.
Both lifestyle interventions are accessed online.
Intervention
The HELI multidomain lifestyle intervention contains five domains, namely (1)
diet, (2) physical activity, (3) sleep, (4) stress/mindfulness, (5) cognitive
training. Every domain will be presented in a comparitive amount during the 26
weeks of the intervention.
Participants are randomised in a 1:1 ratio to either one of two groups of the
multidomain lifestyle intervention: high-intensity or low-intensity.
The high-intensity intervention group contains online group meetings and
individual progress-meetings. The high-intensity intervention will take on
average 3 hours each week for 26 weeks in total. These 3 hours contain the
weekly online group meeting of 1.5 hours (where one or more specific domains
are explained and where tips can be shared between participants), and 1.5 hours
of exercises or training that are completed at home by the participant. The
content of the 5 lifestyle domains that are presented in the lifestyle
intervention are developed and judged by experts of each respective domain, to
oversee and reduce (where needed) the possible risks of the intervention.
The low-intensity intervention group receives online access to general
lifestyle-related health information that is published on a monthly basis.
Participants in this group will spend an average of 30 minutes each month on
this information during 26 weken (around 6 months).
The high-intensity intervention is primarily presented online, although several
on-site meetings will take place (especially during the physical activity
domain, to be able to practice physical exercises). The low-intensity
intervention will be fully presented online.
Study burden and risks
The high-intensity intervention group contains online group meetings and
individual progress-meetings. The high-intensity intervention will take on
average 3 hours each week for 26 weeks in total. These 3 hours contain the
weekly online group meeting of 1.5 hours (where one or more specific domains
are explained and where tips can be shared between participants), and 1.5 hours
of exercises or training that are completed at home by the participant. The
content of the 5 lifestyle domains that are presented in the lifestyle
intervention are developed and judged by experts of each respective domain, to
oversee and reduce (where needed) the possible risks of the intervention.
The low-intensity intervention group receives online access to general
lifestyle-related health information that is published on a monthly basis.
Participants in this group will spend an average of 30 minutes each month on
this information during 26 weken (around 6 months).
Apart from the intervention-related activities, both intervention groups will
visit both of the study centres in Nijmegen and Wageningen two times (at
baseline before intervention start, and at follow-up after the intervention has
concluded) for outcome measurements, including neuropsychologic tests,
MRI-scan, faecal- and urine sampling, blood-drawing, breath test and
questionnaires. Thus, there will be 4 total visits to the study centres (1 time
to Nijmegen and Wageningen at baseline, and 1 time to Nijmegen and Wageningen
after the intervention). Each visit will take an average of 3 hours.
Participation to this study could be beneficial for the participant, as the
participant will receive information to make improvements of lifestyle patterns
that could lead to a participant improving their own (brain) health.
Undergoing MRI-scanning can be experienced as tiresome. The blood-drawing can
cause mild pain or discomfort, and sometimes it causes a bruise. All these
symptoms will dissapear with time.
Kapittelweg 29
Nijmegen 6525EN
NL
Kapittelweg 29
Nijmegen 6525EN
NL
Listed location countries
Age
Inclusion criteria
- Age between 60-75 years (at pre-screening)
- Fluency in Dutch (speaking, reading and writing)
- Lives near study centres in Nijmegen and Wageningen (maximum of 50km of
traveling to either Nijmegen or Wageningen)
- Score >=2 points on the 6 modifiable cardiovascular risk factors listed below:
1. BMI >=25 (1 point)
2. Physical inactivity (below the 2020 WHO guidelines, meaning: <300 min of
moderate intensity aerobic physical activity, or <150 min of vigorous intensity
aerobic physical activity per week, spread out over several days) (1 point)
3. Hypertension (1 point, 2 points if hypertension is untreated)
4. Hypercholesterolemia (1 point)
5. Diabetes type-II (1 point)
6. Cardiovascular disease (EXCEPT: symptomatic cardiovascular disease such as
stroke, angina pectoris, heart failure, myocardial infarction, OR
revascularisation surgery in the last 12 months at pre-screening) (1 point)
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. MCI, dementia, MS, Parkinson's, epilepsy);
> Current malignant disease(s), with or without 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.
- Answering "Yes" on >=1 of the Donders Institute MRI safety screening protocol
questions (see 8 questions below):
1. Are there metal objects located in your upper body? Exception:
tooth-fillings and/or dental crowns.
2. Are there metal splinters in your body, in particular within the eyes? For
example: through labour work in the metal industry.
3. Are there jewellery items or piercings that you are unable to take off?
4. Have you had a brain surgery in the past?
5. Are there active implants present? For example: pacemaker, neurostimulator,
insulinpump, hearing aid (that is unable to be removed).
6. Are there any medical plasters or patches that you can*t or may not take
off? For example: nicotine patch.
7. Do you suffer from epilepsy?
8. Do you suffer from claustrophobia?
- Cognitive impairment as determined by Telephone Interview for Cognitive
Status (TICS-M1), performed during pre-screening before inclusion.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| Other | Deze studie wordt geregistreerd binnen clinicaltrials.gov voordat de eerste participant is geworven. |
| CCMO | NL78263.091.21 |