In this study we aim to compare postprandial chylomicron/lipid responses in Alzheimer patients and cognitively healthy people and to determine to what extend produced chylomicrons are loaded with Abeta.
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
cognitieve aandoening (dementie)
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Plasma chylomicron profiles and chylomicron-related proteins, such as ApoE and
Abeta.
Secondary outcome
ApoE phenotype will be determined by an APOE genotyping method based on Real
Time PCR. This phenotype will not change and will therefore be determined only
at baseline and not postprandial.
Background summary
The prevalence of Alzheimer disease (AD) and cognitive decline increases
dramatically. High-fat diets seem to increase the risk of getting AD. High fat
meals are taken up by the intestine and their triglyceride content enter the
circulation via chylomicrons. ApoE is highly present in these chylomicrons and
carriers of a specific ApoE phenotype (like E4) have an increased risk for AD.
The intestine and chylomicrons may therefore play a role in AD. The presence of
Abeta protein also plays a crucial role in AD, but the origin of this Abeta is
largely not known. Abeta and their precursor proteins are present in intestinal
cells. We hypothesise that chylomicrons may serve as a vehicle for Abeta
produced in intestinal epithelial cells and thereby may contribute to Abeta
deposition in the brain.
Study objective
In this study we aim to compare postprandial chylomicron/lipid responses in
Alzheimer patients and cognitively healthy people and to determine to what
extend produced chylomicrons are loaded with Abeta.
Study design
This study is an observational proof-of-concept study, in which postprandial
differences in chylomicron responses between Alzheimer patients (n=15) and
cognitively healthy subjects (n=15) will be explored. Each subject will visit
the research facility once. Subjects will consume a low fat evening meal prior
to the test day. On the test day, all subjects will consume a light breakfast
at home (tea and biscuit). Thereafter, they will arrive by taxi to the research
centre, we will insert a cannula and a baseline (t=0) blood sample will be
collected. Participants will thereafter consume a high-fat shake and
postprandial blood samples will be collected from the cannula at 1, 2, 4 and 6
hours after consumption of the shake. Participants will be offered a meal and
will be brought home via a taxi service at the end of the study day.
Study burden and risks
In this study we will explore the potential role of chylomicron/lipid
metabolism in AD. Therefore, it is essential to include (mildly) AD patients in
our study. This study is group-related, non-therapeutic research with
potentially partly mental incompetent participants. AD patients in our study
are diagnosed with mild dementia and therefore mentally capable of signing a
consent form. However, in order to avoid unwanted participation, we will obtain
additional consent from the patients* caregiver. All study procedures will a
second time be explained at the study day and study procedures will not
continue if the subject shows signs of resistance. All items in the high-fat
shake can be bought in the supermarket. Consumption of high amounts of fat may
cause some gastro-intestinal discomfort in rare cases. Blood sampling will be
performed via a cannula and the insertion can be painful and may cause a
bruise. The amount of blood that is drawn from participants is relatively small
(5 times 10-12ml = 50-60 ml in total over 6 hours) and is therefore within
acceptable limits. If needed for the AD patients, the caregiver can be present
during the study for support.
Bornse Weilanden 9
Wageningen 6708WG
NL
Bornse Weilanden 9
Wageningen 6708WG
NL
Listed location countries
Age
Inclusion criteria
- Age > 65years old
Specific inclusion criteria for Alzheimer patients:
- A diagnosis of probable Alzheimer*s disease according to the NIA-AA guidelines, CDR (clinical dementia rating) 1 (mild dementia), established as part of normal patient care at the multidisciplinary Radboudumc memory clinic
- Presence of a caregiver (spouse, child).
- Able to provide written consent (consent will also be obtained from the caregiver).
Specific inclusion criteria for healthy controls:
- Absence of subjective or objective memory impairment, MOCA score >26.
Exclusion criteria
- Any digestive tract disorder that is expected to interfere with this study (e.g. (partial) gastric resection, (hemi)colectomy, Crohn*s disease, ulcerative colitis, colon cancer)
- Use of lipid lowering medication
- Use of antacids
- Dyslipidaemia
- Known allergy for any of the food components used in the study (milk, cream, sugars)
- Diabetic patients (Type I and II)
- Blood clotting disorders
- Drug abuse
- Current smokers
- Participation in other clinical trials in the past three months
- Behavioural disturbances associated with dementia
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 |
|---|---|
| CCMO | NL61616.091.18 |