The primary objective is to evaluate plasma levels of A*1*42/A*1*40 ratio, A*1*40, A*1*42, neurofilament light (NFL), t*tau and anti*tau antibodies as disease*specific markers for AD. The secondary objective is to measure biological age parameters (…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Neurodegenerative disorders
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoints of this study are A*1*42/A*1*40 ratio, A*1*40, A*1*42,
NFL, t*tau and anti*tau antibodies in plasma
Secondary outcome
The secondary endpoint is the combination of biological age with AD markers.
Biological age will be calculated using measurements of FEV1, systolic blood
pressure, total cholesterol, C*reactive protein, cytomegalovirus IgG,
creatinine, urea nitrogen, alkaline phosphatase, albumin and glycated
haemoglobin.
Background summary
Current Alzheimer*s Disease (AD) diagnosis is based on clinical findings and
can only be made after multidisciplinary consultation. Measurement of markers
such as declining amyloid*beta (A*)1*42 and increasing total tau (t*tau) and
hyperphosphorylated tau levels in cerebrospinal fluid (CSF) may support the
diagnosis; however, CSF measurement is invasive, expensive and not easily
accessible. There is thus a need for a
simple biomarker*based blood test, which could facilitate (early) diagnosis of
AD. The biomarker(s) could contribute to the prevention of AD by elucidating
the pathogenesis of AD. The test could also facilitate in exploring new
interventions in clinical trials. AD increases significantly with age implying
that aging is an important risk factor for AD. However, people of the same
chronological age, age differently. Using 10 physiological
parameters correlated with chronological age, it is possible to calculate a
latent variable called *biological age* able to predict mortality more
effectively in 20 years of follow*up than chronological age alone.Therefore, in
addition to studying the association of AD*specific biomarkers, this proposal
will also include measuring biological age. Combining biological age with
disease*specific markers may improve distinction between AD and non*AD
subjects.
Study objective
The primary objective is to evaluate plasma levels of A*1*42/A*1*40 ratio, A*1*
40, A*1*42, neurofilament light (NFL), t*tau and anti*tau antibodies as disease*
specific markers for AD. The secondary objective is to measure biological age
parameters (i.e. forced expiratory volume in 1 second [FEV1], systolic blood
pressure, total cholesterol, C*reactive protein, cytomegalovirus IgG,
creatinine, urea nitrogen, alkaline phosphatase, albumin and glycated
haemoglobin) and determine whether the combination of biological age with AD
markers
can make a distinction between AD and non*AD subjects.
Study design
A cross*sectional, observational study with invasive measurements (blood draw).
Study burden and risks
There are no direct benefits for the participants of the study. There is a
single study visit during which 42.5 ml of blood (5 tubes) will be collected by
venipuncture, and some non*invasive measurements are done: blood pressure,
FEV1, weight, length and grip strength. Healthy controls are administered
questionnaires to assess absence of cognitive complaints and standard physical
examination to verify that they are healthy. The risk
associated with participation is negligible and the burden related to the study
procedures can be considered minimal.
In this study patients are included that are recently diagnosed with AD and
considered not incapacitated. As specified above, the risks are negligible and
the burden is minimal. The topic of this study is markers for AD; this can only
be tested in blood from AD patients and
therefore can only be done with these patients.
Archimedesweg 4-6
Leiden 2333CN
NL
Archimedesweg 4-6
Leiden 2333CN
NL
Listed location countries
Age
Inclusion criteria
- Written informed consent
- Able to communicate well with the investigator in the Dutch language
- Aged 65-85 (including 85) years.;Additional for AD patients:
- New diagnosed with probable AD according to NIA-AA criteria
- MMSE score 18-26
- Imaging evidence to confirm absence of cerebrovascular damage or other neurodegenerative disorder
- Mentally competent for study participation as judged by treating physician and study physician.;Additional inclusion criteria for the healthy controls are:
- No memory complaints;
- MMSE score *27;
- 7MS total score < 0 (formula for total score calculation is described in Solomon et al.
1998);
- Considered healthy defined by absence of any active or chronic disease, based on
medical history (self*reported) and physical examination.
Exclusion criteria
Exclusion criteria for AD subjects are:
- Diagnosis of genetically proven familial AD
- History of concussion or other acute head trauma in the past six months;
- Current or past diagnosis of autoimmune disease;
- Current or past diagnosis of immunosuppressive disorder;
- Ongoing or past (within the last 3 months) treatment with any immunosuppressive
drug (e.g. prednisone);
- Recent (within the last 3 months) transfusion or treatment with blood products such
as intravenous immunoglobulins;
- Ongoing or past (within the last 3 months) treatment with drugs (e.g. Anakinra) that
suppress the interleukin*1, interleukin*6, or TNF** response EXCEPT non*steroidal
anti*inflammatory drugs;
- Current or previous (within the past year) treatment for malignancy;
- Current or previous (within the past year) diagnosis of hematological malignancy;
- Recent (within last 3 months) surgery;
- Recent (within last 2 weeks) acute infection.;Exclusion criteria for healthy elderly:
- Current diagnosis of probable dementia of any etiology;
- Current or past diagnosis of clinically significant pulmonary, cardiovascular,
endocrine, hematologic, neurological, immune, gastrointestinal or genitourinary
disease or cancer;
- Recent (within last 3 months) surgery;
- Recent (within last 2 weeks) acute infection;
- Taking any prescription drugs within 14 days of the study day or within 5 times the
elimination half*life of the medication (whichever is longer). Occasional
acetaminophen/paracetamol use and statins (if given as primary prevention) are
allowed. Exceptions may apply when, judged by the investigator, use of concomitant
medication does not interfere with the study objectives.
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 | NL62498.056.17 |