The main objectives are to understand how clinical markers and biomarkers previously identified in younger and older AD cohorts apply to the extreme elderly (90+ years old) and to identify novel biomarkers linked with resilience to developing…
ID
Source
Brief title
Condition
- Structural brain disorders
- Dementia and amnestic conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary study parameters are:
1. To understand how clinical markers and biomarkers previously identified (and
published) in younger and older dementia cohorts apply to the extreme elderly.
2. To identify novel biomarkers linked with resilience to developing AD in
extreme elderly subjects.
3. To investigate the association of biomarkers tested at baseline for
change in cognitive fuction and progression to dementia during a 3 year
follow-up period.
The clinical markers and biomarkers we will test, can be divided into the
following 6 domains:
- brain reserve capacity
- comorbidity
- genetics
- physical performance
- senescence state
- biomarkers for AD
For each domain we will test one or more parameters. For each parameter we will
study whether this parameter is associated with resilience for dementia in the
oldest old.
Follow-up:
1. The main outcome at follow-up is cognitive performance after 1-2 years.
2. To identify predictors for cognitive decline in non-demented extreme
elderly.
Secondary outcome
The secundary study parameters are:
1. Generate normative data for the oldest old.
2. To measure the concordance between amyloid pathology as assessed in CSF and
by PET in the oldest old.
Background summary
It is estimated that 35.6 million people over age 60 years lived with dementia
worldwide in 2010. In the US, the oldest old individuals (85+ years old)
represent the fastest growing segment of the population; the number of oldest
old living with dementia in the US could grow from 1-2 million in 2010 to more
than 8 million by 2050 or 2060. However, not much is known about dementia in
this specific age group. We want to explore the aetiology of dementia in people
aged 90 years and over by identifying the factors linked with resilience to
dementia in the extreme elderly.
Study objective
The main objectives are to understand how clinical markers and biomarkers
previously identified in younger and older AD cohorts apply to the extreme
elderly (90+ years old) and to identify novel biomarkers linked with resilience
to developing Alzheimer*s disease (AD) in extreme elderly subjects. In addition
we will generate normative data for the oldest and measure the concordance
between amyloid pathology as assessed in CSF and by PET in the oldest old.
The main objective at follow-up is to investigate the change of cognitive
performance over time in non-demented extreme elderly.
Study design
This is a case-control study to identify factors that protect against the
development of AD. We will include cognitvely normal elderly subjects as the
case-group and subjects with cognitive impairment as the control group. The
expected starting date for sample collection is September 2015 and the expected
end date is December 2019.
De subjects will be approached again in Februari 2019 for the follow-up of the
study. We will repeat part of the study: questionnaires, neuropsychological
tests, physical measurements (smelltest, hearingtest and handgrip strenght).
For the second follow-up measurement the same subjects will be approached.
Study burden and risks
Neuropsychological testing might be tiring. CSF collection is associated with
post-lumbar puncture headache in 5% of patients. Other rare (<1%) complications
can include bleeding, infection, or leakage. The PET scan is associated with a
radiation load of 4.1 mSv with 185 MBq and very rarely with an idiosyncratic
reaction to the tracer. The CT-scan which will be conducted in a few
participants is associated with a radiation load of 4.4mSv. For retinal
imaging, pupil dilatation is needed and one hour after dilatation patient*s
eyesight is normal again. The study will not have any direct health benefits
for participants, but it will add enormous value for understanding and
preventing AD.
The follow-up will not have any risks for the participants. To minimize the
burden for the participants, the follow-up will take place at the home of
participants. The second follow-up will be a repition of the first and will not
have any additional risks for the participants.
De Boelelaan 1118
Amsterdam 1081 HZ
NL
De Boelelaan 1118
Amsterdam 1081 HZ
NL
Listed location countries
Age
Inclusion criteria
Age >= 90 years (for the subjects with cognitive impairment an exception will be
made; also subjects between 85 and 90 years will be included)
Candidate is able to walk 400 meter independently (with or without walking aid)
No significant visual or hearing impairment (as judged by clinician),
Cognitively intact group:
- MMSE >= 27 points, , this inclusion criteria is not applicable to the subjects
>= 100 years old (as a consequence of their age, they often score < 27 points
without having dementia)
- Clinical Dementia Rating (CDR) = 0.0 points, Cognitive impairment group:
- MMSE: 20-28 points inclusively
- CDR >= 0.5 point(s)
- Determination that this dysfunction is due to cognitive functional loss and
not physical impairment, as judged by a neurologist, internist-geriatrician or
General Practitioner (GP)., There is an overlap in MMSE score but this has no
effect on the contrast between the two groups. The two groups are based on
dementia diagnosis and the MMSE score has no influence on this diagnosis.
Someone with a MMSE of 27 can be both dement or cognitively healthy., For the
additional follow-up visits only cognitvely intact subjects will be seen for
questionnaires, neuropsychological examination and few physical measurements
(smelltest, hearingtest and handgrip strength). The second follow up visit will
be a repetition of the first, including the same subjects.
Exclusion criteria
Clinical diagnosis of severe AD
Severe head trauma, with loss of consciousness
Brain tumour (past, present)
Schizophrenia, bipolar disorder, or recurrent psychotic disorders
Stroke resulting in physical impairment
Non-AD neurodegenerative disorders (e.g. Huntington disease, cortical basal
degeneration, multiple system atrophy, CreutzfeldtÂJacob disease, primary
progressive aphasia, Parkinson*s disease, diffuse Lewy body disease,
frontotemporal dementia, primary vascular dementia)
Epilepsy, currently using antiepileptic drugs (AEDs)
Brain infections (e.g. herpes simplex encephalitis)
Cancer with terminal life expectancy (life expectancy <12 months)
Cancer chemotherapy or radiotherapy within the last 3 months
Known B12 vitamin deficiency without treatment
Uncontrolled diabetes mellitus (last measure HbA1c >80 mmol/mol)
Known thyroid disease without treatment
History of recreational drug use
Alcohol consumption: >35 units per week (1 unit = 10ml of pure alcohol)
Physical morbidity or illness which will not permit attendance at visit sessions
Contraindication for MRI (e.g. metal implants, pacemaker etc.)
Medications that may impair cognition, at the discretion of the investigator,
e.g.:
- Benzodiazepine with known effects on cognitive functioning
- Lithium carbonate
- Antipsychotics including atypical agents
- Antidepressants with known effects on cognitive functioning
- Parkinson*s disease medicines
Design
Recruitment
Medical products/devices used
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 |
|---|---|
| EudraCT | EUCTR2016-002635-15-NL |
| CCMO | NL53756.029.16 |