Amyloid pathology in cognitively normal elderly subjects

Alzheimer*s disease (AD) is a neurodegenerative disorder characterised by
progressive neuronal loss and eventually death. Abnormal aggregation of beta
amyloid (Aβ) is the first event in AD and is present in 20-40% of cognitively
normal elderly and can be present up to 20 years before clinical dementia. A
better understanding of the pathophysiology of AD in non-demented subjects is
needed in order to enable early diagnosis, prognosis and the discovery of novel
treatment targets.

This study has been transitioned to CTIS with ID 2024-518559-41-01 check the CTIS register for the current data.

The main objectives are to identify markers for amyloid pathology in
cognitively normal subjects, to identify risk factors for amyloid pathology in
cognitively normal subjects and to identify predictors for cognitive decline in
cognitively normal subjects with amyloid pathology. Secondary objectives are to
determine the concordance of amyloid and other AD markers in monozygotic twins,
to investigate the overlap between amyloid pathology as assessed in CSF and
assessed on PET scan and to create a substantial control group of healthy
elderly without amyloid pathology.

A longitudinal observational two-site cohort study.

Neuropsychological testing might be tiresome.

Vena puncture: This is a very common procedure therefore there is a lot of
knowledge and experience in the medical practice. There is a very small risk of
bleeding or infection, however, if this is performed lege artis the risk is
negligible. The severity of any infection or hematoma is very low.

CSF collection: This is often performed in neurology. On the screening day at
the Alzheimer Center it is basically performed in any patient. An lumbar
puncture can cause post-punctional headache in less than 5% of cases, this is
basically self-limiting, if symptoms persist, then a blood patch can be
performed. Other very rare side effects are bleeding or infection, this risk is
negligible. The severity of post-puncture headache is light. The severity of an
infection or hemorrhage depending on the extent of the complication.

MRI scan: The MRI scan is widely used in medical practice. Therefore, there is
a lot of experience and knowledge. It is possible that the narrow space and the
loud sounds generate anxiety. The severity of possible adverse effects is
negligible.

MEG: The MEG is a relatively new, but it's harmless. The narrow space can be
frightening.

The PET scan: The PET flutemetamol scan is performed with a relatively new
tracer, which has already been extensively tested and approved. This scan
produces a radiation dose of 6.1 mSv with 185 MBq, which is within the
standards, and very rarely an allergic reaction to the tracer. However, this
risk is negligible. The severity of an allergic reaction to the tracer can vary
from mild to moderate. The severity of the radiation exposure is light.

For retinal imaging, pupil dilatation is needed. Pupil dilation at an
ophthalmological examination is very common. Therefore there is a lot of
knowledge and experience. It gives transient blurred vision, this will be
restored after a few hours. The severity of the reduced vision is low.

Tears are sampled using paper Schirmer strips that are gently placed in the
lower eyelid. This procedure is not considered uncomfortable. In some cases,
insertion of the paper strip causes reflex tearing (excessive tearing similar
to tearing in reaction to foreign body, smoke or onions). The procedure is
considered harmless.

Regarding the extensive knowledge on the above tests, the probability of the
occurrence of unknown risks is virtually zero.
For PET flutemetamolscan there would be a negligible probability of occurrence
of unknown risks.

There is a small to very small risk of complications in all the separate parts
of the protocol, as described above. The damage that could occur can be called
light. The subjects are all healthy, mentally competent elderly for whom we
think the burdening is acceptable in the context of the importance of our
research. Therefore, we think there is a negligible risk.

To minimize burden, data collection will be concentrated on 2 days at baseline,
1 day at follow-up, 2 days at second follow-up,1 day at third follow-up and 2
days at fourth follow-up. The study will not have any direct benefits for
participants, but it will add enormous value to studies on the understanding
and diagnosis of AD.