Cerebral amyloid angiopathy fluid biomarkers evaluation (CAFE)

Cerebral amyloid angiopathy (CAA), i.e. accumulation of the amyloid * protein
(AbP) in the brain vasculature, is increasingly recognized as an important
cause of cognitive decline and dementia in old age. Biomarkers that reveal the
contribution of CAA to cognitive decline and, consequently, biomarkers to
detect its presence, have so far not been developed.

Primary Objective:
To further characterize, develop and validate assays for candidate protein
biomarkers for the diagnosis of CAA.

Secondary Objective(s):
To correlate the novel neurochemical biomarkers with each other and with
measures of cognitive decline

Study design/Methods: Cohort study: discovery and validation of novel
neurochemical biomarkers (in CSF/blood)

Benefits: participants will not benefit from their participation in this study.
At the group level, we will obtain novel information (biomarkers) to diagnose
CAA, a condition that leads to cognitive decline and cerebral hemorrhages,
which currently cannot be well diagnosed.
Risks: there are minor risks associated with the lumbar puncture, vena puncture
and MRl. Complications may occur after lumbar puncture, such as leakage of CSF,
subdural haematoma, CSF fistula, a superficial infection or post-puncture
headache. These complications are rare and were not seen in a recent study on
lumbar puncture complication in 1089 patients (Zetterberg et al, 2010).
However, if identified, complications will be managed according to the latest
standards of medical practice.

As part of the MRI-protocol, a conventional MRI scan of the cerebrum and the
large cerebral vasculature will be made in all subjects, which will be examined
by a neuroradiologist for unexpected findings. ln case an unexpected finding
requires further attention, the neuroradiologist will consult a neurologist and
the case will be discussed. lf the finding is assessed to be clinically
relevant, the subjects' general practitioner will be notified within three
weeks after the experiment. The subject will be notified that the general
practitioner was contacted, and further information to the subject will be,
from that moment on, be provided by the general practitioner. Participating
subjects will be informed that these scans are collected for research purposes
and not for medical diagnostics and that the absence of unexpected findings
does not indicate that there are no abnormal conditions. Subjects agree prior
to the experiment that their general practitioner will be contacted in case of
unexpected findings.

ln this project we are seeking for novel biomarkers of CAA, a hitherto largely
neglected cerebral pathology, which , however, may occur in a large proportion
of elderly subjects. These biomarkers can only be discovered by studying groups
of patients, given the expected biological variability and thus not in a single
patient. We consider the risks associated with the participation as negligible
since the procedures used in this project are all routine procedures that are
widely applied in clinical practice.