Longitudinal ultra-high field imaging in Parkinson*s Disease: Tracking the disease course

Parkinson*s disease (PD) is the second most common neurodegenerative disorder
after Alzheimer*s disease. It is characterized by both motor symptoms and
non-motor symptoms, such as neuropsychiatric disturbances and autonomic
dysfunction. The diagnosis of PD is currently based on the assessment of
clinical symptoms and monitoring these symptoms over time. But the early
diagnosis of PD can be challenging and it is often not immediately recognised.
During the past years it has become well-established that MR imaging may be
able to serve as a valuable method in the diagnostic work-up of PD. Early MRI
biomarkers have been discovered that suggest a possibility to distinguish PD
patients from healthy controls based on ultra-high field neuroimaging. However,
until now insufficient sensitivity and specificity is reached for the MRI
characteristics in the performed studies to determine whether a single
individual has PD.
Furthermore, over the last few years there has been growing interest in the
heterogeneous nature of PD. A great variability exists not only in motor
manifestations, but also in cognitive functions, autonomic complaints,
prognosis and response to therapy. As a result, several attempts have been made
to subdivide PD patients into different clinical subtypes, which might be
influenced by a combination of environmetnal and genetic factors. However, the
underlying aetiology of this clinical heterogeneity in PD is still not
understood and at this moment we are not able to predict the individual disease
course of a patient. Nevertheless, previous studies have suggested that
different motor subtypes of PD may show dissimilar MR characteristics,
especially in the substantia nigra. Unfortunately, most studies contain only
small groups of subjects and results are not unambiguously. Until now it is
still not clear to what extend changes on MR imaging in PD patients correlate
to the clinical subtype of these patients and if certain MRI characteristics
can predict the individual disease course.
With this longitudinal ultra-high field 7T study, which combines several
different MRI techniques, we believe that we can make an important contribution
to the development of a distinctive MRI pattern for PD. Furthermore, we expect
different clinical subgroups of PD patients to show dissimilar MRI profiles.

The primary objective of this study is to confirm early and subtle MRI changes
in PD patients which distinguish them from the healthy population and to create
a diagnostic tool for neurologists based on these differences. Secondary
objectives are to detect whether different clinical phenotypes of PD patients
also show different imaging characteristics and to correlate MRI
characteristics to clinical phenotype, genetic characteristics and progression
of symptoms.

We will perform a longitudinal observational 7T MRI study in PD patients and
healthy controls (HC). All subjects will undergo a 7T MRI scan of the brain at
baseline and after 2 and 4 years. Moreover, a blood sample for genetic testing
and the detection of brain-enriched microvesicle miRNAs will be collected at
baseline and at the second follow-up visit. Furthermore, motor, psychological,
cognitive and autonomic functions of the PD subjects will be assessed at each
follow-up moment. During all test days, subjects will also be asked to wear 3
wearable sensors (one at each wrist and one at their chest) to assess motoric
function. Based on these clinical parameters, PD patients will be subdivided
into different clinical subgroups.

The burden for the subjects related to this study is limited. Patients will
undergo an assessment at baseline, after 2 and after 4 years. For this MRI
scan, medication does not have to be discontinued. The duration of the scan
will be approximately 60 minutes, which is considered to be acceptable. Only
patients without contra-indications for MRI will be included, therefore the
procedure is safe. Furthermore, assessments of motor, psychological, cognitive
and autonomic functions will be performed during the follow-up moments. During
these assessments, participants are asked to wear three wearable sensors, which
are not considered to be a risk or burden. Furthermore, we will ensure that
sufficient moments of rest are scheduled between the tests. Finally, if
patients give their permission for this, a sample of blood will be drawn from
all subjects at baseline and during the second follow-up visit. There is a
small risk for all participating subjects that incidental observations can be
found within this study. Only subjects who give permission to inform their
treating physician in case of an incidental observation will be included in the
study.
There are no immediate benefits for the participants. However, PD patients can
benefit from optimised treatment in the future, as will other PD patients not
included in the study due to group-relatedness.