Brain patterns in patients with neurodegenerative diseases

The differential diagnosis of neurodegenerative brain diseases may be difficult
on clinical grounds only, especially at an early disease stage.
Neurodegenerative brain diseases such as Parkinson*s disease (PD), multiple
system atrophy (MSA), progressive supranuclear palsy (PSP), corticobasal
degeneration (CBD), dementia with lewy bodies (DLB, Alzheimer*s disease (AD)
and frontotemporal dementia (FTD) have overlapping features at presentation,
while the typical clinical syndrome may become clear only at later disease
stages. For this reason, there is increasing interest to use neuroimaging
techniques in the hope to discover biomarkers, that is, abnormal patterns of
brain structure, energy consumption or network activity which are
characteristic of such diseases. Many in vivo brain imaging techniques are
nowadays available for this purpose. [18F]-fluoro- deoxyglucose (FDG) PET
imaging has been used to identify characteristic patterns of regional glucose
metabolism in patients with neurodegenerative brain diseases. With MR based
imaging using Voxel Based Morphometry (VBM) analysis, patterns of cerebral
atrophy can be detected in an earlier stage of the disease. Diffusion Tensor
MRI (DTI) is able to detect such microscopic abnormalities by measuring the
directionality of molecular diffusion in brain tissue. Arterial Spin Labelling
(ASL) MR-imaging, at which arterial blood water is labelled as an endogenous
diffusible tracer for perfusion, allows for quantitative assessment of tissue
perfusion. In resting state fMRI subjects are scanned without external stimulus
to derive brain connectivity patterns which are assumed to represent a
default-mode network. It is increasingly recognised that combining information
derived from different image modalities is essential for improvements in the
sensitivity and specificity of proposed biomarkers for neurodegenerative
diseases. The method should allow individual patients to be diagnosed at an
early stage of the disease.

Databases with multimodal brain imaging data (FDG-PET, VBM, DTI, ASL and
resting state fMRI) will be created. From these data image features will be
extracted, to be used to create a supervised classification method for
associating brain patterns to various stages of neurodegenerative diseases.

In this observational study, 15 subjects per group of patients with PSP, CBD,
DLB, AD and FTD will be included. All subjects will undergo
neuro(psycho)logical examination as well as 1 FDG PET scan and 1 MRI scan.
Patients with PD and MSA as well as 15 gender- and age matched healthy
volunteers are already recruited in a previous study (METc 2008/274)

The risks associated with participation are considered negligible and the
burden can be considered minimal since there is great experience with these PET
and MRI investigations in normal diagnostic work up of patients with
neurodegenerative brain diseases and significant side effects are not known.
This study can not be conducted without the participation of sufficient
subjects in each group. This study can contribute to a better understanding and
early diagnosis in patients with neurodegenerative brain diseases.