Cognitive phenotypes in Parkinson's disease: anatomical and functional correlates

Cognitive deficits are common in Parkinson's disease (PD). In cross-sectional
studies, 30-40% of PD patients meet the criteria for dementia. Moreover, a
number of longitudinal studies have revealed that the cumulative incidence of
dementia in PD patients may be as high as 80-90% - a percentage that increases
with age and disease duration. In approximately one third of patients, deficits
are present at or near the time of PD diagnosis. They commonly present as a
dysexecutive syndrome with difficulties in mental speed, attention and
concentration, cognitive flexibility, p[lanning and decision-making. Such
executive dysfunction is fairly common in PD and concerns 40% of the patients
but it is not universal and there is a substantial heterogeneity in the
clinical presentation of cognitive deficits in PD but also in their
progression. This heterogeneity possibly reflects the diversity of the neural
damage caused by the disease but factors like age visual hallucinations or REM
sleep behavior disorders also influence cognitive presentations in PD.

We have recently used a cluster analysis to identify different cognitive
phenotypes in PD. With such an approach where phenotypical profiles arise from
the data without a priori assumptions, five cognitive presentations were
identified:
1) cognitively intact patients (19.39%),
2) patients with slight mental slowing and mild executive dysfunction (41.29%),
3) patients with slightly impaired overall cognitive efficiency and deficits in
all cognitive domains except recognition memory (12.93%),
4) patients with severe mental slowing, impaired overall cognitive efficiency,
and severe cognitive impairment in all domains, including memory (23.88%), and
5) patients with very severe impairment in all cognitive domains (2.51%).

From these identified clusters it can be concluded that cogniitve decline
follows a continuum from cognitively healthy to demented patients, with the
exception of cluster 4, which is characterized by memory dysfunction.

Main Objective:
- to validate the identified cognitive profiles prospectively in a new
population using confirmatory cluster analysis

Secondary Objectives:
- to identify the clinical and demographical factors associated to the
identified cognitive profiles
- to identify structural-anatomical characteristics of the identified cognitive
profiles by way of MRI
- to identify functional-neurophysiological characteristics of the identified
cognitive profiles by way of hd EEG

This is a multicentric, two year cross-sectional study involving 150 PD
patients recruited in two centers in Europe (Lille, France and Maastricht, the
Netherlands): 75patients per center.

Patients wiull undergo a single clinical assessment consisting of
questionnaires and neuropsychological tests, an MRI scan and an EEG.

The study will take 3.5 hours per patient, divided over two appointments. There
is no physical burden of participation. The risks are confined to the general
risks of undergoing an MRI scan and an EEG. These are considered negligable.