Cognitive Phenotypes in Parkinson's Disease: Anatomical and Functional Correlates
Defining Cognitive Phenotypes of Parkinson’s Disease, 2011
Cognitive impairment with and without dementia is frequent in Parkinson's disease (PD). However, there is a high heterogeneity in the clinical presentation of these cognitive deficits. We assume that a data-driven approach may overcome this issue and help define specific cognitive presentations of PD patients.
The objective of this study is to identify different clinical presentations of cognitive deficits in PD by performing an exploratory cluster analysis using a data-driven approach.
This is a six-month cross-sectional study involving PD patients recruited in two centers in Europe (Lille, France and Maastricht, the Netherlands). To identify cognitive profiles in PD, an exploratory cluster analysis will be performed on the existing databases in both institutions. This is a statistical multivariate procedure used to classify patients in different groups or clusters according to different profiles. These clusters are not defined a priori and are such that individuals in a given cluster are close to each other in the sense of a similarity measure and individuals in different clusters tend to be dissimilar.
In order to achieve a representative study sample, patients with idiopathic PD according to usual diagnostic criteria will be included irrespective of their disease stage or their current antiparkinsonian medication.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Once these profiles have been identified, it is then relevant to explore their anatomical and functional correlates. In addition to a significant contribution to the knowledge of the pathophysiology of cognitive disorders in PD, this exploration may lead to the definition of markers specific to each profile. The availability of such markers is essential to evaluate the efficacy of existing and future treatments, especially in the context of personalized medicine.
We predict that different cognitive profiles (such as mental slowing, dysexecutive syndrome, amnestic mild cognitive impairment, early and late dementia) will emerge from the exploratory cluster analyses.
At the end of this first phase of the study, we hope to perform a confirmatory analysis on a new independent population to validate the identified profiles. If the profiles are validated, the anatomical and functional correlates of each profile will be investigated.
Cognitive impairments are frequent in Parkinson's disease (PD), but there is a substantial heterogeneity in the clinical presentation of cognitive deficits in PD and also in their progression. This heterogeneity possibly reflects the diversity of the neuronal damage caused by the disease. In a first phase of our project, we investigated how profiles emerged from our data (557 patients from two centers in Europe) without a priori hypothesis, and we have identified five different clinical presentations along a continuum ranging from cognitively intact patients to patients with severe deficits in all cognitive domains.
In the second phase of our study, we confirmed these five phenotypes on a new prospective sample of 156 patients. In addition, we sought to identify anatomical and functional markers of each profile from the data of MRI and high-density EEG. Our preliminary results show that at the first signs of a mental slowing, there are already changes in the temporal and frontal regions. We hope to set-up a follow-up of these patients in order to identify markers of decline but also of protection of their cognitive status.
Presentations & Publications
Dujardin K, Leentjens AF, Langlois C, Moonen AJ, Duits AA, Carette AS, Duhamel A. The spectrum of cognitive disorders in Parkinson's disease: A data-driven approach. Mov Disord, 2013;28(2):183-189.
Professor of Clinical Neurosciences at Lille University Medical Center
Location: Lille, France