Title: ENIGMA-PD-Vasc: An international multicentre analysis of cerebral vascular changes in Parkinson's disease
Funder: The Academy of Medical Sciences

Abstract: The aim is to investigate cerebral vascular contributions in Parkinson’s disease (PD). This is based on both the vascular hypothesis of neurodegeneration but also the increasingly recognised association between vascular risk factors and PD progression. The objective is to analyse MRI datasets from the worldwide ENIGMA-PD (Enhancing NeuroImaging Genetics through MetaAnalysis- Parkinson’s Disease) consortium, that has currently amassed >2500 scans from PD patients and >1500 matched control subjects. We intend to specifically analyse MR vascular markers. ENIGMA-PD is an international network bringing together, over 50, researchers in imaging in PD to form large group analyses successfully overcoming problems of small datasets and heterogeneous sample sizes. The first line of our analysis would be measurement of white matter lesion (WML) burden, a surrogate marker of small vessel disease. Studies reveal it is not only the burden of WML but also the distribution that contributes to PD severity and certain clinical features such as gait and cognitive problems. A secondary objective would be to correlate the vascular burden with phenotype, disease severity and other clinical markers. This builds upon our previous work developing a range of MRI markers, which revealed both structural and physiological cerebral vascular changes in the clinical setting in PD, when compared to controls e.g. increased blood-brain barrier permeability. Whether vascular changes are causal, in or an effect of, the neurodegenerative process is still unknown, but as vascular processes are potentially modifiable, understanding these changes can help to lead to much needed disease-modifying and neuroprotective treatments.

Lay abstract: Unfortunately, there are still no treatments that can stop or slow down disease progression in Parkinson’s disease (PD);a disabling disease resulting from the progressive loss of brain cells. Blood vessel disease in the brain is believed to contribute to PD. This has been associated with more severe walking problems, thinking and memory problems and greater PD-related disability. As factors underlying blood vessel problems are potentially modifiable, it is essential to better understand the relationship between blood vessel changes and PD. Our collaboration with the world-wide ENIGMA-PD consortium – a network which aims to bring together researchers in PD to pool together brain scans (MRI) in order to allow for largescale analyses- has paved the way for us to lead analysis in vascular MR measures. This will build upon our previous work using MRI to evaluate different aspects of blood vessel disease, which revealed significant differences in blood vessels between those with PD and those without. Given the large scale of the ENIGMA project, this is a unique opportunity to overcome difficulties of small sample sizes, which often occurs with MRI studies, to allow us to evaluate the extent and role of blood vessel changes in PD. In addition, we would like to see how this relates to certain features of PD, such as walking and thinking problems and the severity of the disease. Measuring the blood vessel changes will help us to understand the burden and contribution of blood vessel changes in PD, on the path to finding effective treatments.

Research activity codes: 1.1 NORMAL BIOLOGICAL DEVELOPMENT AND FUNCTIONING;2.1 BIOLOGICAL AND ENDOGENOUS FACTORS
Health categories: NEUROLOGICAL