PD Research Clinic
Our Parkinson’s Disease Research Clinic runs every Thursday at the John Van Geest Centre for Brain Repair. Visits generally last for around 1.5 to 2 hours, and involve a session with a neurologist and a session with a neuropsychologist, as well as a blood test. During a visit, we collect detailed information on symptoms and problems associated with Parkinson’s, other co-existing medical problems, medications, and perform a range of clinical assessments as well as tests of memory and thinking. We try to see patients as soon as possible after diagnosis, and then follow them up with repeat assessments every 2 years. Through detailed assessments in large numbers of people over time, we are developing a much clearer picture of the clinical variability in the condition, and the factors that predict differences in progression rates over time. In addition to investigating clinical predictors, we are also collecting blood samples to look at genetic, metabolic and immune factors which might be contributing to differences in rates of disease progression between individuals. Individuals who have been assessed in the research clinic may be eligible to go on to be involved in a range of other research studies.
The Parkinson’s Research Clinic and all of our clinical research studies are supported by the National Institute of Health Research Cambridge Biomedical Research Centre.
The CamPaIGN (Cambridgeshire Parkinson’s Incidence from GP to Neurologist) study was set up in the year 2000 by Professor Roger Barker and Dr Tom Foltynie, and has been run in more recent years by a team led by Dr Caroline Williams-Gray. This observational cohort study aimed to include every new case of Parkinson’s diagnosed in Cambridgeshire over a 2 year period (2000-2002) and to track disease progression in this group of patients over time. It was the first study to take this approach of studying a population-representative, unbiased group with Parkinson’s and describing the evolution of not only movement problems but also cognitive problems over time. This long-running study continues to generate critically important information about rate of disease progression, and how variable this is, in a typical Parkinson’s population. CamPaIGN participants continue to be assessed every 2 years. To date, the CamPaIGN study has:
- demonstrated that memory and thinking problems are common in Parkinson’s but they are of different types – not all of which are associated with developing dementia;
- helped us to work out the key genetic factors that contribute to memory problems in Parkinson’s;
- showed us how variable the rate of progression is in this disease, and allowed us to identify key factors at diagnosis which predict outcomes 10 years later;
- contributed information to a number of large international studies looking at patterns of disease progression and the genetic basis of this.
This internationally-recognised study has led to many research publications, and is helping to pave the way for our ultimate goal of developing more targeted treatment approaches for different groups of patients. We are hugely grateful to all the participants who have been involved in this important study for so many years.
CamPaIGN has received funding from a number of organisations over the years including the Wellcome Trust, the Patrick Berthoud Trust, the Parkinson’s Disease Society (now Parkinson’s UK) and the MRC.
Proposed pathways leading to cognitive dysfunction in early Parkinson’s disease and their relationship to the development of later dementia.
Adapted from Williams-Gray CH, Evans JR, Goris A et al, Brain 2009;132:2958-69.
The PICNICS (Parkinsonism: Incidence and Cognitive and Non-motor heterogeneity In Cambridgeshire) study is a second observational cohort study which tracks the progression of patients with Parkinson’s disease over time, and is similar in design to the CamPaIGN study. The study recruited a large group of patients (299) who were newly-diagnosed with Parkinson’s disease between 2008 and 2013, and assessed them with detailed clinical measures, as well as memory and thinking tests and blood tests. We are continuing to follow-up PICNICS study participants every 18 months in our Parkinson’s Research Clinic. One of the aims of this study is to replicate our findings in the CamPaIGN study in a second independent group of people, which is important to strengthen our research and make sure our findings are robust. We have already found that the characteristics of the patients recruited to the CamPaIGN and PICNICS studies were very similar at diagnosis, and we are now exploring whether the same predictors of disease outcome are valid in PICNICS as in CamPaIGN. The PICNICS study is also allowing us to explore new research questions focusing on non-motor symptoms such as gastrointestinal problems, as well as genetic and other biological markers of the disease which are measurable in blood samples.
PICNICS has received funding from Cure-PD, the Van Geest Foundation, the MRC and Parkinson’s UK.
ICICLE-PD (Incidence of Cognitive Impairment in Cohorts with Longitudinal Evaluation–PD) is a study run jointly between the University of Cambridge and the University of Newcastle, which is aiming to better understand how memory and thinking problems evolve in Parkinson’s. Just over a hundred people with newly-diagnosed Parkinson’s were recruited here at the Cambridge site between 2009-2011 and many of these are still being followed up in our research clinic every 18 months. Participants perform a detailed set of memory and thinking tests at each appointment, and blood samples are collected. A subset of participants have also had MRI brain scans and lumbar punctures done as part of this study. The study has already led to over 60 separate research publications focusing on a range of topics such as the role of brain imaging in predicting dementia, inflammatory markers in the blood as predictors of faster disease progression, and walking/balance problems and how these are linked to memory problems. We are continuing to work on blood and cerebrospinal fluid samples as well as brain imaging data, to establish the best biological markers to predict and track memory problems – which is important for future clinical trials.
ICICLE-PD is funded by Parkinson’s UK.
TRACKING PARKINSONS (PRoBaND)
Tracking Parkinson’s, also known as the PRoBaND study, is one of the world’s largest long-term studies into Parkinson’s disease. This is a UK-based multi-centre prospective longitudinal study that has been collecting clinical data and biological samples from over 2,500 participants since 2012. As one of the 70 sites across the UK, we have recruited and collected information and blood samples of 53 patients, many of whom are still in active follow-up. Further details on the progress of the study can be found at https://www.trackingparkinsons.org.uk/.
Tracking Parkinsons is funded by Parkinson’s UK.
The role of the immune system in Parkinson’s disease
Our cohort studies, following large groups of individuals with Parkinson’s disease over time, have shown us that the disease progresses at different speeds in different individuals. Whilst some have a rapid disease course and may develop memory problems and even dementia within a few years of diagnosis, others have a much more benign course with relatively little motor or cognitive disability for many years. We propose that the immune response to the disease is an important factor which contributes to this variability in the disease course. Caroline Williams-Gray is leading a programme of studies investigating this theory. These include:
- Clinico-pathological studies, characterising inflammation in post mortem brains of individuals with Parkinson’s, and investigating the relationship with the rate of clinical and cognitive progression during life;
- PET neuroimaging studies using the ligand PK-11195 to measure inflammation within the brain in early Parkinson’s disease;
- Investigating inflammatory cytokines and other immune markers in blood samples from our large Parkinson’s cohorts, and assessing their value in predicting and tracking disease progression;
- Immunophenotyping studies which characterise immune cell subtypes in blood and cerebrospinal fluid samples;
- Assessing the role of Toll like receptors in mediating the immune response in Parkinson’s using ‘in vitro’ and ‘in vivo’ models.
Ultimately, all of this work is helping us to better understand the immune changes that occur in both the brain and the peripheral blood in Parkinson’s. Furthermore, it is providing critical evidence that these changes are relevant in driving disease progression – with important implications for new treatment strategies targeting the immune system to slow the progression of Parkinson’s.
This programme of work has received funding from the Academy of Medical Sciences, the Rosetrees Trust, Addenbrooke’s Charitable Trust, the Wellcome Trust, Stevenage Biosciences Catalyst, the Evelyn Trust, the Medical Research Council.
NET-PDD (the role of NEuroinflammation and Tau Aggregation in PD Dementia) – is a longitudinal PET neuroimaging study led by Caroline Williams-Gray and co-ordinated by Antonina Kouli.
The primary goal of the study is to better understand the earliest changes in the brain that lead to memory problems and dementia in PD. Our previous research has contributed to the theory that two processes – tau aggregation, and inflammation within the brain – might play a critical early role. The NET-PDD study is investigating this theory by comparing markers of these processes in two groups of newly-diagnosed patients: a group at high dementia risk, and a group at low dementia risk; as well as healthy volunteers of similar age for comparison, recruited from the NIHR Cambridge Bioresource. Inflammation and tau deposits are measured using PET neuroimaging, as well as in the cerebrospinal fluid and the blood. Participants are assessed with PET scans, lumbar punctures and blood tests as well as detailed clinical and cognitive assessments at baseline and again at 3 years, to assess how measures of inflammation and tau accumulation change over time, and how they relate to the development of memory problems and dementia. Clinical follow-up will continue for up to 10 years.
Establishing whether inflammation and tau deposition are important early events in Parkinson’s disease dementia will bring us much closer to developing new treatments to prevent or slow the onset of this complication of the disease, which has such devastating consequences for patients and their families. We also aim to determine which combination of the imaging, CSF and blood-based markers we are studying is likely to be most useful for tracking progression of dementia and the effect of treatments on this over time – which will be critical for future clinical trials of these treatments.
This study is supported by funding from the Evelyn Trust and the Medical Research Council.
PET scan showing uptake of the ligand [18F]AV1451, indicating widespread cortical accumulation of tau in a patient with Parkinson’s disease.