By Professor Tim Anderson
Parkinson's disease is the second most common neurodegenerative disease after Alzheimer’s disease and our Christchurch group at the New Zealand Brain Research Institute (NZBRI) has shown that 1% of those over 60 years in New Zealand have PD, with some 11,000 people having the condition.
For reasons that we don't know but are presently exploring, the prevalence of PD in Māori appears to be considerably lower than in European New Zealanders. We have calculated that the number of New Zealanders with PD will double to 20,000 over the next 25 years. This will be an increasing burden of PD on individuals, carers, families and the health system. Presently there is no cure or indeed treatment that will slow the progress of Parkinson’s.
Our Parkinson’s research team at the NZBRI in Christchurch is multidisciplinary and engaged in multi-faceted clinical research, based around people with PD. We have established the Christchurch Longitudinal Parkinson’s Study in which we are undertaking regular assessments of individual PD volunteers about every two years for up to 10 years. These assessments include tests of clinical status using standard scales (e.g. Unified Parkinson's Disease Rating Scale), extremely detailed neuropsychological (thinking and memory) and behavioural assessments, sensitive eye movement recordings, advanced brain imaging including MRI and PET (positron emission tomography) scans and, over recent years, blood collection for genetic and blood protein markers. So far we have baseline assessments in some 350 PD patients and 75 healthy controls (non-PD volunteers) and have regularly followed up 210 of the PD and 50 control participants.
An area of particular research focus at the NZBRI, led by Prof John Dalrymple-Alford, has been in the distressing cognitive decline that many PD people experience, sometimes culminating in a type of dementia that is different from Alzheimer’s dementia – with less memory loss but greater problems with planning ahead and making decisions. Before reaching dementia people usually go through a phase of mild cognitive impairment (MCI) whereby independence is maintained but there is clear evidence of a decline in cognitive abilities. We have shown that PD patients with MCI are at much greater risk of imminent dementia than those with preserved cognition. In our longitudinal cohort, 50% of those with MCI developed dementia over the next four years but only 6% with normal cognition did so. On the other hand, dementia is not inevitable in PD and our (unpublished) observations indicate that some 50% of PD patients will get dementia.
Genetic causes of PD are uncommon, and the cause of PD in most patients is unknown, but it is becoming apparent that there is a genetic contribution in many. The most common gene mutations known to increase the risk – but not be the sole cause - for PD in any individual are those in the GBA (glucocerebrosidase) gene.
In a study led by Dr Toni Pitcher and Prof Martin Kennedy, we have recently detected GBA mutations in 10% of our Longitudinal PD cohort, similar to findings overseas. We, and others, have shown that there is a higher rate of cognitive impairment and dementia in patients with a GBA mutation. Such genetic testing is likely to become important in the future as specific therapies tailored to those people with specific gene mutations, such as GBA, are currently being explored.
Brain imaging can provide a variety of objective indicators of brain status. Dr Tracy Melzer has led a number of MRI and PET projects in the Longitudinal cohort, especially relating to cognitive changes in the PD patients. He showed that the earliest changes are a reduction in blood flow and some thinning of the deeper white matter tracts even when there is only mild cognitive impairment. In PD patients with dementia these changes are greater and accompanied by brain atrophy – a reduction in overall brain size – and increase in white matter hyperintensities (hardening of small blood vessels). Presently we are exploring whether measuring these changes in individual patients early in their disease, in concert with other clinical and blood markers, can predict their long-term outcome. If so, then we could use such information to choose the right type of patient for trials of new therapies and ultimately tailoring individualised treatment.
The pathological change in the brains of people with PD is the abnormal accumulation of alpha-synuclein – an abundant protein we all have but which goes out of shape (is misfolded) in PD. It has been proposed that one of the main causes of dementia in PD is the additional build up of Alzheimer’s-type amyloid protein in the brain. However, in the largest published study of its type, we undertook amyloid PET scans in PD patients and demonstrated that coexistent Alzheimer’s is not a factor in PD dementia.
One of our present research thrusts is to collaborate with researchers at the National Institute of Ageing (NIA) in the US to measure concentrations of proteins that come from the brain, but are found in the blood in tiny packages called exosomes, to determine if changes in these proteins relate to cognitive and motor status in Parkinson’s.
Professor Tim Anderson is a neurologist, with subspecialty expertise in movement disorders including Parkinson’s, Huntington’s disease and botulinum toxin therapy. He undertakes two specialty clinics in movement disorders per week and fortnightly botulinum toxin clinics for the CDHB, as well as teaching 5th year University of Otago medical students and hosting students at his outpatient clinics.
Tim regularly conducts clinical pharmaceutical trials in Parkinson’s and other neurological conditions and this has enabled patients not only to have early access to new treatments but also regular clinical review and oversight. He is the Clinical Director of the New Zealand Brain Research Institute.