Wednesday, 17 January 2018

Comparing apples and apples

Drug trials (or trials of any new treatment for that matter) are designed by comparing a group on the new treatment against a group on something else. That may be no treatment, the best available treatment, or placebo (or dummy treatment). In order to make a fair comparison, it is essential to compare like with like.

An extreme example of this would be to say that “men are faster than women”, having compared the Jamaican mens olympic sprint team, against a selection of girls from the local secondary school. This is obviously ridiculous in so many ways: adult men vs teenage girls, trained atheletes vs untrained and so on…

In studies of Parkinson’s, it is also important that we compare like with like. For the past 50 years, researchers have used the “Hoehn and Yahr Scale” to create standardised definitions. (The scale is named after Margaret Hoehn and Melvin Yahr who pioneered research into progression and epidemiology of Parkinson’s in the 1960s.) Designed to give researchers a simple and global assessment of disease severity, this is probably the most widely used Parkinson’s staging system in use. According to the latest version of this scale there are 6 stages from 0= Asymptomatic to 5 = wheelchair bound or bedridden unless unaided.

Despite its widespread use, until now there have been no systematic attempts to prove how useful and reproducible it is. The researchers in this study assessed the acceptability, reproducibility, content and validity of the scale. They compared how different raters scored people (known as inter-rater reliability), and how that compared with other scoring systems of stiffness, tremor and other features of Parkinson’s. They also looked at whether the same assessor gave the same patient the same score at different times (known as test-retest reliability).

The good news is that inter-rater reliability and test-retest reliability are incredibly high. In other words, if one clinician judges a person to have stage II, so will almost every other (trained) clinician. It also correlated quite well with other physical assessment scores.

As ever, it is not a perfect test. The difference between stages is not the same (in other words, going from I to II is not the same as going from III-IV). Nor does it correlate at all well with quality of life. It also does not take into account non-motor features of Parkinson’s. Furthermore, only 2.9% of more than 3000 participants were at the most advanced stage V, so may not be quite as reliable for these people.

In summary, we have a pretty good measure of giving a number to the amount that an individual is affected by Parkinson’s. Until we have a blood test/scan/marker of progression, this is the best we have, and we need to make sure we have ways of addressing its weaknesses. Using it we can compare like with like, and, hopefully, get ever closer to preventing people advancing through the scale.


Martinez-Martin P, Skorvanek M, Rojo-Abuin JM, Gregova Z, Stebbins GT, Goetz CG, et al. Validation study of the hoehn and yahr scale included in the MDS-UPDRS. Mov Disord. 2018 Jan 11;17:427. 

Tuesday, 16 January 2018

Interaction between caffeine and polymorphisms of glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) and cytochrome P450 1A2 (CYP1A2) on Parkinson's disease risk.

People have been trying to pin down the association between caffeine and Parkinson's disease for some time... numerous observational studies have suggested a that those that consume caffeine are at lower risk of Parkinson's disease. The explanations for this association are those that are common to most associations arising in observational studies: 

1) that caffeine is causally associated with PD (i.e. something about caffeine truly reduces ones risk), 

2) that the association is driven by reverse causation (i.e. in the pre-diagnostic phase of PD people have less of a tendency to consume caffeinated drinks and the effect of this reduction means that those that do consume caffeine appear relatively protected from PD), and 

3) that the association is driven by a third factor (i.e. confounding - for example caffeine consumption is associated smoking and it is in fact smoking that is protective against PD).

The authors here try to go a step further and look at whether or not certain genetic variants explain some of the variation in PD risk with caffeine intake... their hypothesis was that the protective effect of caffeine may depend on whether you carry one gene variant or another... they did not observe any convincing evidence of this... but interaction tests such as these are notoriously underpowered (meaning that although it was a relatively big study, there may have been insufficient participants included to give the correct answer).

Overall the jury is still out on caffeine and risk of PD. One clinical trial a few years ago suggested that caffeine may reduce the motor symptoms of PD, but the follow up randomised trial failed to meet its primary end point, and perhaps most importantly, did not continue to the point that it tested whether caffeine might affect the underlying disease process.

- Alastair Noyce

Mov Disord. 2018 Jan 10. doi: 10.1002/mds.27279. [Epub ahead of print]
Kim IY, O'Reilly ÉJ, Hughes KC, Gao X, Schwarzschild MA, McCullough ML, Hannan MT, Betensky RA, Ascherio A.

BACKGROUND: Caffeine intake has been inversely associated with Parkinson's disease (PD) risk. This relationship may be modified by polymorphisms of glutamate ionotropic receptor NMDA type subunit 2A (GRIN2A) and cytochrome P450 1A2 (CYP1A2), but the results of previous studies have been inconsistent.

METHOD: We examined the interaction of caffeine intake with GRIN2A-rs4998386 and CYP1A2-rs762551 polymorphisms in influencing PD risk among 829 incident cases of PD and 2,754 matched controls selected among participants in the following 3 large prospective ongoing cohorts: the Nurses' Health Study, the Health Professionals' Follow-up Study, and the Cancer Prevention Study II Nutrition Cohort. Matching factors included cohort, birth year, source of DNA, date of DNA collection, and race. Relative risks and 95% confidence intervals were estimated using conditional logistic models. Interactions were tested both on the multiplicative scale and on the additive scale.

RESULTS: Overall, caffeine intake was associated with a lower PD risk (adjusted relative risk for highest versus lowest tertile = 0.70; 95% confidence interval, 0.57-0.86; p < .001). In analyses stratified by the GRIN2A-rs4998386 genotype, the multivariable-adjusted relative risk of PD comparing the highest to the lowest tertile of caffeine was 0.69 (95% confidence interval, 0.55-0.88; p < .01) among individuals homozygous for the C allele, and 0.85 (95% confidence interval, 0.55-1.32; p = .47; pRERI  = .43) among carriers for the T allele. Interactions between caffeine and GRIN2A were not significant in either the multiplicative or additive scales. We also did not observe significant interactions for CYP1A2-rs762551 and incident PD risk.

CONCLUSION: Our findings do not support the hypothesis of an interaction between the GRIN2A-rs4998386 or CYP1A2-rs762551 polymorphism and caffeine intake in determining PD risk.

© 2018 International Parkinson and Movement Disorder Society.

Friday, 12 January 2018

Sniffing around for answers

We are somewhat preoccupied with smell at PREDICT-PD; smell loss is one of the most sensitive risk factors for development of Parkinson's - although it is non specific and may be seen in a number of conditions. It is particularly interesting as it can be studied non-invasively and remotely. While self-reported smell loss is less reliable, objective tests such as the University of Pennsylvania Smell Idenfification Test (UPSIT) have a high degree of accuracy and can be completed at home by research participants. 

This recognition sits well with the finding from post-mortem studies that there are early pathological changes in the olfactory bulb, the area just above the nose which receives smell inputs. The progressive brain changes in Parkinsons, defined by pathologist Heiko Braak, are now known as Braak stages, and the earliest stage, Braak stage 1 involves olfactory bulb involvement.

While smell loss is well characterised, its link with other features and particularly cognitive changes in in Parkinson's is less well explored. Smell loss is also associated with Alzheimer's so it wouldn't be surprising if it was also linked to cognitive changes in Parkinson's. The study below, from researchers in South Korea, looked at the relationship between these two features. 

They took a group of people just diagnosed with Parkinson's and compared those with cognitive impairment to those without, showing poorer smell in all aspects of the smell tests in patients with cognitive impairment. In many ways, this goes against the 'Braak hypothesis' which posits that pathology in the higher cortical areas and the cognitive impairment which goes with it is a later phenomenon. It would be interesting to see if smell loss was particularly associated with specific domains of cognition and the areas more directly connected with the olfactory bulb.  

As we have previously mentioned, cognitive impairment may be related to many underlying pathologies and it may be that the pathology described in Braak staging is not primarily responsible for cognitive impairment in Parkinson's. Certainly more work is needed in this area to tease out these relationships. 


Parkinsonism Relat Disord. 2018 Jan;46:69-73. doi: 10.1016/j.parkreldis.2017.11.334. Epub 2017 Nov 14.

Olfactory dysfunctions in drug-naïve Parkinson's disease with mild cognitive impairment.
Park JW, Kwon DY, Choi JH, Park MH, Yoon HK.
Evaluation of olfactory function is valuable for the detection of pre-motor state of Parkinson's disease (PD). PD patients have an increased risk of associated dementia and one-third of PD patients have mild cognitive impairment (MCI) at the time of diagnosis. However, the characteristics of olfactory dysfunction in PD-MCI patients are unclear. This study examined the relationship between olfactory dysfunction and cognitive function in drug-naïve PD at the time of diagnosis with the patterns of olfactory function in PD-MCI patients using the Korean version of the Sniffin' stick test II (KVSS II).METHODS:
A total of 66 drug-naïve PD patients were enrolled. A neuropsychiatric assessment battery and KVSS II were performed. For the statistical analyses, univariate, multivariable linear regression and Student's t-test were used to determine the relationship between the variables and olfactory function.RESULTS:
Olfactory dysfunction was more prevalent in the PD-MCI group than in the PD-normal cognition (PD-CN) group. Each domains of odor threshold, discrimination, identification and total olfactory score were more impaired in the PD-MCI group than the PD-CN group. Whether cognitive impairment was single or multiple domain was not affected.CONCLUSION:
PD-MCI is more likely to be associated with severe olfactory impairment than PD-CN. There may be more extensive neurodegenerative processes affecting olfaction in PD-MCI patients. With further investigation and validation using neuropathological data, an objective olfactory function test could be used as a tool to evaluate disease progression. Further studies with prospective design investigating the prognostic value of olfactory dysfunction in PD-MCI patients are essential.

Wednesday, 10 January 2018

Progression in the LRRK2-Asssociated Parkinson Disease Population.

I think this is a really important study.

We have long suspected that patients with LRRK2-associated PD manifest Parkinson's in a different way to those that don't carry LRRK2 mutations. Here the authors show differences in the rate of progression of motor features – those with LRRK2-associated PD progress at a slower rate. This fits somewhat with notion that LRRK2 patients run a more benign course than 'regular PD' but what is at odds with this is that more of them had the postural instability gait disorder (PIGD) type of PD which is usually associated with a poor prognosis. The authors don't mention it much in the discussion but what is interesting to me is that the increase in PIGD type cases is not the result of a reduction in tremor-dominant cases, so much as a reduction in the indeterminate type. To me these observations lead to interesting questions:

1) Do LRRK2 patients fit into these two subtypes of PD better than those without LRRK2 mutations?? This is plausible because one would expect the pathology of LRRK2 to perhaps be less heterogeneous (even though a range of pathologies have been reported). 

2) Is there an imaging correlate for these different types in LRRK2 cases?

3) Does this tells us about the outcome measures we should be selecting for clinical trials in LRRK2 patients? And indeed,

4) Does it give us increased confidence that as a result of less heterogeneity (whether clinical or pathological) we would be more likely to detect an effect of a disease modifying therapy?

I was interested in the cognitive progression too. It fell short of nominal statistical significance but the MoCA is a relatively blunt tool for testing cognition and I expect that there would be differences in favour of slower progression in LRRK2 carriers if domains were studied more fully.

Important to exclude the GBA carriers in this work because they could bias the results, but there are other genetic factors that can influence seemingly monogenic forms of PD and should be kept in mind in future work.

- Alastair Noyce

JAMA Neurol. 2018 Jan 8. doi: 10.1001/jamaneurol.2017.4019. [Epub ahead of print]

Saunders-Pullman R, Mirelman A, Alcalay RN, Wang C, Ortega RA, Raymond D, Mejia-Santana H, Orbe-Reilly M, Johannes BA, Thaler A, Ozelius L, Orr-Urtreger A, Marder KS, Giladi N, Bressman SB; LRRK2 Ashkenazi Jewish Consortium.

IMPORTANCE: Few prospective longitudinal studies have evaluated the progression of Parkinson disease (PD) in patients with the leucine-rich repeat kinase 2 (LRRK2 [OMIM 609007]) mutation. Knowledge about such progression will aid clinical trials.

OBJECTIVE: To determine whether the longitudinal course of PD in patients with the LRRK2 mutation differs from the longitudinal course of PD in patients without the mutation.

DESIGN, SETTING, AND PARTICIPANTS: A prospective comprehensive assessment of a large cohort of patients from 3 sites with LRRK2 PD or with nonmutation PD was conducted from July 21, 2009, to September 30, 2016. All patients of Ashkenazi Jewish ancestry with PD were approached at each site; approximately 80% agreed to an initial visit. A total of 545 patients of Ashkenazi Jewish descent with PD who had 1 to 4 study visits were evaluated. A total of 144 patients (26.4%) had the LRRK2 G2019S mutation. Patients with GBA (OMIM 606463) mutations were excluded from the analysis.

MAIN OUTCOMES AND MEASURES: Linear mixed-effects models for longitudinal motor scores were used to examine the association of LRRK2 mutation status with the rate of change in Unified Parkinson's Disease Rating Scale III scores using disease duration as the time scale, adjusting for sex, site, age, disease duration, cognitive score, and levodopa-equivalent dose at baseline. Mixed-effects models were used to assess change in cognition, as measured by Montreal Cognitive Assessment scores.

RESULTS: Among the 545 participants, 233 were women, 312 were men, and the mean (SD) age was 68.2 (9.1) years for participants with the LRRK2 mutation and 67.8 (10.7) years for those without it. Seventy-two of 144 participants with the LRRK2 mutation and 161 of 401 participants with no mutation were women. The estimate (SE) of the rate of change in the Unified Parkinson's Disease Rating Scale III motor score per year among those with the LRRK2 mutation (0.689 [0.192] points per year) was less than among those without the mutation (1.056 [0.187] points per year; difference, -0.367 [0.149] points per year; P = .02). The estimate (SE) of the difference in the rate of change of the Montreal Cognitive Assessment score between those with the LRRK2 mutation (-0.096 [0.090] points per year) and those without the mutation (-0.192 [0.102] points per year) did not reach statistical significance (difference, 0.097 [0.055] points per year; P = .08).

CONCLUSIONS AND RELEVANCE: Prospective longitudinal follow-up of patients with PD with or without the LRRK2 G2019S mutation supports data from a cross-sectional study and demonstrates a slower decline in motor Unified Parkinson's Disease Rating Scale scores among those with LRRK2 G2019S-associated PD.

Tuesday, 9 January 2018

Clinical correlates of cerebral white matter abnormalities in patients with Parkinson's disease

This study considers the potential relevance of changes in the white matter of the brain seen on MRI scans in patients with Parkinson's... confluent and scattered white lesions are commonly observed on T2 weighted MRI scans as people get older. By and large these lesions are attributed to small vessel disease (SVD). SVD is different to diseases of the large blood vessels which cause stroke and the accumulating SVD burden largely passes under the clinical radar, unless it causes problems with walking and cognition over time. Control of vascular risk factors is all that can be done to reduce an increasing burden of SVD... controlling blood glucose, hypertension and cholesterol, and stopping smoking.

The authors here set out to see if posturally-related drops in blood pressure (orthostatic hypotension) might explain an increasing burden of these WM lesions. It is plausible for example that transient drops in blood pressure related to standing could temporarily reduce blood flow to the brain and cause WM lesions to accumulate. This is an important research question that the authors raise. However, the design they used (cross-sectional) makes it very difficult to know what comes first... is it the WM lesions or the low blood pressure??

Perhaps more concerning is that whilst they take account of some potential confounding factors such as age, l-dope use and hypertension, they do not adjust for blood glucose or diabetes status. I think this could be important... we are seeing increasing evidence that diabetes may be linked to Parkinson's and evidence that diabetes drugs may be able to treat Parkinson's... it could be that unmeasured blood glucose or undiagnosed diabetes explains at least some of the association between the two given that it is separately associated with orthostatic hypotension and WM lesions, and does not lie on a causal pathway between them... I think the authors should have clarified the number of people that had blood glucose measured and/or a diagnosis of diabetes and indicated whether this affected the results...

It is worth mentioning that what we see on a scan in any case is only the tip of the iceberg and does not identify what is going on at a cellular/microscopic level...

Alastair Noyce

Parkinsonism Relat Disord. 2017 Dec 27. pii: S1353-8020(17)30868-4. doi: 10.1016/j.parkreldis.2017.12.029. [Epub ahead of print]
Ten Harmsen BL, van Rumund A, Aerts MB, Bergkamp MI, Esselink RAJ, Richard E, Meijer FJA, Bloem BR, van Wamelen DJ

OBJECTIVE: To determine if autonomic dysfunction, cognitive disorders or axial disability are associated with white matter lesions (WML) in Parkinson disease (PD).

METHODS: We performed a retrospective cross-sectional review study on 204 consecutive PD patients who underwent cerebral MRI in our center between January 2012 and July 2016. For each patient, we scored the severity of WML and PV (periventricular) WML using the Fazekas score and using the ARWMC scale for WML and BG (basal ganglia) and clinical characteristics such as neurogenic orthostatic hypotension and cognitive function.

RESULTS: 204 PD patients were included of whom n = 53 (26.0%) had neurogenic orthostatic hypotension (nOH). The presence of nOH was significantly associated with the severity of WML as defined by the Fazekas score and the ARWMC scale. An ordinal regression model confirmed this association with an OR of 0.41 (95% CI 0.18-0.92: p = .03) and an OR of 0.39 (95% CI 0.17-0.88: p = .02). There were no significant associations between WML and other co-variables, including hypertension, dopaminergic medication use, Hoehn and Yahr stage, gender and cognitive decline.

CONCLUSION: The presence of nOH is associated with WML severity in PD patients.

Does the brain in Alzheimer's and Parkinson's look similar?

Happy new year! I hope you've had a relaxing break and taken the time to catch up on some all-important sleep (see I'm continuing this year to look at cognitive function in participants in the PREDICT-PD study and we have been talking about using imaging as a tool to understand better the reasons that cognition may deteriorate in the early stages or even before Parkinson's develops. One of the suggestions is that there may also be Alzheimers-type pathology in these patients.

This study, from a team based in the states, used three different types of imaging as well as cognitive tests to ask the question "Do the brains of people with Parkinson's who have declining cognition look similar to people with Alzheimer's?" We know that in Alzheimer's there is build up of a protein called amyloid outside cells and a protein called tau inside cells. We now have techniques that use nuclear tracers to label both amyloid and tau in the brain - this signal can be detected using a PET scan so that we can build up a picture of protein deposition in the brain. In advanced Alzheimers disease, amyloid "lights up" throughout the brain - shown in red in the image - indicating the areas with abnormal deposits of the protein.

Image result for amyloid pet alzheimer's disease

In this study, where 30 patients with Parkinson's disease and 49 healthy participants underwent scanning, they didn't find any differences in scan results between people with Parkinson's disease who had normal cogntive function, those who had poorer cognitive function. In fact, all the scans looked similar to healthy participants.

This is an important finding, but we should take some caution with the interpretation that cognitive decline in Parkinson's has nothing to do with Alzheimer's-like pathology. Previous studies have shown an association between cognitive decline over time and amyloid - which this cross-sectional study was unable to address. The level of cognitive function in the study was generally high (on correspondence with the author only 1/29 were cognitively impaired on a standard screening test which is far lower than in other studies) and the criteria for classifying cognitive impairment was relatively lax so may have included participants with borderline cognition not just those at the more severe end of the spectrum. More work needs to be done in this area with larger numbers of patients who have significant cognitive problems before we will have a clear answer.


JAMA Neurol. 2017 Dec 11. doi: 10.1001/jamaneurol.2017.3713. [Epub ahead of print]

Associations Between Tau, β-Amyloid, and Cognition in Parkinson Disease.

Winer JR, Maass A, Pressman P, Stiver J, Schonhaut DR, Baker SL, Kramer J, Rabinovici GD, Jagust WJ.


Multiple disease processes are associated with cognitive impairment in Parkinson disease (PD), including Lewy bodies, cerebrovascular disease, and Alzheimer disease. It remains unknown whether tau pathology relates to cognition in patients with PD without dementia.

To compare tau aggregation in patients with PD who are cognitively normal (PD-CN), patients with PD with mild cognitive impairment (PD-MCI), and healthy control participants, and evaluate the relationships between β-amyloid (Aβ), tau, and cognition in patients with PD who did not have dementia.
Design, Setting, and Participants:
This cross-sectional study recruited 30 patients with Parkinson disease (15 with PD-CN and 15 with PD-MCI) from a tertiary care medical center and research institutions from July 2015 through October 2016. One patient with PD-MCI did not receive a magnetic resonance imaging scan and thus was excluded from all analyses; 29 patients with PD were included in the present study. Participants underwent tau positron emission tomographic (PET) scanning with fluorine 18-labeled AV-1451, Aβ PET scanning with carbon 11-labeled Pittsburgh compound B, magnetic resonance imaging, cognitive testing, and neurologic evaluation. Imaging measures were compared with 49 healthy control participants.

Main Outcomes and Measures:
Outcomes were tau PET measurements of groups of patients with PD-CN and PD-MCI. We hypothesized that tau aggregation across groups would be related to age and Aβ status.

Of the 78 participants, 47 (60%) were female, and the mean (SD) age was 71.1 (6.6) years. Six patients with PD (21%) were Aβ-positive, of whom 1 was mildly cognitively impaired; 23 were Aβ-negative (79%). (Of the 49 healthy controls, 25 were Aβ-negative and 24 Aβ-positive.) Voxelwise contrasts of whole-brain tau PET uptake between patients with PD-CN and patients with PD-MCI, and additionally between all patients with PD and Aβ-negative controls, did not reveal significant differences. Tau PET binding did not differ between patients with PD-MCI and PD-CN in brain regions reflecting Alzheimer disease Braak stages 1/2, 3/4, or 5/6, and did not differ from Aβ-negative healthy older adults. Mean (SD) tau PET binding was significantly elevated in Aβ-positive patients with PD relative to Aβ-negative patients with PD within brain regions reflecting Alzheimer disease Braak stage 3/4 (1.22 [0.07] vs 1.14 [0.07]; P = .03) and Braak stage 5/6 (1.20 [0.07] vs 1.11 [0.08]; P = .02).

Conclusions and Relevance:
These findings suggest that patterns of cortical Aβ and tau do not differ in people with PD-CN, people with PD-MCI, and healthy older adults. Age, Aβ, and tau do not differentiate patients with PD-CN and PD-MCI. Tau deposition is related to Aβ status and age in both people with PD and healthy older adults. Cognitive deficits in people with PD without dementia do not appear to reflect measureable Alzheimer disease.


Friday, 5 January 2018

Variability of presynaptic nigrostriatal dopaminergic function and clinical heterogeneity in a dopa-responsive dystonia family with GCH-1 gene mutation

These families are very interesting. GCH-1 released dopa responsive dystonia (DRD) is an inherited problem with the metabolic pathways that involve dopamine and other neurotransmitters. Typical features include dystonia and tremor, which tend to respond dramatically to small doses of levodopa. Here the authors describe a family in which some members had the DRD phenotype and others have a degenerative form of parkinsonism akin to Parkinson's disease.

This is not the first time that this link has been noted, but many people are were skeptical. A good friend of mine, Niccolo Mencacci, described 4 or 5 similar families in his paper in Brain in 2014. Subsequently it was shown through a different method, genome wide association study (GWAS), that variation in the region of the GCH-1 gene is associated with Parkinson's disease also. The GWAS findings have been replicated.

To me this raises important questions about the role of dopamine in PD and suggests that depletion may not only be a consequence of PD but also a causative factor. Importantly not all of the cases that developed degenerative parkinsonism had been treated long term for DRD with replacement dopamine, otherwise we might be talking about a potentially toxic effect of levodopa replacement therapy. As it stands, we are not... but the link between endogenous depletion of dopamine due to a metabolic defect and the eventual emergence of symptoms and imaging features of degenerative parkinsonism requires further exploration...

Alastair Noyce

J Neurol. 2017 Dec 30. doi: 10.1007/s00415-017-8723-5. [Epub ahead of print]
Lin JJ, Lu CS, Tsai CH.

We studied the presynaptic nigrostriatal dopaminergic function using single photon emission computed tomography (SPECT) imaging of a 99mTc-TRODAT-1 (TRODAT) scan in a dopa-responsive dystonia (DRD) family with the guanosine triphosphate cyclohydrolase 1 (GCH-1) gene mutation. Clinically, there was presentation of intrafamilial variability in the DRD family. The index patient was a 10-year-old girl with classic DRD and normal presynaptic nigrostriatal dopaminergic function. However, her grandmother, a 79-year-old woman, presented with slowly progressive Parkinson's disease (PD) without dystonic symptoms and excellent response to dopaminergic therapy for 21 years. Her brain TRODAT SPECT imaging revealed a markedly and asymmetrically reduced uptake of dopamine transporter at the bilateral striatum. Her father, a 54-year-old man, was an asymptomatic gene carrier and his brain TRODAT SPECT imaging revealed asymmetrically reduced nigrostriatal dopaminergic transmission in the bilateral striatum. We conclude variability of presynaptic nigrostriatal dopaminergic function in patients with DRD is related to their clinical heterogeneity. Significantly, impairment of presynaptic dopamine function actually occurs in the asymptomatic gene carrier.

Tuesday, 2 January 2018

New Challenges for a New Year.

I return rested and refreshed after a short break, and with renewed energy to chip away at the challenge before us: beating Parkinson’s disease.

Along with all the repeats and reviews on TV and newspapers, the medical literature often uses the Christmas editions to summarise and review the progress (or lack thereof) made in the previous 12 months, and to stir the spirits (metaphorical not literal) for a new year of discovery.

The Lancet Neurology is one of the leading journals in our field. This year UCL hog the limelight, with Professor John Hardy writing the review of neurodegeneration and Professor Andrew Lees writing “Advice for those trying to find a cure for the shaking palsy”.

Prof Lees challenges us to look beyond the obvious and be brave in our pursuits of new treatments. Paraphrasing William Burroughs he observes, “doctors are, by and large, drastically limited in their outlook”.

Perhaps the community of Parkinson’s researchers should adopt as our collective new year’s resolution to feed our imagination, widen our outlook, embrace humility and “regain the power to explore”.

Here’s to a year of breakthroughs!


Comparing apples and apples

Drug trials (or trials of any new treatment for that matter) are designed by comparing a group on the new treatment against a group on some...