Olfaction in Parkinson's disease and related disorders

Abstract

Neurobiol Dis. 2011 Dec 20. [Epub ahead of print]

Doty RL.

Olfactory dysfunction is an early 'pre-clinical' sign of Parkinson's disease (PD). The present review is a comprehensive and up-to-date assessment of such dysfunction in PD and related disorders. The olfactory bulb is implicated in the dysfunction, since only those syndromes with olfactory bulb pathology exhibit significant smell loss. The role of dopamine in the production of olfactory system pathology is enigmatic, as overexpression of dopaminergic cells within the bulb's glomerular layer is a common feature of PD and most animal models of PD. Damage to cholinergic, serotonergic, and noradrenergic systems is likely involved, since such damage is most marked in those diseases with the most smell loss. When compromised, these systems, which regulate microglial activity, can influence the induction of localized brain inflammation, oxidative damage, and cytosolic disruption of cellular processes. In monogenetic forms of PD, olfactory dysfunction is rarely observed in asymptomatic gene carriers, but is present in many of those that exhibit the motor phenotype. This suggests that such gene-related influences on olfaction, when present, take time to develop and depend upon additional factors, such as those from aging, other genes, formation of α-synuclean- and tau-related pathology, or lowered thresholds to oxidative stress from toxic insults. The limited data available suggest that the physiological determinants of the early changes in PD-related olfactory function are likely multifactorial and may include the same determinants as those responsible for a number of other non-motor symptoms of PD, such as dysautonomia and sleep disturbances.

Incidence and mortality of Parkinson's disease in older Canadians

Abstract

Parkinsonism Relat Disord. 2011 Dec 23. [Epub ahead of print]

Allyson Jones C, Wayne Martin WR, Wieler M, King-Jesso P, Voaklander DC.

Source

School of Public Health, University of Alberta, Canada.

OBJECTIVE:

To estimate the age-specific incidence of Parkinson's disease (PD) in elderly persons in the Canadian province of British Columbia (BC). All-cause and injury mortalities and relative risk of death for those persons with PD were also examined.

METHODS:

A historical cohort study was conducted using 5 provincial administrative databases from 1991/92 to 2000/2001. A series of algorithms based on the databases were created for case ascertainment of PD for persons 65 years or older. Crude and age-specific incidence and mortality rates were calculated using person-years of follow-up as the denominator. The impact of PD on all-cause and injury mortalities was examined using multivariate Cox regression models to provide adjusted hazard ratios.

RESULTS:

10,910 incidence cases over 6,051,682 person-years of follow-up were identified. The crude annual incidence rate was 252 per 100,000 person-years. Over the nine year period, age standardized incidence for males ranged from 207 to 396 per 100,000 person-years and 127 to 259 per 100,000 person-years for females. Persons with PD were at a 43% greater risk of all-cause mortality and specifically, 51% greater risk of injury mortality.

CONCLUSIONS:

Incidence of PD is substantially higher in advanced age with age adjusted increases for both all-cause and injury mortalities. These findings also highlight falls as a primary factor for injury mortality in PD.

Merry Christmas to all PREDICT-PD supporters and participants

Small study of caffeine in PD

Abstract

"This is a small study of treatment with caffeine in Parkinson's. Previous studies suggest that people who drink coffee are less likely to be diagnosed with Parkinson's. Reasons for this observation include: 1) caffeine protects you against Parkinson's, 2) coffee delays the onset of Parkinson's or 3) people with early undiagnosed Parkinson's do not get the normal positive effect from coffee and therefore don't use it. Whatever the reason, caffeine remains a good candidate drug for treating Parkinson's. This small study shows some benefit from treatment with caffeine in certain aspects of the disease and not in others. It also suggests a dose that can be tolerated. Clearly larger studies are warranted."

PREDICT PD Feedback

"I've been going through the participant feedback from the PREDICT PD study now that we have most of the results in. I will be posting selected feedback on this blog to try and answer outstanding questions from participants".

Dietary patterns and risk of Parkinson's disease: a case-control study in Japan

Background:  Nearly all epidemiologic studies examining the association between the risk of Parkinson's disease (PD) and diet have focused on single foods and specific nutrients. However, epidemiologic evidence for the association of dietary pattern with PD, namely the measurement of overall diet by considering the cumulative effects of nutrients is extremely limited. We conducted a hospital-based case-control study in Japan to examine the relationship between dietary patterns and the risk of PD. Methods:  Patients with PD diagnosed using the UK PD Society Brain Bank criteria (n = 249) and controls without neurodegenerative diseases (n = 368) were recruited. At the time of recruitment, dietary intake during the preceding 1 month was assessed using a validated, self-administered diet history questionnaire. Dietary patterns from 33 predefined food groups (energy-adjusted food g/day) were extracted by factor analysis. Results:  Three dietary patterns were identified: 'Healthy', 'Western' and 'Light meal' patterns. After adjustment for potential non-dietary confounding factors, the Healthy pattern, characterized by a high intake of vegetables, seaweed, pulses, mushrooms, fruits and fish, was inversely associated with the risk of PD with a border-line significance (P for trend = 0.06). Multivariate Odds ratio (95% confidence intervals) for PD in the highest quartile of the Healthy pattern was 0.54 (0.32-0.92) compared with the lowest quartile. No associations with PD were detected for the other two dietary patterns. Conclusion:  In this case-control study in Japan, a dietary pattern consisting of high intakes of vegetables, fruits and fish may be associated with a decreased risk of PD.

Monoamine oxidase B inhibitors for the treatment of Parkinson's disease: a review of symptomatic and potential disease-modifying effects.

http://www.ncbi.nlm.nih.gov/pubmed/22133327

A. Schapira

CNS Drugs. 2011 Dec 1;25(12):1061-71.

Parkinson's disease is a disorder characterized pathologically by progressive neurodegeneration of the dopaminergic cells of the nigrostriatal pathway. Although the resulting dopamine deficiency is the cause of the typical motor features of Parkinson's disease (bradykinesia, rigidity, tremor), additional non-motor symptoms appear at various timepoints and are the result of non-dopamine nerve degeneration. Monoamine oxidase B (MAO-B) inhibitors are used in the symptomatic treatment of Parkinson's disease as they increase synaptic dopamine by blocking its degradation. Two MAO-B inhibitors, selegiline and rasagiline, are currently licensed in Europe and North America for the symptomatic improvement of early Parkinson's disease and to reduce off-time in patients with more advanced Parkinson's disease and motor fluctuations related to levodopa. A third MAO-B inhibitor (safinamide), which also combines additional non-dopaminergic properties of potential benefit to Parkinson's disease, is currently under development in phase III clinical trials as adjuvant therapy to either a dopamine agonist or levodopa. MAO-B inhibitors have also been studied extensively for possible neuroprotective or disease-modifying actions. There is considerable laboratory evidence that MAO-B inhibitors do exert some neuroprotective properties, at least in the Parkinson's disease models currently available. However, these models have significant limitations and caution is required in assuming that such results may easily be extrapolated to clinical trials. Rasagiline 1 mg/day has been shown to provide improved motor control in terms of Unified Parkinson's Disease Rating Scale (UPDRS) score at 18 months in those patients with early disease who began the drug 9 months before a second group. There are a number of possible explanations for this effect that may include a disease-modifying action; however, the US FDA recently declined an application for the licence of rasagiline to be extended to cover disease modification.

NSAID use and the risk of Parkinson's

Abstract

1. C. Becker, 
2. S. S. Jick, 
3. C. R. Meier

1. European Journal of Neurology, Nov. 2011

Background:  Previous epidemiologic studies have produced inconsistent findings regarding the association between the use of non-steroidal anti-inflammatory drugs (NSAIDs) and the risk of Parkinson disease (PD).

Methods:  We conducted a case–control analysis using the General Practice Research Database. Cases (≥40 years) had a new diagnosis of PD between 1994 and 2009. We matched four controls to each PD case on age, sex, general practice, and index date. Use of NSAIDs, aspirin, and acetaminophen was stratified by exposure timing and duration for both cases and controls. We calculated odds ratios (OR) using conditional logistic regression. For additional analyses, the index date was brought backward 1, 2, and 3 years, respectively.

Results:  We identified 4026 cases with an incident idiopathic PD diagnosis and 15 969 matched controls. Compared with patients without any previous prescription for NSAIDs, those with prior use had no increased risk of a PD diagnosis (OR 1.07, 95% CI 0.99–1.16). Long-term use (≥15 prescriptions) was associated with a slightly lower PD risk (adjusted OR 0.94, 95% CI 0.83–1.07). The relative PD risks of the use of aspirin or acetaminophen were not materially higher (PD risk of long-term use: adjusted ORs 1.16, 95% CI 1.03–1.30 and 1.15, 95% CI 1.02–1.30, respectively) compared with those for non-users. The risk estimate diminished toward the null in subsequent analyses with shifted index dates.

Conclusion:  In this large observational study with data from the UK primary care, the long-term use of NSAIDs, aspirin, or acetaminophen was not associated with a substantially altered risk of developing PD.

Peripheral Neuropathy and Parkinson's

Full Free Article

"This is a free article in this week's Neurology Journal. It is a study which looked at the relationship between Parkinson's and peripheral neuropathy. It was been written to explain to the public how this particular research study was performed."

The promise of neuroprotective agents in Parkinson's disease

http://www.ncbi.nlm.nih.gov/pubmed/22125548?dopt=Abstract

 

Front Neurol. 2011;2:68. Epub 2011 Nov 21.

Seidl SE, Potashkin JA.

 

Parkinson's disease (PD) is characterized by loss of dopamine neurons in the substantia nigra of the brain. Since there are limited treatment options for PD, neuroprotective agents are currently being tested as a means to slow disease progression. Agents targeting oxidative stress, mitochondrial dysfunction, and inflammation are prime candidates for neuroprotection. This review identifies Rasagiline, Minocycline, and creatine, as the most promising neuroprotective agents for PD, and they are all currently in phase III trials. Other agents possessing protective characteristics in delaying PD include stimulants, vitamins, supplements, and other drugs. Additionally, combination therapies also show benefits in slowing PD progression. The identification of neuroprotective agents for PD provides us with therapeutic opportunities for modifying the course of disease progression and, perhaps, reducing the risk of onset when preclinical biomarkers become available.

Markers of inflammation in prevalent and incident Parkinson's disease in the Cardiovascular Health Study.

http://www.ncbi.nlm.nih.gov/pubmed/22119505?dopt=Abstract

Parkinsonism Relat Disord. 2011 Nov 25. [Epub ahead of print]

Ton TG, Jain S, Biggs ML, Thacker EL, Strotmeyer ES, Boudreau R, Newman AB, Longstreth WT Jr, Checkoway H.

BACKGROUND:

Studies demonstrate existence of inflammation in prevalent Parkinson's disease (PD). We assessed associations of baseline levels of inflammatory markers with prevalent PD at baseline (1989) and incident PD identified over 13 years of follow-up of the Cardiovascular Health Study.

METHODS:

Blood samples at baseline were measured for fibrinogen, interleukin-6, tumor necrosis factor-α, C-reactive protein, albumin, and white blood cells. The analysis included 60 prevalent and 154 incident PD cases.

RESULTS:

Risk of prevalent PD was significantly higher per doubling of IL-6 among women (odds ratio [OR]=1.5, 95% confidence interval [CI]: 1.0, 2.4) and WBC among men (OR: 2.4, 95% CI: 1.2, 4.9) in multivariate models. Risk of incident PD was not associated with higher levels of any biomarker after adjusting for age, smoking, African American race, and history of diabetes. Inverse associations with incident PD were observed per doubling of C-reactive protein (OR=0.9; 95% CI: 0.8, 1.0) and of fibrinogen among women (OR=0.4; 95% CI: 0.2, 0.8).

CONCLUSIONS:

Although inflammation exists in PD, it may not represent an etiologic factor. Our findings suggest the need for larger studies that measure inflammatory markers before PD onset.

Sleep disorders in Parkinson's disease: Many causes, few therapeutic options.

http://www.ncbi.nlm.nih.gov/pubmed/22118862?dopt=Abstract

J Neurol Sci. 2011 Nov 24. [Epub ahead of print]

Diederich NJ, McIntyre DJ.

Abstract

Sleep symptoms in Parkinson's disease (PD) are frequent and have multifactorial and multilayered causes. Primary involvement of sleep/wake regulating centers in the brainstem, sleep problems caused by the nocturnal manifestation of motor and dysautonomic signs and medication-induced sleep problems are often impossible to disentangle in the individual patient. Two syndromes, hypersomnia and REM sleep behavior disorder (RBD), are increasingly recognized as harbingers of the core PD motor syndrome. RBD, associated with a panoply of other nonmotor symptoms, may predispose to a specific PD phenotype. Long-acting dopaminergic stimulation, when abating nocturnal akinesia, also improves subjective sleep quantity. While this strategy is backed up by several randomized controlled trials (RCT), other treatment recommendations are mostly based on case series or expert opinion. Thus we identified only two other RCT, one treating insomnia with eszopiclone, the other nocturnal behavioral abnormalities in demented PD patients with memantine. While the causal complexity of sleep problems in PD certainly hampers the design of therapeutic studies, multiple general treatment strategies against sleep disorders can however be applied efficiently in PD patients as well.

Changes in quality of life, burden and mood among spouses of Parkinson's disease patients receiving neurostimulation

http://www.ncbi.nlm.nih.gov/pubmed/22118900?dopt=Abstract

Parkinsonism Relat Disord. 2011 Nov 23. [Epub ahead of print]
Soulas T, Sultan S, Gurruchaga JM, Palfi S, Fénelon G.

BACKGROUND:

Deep brain stimulation improves motor function and quality of life in patients with Parkinson's disease. The impact of these changes on patients' spouses is largely unknown.

METHODS:

Twenty-six spouses of patients undergoing surgery were evaluated before and 12 months after surgery, using the 36-Item Short Form Health Survey for quality of life, the Beck Depression Inventory, and the Zarit Burden Inventory.

RESULTS:

The spouses' mean mood and quality of life scores changed little, while burden improved in younger spouses. There was no significant change in the spouses' overall status. However, at the individual level the effect of surgery was more frequently negative than positive. Changes in psychological status and quality of life in the spouses did not correlate with changes in the patients' motor status or quality of life.

CONCLUSIONS:

Spouses' experience of neurostimulation for Parkinson's disease is variable and complex. The improvement in burden experienced by younger spouses may reflect a greater capacity to cope with new situations.

Living with Parkinson's

http://www.parkinsons.org.au/media-advocacy/docs/AEReport_2011.pdf

Above is a link to the Deloitte Access Economics report for Parkinson's Australia. This is freely accessible on the Parkinson's Australia website.

Why Do We Need Multifunctional Neuroprotective and Neurorestorative Drugs for Parkinson's and Alzheimer's Diseases as Disease Modifying Agents.

http://www.ncbi.nlm.nih.gov/pubmed/22110336?dopt=Abstract

Parkinson's disease (PD) and Alzheimer's Disease (AD) are severe neurodegenerative disorders, with no drugs that are currently approved to prevent the neuronal cell loss characteristic in brains of patients suffering from PD and AD and all drug treatment are synptomactic. Due to the complex pathophysiology, including a cascade of neurotoxic molecular events that results in neuronal death and predisposition to depression and eventual dementia and etiology of these disorders, an innovative approach towards neuroprotection or neurorestoration (neurorescue) may be the development and use of multifunctional pharmaceuticals. Such drugs target an array of pathological pathways, each of which is believed to contribute to the cascades that ultimately lead to neuronal cell death. In this short review, we discuss examples of novel multifunctional ligands that may have potential as neuroprotective-neurorestorative therapeutics in PD and AD. The compounds discussed originate from synthetic chemistry as well as from natural sources.

Can nicotine be used medicinally in Parkinson's disease?

http://www.ncbi.nlm.nih.gov/pubmed/22114853?dopt=Abstract

The risk of Parkinson's disease is reduced by cigarette smoking, which raises some unanswered questions. Nicotine, a major component of tobacco smoke, could exert either non-receptor-mediated biological effects or, more importantly, act on the different subtypes of nicotinic brain receptors, in particular those associated with the nigrostriatal dopaminergic pathway. There is now robust experimental evidence for a neuroprotective effect of nicotine upon dopaminergic neurons. By contrast, in animal models of Parkinson's disease, nicotine alone has slight or no motor effects. However, nicotine may modulate dopamine transmission and has clear motor effects when associated with L-DOPA, reducing L-DOPA-induced dyskinesias. Clinical trials have yielded inconclusive results thus far and are hampered by different designs and small cohorts. Ongoing studies address either symptomatic motor or non-motor symptoms, or neuroprotection. There is still no agreement on the daily dosage of nicotine or the method of administration. Together, these data suggest that nicotine or nicotinic receptor drugs have therapeutic potential for Parkinson's disease, although the specific treatment regimens remain to be determined.

Intranasally applied l-DOPA alleviates parkinsonian symptoms in rats with unilateral nigro-striatal 6-OHDA lesions.

http://www.ncbi.nlm.nih.gov/m/pubmed/22108632/

Chao OY, et al. 

JournalBrain Res Bull. 2011 Nov 15. [Epub ahead of print]

Abstract

l-3,4-Dihydroxyphenylalanine (l-DOPA) remains the most effective drug for therapy of Parkinson's disease. However, the current clinical route of l-DOPA administration is variable and unreliable because of problems with drug absorption and first-pass metabolism. Administration of drugs via the nasal passage has been proven an effective alternate route for a number of medicinal substances. Here we examined the acute behavioral and neurochemical effects of intranasally (IN) applied l-DOPA in rats bearing unilateral lesions of the medial forebrain bundle, with severe depletion (97%) of striatal dopamine. Turning behavior in an open field, footslips on a horizontal grid and postural motor asymmetry in a cylinder were assessed following IN l-DOPA or vehicle administration with, or without, benserazide pre-treatment. IN l-DOPA without benserazide pre-treatment mildly decreased ipsilateral turnings and increased contralateral turnings 10-20min after the treatment. IN l-DOPA with saline pre-treatment reduced contralateral forelimb-slips on the grid while no effects were evident in the cylinder test. These results support the hypothesis that l-DOPA can bypass the blood-brain barrier by the IN route and alleviate behavioral impairments in the hemiparkinsonian animal model.

Controversies in Neurology: why monoamine oxidase B inhibitors could be a good choice for the initial treatment of Parkinson's disease

Abstract

BMC Neurology 2011, 11:112doi:10.1186/1471-2377-11-112

Background 

Early initiation of pharmacotherapy in Parkinson's disease (PD) is nowadays widely advocated by experts since the delay of treatment has shown to be associated with a significant deterioration of health related quality of life in affected patients. Due to marked advances in PD treatment during the last decades, physicians are nowadays fortunately equipped with a variety of substances that can effectively ameliorate emerging motor symptoms of the disease, among them levodopa, dopamine agonists and monoamine oxidase type B (MAO-B) inhibitors. Despite numerous drug intervention trials in early PD, there is however still ongoing controversy among neurologists which substance to use for the initial treatment of the disease. 

Discussion 

In multiple studies, MAO-B inhibitors, such as selegiline and rasagiline, have shown to provide mild symptomatic effects, delay the need for levodopa, and to reduce the incidence of motor fluctuations. Although their symptomatic efficacy is inferior compared to dopamine agonists and levodopa, MAO-B inhibitors undoubtedly have fewer side effects and are easy to administer. In contrary to their competitors, MAO-B inhibitors may furthermore offer a chance for disease modification, which so far remains a major unmet need in the management of PD and eventually makes them ideal candidates for the early treatment of the disease. 

Summary 

MAO-B inhibitors may constitute a preferable therapeutic option for early PD, mainly due to their favourable safety profile and their putative neuroprotective capabilities. Since the symptomatic effects of MAO-B inhibitors are comparatively mild, dopamine agonists and levodopa should however be considered for initial treatment in those PD patients, in whom robust and immediate symptomatic relief needs to be prioritized.

Low BMI in people with Parkinson's

Abstract

"This meta-analysis supports the long-standing observation that people with Parkinson's tend to have lower BMI than members of the general population. BMI is a proxy for body fat in humans and is calculated using height and weight. This observation was not dependent on the duration of disease.


A number of studies have looked at whether changes in BMI occur prior to the movement features of Parkinson's. These studies are largely in disagreement with one another and differences in the BMI ranges used make them difficult to compare directly. As it stands, there is no compelling literature to suggest that changes in BMI predate the movement problems."

Passive smoking reduces Parkinson's risk

Abstract

"This case control study shows that passive smoking is associated with a reduced risk of Parkinson's. A previous study has shown similar reduction in risk if both parents smoked. Whilst a protective effect of cigarette smoke has long been suspected, this not yet prove. What is certain is that regardless of its role in Parkinson's, smoking causes a large number of other illnesses including heart disease, stroke and cancer."

Solvent exposure and risk of Parkinson's

Abstract

"This is a new report of a twin study from the US looking at the role that specific solvents/chemicals may have in causing Parkinson's. A number of other chemicals have also been suggested to increase individual risk of Parkinson's. The authors acknowledge the need for further work in this area."

Restless legs in Parkinson's

Abstract

"This is a new research article reporting on a case control study of the rate of restless legs syndrome (RLS) in early untreated Parkinson's and healthy controls. RLS is a diagnosis made on the basis of certain criteria and is not simply isolated leg restlessness. This is an important point because this study shows that isolated leg restlessness is more common in persons with early Parkinson's than healthy controls, but there is no difference in the rate of true RLS between these two groups."

Cochrane review on H.pylori and Parkinson's

Abstract


"A number of Predict PD participants have asked about the role of the bacteria H. pylori and Parkinson's following some publicity on the subject earlier this year. This Cochrane review looks at the current literature on how H. pylori may reduce response to treatment and concludes that at the moment there is insufficient evidence in this area. A further study is ongoing which may serve to answer this question."

A review of the role of the gut in Parkinson's

"An interesting 'Views and Reviews' article has just been published by Derkinderen et al in this week's Neurology journal. It outlines the evidence base for the gut as a window to the brain and it's potential role in Parkinson's diagnosis and monitoring.


I will post a link to the abstract as soon as it is available."

1000 smell tests have now been sent

" I'm pleased to say all 1000 smell tests have been dispatched and over 600 have now been completed online with a further 100 or so complete manually. We will be following up on the ones that have not yet been completed in the coming weeks, so if you are yet to do it please do so at your earliest convenience."

Hand dominance and Parkinson's onset

http://www.ncbi.nlm.nih.gov/pubmed/21994149

"This systematic review and meta-analysis shows that hand dominance appears to have a role in how Parkinson's disease presents. It shows that symptoms are twice as likely to begin in the dominant hand than in the non-dominant hand."

Levodopa treatment does not appear to accelerate Parkinson's disease

http://www.ncbi.nlm.nih.gov/pubmed/21917769
"Some laboratory-based studies have previously suggested that levodopa administration may lead to degeneration of dopaminergic nerve cells. This has not been shown in studies in patients. This latest report shows that there is no evidence that long term dopamine replacement has toxic effects on nerve cells."

American smell test in UK-based study

"Some of our participants have expressed their concern over our use of an American smell test in this UK-based study. Some of the smells are felt to not be familiar to members of the UK population. Please let me reassure you that we have a great many years experience using this test and have hundreds of sets of results from normal British people - we know what is a normal score for people in this country. It is these normal results we will be comparing your scores in the study to. If you have any further comments or questions, please email me at - a.noyce@qmul.ac.uk"

Combining smell tests and ultrasound to diagnose Parkinson's

http://www.ncbi.nlm.nih.gov/pubmed/21978091

"A study in a small number of Parkinson's patients suggesting that ultrasound scanning across the skull and smell testing could help in the diagnosis of Parkinson's disease. If combined, they may be even more helpful. However, such tests need further investigation and as such should not currently be used routinely when making a diagnosis of Parkinson's."

The Oral Contraceptive Pill and risk of Parkinson's

Abstract
This case-control study suggests that previous use of the oral contraceptive pill (OCP) in women may increase the risk of subsequent Parkinson's. There is no demonstrable effect conveyed by previous post-menopausal hormone replacement therapy. It is worth pointing out that 4 previous reports have considered an association between the oral contraceptive pill and subsequent Parkinson's. One showed a decreased risk of Parkinson's in previous users of the OCP, two studies showed no association at all and one showed a minor risk increase but only if there was over 5 years of OCP use. In summary, any link remains uncertain and more work is required.

Blood urate levels as a biomarker for Parkinson's

Abstract

"This article demonstrates the potential use of blood levels of urate in differentiating individuals with true Parkinson's that have abnormal dopamine transport on imaging studies and individuals that have symptoms of Parkinson's without the characteristic imaging findings."

More Smell Tests On Their Way

"Thank you to those who have been patiently waiting for their smell tests. There is a batch arriving from the US in the next couple of days, so we'll be sending them straight out to our participants. We will then add up then how many more we need to get to the 1000 figure mark and order the remaining smell tests. Thank you once again."

Smell Test Delay

" Further apologies to those participants that are still waiting for smell tests to be delivered. We are yet to receive them from the US and will send them out as soon as we possibly can."

BRAIN test published online

http://onlinelibrary.wiley.com/doi/10.1002/mds.23947/abstract

"Many of you will have been wondering about the Tap test we asked you to do as part of the Predict PD pilot study. The Tap test's other name is the BRAIN test, which stands for the Bradykinesia, Akinesia, Incoordination test and pays reference to some of the abnormalities of movement that exist in Parkinson's. The BRAIN test was originally published about 10 years ago, but this year is the first time that it has been available online. This 'Letter to the Editor' of Movement Disorders Journal describes the findings from it's use in a small number of patients with Parkinson's. There is no abstract available but the results will also be presented at the Association of British Neurologists next month and I will upload this in due course."

Nike MAG trainers to raise money for Parkinson's

http://nikemag.ebay.com/

"American sports giant NIKE has released 1500 pairs of the Nike Mag training shoe, which are currently being auctioned on ebay.com. These replica trainers were originally worn by Michael J. Fox's character, Marty McFly, 20 years ago in the film Back to the Future II. The estimated price of each pair will be in the region of $5000, however the highest price paid so far is $37,000 on 8th September. All revenue generated will go to the Michael J. Fox Foundation for Parkinson's Research."

Rasagiline (Azilect) improves motor OFF periods in Parkinson's

Abstract

"Patients treated with levodopa for a number of years often recognise periods through the day when they feel a good effect from their medication ('ON' periods) and times when the effect wears off ('OFF' periods). New results from the LARGO study show that Rasagiline (Azilect) in addition to levodopa improves scores of motor function and activities of daily living during 'OFF' periods."

Botulinum toxin to treat excessive saliva in Parkinson's

Abstract

"Excessive saliva is a common problem in Parkinson's and is due to reduced frequency of swallowing. This placebo-controlled study demonstrates improvement of this troublesome symptom with injection of botulinum toxin type B into the salivary glands. It is more common to treat excessive saliva with drugs that affect the autonomic nervous system, but these can cause side effects such as confusion. Botulinum toxin offers an alternative treatment option."

New research on the role of gut biopsies in PD

Abstract

"The nervous system of the gut is affected by some of the same abnormalities as the brain in individuals with Parkinson's. The idea has therefore been put forward that the gut might provide a 'window to the brain' through which we can see the changes of Parkinson's whilst the disease is in it's earliest stages. This might have implications, not only for diagnosis, but also for monitoring of early disease.

This new study reports the likelihood of picking up these gut abnormalities in individuals with Parkinson's and shows that the likelihood is site dependent. Biopsy of the gut is not a standard investigation in people with Parkinson's currently and is unlikely to be in the near future. However, this study is relevant because clinical trials of early disease may consider using gut biospies, and this study shows that biospy of the rectum alone is unlikely to be adequate."

Smell Test Delay

Unfortunately there has been a delay in receiving a batch of smell tests from the US and therefore many Predict PD study participants have not had their test delivered. We are hoping to get the tests in the coming days and will get these out to you as soon as possible. Please feel free to email if you have any questions.

Alastair Noyce
Predict PD

The Role of the Neurologist in PD

Abstract

"This is an article from the US that considers the role of Neurologists in the management of Parkinson's. The findings, whilst interesting, are less relevant for us in the UK due to differences in the way that our healthcare is delivered. For example, our guidelines from NICE state that all individuals with suspected Parkinson's should be referred untreated to a neurologist or doctor with a special interest in movement disorders. Therefore the aim is that all patients with Parkinson's are seen by an expert early on, who can then make subsequent management decisions."

Interesting article about sham surgery in Parkinson's

Why Fake It?

"This is an interesting article about the use of sham (or placebo) surgery in trials of surgical treatments for Parkinson's. It examines the viewpoints of Neurologists from the U.S. and Europe about the role and ethics of sham surgery."

Pilot Study Reaches Target

"After a very busy end of July and beginning of August, I am pleased to say that the pilot study has recruited well over 1000 participants. If you joined after we reached 1000 or indeed want to join and haven't done so yet, please don't be put off. We need to spend some time establishing carefully that everyone is eligible for the study before sending a smell test to them.

We have already sent out a massive number of smell tests to participants and are just waiting for some more to arrive from the U.S. I hope that these will be sent out in the next week or so."

New research on sleep disorders and Parkinson's

http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(11)70152-1/abstract

"This study followed individuals with an established diagnosis of REM Sleep Behaviour Disorder (RBD) and shows that in proportion of them the appearance of their DaTSCANs (a scan used to look for evidence of reduced dopamine in the brain) changes towards an appearance seen in Parkinson's. RBD has previously been found to be a risk factor for Parkinson's and other degenerative conditions of the neurological system. Further work is needed to determine how RBD could be used to identify these diseases at an earlier stage."

Experimental evidence that smoking might be protective in Parkinson's

http://www.fasebj.org/content/25/8/2563.abstract

"New research reported in this week's FASEB Journal. This group's experimental animal model suggests a protective benefit of nicotine on the dopamine cells that are lost in Parkinson's. Such experimental findings support epidemiological studies that show that Parkinson's is less common in smokers. However, as it stands the harmful effects of all the toxins contained within cigarettes far outweigh any potential benefits that nicotine might have in isolation. As such, it would be against medical advice for patients and the public to start or continue smoking in attempt to protect against Parkinson's"

Approaching target number

"After a very busy 8 days for the Predict PD team, I'm pleased to say we are nearing our target of 1000 participants in the pilot study. Not all will be eligible, so if you have not yet signed up or can think of others who would like to be involved please continue to spread the word. 


We have now sent out 300 smell tests and aim will aim to get another 300 out next week, and more the week after. 


Thank you to all of you that are supporting the project."

Predict PD Update

"Of the 600 people who have registered in the last few days, 500 have completed the questionnaire and can expect a smell test to to be delivered to the address they provided. 


The smell tests should be with you in 1-2 weeks. But given the high rate of participation, please be patient if it takes a little longer.


Contact me on support@predictpd.com if you have an questions"


BW


Alastair Noyce

Still going strong

"Another 200 today!

Thank you all for supporting the study."

Predict PD Gains Momentum!

"What a day it has been for the Predict PD pilot study!! 250 participants in just 6 hours and no signs of slowing down. 


Thank you to all those who have registered and participated so far. Your smell tests will be dispatched and should get to you in 1-2 weeks (we have more on order). I have been looking through the feedback and want to thank many of you for your kind comments. Those that have asked questions in the feedback, I will be getting round to answering them as soon as possible.


Thank you to Parkinson's UK for their wonderful ongoing support and thank you to Grass Roots Group who support our web site and tests.


I hope that many more of you will join and invite friends and colleagues you think may also like to participate."


Alastair Noyce
Predict PD

Gut biopsies in early Parkinson's

Alpha-synuclein in colonic submucosa in early untreated Parkinson's disease.

Shannon KM, Keshavarzian A, Mutlu E, Dodiya HB, Daian D, Jaglin JA, Kordower JH.

Mov Disord. 2011 Jul 15. doi: 10.1002/mds.23838. [Epub ahead of print]

" Alpha-synuclein is a protein that accumulates in the brain cells of people with Parkinson's. It is considered the key finding for confirming a diagnosis of Parkinson's at post-mortem. This study shows that it may be possible to identify this protein in other tissues, potentially very early in the disease. It may prove a useful marker for disease progression or monitoring response to treatment. However, further work is needed in the gut and other tissues."

Biomarkers in Parkinson's disease

Biomarker candidates of neurodegeneration in Parkinson's disease for the evaluation of disease-modifying therapeutics.

Gerlach M, Maetzler W, Broich K, Hampel H, Rems L, Reum T, Riederer P, Stöffler A, Streffer J, Berg D.

J Neural Transm. 2011 Jul 14. [Epub ahead of print]

"Biomarkers are biological markers that can be objectively measured to monitor normal physiological processes, pathological/disease processes and responses to drug treatment. This article reviews candidate biomarkers for Parkinson's disease that may help us monitor disease progression, but most importantly could be used to measure response to new drug treatments" 

An introduction to PD

A short video on PD. Does it address your needs? If not please post a comment and we will answer your questions. 

History of PD (1) - James Parkinson

Dr James Parkinson wrote the first description of 'The Shaking Palsy', or what is now known as Parkinson's disease, in 1817. He was a man for the ages and lived in London around the Age of Enlightenment. He was a political activist, geologist, scientist, humanist, leading public health and ethical thinker and a doctor to the people in the Parish of St Leonard's, Shoredicth, North London. This short documentary film takes the viewer through James's life and gives a glimpse of the streets in which he lived, worked and first came across people who had Parkinson's disease. This film has been carefully and lovingly researched and filmed by Dr David Williams (who is also a Neurologist) and is narrated by Dr Gerald Stern. It has been shown in London, Berlin, Chicago and New Orleans.

Ultrasound used to predict Parkinson's

Enlarged substantia nigra hyperechogenicity and risk for Parkinson disease: a 37-month 3-center study of 1847 older persons.

Berg D, Seppi K, Behnke S, Liepelt I, Schweitzer K, Stockner H, Wollenweber F, Gaenslen A, Mahlknecht P, Spiegel J, Godau J, Huber H, Srulijes K, Kiechl S, Bentele M, Gasperi A, Schubert T, Hiry T, Probst M, Schneider V, Klenk J, Sawires M, Willeit J, Maetzler W, Fassbender K, Gasser T, Poewe W.

Arch Neurol. 2011;68(7):932-937. doi:10.1001/archneurol.2011.141

"These are the emerging data from the novel PRIPS study taking place in Germany and Austria, which looks at markers for early Parkinson's disease. This article shows how ultrasound scanning of brain structure through the temple of the head can be used to identify people at increased risk of Parkinson's. Whilst there are some problems with this technology, such as it cannot be used in 10% of people due to differences in skull bones, this report underlines the potential for this technique in predicting Parkinson's. It is a cheaper and simpler imaging technique than other imaging options that look to achieve the same thing."

Physical activity and Parkinson's disease

How might physical activity benefit patients with Parkinson disease?

Speelman AD, van de Warrenburg BP, van Nimwegen M, Petzinger GM, Munneke M, Bloem BR

Nat Rev Neurol. 2011 Jul 12. doi: 10.1038/nrneurol.2011.107. [Epub ahead of print].

"This is an article about the potential role of exercise in Parkinson's. There is increasing evidence of a therapeutic role of exercise in managing Parkinson's. At Predict PD, we are particularly interested in physical activity because two separate studies have shown that physical activity may reduce the risk of Parkinson's in the future. However, further work must be done on both physical activity during Parkinson's and preceding Parkinson's to confirm these observations"

wearingoff.com

This is a nice website funded by Orion Pharmaceuticals. It includes some basic information on Parkinson's and also questionnaires and a diary for patients encountering fluctuations in their symptoms as a result of their medication.

No relationship between obesity or diabetes and subsequent risk of Parkinson's

Obesity, diabetes, and risk of Parkinson's disease

Palacios N, Gao X, McCullough ML, Jacobs EJ, Patel AV, Mayo T, Schwarzschild MA, Ascherio A.

Movement Disorders 2011 Jul 7. doi: 10.1002/mds.23855. [Epub ahead of print]

"New research from a large cohort showing that markers for obesity and diabetes mellitus do not influence subsequent risk of developing Parkinson's. These findings are generally in keeping with other research on obesity and diabetes as risk factors and suggests that neither will be particularly helpful when trying to determine which individuals are at increase risk of Parkinson's"

News from the 23andMe project

News from the 23andMe project

"23andMe is a project running in the US that invites people to submit a sample of saliva for genetic testing and recruits people over the Internet. Using thousands of participants, both those that are healthy and those with diseases, it then compares differences in genetic make-up between groups. In this new report, the scientists from 23andMe present 2 new genetic areas of interest in Parkinson's. Whilst these are potentially important in unravelling the biology of Parkinson's, it also demonstrates the power and potential of research conducted over the Internet. Research like we are doing at Predict PD"

Medicine and Technology Talk

"Take a look at this rapid overview of emerging medical technology for the next few years. A great presentation by Daniel Kraft from Stanford."

http://www.ted.com/talks/daniel_kraft_medicine_s_future.html

NEW ARTICLE - SMELL SENSE IN PARKINSON'S

Motor and non-motor correlates of olfactory dysfunction in Parkinson's disease.

Berendse HW, Roos DS, Raijmakers P, Doty RL.

J Neurol Sci. 2011 Jun 24. [Epub ahead of print]

"We know that smell sense is abnormal in the majority of people with Parkinson's and is at least as common as the tremor. It has previously been suggested that abnormal smell sense (hyposmia) does not worsen with progression of Parkinson's and therefore whilst a useful marker for Parkinson's overall, it might be less useful for monitoring disease. However, this study suggests that in the early stages of Parkinson's, deterioration in smell sense did correlate with disease severity - the movement symptoms, the other symptoms and the imaging. This is a useful finding and suggests that smell sense could possibly be used to monitor Parkinson's in the early stages"

NEW ARTICLE - PARKINSON'S AND THE GUT

A Prospective Study of Bowel Movement Frequency and Risk of Parkinson's Disease

Am J Epidemiol. 2011 Jun 30. [Epub ahead of print]

Gao X, Chen H, Schwarzschild MA, Ascherio A

This is another prospective study in two large cohorts (the Health Professionals Follow Up Study and the Nurses Health Study) that supports the theory that constipation precedes the movement symptoms in people with Parkinson's disease. 

It is important to recognise that constipation can have many causes and is common in the older general population. Parkinson's disease is much less common and as such only a very small number of people with constipation will later get the symptoms of Parkinson's disease. However, this association between Parkinson's and constipation may help scientists identify people at-risk far earlier. The Predict PD pilot study incorporates constipation in its questionnaire.

New diagnostic scan for PD

GE Healthcare has announced the availability of new diagnostic scan for Parkinson's disease called the DaTscan (Ioflupane I 123 Injection).

"The DaTscan is of great interest to us. If this scan can be used in the pre-symptomatic phase of PD, that is before PD'ers are are aware that they have the disease, we may be able to target PD at a time-point with the greatest potential to modify the course of the disease."

For more information see the Diagnostic Imaging press release.

Conflict of interest: I have consulted for GE-Heathcare in the past in relation to multiple sclerosis.

NEW ARTICLE - PARKINSON'S AND CLINICAL TRIALS

What motivates Parkinson's disease patients to enter clinical trials? 
Valadas A, Coelho M, Mestre T et al.
Parkinsonism Relat Disord. 2011 Jun 27


Important survey of patients to determine willingness and motivation to be involved in research into drug treatments against Parkinson's.

NEW ARTICLE - BASIC SCIENCE AND PARKINSON'S

Lithium protects against oxidative stress-mediated cell death in α-synuclein-overexpressing in-vitro and in-vivo models of Parkinson's disease.

Yong-Hwan Kim, Anand Rane, Stephanie Lussier, Julie K. Andersen
Journal of Neuroscience Research
Article first published online: 24 JUN 2011

An interesting article published this week online. Whilst this is an encouraging finding given that lithium was shown to reduce cell loss in this animal model of Parkinson's, it is important to remember that this is very early work and must be investigated further. The animal models of Parkinson's, whilst similar to the disease in humans, are not identical and therefore what works in animals may not perform the same in humans. However, if these results could be replicated, this would be important. Lithium is a well established drug that has been used for many years in psychiatric medicine and the safety/side effects are well known. It would also be much cheaper than emerging, newly designed drugs.

In summary, an interesting finding but one that needs a lot more study.

Secondary Analysis of the ADAGIO study

The ADAGIO study investigated whether rasagiline has disease-modifying effects in Parkinson's disease. In the original/primary analysis it was shown that 1mg of rasagiline showed some benefit, but that 2mg did not. The reason for this was difficult to explain but it raised a number of questions, such as:

1) Does the design of these trials allow you to determine whether the study is truly modifying the underlying disease process or not?

2) Does the drug in question (rasagiline) truly modify the underlying disease or is it just improving symptoms?

3) Are the right patients being selected into these trials?

The new, secondary analysis is available online at the Lancet Neurology site. http://www.thelancet.com/journals/laneur/article/PIIS1474-4422(11)70073-4/abstract

Parkinson's artificial brain bank

http://www.bbc.co.uk/news/health-13810653

This link takes you to an article on the BBC's website about the Oxford University team that are using a variety of approaches to try and cure Parkinson's. Their exciting project has 3 different strands of investigation that are all complimentary and will hopefully lead to significant advances in the field.

Researchers in this area think it is important not just find out about the symptoms that precede typical Parkinson's, but also what is going on under the microscope in various organs of the body including the brain, eyes, skin and gut. That is why so many projects in this field ask their participants if they will contribute biological samples such as blood, for further analysis.

The Predict PD Blog

Thank you to those of you that are accessing this blog for the first time. This is a new forum for discussion of Parkinson's-related research, comments and questions. I hope that people with Parkinson's, doctors that treat Parkinson's and the participants in the Predict PD study will use it regularly. Over the next few weeks I will blog on the feedback points that Predict PD participants have highlighted, as there are some common themes. Please submit your comments and any further thoughts that this blog generates.

Do non-motor symptoms in Parkinson's disease differ from normal aging?

Movement Disorders Journal 
Syam Krishnan, Gangadhara Sarma, Sankara Sarma and Asha Kishore
Article first published online: 9 JUN 2011 | DOI: 10.1002/mds.23826


Background: Non-motor symptoms in Parkinson's disease are frequent and affect health-related quality of life of patients. The severity and domains of nonmotor symptoms involved in Parkinson's disease and normal aging have not been compared before.Methods: We performed a prospective case–control study to assess the frequency and severity of non-motor symptoms in patients with Parkinson's disease (n = 174) and age-matched normal controls (n = 128) using the Non-Motor Symptoms Scale.Results:Nonmotor symptoms in Parkinson's disease were ubiquitous, more frequent, and more severe than in normal aging, particularly in women. Cardiovascular, mood/cognition, and perceptual problems/hallucinations domains were rarely involved in age-matched controls. Age had no effect and sex some influence on nonmotor symptoms in Parkinson's disease. In contrast, in controls, nonmotor symptoms increased with age, and sex had no effect.Conclusions: Non-motor symptoms in Parkinson's disease differ from those in aging in frequency, severity, sex predilection, and domain involvement.

New Parkinsons and Predict PD information site

I'm pleased to say that a sister site for the Predict PD project, which contains both study information and also general Parkinson's information is close to being launched. Please advise if there is any information you would specifically like to see on this site. Further details on launch to follow.

Movement Disorders Society 15th Annual Congress Toronto

The 15th Annual MDS Congress was held last week in Toronto. There was a wide range of presentations on current hot topics including the genetics of Parkinson's, recent clinical trials of drugs to treat Parkinson's and early reports from studies trying to identify people at risk of Parkinson's. I would invite interested people to suggest which of these, and related topics, they would like to see represented in this blog. Please email me on a.noyce@qmul.ac.uk or post a response below.

Predict PD

The Predict PD Pilot Study has started tremendously well, with nearly 100 people joining the study in the first week. For those of you that haven't yet joined, and want to be involved, please register with the site.

Welcome to the PredictPD Blog: Predict PD

Welcome to the PredictPD Blog: Predict PD: "This site is about Parkinsons disease"

Predict PD

This site is about Parkinsons disease

Launch

We will be launching shortly