Friday, 30 January 2015

The burden of non-motor symptoms in Parkinson's disease using a self-completed non-motor questionnaire: A simple grading system.

Parkinsonism Relat Disord. 2015 Jan 5. pii: S1353-8020(14)00505-7. doi: 10.1016/j.parkreldis.2014.12.031. [Epub ahead of print]

Chaudhuri KR, Sauerbier A, Rojo JM, Sethi K, Schapira AH, Brown RG, Antonini A, Stocchi F, Odin P, Bhattacharya K, Tsuboi Y, Abe K, Rizos A, Rodriguez-Blazquez C, Martinez-Martin P.

BACKGROUND:
Non-motor symptoms (NMS) of Parkinson's disease (PD) affect virtually every patient, yet they are under-recognized and under-treated. The NMS Questionnaire (NMSQuest) is a validated 30-item self-assessment instrument useful for NMS screening in clinic.

OBJECTIVE:
Development of a straight forward grading classification of the burden of non-motor symptoms in PD based on the number of NMS as assessed by the NMS Questionnaire.

METHODS:
In an observational, cross-sectional, international study of 383 consecutive patients distribution of the declared NMS as per NMSQuest was analyzed according to previously published levels based on the Non-Motor Symptoms Scale and also the median and interquartile range (IR, percentiles 25 and 75) of the total NMSQuest scores. After post hoc checking, these values were proposed as cut-off points for estimating NMS burden based only on the accumulation of symptoms.

RESULTS:
Burden and number of NMS correlate closely (r ≥ 0.80). On the basis of this finding, five levels (0 = No NMS to 4 = Very severe) of NMSQuest grading were proposed after identification of their cut-offs by ordinal logistic regression and median and interquartile range distribution. These values coincided almost completely with those obtained by median and interquartile range in an independent sample. Concordance between this classification and HY staging was weak (weighted kappa = 0.30), but was substantial (weighted kappa = 0.68) with the Non-Motor Symptoms Scale grading.

CONCLUSION:

Completion of NMSQuest and subsequent grading of the burden could allow the health care professional to approach the severity of NMS burden using the self completed NMSQuest in a primary care setting.

Thursday, 29 January 2015

Usefulness of Genetic Testing in PD and PD Trials: A Balanced Review.

J Parkinsons Dis. 2015 Jan 26. [Epub ahead of print]
Gasser T

Abstract

An increasing proportion of the individual and population risk to develop Parkinson's disease (PD) can be explained by genetic variants of different effect strength, forming a continuum from rare high penetrance gain or loss of function mutations to relatively common genetic risk variants that only mildly modify disease risk. In the coming years, further advances in molecular genetic technologies, in particular the increasing use of next generation sequencing, is likely to generate a wealth of new knowledge about the genetic basis of PD. Although specific treatments for PD based on the underlying genetic etiology will probably not be available in the near future, genetic testing is therefore likely to play an increasing role, both in the counselling of individual patients and their families with respect to the expected disease course and recurrence risks, and in the stratification of patient groups in clinical trials. Thus, the usefulness of genetic testing strongly depends on question asked and needs to be considered within each particular setting.

Friday, 23 January 2015

Head injury, potential interaction with genes, and risk for Parkinson's disease

Are timing of injury or carrying a gene variant important for the increased risk of PD that head injury conveys??

Parkinsonism Relat Disord. 2015 Jan 8. pii: S1353-8020(15)00003-6. doi: 10.1016/j.parkreldis.2014.12.033. [Epub ahead of print]
Gao J, Liu R, Zhao E, Huang X, Nalls MA, Singleton AB, Chen H.

INTRODUCTION:
To evaluate the association between head injury and Parkinson's disease (PD), focusing on the timing of head injury, and to explore potential interactions between head injury and genetic factors in PD etiology.

METHODS:
The analysis included 507 PD cases and 1330 controls, all non-Hispanic Whites. Head injury was retrospectively asked, and genotyping was performed mainly as part of a previous GWAS.

RESULTS:
We found a positive association between head injury and PD risk. Compared with no previous head injury, the odds ratio (OR) was 1.39 (95% confidence interval [CI]: 1.00, 1.94) for one and 2.33 (95% CI: 1.25, 4.35) for two or more head injuries (P for trend = 0.0016). We further found that the higher risk was largely attributed to head injuries before age 30. Compared with no previous head injury, the OR was 2.04 (95% CI: 1.33, 3.14) for head injury that occurred before age 18, 1.39 (95% CI: 0.81, 2.36) for head injury between ages 18-<30, and 1.04 (95% CI: 0.58, 1.87) for head injury that occurred at age 30 or older (P for trend = 0.001). Exploratory interaction analyses showed a significant interaction between head injury and a SNP at the RBMS3 locus (rs10510622, uncorrected P = 0.0001). No interaction was found with GWAS tag SNPs at or near the MAPT, SNCA, LRRK2, and HLA loci.

CONCLUSION:

Our study suggests that head injury early in life may be an important risk factor for PD. The potential interaction with RBMS3 needs confirmation.

Wednesday, 21 January 2015

Saliva α-Synuclein and A High Extinction Coefficient Protein: A Novel Approach in Assessment Biomarkers of Parkinson's Disease

N Am J Med Sci. 2014 Dec;6(12):633-7. doi: 10.4103/1947-2714.147980.
Al-Nimer MS, Mshatat SF, Abdulla HI.

BACKGROUND:
The pathological hallmark of Parkinson's disease (PD) is the appearance of intracytoplasmic inclusions known as Lewy bodies in which its principal component is α-synuclein.

AIM:
This study aimed to determine salivary α-synuclein and the extinction coefficient of the saliva protein as biomarkers of PD.

MATERIALS AND METHODS:
This observational study was done in Department of Pharmacology, College of Medicine in cooperation with Department of Oral Medicine, College of Dentistry at Al-Mustansiriya University in Baghdad, Iraq from September 2013 to March 2014. A total number of 20 PD patients and 20 healthy subjects were enrolled in the study. Unstimulated saliva obtained from each participant obtained for determination of salivary flow rate, saliva protein and α-synuclein using enzyme linked immune sorbent assay (ELISA) technique.

RESULTS:
Total saliva protein and uncontaminated protein with nucleic acids are significantly higher in PD compared with healthy subjects. The mean extinction coefficient of that protein is 27.25 M.cm(-1) which significantly (P < 0.001) less than corresponding value of healthy subjects (33.48 M.cm(-1) ). Saliva α-synuclein level is significantly less in PD (65 ± 52.2 pg/ml) than healthy subjects (314.01 ± 435.9 pg/ml).

CONCLUSIONS:

We conclude that saliva α-synuclein serves as a biomarker for PD if its level compared with healthy subjects, and a specific protein with extinction coefficient 27.25 M.cm-1 is detected in saliva of Parkinson's patients.

Monday, 19 January 2015

Colonic mucosal α-synuclein lacks specificity as a biomarker for Parkinson disease

An important observation in light of the huge amount of research that is going on in this area right now...

Neurology. 2015 Jan 14. pii: 10.1212/WNL.0000000000001240. [Epub ahead of print]
Visanji NP, Marras C, Kern DS, Al Dakheel A, Gao A, Liu LW, Lang AE, Hazrati LN.

OBJECTIVE:
To determine the utility of detecting α-synuclein (αSyn) in colonic mucosal biopsy tissue as a potential diagnostic biomarker for Parkinson disease (PD).

METHODS:
We used the paraffin-embedded tissue (PET) blot, which degrades physiologic nonaggregated αSyn using proteinase K and enhances antigen retrieval allowing sensitive and selective detection of remaining protein aggregates, to detect αSyn in colonic mucosal biopsies from 15 patients with early PD (<3 years), 7 patients with later PD (>5 years), and 11 individuals without PD. αSyn and serine 129-phosphorylated αSyn (Ser129p-αSyn) were assessed by PET blot and conventional immunohistochemistry.

RESULTS:
PET blot-resistant aggregated αSyn and Ser129p-αSyn was present in 12 of 15 individuals with early PD, 7 of 7 individuals with later PD, and 11 of 11 control subjects. The number of biopsies positive by PET blot relative to conventional immunohistochemistry was significantly lower in both PD groups compared with the control group for both αSyn and Ser129p-αSyn, whereas routine immunohistochemistry was positive more often in PD, but was positive in as many as 9 of 11 control individuals.

CONCLUSION:

Strong evidence of the presence of aggregated hyperphosphorylated αSyn in individuals with and without PD, using such a sensitive and specific method as the PET blot, suggests that colonic deposition of αSyn is not a useful diagnostic test for PD. The utility of detecting αSyn in the colon as a biomarker in combination with other assessments remains to be determined.

Sunday, 18 January 2015

A panel of nine cerebrospinal fluid biomarkers may identify patients with atypical parkinsonian syndromes.

Good bit of CSF biomarker research from my good friend and colleague...


J Neurol Neurosurg Psychiatry. 2015 Jan 14. pii: jnnp-2014-309562. doi: 10.1136/jnnp-2014-309562. [Epub ahead of print]
Magdalinou NK, Paterson RW, Schott JM, Fox NC, Mummery C, Blennow K, Bhatia K, Morris HR, Giunti P, Warner TT, de Silva R, Lees AJ, Zetterberg H.

BACKGROUND:
Patients presenting with parkinsonian syndromes share many clinical features, which can make diagnosis difficult. This is important as atypical parkinsonian syndromes (APSs) such as progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and corticobasal syndrome (CBS) carry a poor prognosis, compared with patients with Parkinson's disease (PD). In addition, there is overlap between APS and dementia diseases, such as Alzheimer's disease (AD) and frontotemporal dementia (FTD).

OBJECTIVE:
To use a panel of cerebrospinal fluid (CSF) biomarkers to differentiate patients with APS from PD and dementia.

METHODS:
A prospective cohort of 160 patients and 30 control participants were recruited from a single specialist centre. Patients were clinically diagnosed according to current consensus criteria. CSF samples were obtained from patients with clinical diagnoses of PD (n=31), PSP (n=33), CBS (n=14), MSA (n=31), AD (n=26) and FTD (n=16). Healthy, elderly participants (n=30) were included as controls. Total τ (t-τ), phosphorylated τ (p-τ), β-amyloid 1-42 (Aβ42), neurofilament light chain (NFL), α-synuclein (α-syn), amyloid precursor protein soluble metabolites α and β (soluble amyloid precursor protein (sAPP)α, sAPPβ) and two neuroinflammatory markers (monocyte chemoattractant protein-1 and YKL-40) were measured in CSF. A reverse stepwise regression analysis and the false discovery rate procedure were used.

RESULTS:
CSF NFL (p<0.001), sAPPα (p<0.001) and a-syn (p=0.003) independently predicted diagnosis of PD versus APS. Together, these nine biomarkers could differentiate patients with PD from APS with an area under the curve of 0.95 and subtypes of APS from one another. There was good discriminatory power between parkinsonian groups, dementia disorders and healthy controls.

CONCLUSIONS:

A panel of nine CSF biomarkers was able to differentiate APS from patients with PD and dementia. This may have important clinical utility in improving diagnostic accuracy, allowing better prognostication and earlier access to potential disease-modifying therapies.

Saturday, 17 January 2015

Systematic review and meta-analysis of hydrocarbon exposure and the risk of Parkinson's disease


Parkinsonism Relat Disord. 2014 Dec 26. pii: S1353-8020(14)00491-X. doi: 10.1016/j.parkreldis.2014.12.017. [Epub ahead of print]
Palin O, Herd C, Morrison KE, Jagielski AC, Wheatley K, Thomas GN, Clarke CE.

BACKGROUND:
There is no consensus on the association between exposure to hydrocarbons and the risk of Parkinson's disease (PD). We conducted a systematic review and meta-analysis to summarise the epidemiological evidence and included a new large case-control study.

METHODS:
Data were extracted following a predefined protocol. Risk estimates regarding the association between hydrocarbon exposure and PD were consolidated to produce a summary odds ratio (OR), 95% confidence intervals (CI), and p-value. In our case-control study, 1463 PD patients and 685 controls were recruited from clinical trials and completed a structured questionnaire describing their previous working exposure to hydrocarbons and other demographic measures. The association between exposure to hydrocarbons and risk of PD was evaluated using logistic regression.

RESULTS:
The systematic search identified 13 case-control studies matching the inclusion criteria. The meta-analysis included 3020 PD cases and 6494 controls. The summary OR was 1.32 (95% CI 1.08-1.62, p = 0.006) for hydrocarbon exposure (ever versus never). In the PD GEN study, occupational exposure to hydrocarbons significantly increased the risk of PD (OR = 1.61; 95% CI 1.10-2.36, p = 0.014), and risk dose-dependently increased for subjects exposed greater than 10 years compared to subjects never exposed (OR = 2.19; 95% CI 1.13-4.26, p = 0.021). The addition of PD GEN data increased the total numbers to 4483 PD cases and 7179 controls and strengthened the significant association (summary OR = 1.36; 95% CI 1.13-1.63, p = 0.001).

CONCLUSIONS:

This systematic review supports a positive association between hydrocarbon exposure and PD. Data from prospective studies are required to reinforce the relationship between hydrocarbon exposure and PD.

Friday, 16 January 2015

Alpha-synuclein biology in Lewy body diseases

http://alzres.com/content/6/5/73

Alzheimers Res Ther. 2014 Oct 27;6(5):73. doi: 10.1186/s13195-014-0073-2. eCollection 2014.
Kim WS, Kågedal K, Halliday GM.

Abstract

α-Synuclein is an abundantly expressed neuronal protein that is at the center of focus in understanding a group of neurodegenerative disorders called α-synucleinopathies, which are characterized by the presence of aggregated α-synuclein intracellularly. Primary α-synucleinopathies include Parkinson's disease (PD), dementia with Lewy bodies and multiple system atrophy, with α-synuclein also found secondarily in a number of other diseases, including Alzheimer's disease. Understanding how α-synuclein aggregates form in these different disorders is important for the understanding of its pathogenesis in Lewy body diseases. PD is the most prevalent of the α-synucleinopathies and much of the initial research on α-synuclein Lewy body pathology was based on PD but is also relevant to Lewy bodies in other diseases (dementia with Lewy bodies and Alzheimer's disease). Polymorphism and mutation studies of SNCA, the gene that encodes α-synuclein, provide much evidence for a causal link between α-synuclein and PD. Among the primary α-synucleinopathies, multiple system atrophy is unique in that α-synuclein deposition occurs in oligodendrocytes rather than neurons. It is unclear whether α-synuclein originates from oligodendrocytes or whether it is transmitted somehow from neurons. α-Synuclein exists as a natively unfolded monomer in the cytosol, but in the presence of lipid membranes it is thought to undergo a conformational change to a folded α-helical secondary structure that is prone to forming dimers and oligomers. Posttranslational modification of α-synuclein, such as phosphorylation, ubiquitination and nitration, has been widely implicated in α-synuclein aggregation process and neurotoxicity. Recent studies using animal and cell models, as well as autopsy studies of patients with neuron transplants, provided compelling evidence for prion-like propagation of α-synuclein. This observation has implications for therapeutic strategies, and much recent effort is focused on developing antibodies that target extracellular α-synuclein.

Thursday, 15 January 2015

Predictors for mild parkinsonian signs: A prospective population-based study

http://www.prd-journal.com/article/S1353-8020(14)00495-7/abstract

Parkinsonism Relat Disord. 2014 Dec 31. pii: S1353-8020(14)00495-7. doi: 10.1016/j.parkreldis.2014.12.021. [Epub ahead of print]
Mahlknecht P, Kiechl S, Stockner H, Willeit J, Gasperi A, Poewe W, Seppi K.

OBJECTIVE:
Mild parkinsonian signs (MPS) are common in the elderly population and are associated with a wide range of adverse health outcomes, including incident Parkinson's disease (PD). We aimed to prospectively evaluate potential risk factors for incident MPS.

METHODS:
Participants of the population-based Bruneck Study representative for the general elderly community underwent a baseline assessment of substantia nigra (SN)-echogenicity with transcranial sonography, olfactory function with the Sniffin' Sticks identification test and vascular risk according to the Framingham risk score as well as a baseline and 5-year follow-up neurological examination. MPS were defined according to established criteria based on the entire motor section of the Unified PD Rating Scale. Participants with PD at baseline or follow-up and subjects with MPS at baseline were excluded. A logistic regression analysis adjusted for age and sex was used to detect risk factors for incident MPS in the remaining 393 participants.

RESULTS:
SN-hyperechogenicity and hyposmia were related to the development of MPS with odds ratios of 2.0 (95%CI, 1.1-3.7) and 1.6 (95%CI, 1.0-2.7), respectively, while increased vascular risk was not. Having both, SN-hyperechogenicity and hyposmia, was associated with an odds ratio of 3.0 (95%CI, 1.2-7.7) for incident MPS. Among the various motor domains, increased SN-echogenicity predicted the development of bradykinesia and rigidity, whereas diminished olfactory function predicted the development of impaired axial motor function.

CONCLUSIONS:

In addition to their established roles as risk factors for PD, SN-hyperechogenicity and hyposmia are associated with an increased risk for MPS in the general elderly community.

Monday, 12 January 2015

Google Glass for Parkinson’s disease: benefits and drawbacks

WHAT IS GOOGLE GLASS
Google Glass is a wearable technology that looks like a set of designer glasses. It was developed by Google and works in the same way as a smart-phone, displaying information on its lens. However the difference is it is mostly voice-operated, which makes it easier to use- compared to a touch-screen- for Parkinson’s patients experiencing tremor and “off” periods of medication.

HOW CAN GLASS HELP WITH PARKINSON’S
For now researchers have focused on two aspects of Parkinson’s that Glass might be useful with: preventing gait disturbances and enabling patients to live more independently.
In 2013 researchers in the Netherlands from the University of Twente have started developing new apps to improve the gait and prevent falls in patients with Parkinson’s. It is already established that the gait of patients improves with regular visualisation and/or hearing of a pattern. Technology such as Google Glass can be used to provide visual overlays, in form of shapes or stripes that the person would see through the glasses or patters of music, which they would hear through the device’s earphone.
In UK in 2014, doctors at Newcastle University started looking at how the Google Glass technology can be used to help control behaviours associated with Parkinson’s. The idea is that the device can be used to provide discrete prompts such as to swallow in order to prevent drooling and to speak up when people’s voice and volume gets affected by the disease. In addition, the device could also be used as a reminder about when exactly to take the different medications during the day. Researchers are also taking on the work done by scientists in the Netherlands and exploring how Glass’s motion sensors can help patients experiencing “freezing”, the blocking of movement which is a common symptom in Parkinson’s disease.

WHAT ARE GLASS’S SHORTCOMINGS FOR PARKINSON’S DISEASE USERS
As mentioned earlier, people suffering of Parkinson’s experience alteration to their voice, therefore it is felt that the Glass voice recognition system needs improvement. "The fact that it wasn't recognising what I wanted was very irritating and very frustrating," said one of the Newcastle study participants.
Patients also had trouble with navigation gestures, a mixture of tapping on the device’s side and swiping to navigate the menus.
Lastly a drawback of Google Glass
 is that it stands out: participants of the study felt that members of the public had various reaction to the device, which varied from some not noticing it to others starting suspiciously at the Glass user as if they were up to something bad.

CONCLUSION
Google Glass is a device with a lot of potential for being a tool to help people with Parkinson’s disease, however to make the most of this technology researchers need to continue working in partnership with people living with the condition. Only they can give valuable feedback to the researchers as to what needs working on to meaningfully improve their lives.

 View the full press release from University of Newcastle here

Saturday, 10 January 2015

The prevalence of Parkinson's disease ontinues to rise after 80 years of age: a cross-sectional study of Chinese veterans.


Eur Rev Med Pharmacol Sci. 2014 Dec;18(24):3908-15.
Zou YM, Tan JP, Li N, Yang JS, Yu BC, Yu JM, Du W, Zhang WJ, Cui LQ, Wang QS, Xia XN, Li JJ, Zhou PY, Zhang BH, Liu ZY, Zhang SG, Sun LY, Liu N, Deng RX, Ma LH, Chen WJ, Zhang YQ, Liu J, Zhang SM, Lan XY, Zhao YM, Wang LN.

OBJECTIVE:
The purpose of this study was to examine whether the prevalence of Parkinson's disease (PD) continues to rise after 80 years of age.

METHODS:
This is a two-stage, multi-center, cross-sectional study using a stratified cluster sampling approach was employed. Subjects included veterans at ≥ 60 years of age living in veterans' communities for at least one month in 18 major cities across China. In the first step, possible PD was screened using a PD screening scale. Demographic and relevant information were collected. In the second step, PD diagnosis was established using the United Kingdom Parkinson's Disease Society Brain Bank (UKPDSBB) diagnostic criteria.

RESULTS:
The study was conducted during the period from December 2009 to December 2012. The study included 277 veterans' communities. Among the approached 11,593 subjects, 9676 subjects, (9096 men, 580 women) responded. The response rate was 83.46%.The age was ≥ 80 years in 6722 (69.47%) subjects. A diagnosis of PD was established in 228 subjects (2.36%) in the entire sample. The rate of PD was 2.65% in those with an age of ≥ 80 years. The rate of PD increased with increasing age (0%, 1.84%, 2.60% and 3.68% in the subjects at < 70, 70-79, 80-89 and ≥ 90 years of age, respectively; χ2 = 10.891, p = 0.001 in chi-square test). The rate of PD was higher in men (2.44%) than in women (1.46%) on the surface. However, no significant difference was detected (p = 0.241).

CONCLUSIONS:

The prevalence of PD continues to increase beyond the age of 80 years. The prevalence of PD in Chinese veterans is not lower than that in other countries and regions.

Friday, 9 January 2015

My talk at the Royal Institution London November 2014


Helicobacter pylori infection is associated with worse severity of Parkinson's disease


Parkinsonism Relat Disord. 2014 Dec 18. pii: S1353-8020(14)00483-0. doi: 10.1016/j.parkreldis.2014.12.009. [Epub ahead of print]
Tan AH, Mahadeva S, Marras C, Thalha AM, Kiew CK, Yeat CM, Ng SW, Ang SP, Chow SK, Loke MF, Vadivelu JS, Ibrahim N, Yong HS, Tan CT, Fox SH, Lang AE, Lim S.

BACKGROUND:
Some studies have suggested that chronic Helicobacter pylori (HP) infection can aggravate the neurodegenerative process in Parkinson's disease (PD), and targeted intervention could potentially modify the course of this disabling disease. We aimed to study the impact of HP infection on motor function, gastrointestinal symptoms, and quality of life in a large cohort of PD patients.

METHODS:
102 consecutive PD patients underwent 13C urea breath testing and blinded evaluations consisting of the Unified Parkinson's Disease Rating Scale (UPDRS) including "On"-medication motor examination (Part III), objective and quantitative measures of bradykinesia (Purdue Pegboard and timed gait), Leeds Dyspepsia Questionnaire, and PDQ-39 (a health-related quality of life questionnaire).

RESULTS:
32.4% of PD patients were HP-positive. HP-positive patients were older (68.4 ± 7.3 vs. 63.8 ± 8.6 years, P = 0.009) and had worse motor function (UPDRS Part III 34.0 ± 13.0 vs. 27.3 ± 10.0, P = 0.04; Pegboard 6.4 ± 3.3 vs. 8.0 ± 2.7 pins, P = 0.04; and timed gait 25.1 ± 25.4 vs. 15.5 ± 7.6 s, P = 0.08). In the multivariate analysis, HP status demonstrated significant main effects on UPDRS Part III and timed gait. The association between HP status and these motor outcomes varied according to age. Gastrointestinal symptoms and PDQ-39 Summary Index scores did not differ between the two groups.

CONCLUSIONS:

This is the largest cross-sectional study to demonstrate an association between HP positivity and worse PD motor severity.

Thursday, 8 January 2015

Alpha-synuclein spreading in Parkinson's disease


Front Neuroanat. 2014 Dec 18;8:159. eCollection 2014.
Recasens A, Dehay B


Formation and accumulation of misfolded protein aggregates are a central hallmark of several neurodegenerative diseases. In Parkinson's disease (PD), the aggregation-prone protein alpha-synuclein (α-syn) is the culprit. In the past few years, another piece of the puzzle has been added with data suggesting that α-syn may self-propagate, thereby contributing to the progression and extension of PD. Of particular importance, it was the seminal observation of Lewy bodies (LB), a histopathological signature of PD, in grafted fetal dopaminergic neurons in the striatum of PD patients. Consequently, these findings were a conceptual breakthrough, generating the "host to graft transmission" hypothesis, also called the "prion-like hypothesis." Several in vitro and in vivo studies suggest that α-syn can undergo a toxic templated conformational change, spread from cell to cell and from region to region, and initiate the formation of "LB-like aggregates," contributing to the PD pathogenesis. Here, we will review and discuss the current knowledge for such a putative mechanism on the prion-like nature of α-syn, and discuss about the proper use of the term prion-like.

Sunday, 4 January 2015

Olfactory dysfunction in Parkinson's disease: Positive effect of cigarette smoking.

Now this is interesting stuff...heard Prof Doty speak on this topic in 2014


Mov Disord. 2014 Dec 27. doi: 10.1002/mds.26126. [Epub ahead of print]
Sharer JD, Leon-Sarmiento FE, Morley JF, Weintraub D, Doty RL.

BACKGROUND:
There is compelling evidence from over 60 epidemiological studies that smoking significantly reduces the risk of Parkinson's disease (PD). In general, those who currently smoke cigarettes, as well as those with a past history of such smoking, have a reduced risk of PD compared to those who have never smoked. Recently it has been suggested that a cardinal nonmotor sensory symptom of PD, olfactory dysfunction, may be less severe in PD patients who smoke than in PD patients who do not, in contrast to the negative effect of smoking on olfaction described in the general population.

METHODS:
We evaluated University of Pennsylvania Smell Identification Test (UPSIT) scores from 323 PD patients and 323 controls closely matched individually on age, sex, and smoking history (never, past, or current).

RESULTS:
Patients exhibited much lower UPSIT scores than did the controls (P < 0.0001). The relative decline in dysfunction of the current PD smokers was less than that of the never- and past-PD smokers (respective Ps = 0.0005 and 0.0019). Female PD patients outperformed their male counterparts by a larger margin than did the female controls (3.66 vs. 1.07 UPSIT points; respective Ps < 0.0001 and 0.06). Age-related declines in UPSIT scores were generally present (P < 0.0001). No association between the olfactory measure and smoking dose, as indexed by pack-years, was evident.

CONCLUSIONS:

PD patients who currently smoke do not exhibit the smoking-related decline in olfaction observed in non-PD control subjects who currently smoke. The physiological basis of this phenomenon is yet to be defined.

Saturday, 3 January 2015

The significance of motor (A)symmetry in Parkinson's disease.


Mov Disord. 2014 Dec 27. doi: 10.1002/mds.26107. [Epub ahead of print]
Marinus J, van Hilten JJ.


This study was undertaken to evaluate whether the predominant motor distribution pattern (ie, symmetric or asymmetric) observed in patients with Parkinson's disease (PD) contributes independently to disease severity and progression. We further examine whether this pattern is stable over time, and whether a potential change in pattern affects the course of the disease. We used data from the longitudinal PROPARK study (N > 400) to examine the association of the predominant motor distribution pattern with motor, cognitive, depressive, psychotic, and autonomic symptoms, and with excessive daytime sleepiness. We found that a symmetrical distribution of motor features was associated with poorer performance on nearly all domains, but that this was entirely explained by confounding, in particular by higher age and longer disease duration. We also found that greater asymmetry was associated with younger age, younger age at onset, and shorter disease duration. We further observed a clear tendency to develop a more symmetric distribution pattern as the disease advanced. Conversion to a symmetric pattern was associated with more severe disease, but this conversion did not contribute independently to the less favorable disease course. With increasing age and disease duration comes a clear tendency to develop a more symmetric distribution of motor features in PD. Although this change in distribution pattern is associated with more severe disease as compared with nonconvertors, this pattern change did not contribute independently to the less favorable course. We discuss these findings in light of the evidence from the literature.

Friday, 2 January 2015

Quitting smoking: An early non-motor feature of Parkinson's disease?

I am surprised by this even if I agree with some of the conclusions. There are a number of studies that have looked at former versus never smoking prior to PD diagnosis (despite what's stated here) but they generally suggest a weaker negative effect than for current smoking, not a positive association. In conclusion...reverse causality...very likely

http://www.sciencedirect.com/science/article/pii/S1353802014004805

Parkinsonism Relat Disord. 2014 Dec 17. pii: S1353-8020(14)00480-5. doi: 10.1016/j.parkreldis.2014.12.008. [Epub ahead of print]
Moccia M, Erro R, Picillo M, Vassallo E, Vitale C, Longo K, Amboni M, Santangelo G, Palladino R, Nardone A, Triassi M, Barone P, Pellecchia MT.

INTRODUCTION:
Epidemiological studies report a 60-70% reduced risk of Parkinson's disease (PD) in smokers as compared to non-smokers. However, relationships between former smoking and PD have been poorly investigated.

METHODS:
We recruited 116 de novo PD subjects, and investigated current, former and never smoking, and reasons for smoking cessation among former smokers. Two hundred and thirty-two controls were matched by Propensity Score.

RESULTS:
PD subjects and controls were found to be current smokers (7.7 vs. 39.6%), former smokers (43.9 vs. 6.5%) and never smokers (48.2 vs. 53.9%). Logistic regression showed that current smokers were less likely to have PD (p < 0.001; OR: 0.22; 95% CI: 0.10-0.46), while former smokers were more likely to have PD (p < 0.001; OR: 7.6; 95% CI: 4.09-15.75), as compared to never smokers. Fifty-one PD patients reported quitting smoking before PD diagnosis (mean time since cessation 9.4 ± 7.3 years). Most important reasons to quit smoking in PD group were illness different from PD (26 subjects, 51.0%), knowledge of the harmful effects of smoking (24 subjects, 47.0%), and physician's advice (1 subject, 2.0%).

CONCLUSION:

The reduced prevalence of current smokers among PD subjects as compared to healthy controls is consistent with previous findings, suggesting a possible neuroprotective effect of smoking. However, it could be due, at least in part, to the increased prevalence of former smokers among PD patients, that were more prone to quit smoking as compared to healthy controls. We suggest that smoking cessation could be an early preclinical condition occurring in PD.

Thursday, 1 January 2015

Increased Risk of Depression in Patients with Parkinson Disease: A Nationwide Cohort Study

Not sure I agree fully with the conclusion, the effect size looks similar to me...

Am J Geriatr Psychiatry. 2014 Nov 6. pii: S1064-7481(14)00327-3. doi: 10.1016/j.jagp.2014.10.011. [Epub ahead of print]
Hsu Y, Liao C, Chang S, Yang Y, Tsai C, Chen T, Sung F.

OBJECTIVE:
The association between Parkinson disease (PD) and depression remains unclear, particularly in the Asian population. The purpose of this study is to investigate the risk of depression in patients with PD using population-based data.

METHODS:
Based on the National Health Insurance Research Database of Taiwan, we identified 1,698 patients with PD aged 40 years or older diagnosed in 2000-2003. With frequency matching procedure, we randomly selected 6,792 subjects without PD stratified by sex and age. Both cohorts were followed until the end of 2008 or diagnosis of depression. Risk of depression associated with PD was estimated in the multivariate Cox hazards regressions. Diabetes, hypertension, and hyperlipidemia were more prevalent at baseline in patients with PD.

RESULTS:
Compared with the cohort without PD, the hazard ratio (HR) for depression in PD patients was 4.06 (95% CI: 3.15-5.23), which increased to 4.26 (95% CI: 3.29-5.51) after adjustment for age, sex, urbanization, income, and coexisting medical conditions. In the sex stratification, the HR of depression for men with PD was 4.42 (95% CI: 2.93-6.67) compared with men without PD. The HR for the association between PD and depression in women was 4.22 (95% CI: 3.02-5.88).

CONCLUSION:

This study suggests that patients with PD are at an elevated risk of depression, particularly for men. Integrated care for early identification and treatment of depression are crucial for patients with PD.