Scan without evidence of dopaminergic deficit: A 10-year retrospective study

I have often wondered about this and interested by the result... I tend to agree... the term SWEDD is confusing enough for doctors... it is not a fair diagnosis to put on a patient and should be avoided...

Parkinsonism Relat Disord. 2016 Jul 7. pii: S1353-8020(16)30245-0. doi: 10.1016/j.parkreldis.2016.07.002. [Epub ahead of print]

Nicastro N, Garibotto V, Badoud S, Burkhard PR.

http://www.sciencedirect.com/science/article/pii/S1353802016302450

INTRODUCTION:

123I-ioflupane SPECT is a powerful method to assess nigrostriatal dopamine system integrity. Several independent studies have shown that 1-15% of patients with suspected degenerative parkinsonism, mainly PD, have scans without evidence of dopaminergic deficit (SWEDD). It has been proposed that most SWEDD patients either present with a non-degenerative condition mimicking PD, such as atypical tremor or dystonia, or demonstrate an abnormal scan when repeated later. We here hypothesized that scan interpretation methods may also play a crucial yet underestimated role in this issue.

METHODS:

We previously established age-dependent reference values of striatal uptake by analyzing scans from a cohort of patients with non-degenerative conditions. We then studied a large population with well-established degenerative parkinsonism (N = 410, 80% with PD), using identical imaging protocol, to evaluate the prevalence of patients with normal scans based on routine visual assessment. Each scan was eventually reassessed using the same automated method as for controls and a detailed 3D analysis.

RESULTS:

Ten potential SWEDD cases (2.4%) were identified. However, both reassessment methods independently showed that these scans were all outside reference limits and/or visually abnormal when reexamined carefully, except for one case (0.2%) with corticobasal syndrome.

CONCLUSION:

SPECT misinterpretation emerges as an important contributor to the SWEDD population, suggesting that suspected SWEDD cases should prompt not only a serious diagnosis challenge but, equally important, a detailed scan reassessment. True SWEDD cases seem extremely rare in degenerative parkinsonism. We propose that the very concept of SWEDD is more confusing than helpful and should be definitely abandoned.

Copyright © 2016 Elsevier Ltd. All rights reserved.

Functional MRI of disease progression in Parkinson disease and atypical parkinsonian syndromes

I confess I do not know an awful lot about fMRI but I assume that the regions of activity depend largely on the task performed... still this is an encouraging result because progression can be demonstrated and there are specific patterns for other parkinsonian syndromes...

Neurology. 2016 Jul 15. pii: 10.1212/WNL.0000000000002985. [Epub ahead of print]

Burciu RG, Chung JW, Shukla P, Ofori E, Li H, McFarland NR, Okun MS, Vaillancourt DE.

http://www.neurology.org/content/early/2016/07/15/WNL.0000000000002985.long

OBJECTIVE:

To explore longitudinal changes in brain activity in patients with Parkinson disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) using task-based functional MRI (fMRI).

METHODS:

A total of 112 individuals were scanned 1 year apart while performing a unimanual grip force task: 46 PD, 13 MSA, 19 PSP, and 34 healthy controls. The outcome measure was percent signal change in prespecified regions of interest: putamen, primary motor cortex (M1), supplementary motor area (SMA), and superior motor regions of the cerebellum (lobules V-VI).

RESULTS:

Patients with PD showed a decline in functional activity over the course of 1 year in the putamen and M1 compared to controls. Changes after 1 year in MSA were exclusively extrastriatal, and included a reduction in functional activity in M1, SMA, and superior cerebellum. In PSP, all regions of interest were less active at 1 year compared to baseline. The functional activity of these regions did not change in the control group.

CONCLUSIONS:

We provide evidence using task-based fMRI for cortical and striatal functional deterioration in PD over a 1-year period of time. Results also describe more widespread and unique patterns of functional changes in MSA and PSP compared to PD, suggesting distinct rates of disease progression in parkinsonian disorders that may assist in future clinical studies testing the potential efficacy of disease-modifying therapies.

Constipation: an emerging risk factor for Parkinson's disease?

I am not sure about emerging... I would argue that constipation is well established risk factor for PD... so much so that we published a meta-analysis on it last year that included 10 separate studies. The question is how to measure it and what is the mechanistic basis???

Eur J Neurol. 2016 Jul 22. doi: 10.1111/ene.13082. [Epub ahead of print]

Stirpe P, Hoffman M, Badiali D, Colosimo C.

http://onlinelibrary.wiley.com/doi/10.1111/ene.13082/abstract;jsessionid=3CC9E454038FAA56A76E44941FE74C09.f02t02?systemMessage=Wiley+Online+Library+will+be+unavailable+on+Saturday+30th+July+2016+from+08%3A00-11%3A00+BST+%2F+03%3A00-06%3A00+EST+%2F+15%3A00-18%3A00+SGT+for+essential+maintenance.Apologies+for+the+inconvenience.

Constipation is the most prominent and disabling manifestation of lower gastrointestinal (GI) dysfunction in Parkinson's disease (PD). The prevalence of constipation in PD patients ranges from 24.6% to 63%; this variability is due to the different criteria used to define constipation and to the type of population enrolled in the studies. In addition, constipation may play an active role in the pathophysiological changes that underlie motor fluctuations in advanced PD through its negative effects on absorption of levodopa. Several clinical studies now consistently suggest that constipation may precede the first occurrence of classical motor features in PD. Studies in vivo, using biopsies of the GI tract and more recently functional imaging investigations, showed the presence of α-synuclein (α-SYN) aggregates and neurotransmitter alterations in enteric tissues. All these findings support the Braak proposed model for the pathophysiology of α-SYN aggregates in PD, with early pathological involvement of the enteric nervous system and dorsal motor nucleus of the vagus. Therefore, constipation could have the potential sensitivity to be used as a clinical biomarker of the prodromal phase of the disease. The use of colonic biopsies to look at α-SYN pathology, once confirmed by larger prospective studies, might eventually represent a feasible, albeit partially invasive, new diagnostic biomarker for PD.

Prodromal Markers in Parkinson's Disease: Limitations in Longitudinal Studies and Lessons Learned

As with everything, unless you know where you have been in the past, it's hard to know which way to go in the future... a coordinated approach is needed...

Front Aging Neurosci. 2016 Jun 22;8:147. doi: 10.3389/fnagi.2016.00147. eCollection 2016.

Heinzel S, Roeben B, Ben-Shlomo Y, Lerche S, Alves G, Barone P, Behnke S, Berendse HW, Bloem BR, Burn D, Dodel R, Grosset DG, Hu M, Kasten M, Krüger R, Moccia M, Mollenhauer B, Oertel W, Suenkel U, Walter U, Wirdefeldt K, Liepelt-Scarfone I, Maetzler W, Berg D

http://journal.frontiersin.org/article/10.3389/fnagi.2016.00147/full

A growing body of evidence supports a prodromal neurodegenerative process preceding the clinical onset of Parkinson's disease (PD). Studies have identified several different prodromal markers that may have the potential to predict the conversion from healthy to clinical PD but use considerably different approaches. We systematically reviewed 35 longitudinal studies reporting prodromal PD features and evaluated the methodological quality across 10 different predefined domains. We found limitations in the following domains: PD diagnosis (57% of studies), prodromal marker assessments (51%), temporal information on prodromal markers or PD diagnosis (34%), generalizability of results (17%), statistical methods (accounting for at least age as confounder; 17%), study design (14%), and sample size (9%). However, no limitations regarding drop-out (or bias investigation), or report of inclusion/exclusion criteria or prodromal marker associations were revealed. Lessons learned from these limitations and additional aspects of current prodromal marker studies in PD are discussed to provide a basis for the evaluation of findings and the improvement of future research in prodromal PD. The observed heterogeneity of studies, limitations and analyses might be addressed in future longitudinal studies using a, yet to be established, modular minimal set of assessments improving comparability of findings and enabling data sharing and combined analyses across studies.

Arm swing as a potential new prodromal marker of Parkinson's disease.

I believe this... I think it is one of the earliest things to change...

Mov Disord. 2016 Jul 19. doi: 10.1002/mds.26720. [Epub ahead of print]

Mirelman A, Bernad-Elazari H, Thaler A, Giladi-Yacobi E, Gurevich T, Gana-Weisz M, Saunders-Pullman R, Raymond D, Doan N, Bressman SB, Marder KS, Alcalay RN, Rao AK, Berg D, Brockmann K, Aasly J, Waro BJ, Tolosa E, Vilas D, Pont-Sunyer C, Orr-Urtreger A, Hausdorff JM, Giladi N.

http://onlinelibrary.wiley.com/doi/10.1002/mds.26720/full

BACKGROUND:

Reduced arm swing is a well-known clinical feature of Parkinson's disease (PD), often observed early in the course of the disease. We hypothesized that subtle changes in arm swing and axial rotation may also be detectable in the prodromal phase.

OBJECTIVE:

The purpose of this study was to evaluate the relationship between the LRRK2-G2019S mutation, arm swing, and axial rotation in healthy nonmanifesting carriers and noncarriers of the G2019S mutation and in patients with PD.

METHODS:

A total of 380 participants (186 healthy nonmanifesting controls and 194 PD patients) from 6 clinical sites underwent gait analysis while wearing synchronized 3-axis body-fixed sensors on the lower back and bilateral wrists. Participants walked for 1 minute under the following 2 conditions: (1) usual walking and (2) dual-task walking. Arm swing amplitudes, asymmetry, variability, and smoothness were calculated for both arms along with measures of axial rotation.

RESULTS:

A total of 122 nonmanifesting participants and 67 PD patients were carriers of the G2019S mutation. Nonmanifesting mutation carriers walked with greater arm swing asymmetry and variability and lower axial rotation smoothness under the dual task condition when compared with noncarriers (P < .04). In the nonmanifesting mutation carriers, arm swing asymmetry was associated with gait variability under dual task (P = .003). PD carriers showed greater asymmetry and variability of movement than PD noncarriers, even after controlling for disease severity (P < .009).

CONCLUSIONS:

The G2019S mutation is associated with increased asymmetry and variability among nonmanifesting participants and patients with PD. Prospective studies should determine if arm swing asymmetry and axial rotation smoothness may be used as motor markers of prodromal PD.

New methods for the assessment of Parkinson's disease (2005 to 2015): A systematic review

Lots of reviews about tech to support people with PD at the moment, but this looks like one of the better ones... Alvaro knows what he is talking about...

Mov Disord. 2016 Jul 19. doi: 10.1002/mds.26723. [Epub ahead of print]

Sánchez-Ferro Á, Elshehabi M, Godinho C, Salkovic D, Hobert MA, Domingos J, van Uem JM, Ferreira JJ, Maetzler W.

http://onlinelibrary.wiley.com/doi/10.1002/mds.26723/abstract;jsessionid=D63177C8C1098212F4D33CB552045411.f02t03

BACKGROUND:

The past decade has witnessed a highly dynamic and growing expansion of novel methods aimed at improving the assessment of Parkinson's disease with technology (NAM-PD) in laboratory, clinical, and home environments. However, the current state of NAM-PD regarding their maturity, feasibility, and usefulness in assessing the main PD features has not been systematically evaluated.

METHODS:

A systematic review of articles published in the field from 2005 to 2015 was performed. Of 9,503 publications identified in PubMed and the Web of Science, 848 full papers were evaluated, and 588 original articles were assessed to evaluate the technological, demographic, clinimetric, and technology transfer readiness parameters of NAM-PD.

RESULTS:

Of the studies, 65% included fewer than 30 patients, < 50% employed a standard methodology to validate diagnostic tests, 8% confirmed their results in a different dataset, and 87% occurred in a clinic or lab. The axial features domain was the most frequently studied, followed by bradykinesia. Rigidity and nonmotor domains were rarely investigated. Only 6% of the systems reached a technology level that justified the hope of being included in clinical assessments in a useful time period.

CONCLUSIONS:

This systematic evaluation provides an overview of the current options for quantitative assessment of PD and what can be expected in the near future. There is a particular need for standardized and collaborative studies to confirm the results of preliminary initiatives, assess domains that are currently underinvestigated, and better validate the existing and upcoming NAM-PD. © 2016 International Parkinson and Movement Disorder Society.

© 2016 International Parkinson and Movement Disorder Society.

More Time with Tremor: The Experience of Essential Tremor Versus Parkinson's Disease Patients

It would be interesting to know how duration of tremor could be used to aid differentiation of these two disorders, in addition to the other characteristics of the tremor such as frequency, phase, symmetry etc...

Mov Disord Clin Pract. 2016 Jan-Feb;3(1):36-42. Epub 2015 Jul 14.

Louis ED.

BACKGROUND:

A broad range of tremors occur in patients with essential tremor and Parkinson's disease; despite this, there are virtually no published data that focus on the patient perspective. The aims were to (1) assess the subjective experience of tremor, comparing essential tremor and Parkinson's disease patients, and (2) assess the clinical correlates of that experience (i.e., what specific clinical characteristics were associated with more experienced tremor)?

METHODS:

121 essential tremor and 100 Parkinson's disease cases enrolled in a cross-sectional, clinical-epidemiological study underwent a detailed clinical assessment, which included a series of standardized questionnaires and neurological examination. The question, "On a typical day, how many waking hours do you have tremor in any body part?", was also administered.

RESULTS:

Essential tremor cases reported more than three times the median number of waking hours experiencing tremor than Parkinson's disease cases: 10.1 ± 7.8 (median 10.0) vs. 5.5 ± 6.3 (median 3.0) hours (p<0.001). A small number of cases (esp., essential tremor) reported spending ≥16 hours/day shaking. Greater number of hours experiencing tremor was associated with female gender, higher Center for Epidemiological Studies Depression Scale scores, greater perceived disability and, in essential tremor, higher Essential Tremor Embarrassment Assessment scores.

CONCLUSIONS:

Essential tremor patients reported more than three times the median number of waking hours experiencing tremor than Parkinson's disease patients. Certain clinical characteristics tracked with more reported tremor, and the number of such hours had clear clinical ramifications - greater number of hours was associated with both psycho-social and functional consequences.

Impulse control disorder related behaviours during long-term rotigotine treatment: a post hoc analysis

Within the limits of a post-hoc analysis of a clinical trial, it does appear that impulse control behaviours are substantially lower for the rotigotine patch compared with traditional oral dopamine agonists...

Eur J Neurol. 2016 Jul 18. doi: 10.1111/ene.13078. [Epub ahead of print]

Antonini A, Chaudhuri KR, Boroojerdi B, Asgharnejad M, Bauer L, Grieger F, Weintraub D.

BACKGROUND AND PURPOSE:

Dopamine agonists in Parkinson's disease (PD) are associated with impulse control disorders (ICDs) and other compulsive behaviours (together called ICD behaviours). The frequency of ICD behaviours reported as adverse events (AEs) in long-term studies of rotigotine transdermal patch in PD was evaluated.

METHODS:

This was a post hoc analysis of six open-label extension studies up to 6 years in duration. Analyses included patients treated with rotigotine for at least 6 months and administered the modified Minnesota Impulse Disorders Interview. ICD behaviours reported as AEs were identified and categorized.

RESULTS:

For 786 patients, the mean (±SD) exposure to rotigotine was 49.4 ± 17.6 months. 71 (9.0%) patients reported 106 ICD AEs cumulatively. Occurrence was similar across categories: 2.5% patients reported 'compulsive sexual behaviour', 2.3% 'buying disorder', 2.0% 'compulsive gambling', 1.7% 'compulsive eating' and 1.7% 'punding behaviour'. Examining at 6-month intervals, the incidence was relatively low during the first 30 months; it was higher over the next 30 months, peaking in the 54-60-month period. No ICD AEs were serious, and 97% were mild or moderate in intensity. Study discontinuation occurred in seven (9.9%) patients with ICD AEs; these then resolved in five patients. Dose reduction occurred for 23 AEs, with the majority (73.9%) resolving.

CONCLUSIONS:

In this analysis of >750 patients with PD treated with rotigotine, the frequency of ICD behaviour AEs was 9.0%, with a specific incidence timeline observed. Active surveillance as duration of treatment increases may help early identification and management; once ICD behaviours are present rotigotine dose reduction may be considered.

© 2016 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

Bee Venom for the Treatment of Parkinson Disease - A Randomized Controlled Clinical Trial

I confess I don't fully understand the rationale behind this study, but it seems that bee venom was suggested to be effective in some PD models prior to conducting the trial. It looks like the researchers will explore this potential therapy further...

PLoS One. 2016 Jul 12;11(7):e0158235. doi: 10.1371/journal.pone.0158235. eCollection 2016.

Hartmann A, Müllner J, Meier N, Hesekamp H, van Meerbeeck P, Habert MO, Kas A, Tanguy ML, Mazmanian M, Oya H, Abuaf N, Gaouar H, Salhi S, Charbonnier-Beaupel F, Fievet MH, Galanaud D, Arguillere S, Roze E, Degos B, Grabli D, Lacomblez L, Hubsch C, Vidailhet M, Bonnet AM, Corvol JC, Schüpbach M.

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0158235

In the present study, we examined the potential symptomatic and/or disease-modifying effects of monthly bee venom injections compared to placebo in moderately affected Parkinson disease patients. We conducted a prospective, randomized double-blind study in 40 Parkinson disease patients at Hoehn & Yahr stages 1.5 to 3 who were either assigned to monthly bee venom injections or equivalent volumes of saline (treatment/placebo group: n = 20/20). The primary objective of this study was to assess a potential symptomatic effect of s.c. bee venom injections (100 μg) compared to placebo 11 months after initiation of therapy on United Parkinson’s Disease Rating Scale (UPDRS) III scores in the « off » condition pre-and post-injection at a 60 minute interval. Secondary objectives included the evolution of UPDRS III scores over the study period and [123I]-FP-CIT scans to evaluate disease progression. Finally, safety was assessed by monitoring specific IgE against bee venom and skin tests when necessary. After an 11 month period of monthly administration, bee venom did not significantly decrease UPDRS III scores in the « off » condition. Also, UPDRS III scores over the study course, and nuclear imaging, did not differ significantly between treatment groups. Four patients were excluded during the trial due to positive skin tests but no systemic allergic reaction was recorded. After an initial increase, specific IgE against bee venom decreased in all patients completing the trial. This study did not evidence any clear symptomatic or disease-modifying effects of monthly bee venom injections over an 11 month period compared to placebo using a standard bee venom allergy desensitization protocol in Parkinson disease patients. However, bee venom administration appeared safe in non-allergic subjects. Thus, we suggest that higher administration frequency and possibly higher individual doses of bee venom may reveal its potency in treating Parkinson disease.

Newly Diagnosed Anemia Increases Risk of Parkinson's disease: A Population-Based Cohort Study

Not sure what to make of this association... particularly given that anaemia is so multi-factorial. Some types are nutrition-related, others due to occult bleeding. An important 3rd factor to consider here is restless legs syndrome. RLS is associated with anaemia and with PD - it would be important to see whether RLS is associated with PD after adjusting for anaemia, or whether anaemia is associated with PD after adjusting for RLS...

Sci Rep. 2016 Jul 14;6:29651. doi: 10.1038/srep29651.

Hong CT, Huang YH, Liu HY, Chiou HY, Chan L, Chien LN.

http://www.nature.com/articles/srep29651

Anemia and low hemoglobin have been identified to increase Parkinson's disease (PD) risk. This population-based cohort study investigated PD risk in newly diagnosed anemic patients by using data from the Taiwan National Health Insurance Research Database. All newly diagnosed anemic patients (n = 86,334) without a history of stroke, neurodegenerative diseases, traumatic brain injury, major operations, or blood loss diseases were enrolled. A cohort of nonanemic controls, 1:1 matched with anemic patients on the basis of the demographics and pre-existing medical conditions, was also included. Competing risk analysis was used to evaluate PD risk in anemic patients compared with that in their matched controls. The adjusted hazard ratio (aHR) of PD risk in the anemic patients was 1.36 (95% confidence interval [CI]: 1.22-1.52, p < 0.001). Iron deficiency anemia (IDA) patients tended to exhibit a higher PD risk (aHR: 1.49; 95% CI: 1.24-1.79, p < 0.001). Furthermore, Iron supplement did not significantly affect the PD risk: the aHRs for PD risk were 1.32 (95% CI: 1.07-1.63, p < 0.01) and 1.86 (95% CI: 1.46-2.35, p < 0.001) in IDA patients with and without iron supplementation, respectively. The population-based cohort study indicated newly diagnosed anemia increases PD risk.

Subtypes of mild cognitive impairment in patients with Parkinson's disease: evidence from the LANDSCAPE study

Important work exploring the features of mild cognitive impairment in Parkinson's disease...

J Neurol Neurosurg Psychiatry. 2016 Jul 8. pii: jnnp-2016-313838. doi: 10.1136/jnnp-2016-313838. [Epub ahead of print]

Kalbe E, Rehberg SP, Heber I, Kronenbuerger M, Schulz JB, Storch A, Linse K, Schneider C, Gräber S, Liepelt-Scarfone I, Berg D, Dams J, Balzer-Geldsetzer M, Hilker R, Oberschmidt C, Witt K, Schmidt N, Mollenhauer B, Trenkwalder C, Spottke A, Roeske S, Wittchen HU, Riedel O, Dodel R.

http://jnnp.bmj.com/content/early/2016/07/08/jnnp-2016-313838.long

OBJECTIVE:

Inconsistent results exist regarding the cognitive profile in patients with Parkinson's disease with mild cognitive impairment (PD-MCI). We aimed at providing data on this topic from a large cohort of patients with PD-MCI.

METHODS:

Sociodemographic, clinical and neuropsychological baseline data from patients with PD-MCI recruited in the multicentre, prospective, observational DEMPARK/LANDSCAPE study were analysed.

RESULTS:

269 patients with PD-MCI (age 67.8±7.4, Unified Parkinson's Disease Rating Scale (UPDRS-III) scores 23.2±11.6) were included. PD-MCI subtypes were 39.4% non-amnestic single domain, 30.5% amnestic multiple domain, 23.4% non-amnestic multiple domain and 6.7% amnestic single domain. Executive functions were most frequently impaired. The most sensitive tests to detect cognitive dysfunctions were the Modified Card Sorting Test, digit span backwards and word list learning direct recall. Multiple stepwise regression analyses showed that global cognition, gender and age, but not education or disease-related parameters predicted PD-MCI subtypes.

CONCLUSIONS:

This study with the so far largest number of prospectively recruited patients with PD-MCI indicates that non-amnestic PD-MCI is more frequent than amnestic PD-MCI; executive dysfunctions are the most typical cognitive symptom in PD-MCI; and age, gender and global cognition predict the PD-MCI subtype. Longitudinal data are needed to test the hypothesis that patients with PD-MCI with specific cognitive profiles have different risks to develop dementia.

Autophagic lysosome reformation dysfunction in glucocerebrosidase deficient cells: relevance to Parkinson Disease

Further insights into the molecular biology underpinning the relationship between GBA and PD...

Hum Mol Genet. 2016 Jul 4. pii: ddw185. [Epub ahead of print]

Magalhaes J, Gegg ME, Migdalska-Richards A, Doherty MK, Whitfield PD, Schapira AH.

Glucocerebrosidase (GBA1) gene mutations increase the risk of Parkinson disease (PD). While the cellular mechanisms associating GBA1 mutations and PD are unknown, loss of glucocerebrosidase enzyme (GCase) activity, inhibition of autophagy and increased α-synuclein levels have been implicated. Here we show that autophagy lysosomal reformation (ALR) is compromised in cells lacking functional GCase. ALR is a cellular process controlled by mTOR which regenerates functional lysosomes from autolysosomes formed during macroautophagy. A decrease in phopho-S6K levels, a marker of mTOR activity, was observed in models of GCase deficiency, including primary mouse neurons and PD patient derived fibroblasts with GBA1 mutations, suggesting that ALRis compromised. Importantly Rab7, a GTPase crucial for endosome-lysosome trafficking and ALR, accumulated in GCase deficient cells, supporting the notion that lysosomal recycling is impaired. Recombinant GCase treatment reversed ALR inhibition and lysosomal dysfunction. Moreover, ALR dysfunction was accompanied by impairment of macroautophagy and chaperone-mediated autophagy, increased levels of total and phosphorylated (S129) monomeric α-synuclein, evidence of amyloid oligomers and increased α-synuclein release. Concurrently, we found increased cholesterol and altered glucosylceramide homeostasis which could compromise ALR. We propose that GCase deficiency in PD inhibits lysosomal recycling. Consequently neurons are unable to maintain the pool of mature and functional lysosomes required for the autophagic clearance of α-synuclein, leading to the accumulation and spread of pathogenic α-synuclein species in the brain. Since GCase deficiency and lysosomal dysfunction occur in ageing and sporadic PD pathology, the decrease in lysosomal reformation may be a common feature in PD.

Transmission of Neurodegenerative Disorders Through Blood Transfusion: A Cohort Study

No evidence in this study that risk of neurodegenerative disease is higher in those that received blood transfusions from those that had a neurodegenerative disease...

Ann Intern Med. 2016 Jun 28. doi: 10.7326/M15-2421. [Epub ahead of print]

Edgren G, Hjalgrim H, Rostgaard K, Lambert P, Wikman A, Norda R, Titlestad KE, Erikstrup C, Ullum H, Melbye M, Busch MP, Nyrén O.

http://annals.org/article.aspx?articleid=2530857

BACKGROUND:

The aggregation of misfolded proteins in the brain occurs in several neurodegenerative disorders. Aberrant protein aggregation is inducible in rodents and primates by intracerebral inoculation. Possible transfusion transmission of neurodegenerative diseases has important public health implications.

OBJECTIVE:

To investigate possible transfusion transmission of neurodegenerative disorders.

DESIGN:

Retrospective cohort study.

SETTING:

Nationwide registers of transfusions in Sweden and Denmark.

PARTICIPANTS:

1 465 845 patients who received transfusions between 1968 and 2012.

MEASUREMENTS:

Multivariable Cox regression models were used to estimate hazard ratios for dementia of any type, Alzheimer disease, and Parkinson disease in patients receiving blood transfusions from donors who were later diagnosed with any of these diseases versus patients who received blood from healthy donors. Whether excess occurrence of neurodegenerative disease occurred among recipients of blood from a subset of donors was also investigated. As a positive control, transmission of chronic hepatitis before and after implementation of hepatitis C virus screening was assessed.

RESULTS:

Among included patients, 2.9% received a transfusion from a donor diagnosed with one of the studied neurodegenerative diseases. No evidence of transmission of any of these diseases was found, regardless of approach. The hazard ratio for dementia in recipients of blood from donors with dementia versus recipients of blood from healthy donors was 1.04 (95% CI, 0.99 to 1.09). Corresponding estimates for Alzheimer disease and Parkinson disease were 0.99 (CI, 0.85 to 1.15) and 0.94 (CI, 0.78 to 1.14), respectively. Hepatitis transmission was detected before but not after implementation of hepatitis C virus screening.

LIMITATION:

Observational study design, underascertainment of the outcome, and possible insufficient statistical power.

CONCLUSION:

The data provide no evidence for the transmission of neurodegenerative diseases and suggest that if transmission does occur, it is rare.

PRIMARY FUNDING SOURCE:

Swedish Research Council, Swedish Heart-Lung Foundation, Swedish Society for Medical Research, and Danish Council for Independent Research.

Meta-analysis of the association between serum iron levels and Parkinson's disease: Evidence from 11 publications

This is an interesting result... the only Mendelian Randomisation study in this area (by Pichler and colleagues) suggested an effect in the opposite direction i.e that elevated iron is protective against PD... with observational studies and PD it is always difficult to understand the nature of the association - cause or effect??

Brain Res. 2016 Jun 29. pii: S0006-8993(16)30467-X. doi: 10.1016/j.brainres.2016.06.044. [Epub ahead of print]

Jiao J, Guo H, He Y, Wang J, Yuan J, Hu W.

http://www.sciencedirect.com/science/article/pii/S000689931630467X

BACKGROUND:

There is no consensus on the serum iron levels and Parkinson's disease (PD). The aim of this study is to conduct a systematic review and meta-analysis to analyze the relationship between serum iron levels and PD risk.

METHODS:

We searched the databases of PubMed, Web of knowledge, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI) and China Biology Medical literature to assess the association between serum iron levels and PD risk. Standardized mean differences (SMD) and 95% confidence intervals (CI) with random-effect model were used to combine the results.

RESULTS:

Eleven related articles met our selection criteria and contained a total of 829 PD patients and 1219 healthy controls. Our meta-analysis results revealed that the serum iron levels in PD patients were significantly higher than those in healthy controls (SMD = 0.27, 95% CI = 0.18, 0.37, P<0.001). Subgroup analysis by ethnicity showed that the serum iron levels in PD patients were significantly higher than controls both in Asian populations and European populations. Significant associations were also found in prospective studies and case-control studies.

CONCLUSIONS:

Our meta-analysis showed strong evidence that a significantly higher serum iron levels are present in PD patients when compared to the healthy controls.

Copyright © 2016 Elsevier B.V. All rights reserved.

Chronic Inflammation Links Cancer and Parkinson's Disease

Inflammation probably links PD with more than just cancer... the key is unpicking which inflammatory components are at work so that we can start targeting therapies...

Front Aging Neurosci. 2016 Jun 3;8:126. doi: 10.3389/fnagi.2016.00126. eCollection 2016.

Li Z, Zheng Z, Ruan J, Li Z, Tzeng CM.

An increasing number of genetic studies suggest that the pathogenesis of Parkinson's disease (PD) and cancer share common genes, pathways, and mechanisms. Despite a disruption in a wide range of similar biological processes, the end result is very different: uncontrolled proliferation and early neurodegeneration. Thus, the links between the molecular mechanisms that cause PD and cancer remain to be elucidated. We propose that chronic inflammation in neurons and tumors contributes to a microenvironment that favors the accumulation of DNA mutations and facilitates disease formation. This article appraises the key role of microglia, establishes the genetic role of COX2 and CARD15 in PD and cancer, and discusses prevention and treatment with this new perspective in mind. We examine the evidence that chronic inflammation is an important link between cancer and PD.

Patients with Gaucher's disease show symptoms similar to early features of PD

People with a mutation in one of their copies of the GBA gene have previously been shown to be at an increased risk of Parkinson's disease. When people have mutations in both of their copies of the GBA gene, they may suffer from a condition called Gaucher's disease, and may also be at increased risk of developing future PD. In the study below, patients with Gaucher's disease demonstrated some symptoms (such as sleep problems, constipation and depression) which are also early symptoms of Parkinson's. None of the patients in this study have yet developed PD, but perhaps focusing on patients with Gaucher's disease could be a way to identify a group of patients at particularly high risk of developing PD, and an opportunity to intervene early with neuroprotective treatments.

Eur Neurol. 2016 Jun 25;76(1-2):19-21. [Epub ahead of print]

Prodromal Clinical Markers of Parkinson disease in Gaucher Disease Individuals.

Gatto EM1, Etcheverry JL, Sanguinetti A, Cesarini M, Fernandez Escobar N, Drelichman G.

Author information

Abstract

Heterozygous mutations in the glucocerebrosidase (GBA) gene have been reported as a common risk factor for the development of Parkinson's disease (PD) in Gaucher disease (GD) patients and in heterozygous GBA mutation positive carriers. In this study, we analyzed the occurrence of prodromal markers of PD in an Argentinean cohort with type 1 GD. After signed informed consent, we evaluated 26 patients with type 1 GD under enzymatic replacement therapy from a cohort of the Hospital Ricardo Gutierrez GD Study Group in Buenos Aires City, Argentina. We performed an extensive neurological examination, including cognitive assessment by Montreal Cognitive Assessment (MoCA) and a questionnaire performed ad hoc, to identify non-motor PD symptoms. Parasomnias were reported by 7 patients (26.92%), rapid eye movement behavior disorders in 2 (7.69%), constipation in 2 (7.69%), hyposmia in 1 (3.84%), tremor in 1 (3.84%), and depression in 3 cases (11.53%). MoCA assessment was abnormal in 44.44% of patients. No patient fulfilled PD diagnostic criteria (Queen Square Brain Bank criteria). The identification of prodromal markers of PD in type 1 GD suggests that this population represents a very interesting cohort for identifying potential biomarkers and neuroprotective therapies for PD.

© 2016 S. Karger AG, Basel.

PMID:

 

27344356

 

DOI:

 

10.1159/000447510