Saturday, 24 September 2016

Increased suicide risk and clinical correlates of suicide among patients with Parkinson's disease

These authors report a doubling in the rate of suicide in PD patients compared to controls... this feels pretty high and I cannot think of many, if any, patients I know of that have committed suicide. My impression is that it is more common in the atypical parkinsonisms. The authors do acknowledge this and say that the previous literature is mixed... some studies suggest higher risk and some lower risk. There is likely to be wide variability region to region and social support network and professional support (specialist nurses, doctors and support groups) are likely to be strong determinants... the results of such studies may not be generalisable to all populations...

Parkinsonism Relat Disord. 2016 Sep 6. pii: S1353-8020(16)30331-5. doi: 10.1016/j.parkreldis.2016.09.006. [Epub ahead of print]
Lee T, Lee HB, Ahn MH, Kim J, Kim MS, Chung SJ, Hong JP.

Parkinson's disease (PD) is a debilitating, neurodegenerative condition frequently complicated by psychiatric symptoms. Patients with PD may be at higher risk for suicide than the general population, but previous estimates are limited and conflicting. The aim of this study is to estimate the suicide rate based on the clinical case registry and to identify risk factors for suicide among patients diagnosed with PD.

The target sample consisted of 4362 patients diagnosed with PD who were evaluated at a general hospital in Seoul, South Korea, from 1996 to 2012. The standardized mortality ratio for suicide among PD patients was estimated. In order to identify the clinical correlates of suicide, case-control study was conducted based on retrospective chart review. The 29 suicide cases (age: 62.3 ± 13.7 years; females: 34.5%) were matched with 116 non-suicide controls (age: 63.5 ± 9.2 years; females 56.9%) by the year of initial PD evaluation.

The SMR for suicide in PD patients was 1.99 (95% CI 1.33-2.85). Mean duration from time of initial diagnosis to suicide among cases was 6.1 ± 3.5 years. Case-control analysis revealed that male, initial extremity of motor symptom onset, history of depressive disorder, delusion, any psychiatric disorder, and higher L-dopa dosage were significantly associated with suicide among PD patients. Other PD-related variables such as UPDRS motor score were not significantly associated with death by suicide.


Suicide risk in PD patients is approximately 2 times higher than that in the general population. Psychiatric disorders, and also L-dopa medication need further attention with respect to suicide.

Unsupervised home monitoring of Parkinson's disease motor symptoms using body-worn accelerometers.

This is not so much the future, as the present... there are now lots of devices that are available for monitoring of PD symptoms. One of the biggest issues is that almost all have been insufficiently validated... there are lots of examples of pilot studies and very few with replication... PD lends itself better than most other diseases to home monitoring... and this area will only grow over the coming years...

Parkinsonism Relat Disord. 2016 Sep 9. pii: S1353-8020(16)30334-0. doi: 10.1016/j.parkreldis.2016.09.009. [Epub ahead of print]
Fisher JM, Hammerla NY, Ploetz T, Andras P, Rochester L, Walker RW.

Current PD assessment methods have inherent limitations. There is need for an objective method to assist clinical decisions and to facilitate evaluation of treatments. Accelerometers, and analysis using artificial neural networks (ANN), have shown potential as a method of motor symptom evaluation. This work describes the development of a novel PD disease state detection system informed by algorithms based on data collected in an unsupervised, home environment. We evaluated whether this approach can reproduce patient-completed symptom diaries and clinical assessment of disease state.

34 participants with PD wore bilateral wrist-worn accelerometers for 4 h in a research facility (phase 1) and for 7 days at home whilst completing symptom diaries (phase 2). An ANN to predict disease state was developed based on home-derived accelerometer data. Using a leave-one-out approach, ANN performance was evaluated against patient-completed symptom diaries and against clinician rating of disease state.

In the clinical setting, specificity for dyskinesia detection was extremely high (0.99); high specificity was also demonstrated for home-derived data (0.93), but with low sensitivity (0.38). In both settings, sensitivity for on/off detection was sub-optimal. ANN-derived values of the proportions of time in each disease state showed strong, significant correlations with patient-completed symptom diaries.


Accurate, real-time evaluation of symptoms in an unsupervised, home environment, with this sensor system, is not yet achievable. In terms of the amounts of time spent in each disease state, ANN-derived results were comparable to those of symptom diaries, suggesting this method may provide a valuable outcome measure for medication trials.

Bone mass and vitamin D levels in Parkinson's disease: is there any difference between genders?

This study further confirms observations we made in our meta-analysis of bone health in PD... as with individuals that don't have PD... women are at higher risk than men...

J Phys Ther Sci. 2016 Aug;28(8):2204-9. doi: 10.1589/jpts.28.2204. Epub 2016 Aug 31.
Ozturk EA, Gundogdu I, Tonuk B, Kocer BG, Tombak Y, Comoglu S, Cakci A.

[Purpose] The aim of this study was to determine the bone mineral density, vitamin D level, and frequencies of osteopenia and osteoporosis in patients with Parkinson's disease and to compare male and female patients with the controls separately. 

[Subjects and Methods] One hundred fifteen Parkinson's disease patients (47 males, 68 females; age range: 55-85 years) and 117 age- and gender-matched controls (47 males, 70 females) were enrolled in the study. Bone mineral density measured by dual-energy X-ray absorptiometry and serum D vitamin levels of each participant were recorded. 

[Results] The mean lumbar spine, femur neck, and total femur bone mineral density levels, T-scores, and vitamin D levels were found to be significantly lower in Parkinson's disease patients in both genders. Furthermore, osteoporosis rates were found be significantly higher only in female Parkinson's disease patients compared with female controls. 

[Conclusion] Data from the present study revealed that while osteoporosis was significantly higher only in female Parkinson's disease patients, all Parkinson's disease patients had lower bone mineral density scores and vitamin D levels compared with the controls regardless of gender, suggesting that clinicians should pay attention to the osteoporosis risk in Parkinson's disease and that adequate preventive measures should be taken in order to limit the future risk due to osteoporotic fractures.

Thursday, 22 September 2016

Survival and dementia in GBA-associated Parkinson Disease: The mutation matters

This is really interesting isn't? I know that patients with GBA related PD tend to have a more severe form of Parkinson's and that dementia is common. I had assumed that the dementia was an important reason for shorter survival. The only concern I have is whether it is appropriate to adjust for dementia in the analysis... the problem is that although dementia is associated with the exposure (GBA status) and the outcome (death), it may be on the causal pathway between GBA status and death (which means that it ought not to be considered a confounding factor). I would be interested to see survival presented on two levels (dementia and non-dementia) rather than adjusted analysis....

Ann Neurol. 2016 Sep 15. doi: 10.1002/ana.24777. [Epub ahead of print]
Cilia R, Tunesi S, Marotta G, Cereda E, Siri PsyD C, Tesei S, Zecchinelli A, Canesi M, Mariani CB, Meucci N, Sacilotto G, Zini M, Barichella M, Magnani C, Duga S, Asselta R, Soldà G, Seresini A, Seia M, Pezzoli G, Goldwurm S.


Objective To investigate survival, dementia and genotype-phenotype correlations in patients with Parkinson's disease (PD) with and without mutations on the Glucocerebrosidase gene (GBA). Methods We included 2764 unrelated consecutive PD patients: 123 GBA-carriers (67 mild-p.N370S, 56 severe mainly p.L444P) and 2641 non-carriers. Brain perfusion and dopamine transporter imaging was analyzed, including Dementia with Lewy Bodies (DLB) as additional control group. Results Multivariable analysis adjusted by gender, age at onset and disease duration attributed to GBA-carriers a greater risk for dementia (HR=3.16, p<0.001) and death (HR=1.85, p=0.002) than non-carriers. When dementia was introduced in the model as time-dependent covariate, the mortality risk remained greater in carriers (HR=1.65, p=0.016), suggesting that other clinical features are likely to contribute to reduced survival. At last examination GBA-carriers had worse motor symptoms, particularly non-dopaminergic features. Carriers of severe mutations had greater risk for dementia compared to mild mutations (p<0.001), but similar mortality risk. Consistent with clinical data, GBA-carriers showed reduced posterior parietal and occipital cortical synaptic activity and nigrostriatal function than PD non-carriers. Neuroimaging features of carriers of mild mutations overlapped with PD non-carriers, while carriers of severe mutations were closer to DLB. Interpretation Survival is reduced in GBA-carriers compared to non-carriers; this seems to be partially independent from the increased risk for early dementia. The risk for dementia is strongly modulated by the type of mutation. In the clinical continuum between PD and DLB, patients with GBA mutations seem to localize midway, with carriers of severe mutations closer to DLB than to idiopathic PD. 

Monday, 19 September 2016

Weight Change Is a Characteristic Non-Motor Symptom in Drug-Naïve Parkinson's Disease Patients with Non-Tremor Dominant Subtype: A Nation-Wide Observational Study

Weight loss has been reported in a variety of studies after a diagnosis of PD has been made... it is interesting to see that here it appears to associated with just the non-tremor dominant (presumably akinetic rigid) type of PD rather than the tremor dominant type... It may be another feature contributing to the real heterogeneity that we see in PD...

PLoS One. 2016 Sep 13;11(9):e0162254. doi: 10.1371/journal.pone.0162254. eCollection 2016.
Mun JK, Youn J, Cho JW, Oh ES, Kim JS, Park S, Jang W, Park JS, Koh SB, Lee JH, Park HK, Kim HJ, Jeon BS, Shin HW, Choi SA, Kim SJ, Choi SM, Park JY, Kim JY, Chung SJ, Lee CS, Ahn TB, Kim WC, Kim HS, Cheon SM, Kim JW, Kim HT, Lee JY, Kim JS, Kim EJ, Kim JM, Lee KS, Kim JS, Kim MJ, Baik JS, Park KJ, Kim HJ, Park MY, Kang JH, Song SK, Kim YD, Yun JY, Lee HW, Song IU, Sohn YH, Lee PH, Park JH, Oh HG, Park KW, Kwon DY.


Despite the clinical impact of non-motor symptoms (NMS) in Parkinson's disease (PD), the characteristic NMS in relation to the motor subtypes of PD is not well elucidated. In this study, we enrolled drug-naïve PD patients and compared NMS between PD subtypes. We enrolled 136 drug-naïve, early PD patients and 50 normal controls. All the enrolled PD patients were divided into tremor dominant (TD) and non-tremor dominant (NTD) subtypes. The Non-Motor Symptom Scale and scales for each NMS were completed. We compared NMS and the relationship of NMS with quality of life between normal controls and PD patients, and between the PD subtypes. Comparing with normal controls, PD patients complained of more NMS, especially mood/cognitive symptoms, gastrointestinal symptoms, unexplained pain, weight change, and change in taste or smell. Between the PD subtypes, the NTD subtype showed higher total NMS scale score and sub-score about weight change. Weight change was the characteristic NMS related to NTD subtype even after controlled other variables with logistic regression analysis. Even from the early stage, PD patients suffer from various NMS regardless of dopaminergic medication. Among the various NMS, weight change is the characteristic NMS associated with NTD subtype in PD patients.

Sunday, 18 September 2016

The clinical spectrum and natural history of pure akinesia with gait freezing

PAGF is a syndrome that can be recognised in the clinic and is considered a variant of PSP that tends to progress slowly... however PD and other pathologies have also been recognised at post mortem. As the authors say, defining the phenotype is important because it is often slowly progressive, associated with falls and lacks levodopa response...

J Neurol. 2016 Sep 13. [Epub ahead of print]
Owens E, Josephs KA, Savica R, Hassan A, Klassen B, Bower J, Maraganore D, Matsumoto J, Ahlskog JE.

Gait freezing as a presenting and relatively restricted condition is uncommon but a distinctive disorder. This entity was initially defined as "pure akinesia with gait freezing", and later a neuropathological substrate of progressive supranuclear palsy has been recognized. Limited studies have reported the clinical evolution after presentation, which is important for patient counseling. The objective of this study was to assess the demographic and clinical features, treatment-response, neuroimaging, and evolution of pure akinesia with gait freezing. A retrospective review of patients with this phenotype as previously defined was performed. Patients included had no or minimal limb rigidity and/or bradykinesia and no resting tremor, and all underwent neuroimaging of the brain after onset. Inclusion criteria were met by 30 patients, who were followed up to 21 years after symptom onset. During their course, 28 patients had falls (93 %), 12 patients had dysarthria (40 %), and 13 had handwriting changes (43 %). All patients had progression of their gait disorder over time, but with a variable interval until falls occurred. None of the patients developed vertical gaze palsy or met diagnostic criteria for an alternative parkinsonian disorder. Pure akinesia with gait freezing is a distinctive disorder that can be recognized in the clinic. Despite the previously reported progressive supranuclear palsy-like neuropathology, the clinical course is much less aggressive and disabling than classic Richardson syndrome, although fall risk eventually develops in nearly all patients. Bradykinesia, tremor, and rigidity do not develop, distinguishing pure akinesia with gait freezing from Parkinson's disease and other parkinsonian disorders.

Caffeine consumption and the 4-year progression of de novo Parkinson's disease

This is really interesting and there has been plenty about the relationship between caffeine and PD in the past... here the authors suggest that coffee drinkers have slower progression of a range of PD symptoms... whether this represents an effect on the underlying disease or improved symptom control remains to be seen...

Parkinsonism Relat Disord. 2016 Aug 4. pii: S1353-8020(16)30289-9. doi: 10.1016/j.parkreldis.2016.08.005. [Epub ahead of print]
Moccia M, Erro R, Picillo M, Vitale C, Longo K, Amboni M, Pellecchia MT, Barone P.

Higher caffeine consumption has been associated with reduced risk of Parkinson's disease (PD), and with a more benign progression of motor and non-motor symptoms (NMS). The present observational cohort study investigated motor and non-motor correlates of caffeine consumption in de novo PD.

79 newly diagnosed, drug naïve PD patients have been included and followed up for 4 years. The total caffeine use was calculated with the Caffeine Consumption Questionnaire. Following study variables were recorded at baseline, and after 2 and 4 years: UPDRS part III, UPDRS part IV, l-dopa Equivalent Daily Dose (LEDD), NMS Questionnaire (NMSQuest), and the time occurring from PD diagnosis to the need for l-dopa treatment. Age, gender and disease duration were included as covariates in the statistical models.

The average daily caffeine consumption was 296.1 ± 157.2 mg. At Cox regression models, higher caffeine consumption was associated with a lower rate of starting l-Dopa treatment (HR = 0.630; 95%CI = 0.382-0.996). At the mixed-effects linear regression models considering the whole study period, each additional espresso cup per day (50 mg of caffeine) was more likely associated with 5-point lower UPDRS part III total score (Coef = -0.01; 95%CI = -0.02 to 0.00), with 50% reduced LEDD (Coef = -0.01; 95%CI = -0.15 to 0.00; p = 0.021), and with 5-point lower NMSQuest total score (Coef = -0.01; 95%CI = -0.01 to 0.00), but not with UPDRS part IV total score (Coef = -0.00; 95%CI = -0.00 to 0.00).


Caffeine consumption was associated with a reduced accrual of motor and non-motor disability during 4-year follow-up in de novo PD, highlighting the rationale for using adenosine A2A antagonists since the early phases of PD.

Saturday, 17 September 2016

Appendectomy and risk of Parkinson's disease: A nationwide cohort study with more than 10 years of follow-up

Here the authors actually observe the opposite to their starting hypothesis... as always an association does not mean that appendicectomy causes PD as such... it may be that there are other confounding factors that were not measured (residual confounding), something for example that increases both the risk of inflammation of the appendix and also increases the risk of PD...

Mov Disord. 2016 Sep 13. doi: 10.1002/mds.26761. [Epub ahead of print]
Svensson E, Horváth-Puhó E, Stokholm MG, Sørensen HT, Henderson VW, Borghammer P.

The appendix may be a key site for the initiation of Parkinson's disease (PD) pathology. We examined the hypothesis that appendectomy is associated with lower PD risk.

We used Danish medical and administrative registries to construct a cohort of all patients in Denmark with an operation code of appendectomy during 1980-2010 (n = 265,758) and a matched general population comparison cohort (n = 1,328,790). Using Cox regression, we computed hazard ratios and corresponding 95% confidence intervals for PD, adjusting for potential confounders and stratifying on age at appendectomy (≤45 years / > 45 years), sex, and follow-up time.

During follow-up ( > 10 years), PD incidence was 0.19 and 0.15 per 1,000 person-years at risk in the appendectomy cohort and in the general population comparison cohort, respectively, yielding a slightly increased risk of PD (adjusted hazard ratio = 1.14; 95% confidence interval 1.03-1.27). Findings were consistent after more than 20 years of follow-up and when stratified on age of appendectomy and sex.


Appendectomy was associated with a small increase in PD risk 10 or more years after surgery. © 2016 International Parkinson and Movement Disorder Society.

Predicting first fall in newly diagnosed Parkinson's disease: Insights from a fall-naïve cohort

Increased fracture risk in PD has been reported multiple times on this blog... falls are one of the key precipitants of fractures and patients with PD are at high risk... here the authors report multiple predictors of falls... we should be looking out for these things in the clinic to try and prevent adverse outcomes...

Mov Disord. 2016 Sep 13. doi: 10.1002/mds.26742. [Epub ahead of print]
Lord S, Galna B, Yarnall AJ, Coleman S, Burn D, Rochester L.

Falls are common and associated with reduced independence and mortality in Parkinson's disease. Previous research has been conducted on falls-prevalent or advanced disease cohorts.

This study identifies risk factors for first fall for 36 months in a newly diagnosed, falls-naïve cohort.

A total of 121 consecutive Parkinson's disease patients were recruited. Falls data were collected prospectively during 36 months from diagnosis via monthly falls diaries and telephone follow-up for 117 participants. Assessment comprised a comprehensive battery of clinical, gait, and cognitive measures. Significant predictors were identified from decision-tree analysis and survival analysis with time to first fall during 36 months as the dependent variable.

At baseline, 26 (22%) participants reported retrospective falls. At 36 months, the remaining cohort (n = 91) comprised 47 fallers (52%) and 30 (33%) nonfallers and 14 (15%) participants with incomplete diaries. Fallers presented with a significantly higher disease severity, poorer ability to stand on one leg, slower gait speed, increased stance time variability, and higher swing time asymmetry. Median time to first fall was 847 days. Gait speed, stance time, and Hoehn & Yahr III stage emerged as significant predictors of first fall, hazard ratio 3.44 (95% confidence interval [CI] 1.58 to 7.48), 3.31(95% CI 1.40 to 5.65), and 1.97 (95% CI 1.40 to 7.80), respectively. The hazard ratio for risk factors combined was 7.8 (CI 2.79 to 21.8).


Interventions that target gait deficit and postural control in early Parkinson's disease may limit the potential for first fall. © 2016 International Parkinson and Movement Disorder Society.

Tuesday, 13 September 2016

Loss of independence in early Parkinson disease: A 5-year population-based incident cohort study

The things that cause patients to be admitted to long term care facilities are not surprising... each of these are considered independent outcomes in their own right. An important observation here is the irreversible nature of dependency... I suspect that relatively small changes can prompt a switch from independence to dependence, such as prolonged hospital admission or long bone fracture...

Neurology. 2016 Sep 2. pii: 10.1212/WNL.0000000000003213. [Epub ahead of print]
Bjornestad A, Tysnes OB, Larsen JP, Alves G.

To determine the risk, predictors, and prognosis of independence loss and institutionalization in patients with early Parkinson disease (PD).

We conducted a prospective population-based 5-year longitudinal study following 189 patients with incident PD and 174 controls matched for age, sex, and comorbidity. Health care status was assessed repeatedly with standardized interviews.

More newly diagnosed patients with PD (15.9%) than controls (5.7%) were dependent in activities of daily living at baseline (relative risk [RR] 2.8, p = 0.004). During follow-up, 40.9% of the initially independent patients lost their independence vs 9.1% of controls (RR 4.5, p < 0.001). Higher age, shorter symptom duration, increasing motor severity, and presence of mild cognitive impairment at PD diagnosis independently predicted independence loss during follow-up. Dependency was irreversible in most (>95%) patients. Long-term care facility placement was needed in 8.8% of patients vs 0.6% of controls (RR 15.4, p = 0.001). More patients with PD admitted to long-term care facilities were fallers (RR 4.8, p < 0.001), had hallucinations (RR 4.4, p = 0.001), or had dementia (RR 4.2, p < 0.001) than home-dwelling patients. Once admitted to a long-term care facility, the age-adjusted RR for death during the study period was 5.5 (p = 0.002) vs patients never admitted and 25.1 (p < 0.001) vs controls.


Patients with early PD face a substantially greater risk of independence loss and institutionalization than well-matched controls. Independence loss is irreversible in most patients and represents a sinister prognostic factor in early PD. These findings have implications for patient management and health care planning.

Multicenter Assessment of Immunohistochemical Methods for Pathological Alpha-Synuclein in Sigmoid Colon of Autopsied Parkinson's Disease and Control Subjects

This series of papers from these opinion leaders in the field will be very important... if gut biomarkers are to be found, consensus on an approach or series of approaches is absolutely vital.

J Parkinsons Dis. 2016 Aug 31. [Epub ahead of print]
Beach TG, Corbillé AG, Letournel F, Kordower JH, Kremer T, Munoz DG, Intorcia A, Hentz J, Adler CH, Sue LI, Walker J, Serrano G, Derkinderen P.

Conflicting results from studies of Lewy-type α-synucleinopathy (LTS) in colonic biopsies of subjects with Parkinson's disease (PD) prompted a two-part multicenter assessment. The first assessment, now published (Acta Neuropathol Commun 4 : 35, 2016), examined archived colonic biopsies and found that none of the tested methods was adequately sensitive or specific.

As the amount of nervous tissue in typical colonic biopsies may be insufficient, and the clinical diagnosis of PD not completely accurate, the objective of the current study was to use instead full-thickness sections of sigmoid colon from autopsy-proven PD and normal subjects.

Seven different immunohistochemical (IHC) methods were used, employing five different primary antibodies and four different combinations of epitope exposure and signal development protocols. Specific staining was defined as being restricted to morphological features consistent with neuronal elements. Stained slides from each subject were independently categorized as being positive or negative for LTS, and their density semi-quantitatively graded, by four raters blinded to diagnosis.

Agreement and mean diagnostic performance varied markedly between raters. With the two most accurate raters, 5 methods achieved diagnostic accuracies of 70% or greater; one method had 100% accuracy and 100% inter-rater agreement. The submucosa had the highest prevalence of pathological LTS staining, followed by the muscularis and mucosa.


The major conclusion of this study is that, when sufficient submucosa and LTS is present, and when specific staining is defined as being consistent with neuronal morphology, adequately-trained raters may reliably distinguish PD colon from control using suitable IHC methods.

Impulsive-compulsive behaviors in parkin-associated Parkinson disease

Another slow week updating the blog... but this is important work. Really interesting to see that the ICB predated the diagnosis of PD in a number of the cases. As well has further characterising parkin clinical features, I think this has the potential to tell us more about the pathological substrate of ICBs given that parkin cases tend to have restricted pathology compared with idiopathic PD...

Neurology. 2016 Sep 2. pii: 10.1212/WNL.0000000000003177. [Epub ahead of print]
Morgante F, Fasano A, Ginevrino M, Petrucci S, Ricciardi L, Bove F, Criscuolo C, Moccia M, De Rosa A, Sorbera C, Bentivoglio AR, Barone P, De Michele G, Pellecchia MT, Valente EM.

The aim of this multicenter, case-control study was to investigate the prevalence and severity of impulsive-compulsive behaviors (ICBs) in a cohort of patients with parkin-associated Parkinson disease (PD) compared to a group of patients without the mutation.

We compared 22 patients with biallelic parkin mutations (parkin-PD) and 26 patients negative for parkin, PINK1, DJ-1, and GBA mutations (PD-NM), matched for age at onset, disease duration, levodopa, and dopamine agonist equivalent daily dose. A semistructured interview was used to diagnose each of the following ICBs: compulsive sexual behavior, compulsive buying, binge eating, punding, hobbyism, and compulsive medication use. The Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease-Rating Scale (QUIP-RS) was adopted to rate ICB severity.

Frequency of patients with at least one ICB was comparable between parkin-PD and PD-NM. Nevertheless, when analyzing the distribution of specific ICBs, a higher frequency of compulsive shopping, binge eating, and punding/hobbyism was found in the parkin-PD group. Compared to PD-NM, parkin-PD patients with ICB had younger onset age and higher frequency of smokers; in 5 patients, ICB had predated PD onset. Total and partial (compulsive buying, compulsive sexual behavior, binge eating, hobbyism/punding) QUIP-RS scores were higher in patients with parkin-PD compared to patients with PD-NM. Logistic regression analysis showed that the presence of parkin mutations was associated with smoking status and higher QUIP-RS total score.


Our data expand the parkin-associated phenotypic spectrum demonstrating higher frequency and severity of specific ICBs, and suggesting an association between the parkin genotype, smoking status, and ICB severity.

Monday, 5 September 2016

Comparing the Incidence of Falls/Fractures in Parkinson's Disease Patients in the US Population

This is a topic that I have looked at in the past... it adds further support to the results of our systematic review and meta-analysis on the subject... I cannot understand why the authors present combined results for falls and fractures (they are different) but in the main body of the paper (via the link) they present them separately.

PLoS One. 2016 Sep 1;11(9):e0161689. doi: 10.1371/journal.pone.0161689. eCollection 2016.
Kalilani L, Asgharnejad M, Palokangas T, Durgin T.

Patients with Parkinson's disease (PD) may experience falls and/or fractures as a result of disease symptoms. There are limited data available from long-term studies estimating the incidence of falls/fractures in patients with PD. The objective was to compare the incidence rate of falls/fractures in PD patients with non-PD patients in a US population. This was a retrospective study using a US-based claims database (Truven Health MarketScan®) that compared the incidence rate of falls/fractures in PD subjects with non-PD subjects. The study period included the 12 months prior to index date (defined as earliest PD diagnosis [International Classification of Diseases, Ninth Revision, Clinical Modification code 332.0]) and a postindex period to the end of data availability. Fractures were defined by inpatient/outpatient claims as a principal or secondary diagnosis and accompanying procedure codes during the postindex period. Incidence rates and 95% CIs for falls/fractures were calculated as the number of events per 10,000 person-years of follow-up using negative binomial or Poisson regression models. Twenty-eight thousand two hundred and eighty PD subjects were matched to non-PD subjects for the analysis (mean [SD] age, 71.4 [11.8] years; 53% male). A higher incidence rate (adjusted for comorbidities and medications) of all fall/fracture cases and by fall and fracture types was observed for PD subjects versus non-PD subjects; the overall adjusted incidence rate ratio comparing PD to non-PD subjects was 2.05; 95% CI, 1.88-2.24. The incidence rate of falls/fractures was significantly higher in subjects with PD compared with non-PD subjects in a US population.

Short chain fatty acids and gut microbiota differ between patients with Parkinson's disease and age-matched controls

To my knowledge this is the third paper now looking at the gut microbiome and again it demonstrates differences between patients and controls... however my recollection is that the previous papers found different results to one another... a key thing to determine is whether these changes are cause or effect of PD and indeed constipation PD... i.e. does a slowing of gut transit in PD alter the intestinal microbiome or does a change in microbiome drive disease in PD via the gut??? Testing these hypotheses in pre-diagnostic cohorts may be one way to uncover this....

Parkinsonism Relat Disord. 2016 Aug 26. pii: S1353-8020(16)30323-6. doi: 10.1016/j.parkreldis.2016.08.019. [Epub ahead of print]
Unger MM, Spiegel J, Dillmann KU, Grundmann D, Philippeit H, Bürmann J, Faßbender K, Schwiertz A, Schäfer KH.

Patients with Parkinson's disease (PD) frequently have gastrointestinal symptoms (e.g. constipation) and exhibit the PD-typical pathohistology in the enteric nervous system (ENS). Both, clinical symptoms and pathohistological changes in the ENS occur at early stages and can precede the motor manifestations of PD. Two recent studies reported an association between changes in gut microbiota composition and PD. We hypothesized that alterations in gut microbiota might be accompanied by altered concentrations of short chain fatty acids (SCFA), one main metabolic product of gut bacteria.

We quantitatively analyzed SCFA concentrations (using gas chromatography) and microbiota composition (using quantitative PCR) in fecal samples of 34 PD patients and 34 age-matched controls.

Fecal SCFA concentrations were significantly reduced in PD patients compared to controls. The bacterial phylum Bacteroidetes and the bacterial family Prevotellaceae were reduced, Enterobacteriaceae were more abundant in fecal samples from PD patients compared to matched controls.


Our study confirms the recently reported association between PD and the abundance of certain gut microbiota and shows a reduction in fecal SCFA concentrations (one main metabolic product of certain gut bacteria). The reduction in SCFA might, theoretically, induce alterations in the ENS and contribute to gastrointestinal dysmotility in PD. Prospective longitudinal studies in subjects at risk for PD are required to further elucidate the causal role of gut microbiota and microbial products in the development of PD and PD-associated dysmotility.

Plain English - LRRK2 G2019S Parkinson's disease with more benign phenotype than idiopathic

This research study compared patients with Parkinson's who carry the commonest gene mutation associated with the disease (called LRRK2),...