Friday, 19 May 2017
Monday, 24 April 2017
Longitudinal whole-brain atrophy and ventricular enlargement in nondemented Parkinson's disease
Great example of how MRI can to used to supplement clinical trials in PD... I think it very helpful that the authors included the estimation of how use of an imaging biomarker could reduce a required sample size to 1/15th especially at a time when we are adding to our armoury of options for use in clinical trials of disease modifying therapy... MRI is widely available and reasonable in terms of cost too...
Neurobiol Aging. 2017 Mar 16;55:78-90. doi: 10.1016/j.neurobiolaging.2017.03.012. [Epub ahead of print]
Mak E, Su L, Williams GB, Firbank MJ, Lawson RA, Yarnall AJ, Duncan GW, Mollenhauer B, Owen AM, Khoo TK, Brooks DJ, Rowe JB, Barker RA, Burn DJ, O'Brien JT.
http://www.neurobiologyofaging.org/article/S0197-4580(17)30083-0/abstract
We investigated whole-brain atrophy and ventricular enlargement over 18 months in nondemented Parkinson's disease (PD) and examined their associations with clinical measures and baseline CSF markers. PD subjects (n = 100) were classified at baseline into those with mild cognitive impairment (MCI; PD-MCI, n = 36) and no cognitive impairment (PD-NC, n = 64). Percentage of whole-brain volume change (PBVC) and ventricular expansion over 18 months were assessed with FSL-SIENA and ventricular enlargement (VIENA) respectively. PD-MCI showed increased global atrophy (-1.1% ± 0.8%) and ventricular enlargement (6.9 % ± 5.2%) compared with both PD-NC (PBVC: -0.4 ± 0.5, p < 0.01; VIENA: 2.1% ± 4.3%, p < 0.01) and healthy controls. In a subset of 35 PD subjects, CSF levels of tau, and Aβ42/Aβ40 ratio were correlated with PBVC and ventricular enlargement respectively. The sample size required to demonstrate a 20% reduction in PBVC and VIENA was approximately 1/15th of that required to detect equivalent changes in cognitive decline. These findings suggest that longitudinal MRI measurements have potential to serve as surrogate markers to complement clinical assessments for future disease-modifying trials in PD.
Neurobiol Aging. 2017 Mar 16;55:78-90. doi: 10.1016/j.neurobiolaging.2017.03.012. [Epub ahead of print]
Mak E, Su L, Williams GB, Firbank MJ, Lawson RA, Yarnall AJ, Duncan GW, Mollenhauer B, Owen AM, Khoo TK, Brooks DJ, Rowe JB, Barker RA, Burn DJ, O'Brien JT.
http://www.neurobiologyofaging.org/article/S0197-4580(17)30083-0/abstract
We investigated whole-brain atrophy and ventricular enlargement over 18 months in nondemented Parkinson's disease (PD) and examined their associations with clinical measures and baseline CSF markers. PD subjects (n = 100) were classified at baseline into those with mild cognitive impairment (MCI; PD-MCI, n = 36) and no cognitive impairment (PD-NC, n = 64). Percentage of whole-brain volume change (PBVC) and ventricular expansion over 18 months were assessed with FSL-SIENA and ventricular enlargement (VIENA) respectively. PD-MCI showed increased global atrophy (-1.1% ± 0.8%) and ventricular enlargement (6.9 % ± 5.2%) compared with both PD-NC (PBVC: -0.4 ± 0.5, p < 0.01; VIENA: 2.1% ± 4.3%, p < 0.01) and healthy controls. In a subset of 35 PD subjects, CSF levels of tau, and Aβ42/Aβ40 ratio were correlated with PBVC and ventricular enlargement respectively. The sample size required to demonstrate a 20% reduction in PBVC and VIENA was approximately 1/15th of that required to detect equivalent changes in cognitive decline. These findings suggest that longitudinal MRI measurements have potential to serve as surrogate markers to complement clinical assessments for future disease-modifying trials in PD.
Sunday, 23 April 2017
Validation of the MDS research criteria for prodromal Parkinson's disease: Longitudinal assessment in a REM sleep behavior disorder (RBD) cohort
Important to seek validation of these criteria and existing prodromal cohorts are a good place to start... of course, as I have written here before, there are some issues with using RBD patients such as: 1) it is a precursor for synucleinopathy rather than PD specifically, and 2) the cases that develop PD tend to be at the more severe end of the spectrum with prominent cognitive impairment. However, aside from these things, RBD is a very important model for studying the pre-diagnostic phase of PD...
Mov Disord. 2017 Apr 21. doi: 10.1002/mds.26989. [Epub ahead of print]
Fereshtehnejad SM, Montplaisir JY, Pelletier A, Gagnon JF, Berg D, Postuma RB.
BACKGROUND: Recently, the International Parkinson and Movement Disorder Society introduced the prodromal criteria for PD. Objectives Our study aimed to examine diagnostic accuracy of the criteria as well as the independence of prodromal markers to predict conversion to PD or dementia with Lewy bodies.
METHODS: This prospective cohort study was performed on 121 individuals with rapid eye movement sleep behavior disorder who were followed annually for 1 to 12 years. Using data from a comprehensive panel of prodromal markers, likelihood ratio and post-test probability of the criteria were calculated at baseline and during each follow-up visit.
RESULTS: Forty-eight (39.7%) individuals with rapid eye movement sleep behavior disorder converted to PD/dementia with Lewy bodies. The prodromal criteria had 81.3% sensitivity and 67.9% specificity for conversion to PD/dementia with Lewy bodies at 4-year follow-up. One year before conversion, sensitivity was 100%. The criteria predicted dementia with Lewy bodies with even higher accuracy than PD without dementia at onset. Those who met the threshold of prodromal criteria at baseline had significantly more rapid conversion into a neurodegenerative state (4.8 vs. 9.1 years; P < 0.001). Pair-wise combinations of different prodromal markers showed that markers were independent of one another.
CONCLUSION: The prodromal criteria are a promising tool for predicting incidence of PD/dementia with Lewy bodies and conversion time in a rapid eye movement sleep behavior disorder cohort, with high sensitivity and high specificity with long follow-up. Prodromal markers influence the overall likelihood ratio independently, allowing them to be reliably multiplied. Defining additional markers with high likelihood ratio, further studies with longitudinal assessment and testing thresholds in different target populations will improve the criteria.
Mov Disord. 2017 Apr 21. doi: 10.1002/mds.26989. [Epub ahead of print]
Fereshtehnejad SM, Montplaisir JY, Pelletier A, Gagnon JF, Berg D, Postuma RB.
BACKGROUND: Recently, the International Parkinson and Movement Disorder Society introduced the prodromal criteria for PD. Objectives Our study aimed to examine diagnostic accuracy of the criteria as well as the independence of prodromal markers to predict conversion to PD or dementia with Lewy bodies.
METHODS: This prospective cohort study was performed on 121 individuals with rapid eye movement sleep behavior disorder who were followed annually for 1 to 12 years. Using data from a comprehensive panel of prodromal markers, likelihood ratio and post-test probability of the criteria were calculated at baseline and during each follow-up visit.
RESULTS: Forty-eight (39.7%) individuals with rapid eye movement sleep behavior disorder converted to PD/dementia with Lewy bodies. The prodromal criteria had 81.3% sensitivity and 67.9% specificity for conversion to PD/dementia with Lewy bodies at 4-year follow-up. One year before conversion, sensitivity was 100%. The criteria predicted dementia with Lewy bodies with even higher accuracy than PD without dementia at onset. Those who met the threshold of prodromal criteria at baseline had significantly more rapid conversion into a neurodegenerative state (4.8 vs. 9.1 years; P < 0.001). Pair-wise combinations of different prodromal markers showed that markers were independent of one another.
CONCLUSION: The prodromal criteria are a promising tool for predicting incidence of PD/dementia with Lewy bodies and conversion time in a rapid eye movement sleep behavior disorder cohort, with high sensitivity and high specificity with long follow-up. Prodromal markers influence the overall likelihood ratio independently, allowing them to be reliably multiplied. Defining additional markers with high likelihood ratio, further studies with longitudinal assessment and testing thresholds in different target populations will improve the criteria.
Monday, 10 April 2017
Prevalence of Prodromal Parkinson's Disease as Defined by MDS Research Criteria among Elderly Patients Undergoing Colonoscopy
J Parkinsons Dis. 2017 Apr 4. doi: 10.3233/JPD-161036. [Epub ahead of print]
This is very similar to an idea our group had a few years ago... here they are just describing the clinical features of the 100 screened participants and how they fit within the MDS Task Force framework... the interesting thing to know is whether the colonoscopies of those people that are higher risk are abnormal... the potential for colonoscopy to give us valid PD biomarkers has taken a bit of a knock in recent years but I still think it may hold some promise...
Matej S, Zuzana L, Vladimir H, Norbert L, Eva F, Dominika J, Barbora R, Peter S, Zuzana U, Adriana V, Laura G, Maria Z, Eduard V, Frantisek T, Eva M, Zuzana.
http://content.iospress.com/articles/journal-of-parkinsons-disease/jpd161036
BACKGROUND: Gastrointestinal symptoms are a well-recognized and common premotor feature of Parkinson's disease (PD). Moreover, multiple studies have assessed the value of colonic α-synuclein as a potential marker of prodromal PD. Recently, the International Parkinson and Movement Disorders Society (MDS) defined research criteria for prodromal PD.
OBJECTIVE: The aim of our study was to test the MDS research criteria in patients undergoing diagnostic colonoscopies as potential candidates for inclusion in prospective trials evaluating colonic biopsies as a potential biomarker of prodromal PD.
METHODS: We evaluated elderly patients without manifest parkinsonism undergoing diagnostic colonoscopies. During the study we assessed all risks and prodromal markers of the MDS research criteria, excluding radiotracer imaging and genetic testing.
RESULTS: The mean age of the 100 enrolled patients was 61.6±9.7 years; 42 were men. The most common prodromal marker in our cohort was constipation (40%), followed by MDS-UPDRS part III scores of >6 points, excluding action tremor items (39%) and hyposmia (37%). Substantia nigra hyperechogenicity was identified in 9%, and polysomnography confirmed REM sleep behavior disorder in 2% of the patients. Five of the 100 enrolled patients (5%) fulfilled the criteria for probable prodromal PD, while another 3 patients met the 50% probability threshold.
CONCLUSIONS: Our findings suggest, that the prevalence of prodromal PD in patients undergoing diagnostic colonoscopies may be higher compared to the general elderly population, although this should be confirmed in further studies including also matched controls not undergoing colonoscopy. The real prevalence of prodromal PD in this cohort will have to be confirmed in longitudinal follow-up. Patients undergoing diagnostic colonoscopies may be good candidates for multistep screening and inclusion in prospective trials.
This is very similar to an idea our group had a few years ago... here they are just describing the clinical features of the 100 screened participants and how they fit within the MDS Task Force framework... the interesting thing to know is whether the colonoscopies of those people that are higher risk are abnormal... the potential for colonoscopy to give us valid PD biomarkers has taken a bit of a knock in recent years but I still think it may hold some promise...
Matej S, Zuzana L, Vladimir H, Norbert L, Eva F, Dominika J, Barbora R, Peter S, Zuzana U, Adriana V, Laura G, Maria Z, Eduard V, Frantisek T, Eva M, Zuzana.
http://content.iospress.com/articles/journal-of-parkinsons-disease/jpd161036
BACKGROUND: Gastrointestinal symptoms are a well-recognized and common premotor feature of Parkinson's disease (PD). Moreover, multiple studies have assessed the value of colonic α-synuclein as a potential marker of prodromal PD. Recently, the International Parkinson and Movement Disorders Society (MDS) defined research criteria for prodromal PD.
OBJECTIVE: The aim of our study was to test the MDS research criteria in patients undergoing diagnostic colonoscopies as potential candidates for inclusion in prospective trials evaluating colonic biopsies as a potential biomarker of prodromal PD.
METHODS: We evaluated elderly patients without manifest parkinsonism undergoing diagnostic colonoscopies. During the study we assessed all risks and prodromal markers of the MDS research criteria, excluding radiotracer imaging and genetic testing.
RESULTS: The mean age of the 100 enrolled patients was 61.6±9.7 years; 42 were men. The most common prodromal marker in our cohort was constipation (40%), followed by MDS-UPDRS part III scores of >6 points, excluding action tremor items (39%) and hyposmia (37%). Substantia nigra hyperechogenicity was identified in 9%, and polysomnography confirmed REM sleep behavior disorder in 2% of the patients. Five of the 100 enrolled patients (5%) fulfilled the criteria for probable prodromal PD, while another 3 patients met the 50% probability threshold.
CONCLUSIONS: Our findings suggest, that the prevalence of prodromal PD in patients undergoing diagnostic colonoscopies may be higher compared to the general elderly population, although this should be confirmed in further studies including also matched controls not undergoing colonoscopy. The real prevalence of prodromal PD in this cohort will have to be confirmed in longitudinal follow-up. Patients undergoing diagnostic colonoscopies may be good candidates for multistep screening and inclusion in prospective trials.
Sunday, 2 April 2017
Viral hepatitis and Parkinson disease: A national record-linkage study
This is a study led by Julia Pakpoor in the HES database, a very large UK cohort study using routinely collected medical data. Two previous studies from Taiwan showed a link between hepatitis and future Parkinson's, but here we show it on a larger scale and in a Western population. It is not clear whether this a feature peculiar to the virus, the treatment or a common risk factor that predisposes to both...
Neurology. 2017 Mar 29. pii: 10.1212/WNL.0000000000003848. doi: 10.1212/WNL.0000000000003848. [Epub ahead of print]
Pakpoor J, Noyce A, Goldacre R, Selkihova M, Mullin S, Schrag A, Lees A, Goldacre M.
http://www.neurology.org/content/early/2017/03/29/WNL.0000000000003848.short
OBJECTIVE: To study associations between viral hepatitis and Parkinson disease (PD).
METHODS: A retrospective cohort study was done by analyzing linked English National Hospital Episode Statistics and mortality data (1999-2011). Cohorts of individuals with hepatitis B, hepatitis C, autoimmune hepatitis, chronic active hepatitis, and HIV were constructed, and compared to a reference cohort for subsequent rates of PD.
RESULTS: The standardized rate ratio (RR) of PD following hepatitis B was 1.76 (95% confidence interval [CI] 1.28-2.37) (p < 0.001), based on 44 observed compared with 25 expected cases. The RR of PD following hepatitis C was 1.51 (95% CI, 1.18-1.9) (p < 0.001), based on 48.5 expected and 73 observed cases. There was no significant association between autoimmune hepatitis, chronic active hepatitis or HIV, and subsequent PD. When including only those episodes of care for PD that occurred first at least 1 year following each exposure condition, the RR for hepatitis B and hepatitis C were 1.82 (1.29-2.5) and 1.43 (1.09-1.84), respectively.
CONCLUSIONS: We report strong evidence in favor of an elevation of rates of subsequent PD in patients with hepatitis B and hepatitis C. These findings may be explained by factors peculiar to viral hepatitis, but whether it reflects consequences of infection, shared disease mechanisms, or the result of antiviral treatment remains to be elucidated. Further work is needed to confirm this association and to investigate pathophysiologic pathways, potentially advancing etiologic understanding of PD more broadly.
Neurology. 2017 Mar 29. pii: 10.1212/WNL.0000000000003848. doi: 10.1212/WNL.0000000000003848. [Epub ahead of print]
Pakpoor J, Noyce A, Goldacre R, Selkihova M, Mullin S, Schrag A, Lees A, Goldacre M.
http://www.neurology.org/content/early/2017/03/29/WNL.0000000000003848.short
OBJECTIVE: To study associations between viral hepatitis and Parkinson disease (PD).
METHODS: A retrospective cohort study was done by analyzing linked English National Hospital Episode Statistics and mortality data (1999-2011). Cohorts of individuals with hepatitis B, hepatitis C, autoimmune hepatitis, chronic active hepatitis, and HIV were constructed, and compared to a reference cohort for subsequent rates of PD.
RESULTS: The standardized rate ratio (RR) of PD following hepatitis B was 1.76 (95% confidence interval [CI] 1.28-2.37) (p < 0.001), based on 44 observed compared with 25 expected cases. The RR of PD following hepatitis C was 1.51 (95% CI, 1.18-1.9) (p < 0.001), based on 48.5 expected and 73 observed cases. There was no significant association between autoimmune hepatitis, chronic active hepatitis or HIV, and subsequent PD. When including only those episodes of care for PD that occurred first at least 1 year following each exposure condition, the RR for hepatitis B and hepatitis C were 1.82 (1.29-2.5) and 1.43 (1.09-1.84), respectively.
CONCLUSIONS: We report strong evidence in favor of an elevation of rates of subsequent PD in patients with hepatitis B and hepatitis C. These findings may be explained by factors peculiar to viral hepatitis, but whether it reflects consequences of infection, shared disease mechanisms, or the result of antiviral treatment remains to be elucidated. Further work is needed to confirm this association and to investigate pathophysiologic pathways, potentially advancing etiologic understanding of PD more broadly.
Saturday, 25 March 2017
Excessive Daytime Sleepiness Predicts Neurodegeneration in Idiopathic REM Sleep Behavior Disorder
Interesting to see how excessive daytime somnolence (sleepiness) predicts which patients with RBD go on to get PD... and strange that it does not predict all neurodegenerative outcomes. I would have thought excessive daytime somnolence was influenced by many factors, but perhaps this suggest specific pathological involvement of a brain structure related to PD (the locus ceruleus?)
Sleep. 2017 Mar 16. doi: 10.1093/sleep/zsx041. [Epub ahead of print]
Zhou J, Zhang J, Lam SP, Chan JW, Mok V, Chan A, Li SX, Liu Y, Tang X, Yung WH, Wing YK.
https://academic.oup.com/sleep/article-abstract/doi/10.1093/sleep/zsx041/3072757/Excessive-Daytime-Sleepiness-Predicts?redirectedFrom=fulltext
STUDY OBJECTIVES: To determine the association of excessive daytime sleepiness (EDS) with the conversion of neurodegenerative diseases in patients with idiopathic REM sleep behavior disorder (iRBD).
METHODS: A total of 179 patients with iRBD (79.1% males, mean age = 66.3 ± 9.8 years) were consecutively recruited. Forty-five patients with Epworth Sleepiness Scale score ≥ 14 were defined as having EDS. Demographic, clinical and polysomnographic data were compared between iRBD patients with and without EDS. The risk of developing neurodegenerative diseases was examined using Cox proportional hazards model.
RESULTS: After a mean follow-up of 5.8 years (SD = 4.3 years), 50 patients (27.9%) developed neurodegenerative diseases. There was a significantly higher proportion of conversion in patients with EDS compared with those without EDS (42.2 % vs 23.1%, P = 0.01). EDS significantly predicted an increased risk of developing neurodegenerative diseases (adjusted hazard ratios [HR] = 2.56, 95% confidence interval [CI] 1.37-4.77) after adjusting for age, sex, body mass index, current depression, obstructive sleep apnea, and periodic limb movement during sleep. Further analyses demonstrated that EDS predicted the conversion of Parkinson's disease (PD) (adjusted HR = 3.55, 95% CI 1.59-7.89), but not dementia (adjusted HR = 1.48, 95% CI 0.44-4.97).
CONCLUSIONS: EDS is associated with an increased risk of developing neurodegenerative diseases, especially PD, in patients with iRBD. Our findings suggest that EDS is a potential clinical biomarker of α-synucleinopathies in iRBD.
Sleep. 2017 Mar 16. doi: 10.1093/sleep/zsx041. [Epub ahead of print]
Zhou J, Zhang J, Lam SP, Chan JW, Mok V, Chan A, Li SX, Liu Y, Tang X, Yung WH, Wing YK.
https://academic.oup.com/sleep/article-abstract/doi/10.1093/sleep/zsx041/3072757/Excessive-Daytime-Sleepiness-Predicts?redirectedFrom=fulltext
STUDY OBJECTIVES: To determine the association of excessive daytime sleepiness (EDS) with the conversion of neurodegenerative diseases in patients with idiopathic REM sleep behavior disorder (iRBD).
METHODS: A total of 179 patients with iRBD (79.1% males, mean age = 66.3 ± 9.8 years) were consecutively recruited. Forty-five patients with Epworth Sleepiness Scale score ≥ 14 were defined as having EDS. Demographic, clinical and polysomnographic data were compared between iRBD patients with and without EDS. The risk of developing neurodegenerative diseases was examined using Cox proportional hazards model.
RESULTS: After a mean follow-up of 5.8 years (SD = 4.3 years), 50 patients (27.9%) developed neurodegenerative diseases. There was a significantly higher proportion of conversion in patients with EDS compared with those without EDS (42.2 % vs 23.1%, P = 0.01). EDS significantly predicted an increased risk of developing neurodegenerative diseases (adjusted hazard ratios [HR] = 2.56, 95% confidence interval [CI] 1.37-4.77) after adjusting for age, sex, body mass index, current depression, obstructive sleep apnea, and periodic limb movement during sleep. Further analyses demonstrated that EDS predicted the conversion of Parkinson's disease (PD) (adjusted HR = 3.55, 95% CI 1.59-7.89), but not dementia (adjusted HR = 1.48, 95% CI 0.44-4.97).
CONCLUSIONS: EDS is associated with an increased risk of developing neurodegenerative diseases, especially PD, in patients with iRBD. Our findings suggest that EDS is a potential clinical biomarker of α-synucleinopathies in iRBD.
Thursday, 23 March 2017
Predictive markers for early conversion of iRBD to neurodegenerative synucleinopathy diseases
Nice new paper on predictors for conversion to a 'degenerative synucleinopathy' in patients with iRBD... as expected DAT SPECT is one of those predictors... this field is shaping up nicely in terms of identifying a group to trial neuroprotective agents directed against abnormal and aggregated synuclein... a word of caution, as always, degenerative synucleinopathy describes PD, MSA and LBD, not simply PD...
Yuanyuan Li, PhD, Wenyan Kang, PhD, Qiong Yang, MS, Lina Zhang, MS, Linyuan Zhang, PhD, Fangyi Dong, MS, Shengdi Chen, MD, PhD and Jun Liu, MD, PhD
Neurology
Published online before print March 22, 2017, doi: http://dx.doi.org/10.1212/WNL.0000000000003838 Neurology 10.1212/WNL.0000000000003838
http://www.neurology.org/content/early/2017/03/22/WNL.0000000000003838.short?rss=1&utm_source=dlvr.it&utm_medium=twitter
Objective: To determine the predictive value of clinical assessment and dopamine transporter (DAT) uptake for the early development of neurodegenerative synucleinopathy diseases from idiopathic REM sleep behavior disorder (iRBD) over 5 years in a Chinese population.
Methods: Forty-three patients with iRBD were administered clinical assessment tests, and 35 were examined by DAT-SPECT imaging during 2011. Cox proportional hazard and Kaplan-Meier analyses were used to evaluate the predictive value of the markers in a follow-up study over 5 years.
Results: Eighteen patients (41.9%) developed neurodegenerative synucleinopathy diseases after a median of 4.1 years of prospective follow-up (median interval of 10.5 years from the estimated onset of iRBD symptoms). Patients with higher scores on the Nonmotor Symptom Questionnaire (hazard ratio [HR] 3.11, 95% confidence interval [CI] 1.15–8.40, p = 0.026) and Scale for Outcomes in Parkinson Disease–Autonomic questionnaire (HR 4.46, 95% CI 1.64–12.10, p = 0.003) were more likely to develop neurodegenerative synucleinopathy diseases. Furthermore, the population with decreased 99mTc-TRODAT-1 binding in the left striatum (HR 2.7, 95% CI 1.02–7.14, p = 0.046) and putamen (HR 3.23, 95% CI 1.16–8.33, p = 0.024) had a relatively higher risk of developing neurodegenerative synucleinopathy diseases.
Conclusions: Our findings elucidate the predictive value of autonomic dysfunction and DAT uptake in identifying patients with iRBD at a high risk of progressing into neurodegenerative synucleinopathy diseases and could form a basis for future disease-prevention trials.
Yuanyuan Li, PhD, Wenyan Kang, PhD, Qiong Yang, MS, Lina Zhang, MS, Linyuan Zhang, PhD, Fangyi Dong, MS, Shengdi Chen, MD, PhD and Jun Liu, MD, PhD
Neurology
Published online before print March 22, 2017, doi: http://dx.doi.org/10.1212/WNL.0000000000003838 Neurology 10.1212/WNL.0000000000003838
http://www.neurology.org/content/early/2017/03/22/WNL.0000000000003838.short?rss=1&utm_source=dlvr.it&utm_medium=twitter
Objective: To determine the predictive value of clinical assessment and dopamine transporter (DAT) uptake for the early development of neurodegenerative synucleinopathy diseases from idiopathic REM sleep behavior disorder (iRBD) over 5 years in a Chinese population.
Methods: Forty-three patients with iRBD were administered clinical assessment tests, and 35 were examined by DAT-SPECT imaging during 2011. Cox proportional hazard and Kaplan-Meier analyses were used to evaluate the predictive value of the markers in a follow-up study over 5 years.
Results: Eighteen patients (41.9%) developed neurodegenerative synucleinopathy diseases after a median of 4.1 years of prospective follow-up (median interval of 10.5 years from the estimated onset of iRBD symptoms). Patients with higher scores on the Nonmotor Symptom Questionnaire (hazard ratio [HR] 3.11, 95% confidence interval [CI] 1.15–8.40, p = 0.026) and Scale for Outcomes in Parkinson Disease–Autonomic questionnaire (HR 4.46, 95% CI 1.64–12.10, p = 0.003) were more likely to develop neurodegenerative synucleinopathy diseases. Furthermore, the population with decreased 99mTc-TRODAT-1 binding in the left striatum (HR 2.7, 95% CI 1.02–7.14, p = 0.046) and putamen (HR 3.23, 95% CI 1.16–8.33, p = 0.024) had a relatively higher risk of developing neurodegenerative synucleinopathy diseases.
Conclusions: Our findings elucidate the predictive value of autonomic dysfunction and DAT uptake in identifying patients with iRBD at a high risk of progressing into neurodegenerative synucleinopathy diseases and could form a basis for future disease-prevention trials.
Sunday, 19 March 2017
Meta-analysis of dorsolateral nigral hyperintensity on magnetic resonance imaging as a marker for Parkinson's disease
Nice paper by friends in Austria... imaging markers for PD, beyond those we already have, are desperately needed. This nice meta-analysis shows that the MRI can be used differentiate patients from controls effectively. The results are shown for 3 Tesla MRI and 7 Tesla. Fortunately 3T MRI performs almost as well as 7T, because lots of hospitals may not have access to 7T imaging. Now it is important to try and work out far before diagnosis this change occurs, and whether it changes over time...
Mov Disord. 2017 Feb 2. doi: 10.1002/mds.26932. [Epub ahead of print]
Mahlknecht P, Krismer F, Poewe W, Seppi K.
http://onlinelibrary.wiley.com/doi/10.1002/mds.26932/abstract
BACKGROUND: Dorsolateral nigral hyperintensity on iron-sensitive magnetic resonance imaging (MRI) sequences seems to be a typical finding in Parkinson's disease (PD), but most studies have involved small samples and have had heterogeneous control populations.
OBJECTIVES: The objective of this study was to perform a meta-analysis on dorsolateral nigral hyperintensity as an imaging marker for PD.
METHODS: The methods included a systematic literature search and a hierarchical summary receiver operating characteristics curve approach.
RESULTS: Of the 16 identified studies, 10 were suitable for analysis, including 364 PD and 231 control cases. The meta-analysis showed an overall sensitivity and specificity of the absence of dorsolateral nigral hyperintensity for PD versus controls of 97.7% and 94.6% (3 and 7 Tesla) and of 94.6% and 94.4% (3 Tesla only). Descriptive analysis among the 4 studies including patients with non-PD parkinsonism showed that dorsolateral nigral hyperintensity was absent in 89.4% of cases with atypical parkinsonian disorders (n = 74), but only in 21.7% of cases with non-neurodegenerative parkinsonism (n = 69). Moreover, in 2 of these studies, the absence of dorsolateral nigral hyperintensity predicted ipsilateral dopamine-transporter deficiency with 87.5% sensitivity and 83.6% specificity.
CONCLUSIONS: Visual assessment of dorsolateral nigral hyperintensity on iron-sensitive MRI sequences provides excellent diagnostic accuracy for PD versus controls. Moreover, its loss appears to be a marker of nigral pathology and holds the potential for the differentiation of neurodegenerative from non-neurodegenerative parkinsonian disorders.
Mov Disord. 2017 Feb 2. doi: 10.1002/mds.26932. [Epub ahead of print]
Mahlknecht P, Krismer F, Poewe W, Seppi K.
http://onlinelibrary.wiley.com/doi/10.1002/mds.26932/abstract
BACKGROUND: Dorsolateral nigral hyperintensity on iron-sensitive magnetic resonance imaging (MRI) sequences seems to be a typical finding in Parkinson's disease (PD), but most studies have involved small samples and have had heterogeneous control populations.
OBJECTIVES: The objective of this study was to perform a meta-analysis on dorsolateral nigral hyperintensity as an imaging marker for PD.
METHODS: The methods included a systematic literature search and a hierarchical summary receiver operating characteristics curve approach.
RESULTS: Of the 16 identified studies, 10 were suitable for analysis, including 364 PD and 231 control cases. The meta-analysis showed an overall sensitivity and specificity of the absence of dorsolateral nigral hyperintensity for PD versus controls of 97.7% and 94.6% (3 and 7 Tesla) and of 94.6% and 94.4% (3 Tesla only). Descriptive analysis among the 4 studies including patients with non-PD parkinsonism showed that dorsolateral nigral hyperintensity was absent in 89.4% of cases with atypical parkinsonian disorders (n = 74), but only in 21.7% of cases with non-neurodegenerative parkinsonism (n = 69). Moreover, in 2 of these studies, the absence of dorsolateral nigral hyperintensity predicted ipsilateral dopamine-transporter deficiency with 87.5% sensitivity and 83.6% specificity.
CONCLUSIONS: Visual assessment of dorsolateral nigral hyperintensity on iron-sensitive MRI sequences provides excellent diagnostic accuracy for PD versus controls. Moreover, its loss appears to be a marker of nigral pathology and holds the potential for the differentiation of neurodegenerative from non-neurodegenerative parkinsonian disorders.
Thursday, 16 March 2017
Oral ambroxol increases brain glucocerebrosidase activity in a non-human primate
Generally speaking, I am not a big fan of animal studies... here we see that Ambroxol (found in cough syrups) can alter GCase activity. Important work no doubt, and I guess the rationale was to demonstrate that it crosses the blood brain barrier....
Synapse. 2017 Mar 12. doi: 10.1002/syn.21967. [Epub ahead of print]
Migdalska-Richards A, Ko WK, Li Q, Bezard E, Schapira AH
Mutations in the glucocerebrosidase 1 (GBA1) gene are related to both Parkinson disease (PD) and Gaucher disease (GD). In both cases, the condition is associated with deficiency of glucocerebrosidase (GCase), the enzyme encoded by GBA1. Ambroxol is a small molecule chaperone that has been shown in mice to cross the blood-brain barrier, increase GCase activity and reduce alpha-synuclein protein levels. In this study we analyze the effect of ambroxol treatment on GCase activity in healthy non-human primates. We show that daily administration of ambroxol results in increased brain GCase activity. Our work further indicates that ambroxol should be investigated as a novel therapy for both PD and neuronopathic GD in humans.
Synapse. 2017 Mar 12. doi: 10.1002/syn.21967. [Epub ahead of print]
Migdalska-Richards A, Ko WK, Li Q, Bezard E, Schapira AH
Mutations in the glucocerebrosidase 1 (GBA1) gene are related to both Parkinson disease (PD) and Gaucher disease (GD). In both cases, the condition is associated with deficiency of glucocerebrosidase (GCase), the enzyme encoded by GBA1. Ambroxol is a small molecule chaperone that has been shown in mice to cross the blood-brain barrier, increase GCase activity and reduce alpha-synuclein protein levels. In this study we analyze the effect of ambroxol treatment on GCase activity in healthy non-human primates. We show that daily administration of ambroxol results in increased brain GCase activity. Our work further indicates that ambroxol should be investigated as a novel therapy for both PD and neuronopathic GD in humans.
Monday, 13 March 2017
Dopamine transporter imaging does not predict the number of nigral neurons in Parkinson disease
How important could this paper turn out to be?!! It addresses one of the key questions regarding DAT-SPECT imaging and PD - does DAT deficit indicate neuronal loss or dysfunction?? This is important because once cells have gone, they are not coming back, but with dysfunction comes the hope of being able to restore function.
The numbers are small I know, but this provides further support that the DAT-SPECT could be a good biomarker of prodromal PD... perhaps not just by showing a slowing of decline over time, but potentially even an improvement in appearances given the right neuro-protective agent...
Neurology. 2017 Mar 10. pii: 10.1212/WNL.0000000000003810. doi: 10.1212/WNL.0000000000003810. [Epub ahead of print]
Saari L, Kivinen K, Gardberg M, Joutsa J, Noponen T, Kaasinen V.
http://www.neurology.org/content/early/2017/03/10/WNL.0000000000003810.long
OBJECTIVE: To examine possible associations between in vivo brain dopamine transporter SPECT imaging and substantia nigra pars compacta (SNc) neuronal survival in Parkinson disease (PD).
METHODS: Nigral neuron numbers were calculated for 18 patients (11 patients with neuropathologically confirmed PD) who had been examined with dopamine transporter (DAT) SPECT before death. Correlation analyses between SNc tyrosine hydroxylase (TH)-positive and neuromelanin-containing neuron counts and DAT striatal specific binding ratios (SBRs) were performed with semiquantitative region of interest-based and voxel-based analyses.
RESULTS: Mean putamen SBR did not correlate with the number of substantia nigra TH-positive (r = -0.11, p = 0.66) or neuromelanin-containing (r = -0.07, p = 0.78) neurons. Correlations remained clearly nonsignificant when the time interval between SPECT and death was used as a covariate, when the voxel-based analysis was used, and when only patients with PD were included.
CONCLUSIONS: This cohort study demonstrates that postmortem SNc neuron counts are not associated with striatal DAT binding in PD. These results fit with the theory that there is no correlation between the number of substantia nigra neurons and striatal dopamine after a certain level of damage has occurred. Striatal DAT binding in PD may reflect axonal dysfunction or DAT expression rather than the number of viable neurons.
The numbers are small I know, but this provides further support that the DAT-SPECT could be a good biomarker of prodromal PD... perhaps not just by showing a slowing of decline over time, but potentially even an improvement in appearances given the right neuro-protective agent...
Neurology. 2017 Mar 10. pii: 10.1212/WNL.0000000000003810. doi: 10.1212/WNL.0000000000003810. [Epub ahead of print]
Saari L, Kivinen K, Gardberg M, Joutsa J, Noponen T, Kaasinen V.
http://www.neurology.org/content/early/2017/03/10/WNL.0000000000003810.long
OBJECTIVE: To examine possible associations between in vivo brain dopamine transporter SPECT imaging and substantia nigra pars compacta (SNc) neuronal survival in Parkinson disease (PD).
METHODS: Nigral neuron numbers were calculated for 18 patients (11 patients with neuropathologically confirmed PD) who had been examined with dopamine transporter (DAT) SPECT before death. Correlation analyses between SNc tyrosine hydroxylase (TH)-positive and neuromelanin-containing neuron counts and DAT striatal specific binding ratios (SBRs) were performed with semiquantitative region of interest-based and voxel-based analyses.
RESULTS: Mean putamen SBR did not correlate with the number of substantia nigra TH-positive (r = -0.11, p = 0.66) or neuromelanin-containing (r = -0.07, p = 0.78) neurons. Correlations remained clearly nonsignificant when the time interval between SPECT and death was used as a covariate, when the voxel-based analysis was used, and when only patients with PD were included.
CONCLUSIONS: This cohort study demonstrates that postmortem SNc neuron counts are not associated with striatal DAT binding in PD. These results fit with the theory that there is no correlation between the number of substantia nigra neurons and striatal dopamine after a certain level of damage has occurred. Striatal DAT binding in PD may reflect axonal dysfunction or DAT expression rather than the number of viable neurons.
Saturday, 11 March 2017
Clinical manifestations of nonmotor symptoms in 1021 Japanese Parkinson's disease patients from 35 medical centers
Good paper showing the distribution of non motor features in Japanese patients with PD... unsurprising to see constipation and sleep disorders among the most frequent... interesting to see that a number of features vary according to gender... this fits with ones experience seeing patients in the clinic as well...
Parkinsonism Relat Disord. 2017 Feb 21. pii: S1353-8020(17)30074-3. doi: 10.1016/j.parkreldis.2017.02.024. [Epub ahead of print] Maeda T, Shimo Y, Chiu SW, Yamaguchi T, Kashihara K, Tsuboi Y, Nomoto M, Hattori N, Watanabe H, Saiki H; J-FIRST group.
INTRODUCTION: We aimed to investigate the prevalence and severity of nonmotor symptoms (NMSs) and to identify factors affecting NMSs and the health-related quality of life of Japanese patients with Parkinson's disease (PD).
METHODS: A total of 1021 patients with PD who had one or more NMS and showed wearing-off under anti-parkinsonian treatment were enrolled from 35 medical centers in Japan for this observational study. The primary measurements were the Movement Disorder Society unified Parkinson's disease rating scale (MDS-UPDRS) part I and the Parkinson's Disease Questionnaire (PDQ-8). The relationships of MDS-UPDRS and PDQ-8 with the patient's clinical background and undertaken medical interventions were determined. Here, we report baseline data of our 52-week ongoing study.
RESULTS: The mean MDS-UPDRS part I and PDQ-8 scores were 10.9 and 7.3, respectively. The most common NMSs were constipation problems (85.4%), sleep problems (73.7%), pain and other sensations (72.7%) and daytime sleepiness (72.0%). Fatigue was an NMS that affected 79.6% of females but only 72.6% of males, whereas features of dopamine dysregulation syndrome affected only 5.6% of females and 10.8% of males. Positive correlations were found between the MDS-UPDRS part I and the PDQ-8 (p < 0.0001, r = 0.56) and between the number of NMSs and the PDQ-8 score (p < 0.0001, r = 0.47).
CONCLUSIONS: This study revealed distinctive patterns of NMSs in Japanese patients with PD and suggested that the prevalence and severity of NMSs vary between sexes, and that the NMSs are important factors affecting the long-term quality of life of PD patients. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Parkinsonism Relat Disord. 2017 Feb 21. pii: S1353-8020(17)30074-3. doi: 10.1016/j.parkreldis.2017.02.024. [Epub ahead of print] Maeda T, Shimo Y, Chiu SW, Yamaguchi T, Kashihara K, Tsuboi Y, Nomoto M, Hattori N, Watanabe H, Saiki H; J-FIRST group.
INTRODUCTION: We aimed to investigate the prevalence and severity of nonmotor symptoms (NMSs) and to identify factors affecting NMSs and the health-related quality of life of Japanese patients with Parkinson's disease (PD).
METHODS: A total of 1021 patients with PD who had one or more NMS and showed wearing-off under anti-parkinsonian treatment were enrolled from 35 medical centers in Japan for this observational study. The primary measurements were the Movement Disorder Society unified Parkinson's disease rating scale (MDS-UPDRS) part I and the Parkinson's Disease Questionnaire (PDQ-8). The relationships of MDS-UPDRS and PDQ-8 with the patient's clinical background and undertaken medical interventions were determined. Here, we report baseline data of our 52-week ongoing study.
RESULTS: The mean MDS-UPDRS part I and PDQ-8 scores were 10.9 and 7.3, respectively. The most common NMSs were constipation problems (85.4%), sleep problems (73.7%), pain and other sensations (72.7%) and daytime sleepiness (72.0%). Fatigue was an NMS that affected 79.6% of females but only 72.6% of males, whereas features of dopamine dysregulation syndrome affected only 5.6% of females and 10.8% of males. Positive correlations were found between the MDS-UPDRS part I and the PDQ-8 (p < 0.0001, r = 0.56) and between the number of NMSs and the PDQ-8 score (p < 0.0001, r = 0.47).
CONCLUSIONS: This study revealed distinctive patterns of NMSs in Japanese patients with PD and suggested that the prevalence and severity of NMSs vary between sexes, and that the NMSs are important factors affecting the long-term quality of life of PD patients. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
Subscribe to:
Posts (Atom)