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.
Monday, 24 April 2017
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.
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