Background. Depression is a common problem in patients with Parkinson's disease, but its mech... more Background. Depression is a common problem in patients with Parkinson's disease, but its mechanism is poorly understood. It is thought that neurochemical changes contribute to its occurrence, but it is unclear why some patients develop depression and others do not. Using a community-based sample of patients with Parkinson's disease, we investigated the contributions of impairment, disability and handicap to depression in Parkinson's disease.Methods. Ninety-seven patients seen in a population-based study on the prevalence of Parkinson's disease completed the Beck Depression Inventory (BDI). Clinical and historical information on symptoms and complications of Parkinson's disease were obtained from the patients by a neurologist. In addition, clinician and patient ratings of disability on the Schwab and England scale were obtained and a quality of life questionnaire was completed.Results. Moderate to severe depression (BDI [ges ] 18) was reported by 19·6% of the pati...
A 45 year-old man presented with a rapid onset of memory impairment Brain computed tomography sho... more A 45 year-old man presented with a rapid onset of memory impairment Brain computed tomography showed multiple abnormal low density areas in the deep cerebral white matter. Magnetic resonance imaging revealed bilateral thalamic infarcts and extensive thrombosis of the vein of Galen and the straight sinus, which was confirmed by cerebral angiography. The only potential cause was protein S deficiency. Heparin therapy was started only after the occurrence of a pulmonary embolism. The outcome was excellent Deep cerebral venous thrombosis must be considered as a possible cause of amnestic syndrome. Clinical awareness and early use of anticoagulation may alter the usual fatal outcome.
An Erratum has been published for this article in Ann Neurol 2004;55:899.The reported inverse ass... more An Erratum has been published for this article in Ann Neurol 2004;55:899.The reported inverse association between the S18Y variant of the ubiquitin carboxy‐terminal hydrolase L1 (UCHL1) gene and Parkinson's disease (PD) has strong biological plausibility. If confirmed, genetic association of this variant with PD may support molecular targeting of the UCHL1 gene and its product as a therapeutic strategy for PD. In this light, we performed a collaborative pooled analysis of individual‐level data from all 11 published studies of the UCHL1 S18Y gene variant and PD. There were 1,970 cases and 2,224 unrelated controls. We found a statistically significant inverse association of S18Y with PD. Carriers of the variant allele (Y/Y plus Y/S vs S/S) had an odds ratio (OR) of 0.84 (95% confidence interval [CI], 0.73–0.95) and homozygotes for the variant allele (Y/Y vs S/S plus Y/S) had an OR of 0.71 (95% CI, 0.57–0.88). There was a linear trend in the log OR consistent with a gene dose effec...
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2009
Early genome‐wide association (GWA) studies on Parkinson's disease (PD) have not been able to... more Early genome‐wide association (GWA) studies on Parkinson's disease (PD) have not been able to yield conclusive, replicable signals of association, perhaps due to limited sample size. We aimed to investigate whether association signals derived from the meta‐analysis of the first two GWA investigations might be replicable in different populations. We examined six single‐nucleotide polymorphisms (SNPs) (rs1000291, rs1865997, rs2241743, rs2282048, rs2313982, and rs3018626) that had reached nominal significance with at least two of three different strategies proposed in a previous analysis of the original GWA studies. Investigators from the “Genetic Epidemiology of Parkinson's Disease” (GEOPD) consortium were invited to join in this study. Ten teams contributed replication data from 3,458 PD cases and 3,719 controls. The data from the two previously published GWAs (599 PD cases, 592 controls and 443 sibling pairs) were considered as well. All data were synthesized using both fixe...
A recent study MacLeod et al. has shown that an interaction between variants at the LRRK2 and PAR... more A recent study MacLeod et al. has shown that an interaction between variants at the LRRK2 and PARK16 loci influences risk of development of Parkinson's disease (PD). Our study examines the proposed interaction between LRRK2 and PARK16 variants in modifying PD risk using a large multicenter series of PD patients (7715) and controls (8261) from sites participating in the Genetic Epidemiology of Parkinson's Disease Consortium. Our data does not support a strong direct interaction between LRRK2 and PARK16 variants; however, given the role of retromer and lysosomal pathways in PD, further studies are warranted.
We aim to clarify the pathogenic role of intermediate size repeat expansions of SCA2, SCA3, SCA6,... more We aim to clarify the pathogenic role of intermediate size repeat expansions of SCA2, SCA3, SCA6, and SCA17 as risk factors for idiopathic Parkinson disease (PD). We invited researchers from the Genetic Epidemiology of Parkinson's Disease Consortium to participate in the study. There were 12,346 cases and 8,164 controls genotyped, for a total of 4 repeats within the SCA2, SCA3, SCA6, and SCA17 genes. Fixed- and random-effects models were used to estimate the summary risk estimates for the genes. We investigated between-study heterogeneity and heterogeneity between different ethnic populations. We did not observe any definite pathogenic repeat expansions for SCA2, SCA3, SCA6, and SCA17 genes in patients with idiopathic PD from Caucasian and Asian populations. Furthermore, overall analysis did not reveal any significant association between intermediate repeats and PD. The effect estimates (odds ratio) ranged from 0.93 to 1.01 in the overall cohort for the SCA2, SCA3, SCA6, and SCA...
Background. Depression is a common problem in patients with Parkinson's disease, but its mech... more Background. Depression is a common problem in patients with Parkinson's disease, but its mechanism is poorly understood. It is thought that neurochemical changes contribute to its occurrence, but it is unclear why some patients develop depression and others do not. Using a community-based sample of patients with Parkinson's disease, we investigated the contributions of impairment, disability and handicap to depression in Parkinson's disease.Methods. Ninety-seven patients seen in a population-based study on the prevalence of Parkinson's disease completed the Beck Depression Inventory (BDI). Clinical and historical information on symptoms and complications of Parkinson's disease were obtained from the patients by a neurologist. In addition, clinician and patient ratings of disability on the Schwab and England scale were obtained and a quality of life questionnaire was completed.Results. Moderate to severe depression (BDI [ges ] 18) was reported by 19·6% of the pati...
A 45 year-old man presented with a rapid onset of memory impairment Brain computed tomography sho... more A 45 year-old man presented with a rapid onset of memory impairment Brain computed tomography showed multiple abnormal low density areas in the deep cerebral white matter. Magnetic resonance imaging revealed bilateral thalamic infarcts and extensive thrombosis of the vein of Galen and the straight sinus, which was confirmed by cerebral angiography. The only potential cause was protein S deficiency. Heparin therapy was started only after the occurrence of a pulmonary embolism. The outcome was excellent Deep cerebral venous thrombosis must be considered as a possible cause of amnestic syndrome. Clinical awareness and early use of anticoagulation may alter the usual fatal outcome.
An Erratum has been published for this article in Ann Neurol 2004;55:899.The reported inverse ass... more An Erratum has been published for this article in Ann Neurol 2004;55:899.The reported inverse association between the S18Y variant of the ubiquitin carboxy‐terminal hydrolase L1 (UCHL1) gene and Parkinson's disease (PD) has strong biological plausibility. If confirmed, genetic association of this variant with PD may support molecular targeting of the UCHL1 gene and its product as a therapeutic strategy for PD. In this light, we performed a collaborative pooled analysis of individual‐level data from all 11 published studies of the UCHL1 S18Y gene variant and PD. There were 1,970 cases and 2,224 unrelated controls. We found a statistically significant inverse association of S18Y with PD. Carriers of the variant allele (Y/Y plus Y/S vs S/S) had an odds ratio (OR) of 0.84 (95% confidence interval [CI], 0.73–0.95) and homozygotes for the variant allele (Y/Y vs S/S plus Y/S) had an OR of 0.71 (95% CI, 0.57–0.88). There was a linear trend in the log OR consistent with a gene dose effec...
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 2009
Early genome‐wide association (GWA) studies on Parkinson's disease (PD) have not been able to... more Early genome‐wide association (GWA) studies on Parkinson's disease (PD) have not been able to yield conclusive, replicable signals of association, perhaps due to limited sample size. We aimed to investigate whether association signals derived from the meta‐analysis of the first two GWA investigations might be replicable in different populations. We examined six single‐nucleotide polymorphisms (SNPs) (rs1000291, rs1865997, rs2241743, rs2282048, rs2313982, and rs3018626) that had reached nominal significance with at least two of three different strategies proposed in a previous analysis of the original GWA studies. Investigators from the “Genetic Epidemiology of Parkinson's Disease” (GEOPD) consortium were invited to join in this study. Ten teams contributed replication data from 3,458 PD cases and 3,719 controls. The data from the two previously published GWAs (599 PD cases, 592 controls and 443 sibling pairs) were considered as well. All data were synthesized using both fixe...
A recent study MacLeod et al. has shown that an interaction between variants at the LRRK2 and PAR... more A recent study MacLeod et al. has shown that an interaction between variants at the LRRK2 and PARK16 loci influences risk of development of Parkinson's disease (PD). Our study examines the proposed interaction between LRRK2 and PARK16 variants in modifying PD risk using a large multicenter series of PD patients (7715) and controls (8261) from sites participating in the Genetic Epidemiology of Parkinson's Disease Consortium. Our data does not support a strong direct interaction between LRRK2 and PARK16 variants; however, given the role of retromer and lysosomal pathways in PD, further studies are warranted.
We aim to clarify the pathogenic role of intermediate size repeat expansions of SCA2, SCA3, SCA6,... more We aim to clarify the pathogenic role of intermediate size repeat expansions of SCA2, SCA3, SCA6, and SCA17 as risk factors for idiopathic Parkinson disease (PD). We invited researchers from the Genetic Epidemiology of Parkinson's Disease Consortium to participate in the study. There were 12,346 cases and 8,164 controls genotyped, for a total of 4 repeats within the SCA2, SCA3, SCA6, and SCA17 genes. Fixed- and random-effects models were used to estimate the summary risk estimates for the genes. We investigated between-study heterogeneity and heterogeneity between different ethnic populations. We did not observe any definite pathogenic repeat expansions for SCA2, SCA3, SCA6, and SCA17 genes in patients with idiopathic PD from Caucasian and Asian populations. Furthermore, overall analysis did not reveal any significant association between intermediate repeats and PD. The effect estimates (odds ratio) ranged from 0.93 to 1.01 in the overall cohort for the SCA2, SCA3, SCA6, and SCA...
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Papers by Peter Silburn