Cortical Thinning Associated with Age and CSF Biomarkers in Early Parkinson’s Disease Is Modified by the SNCA rs356181 Polymorphism

Sampedro, Frederic; Marín‐Lahoz, Juan; Martínez‐Horta, Saül; Pagonabarraga, Javier; Kulisevsky, Jaime

doi:10.1159/000493103

Cited by 7 publications

(7 citation statements)

References 23 publications

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“…c The criteria by which PD was diagnosed. Where “mixed” is indicated for multicenter studies, GEO-PD (included in Chung et al 21 , Elbaz et al 76 , and Maraganore et al 15 ) used UKBB, Gelb, Bower, the Core Assessment Program for Intracerebral Transplantations (CAPIT) and criteria described in Pals et al 81 and PPMI (included in Bjørnarå et al 47 , Sampedro et al 67 , and Caspell-Garcia et al 68 ) used criteria outlined in the study protocol ( http://www.ppmi-info.org ; Parkinson Progression Marker Initiative 82 ). d The number of patients with PD included in the whole study cohort.…”

Section: Resultsmentioning

confidence: 99%

A systematic review of associations between common SNCA variants and clinical heterogeneity in Parkinson’s disease

Pedersen

Lange

Førland

et al. 2021

npj Parkinsons Dis.

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There is great heterogeneity in both the clinical presentation and rate of disease progression among patients with Parkinson’s disease (PD). This can pose prognostic difficulties in a clinical setting, and a greater understanding of the risk factors that contribute to modify disease course is of clear importance for optimizing patient care and clinical trial design. Genetic variants in SNCA are an established risk factor for PD and are candidates to modify disease presentation and progression. This systematic review aimed to summarize all available primary research reporting the association of SNCA polymorphisms with features of PD. We systematically searched PubMed and Web of Science, from inception to 1 June 2020, for studies evaluating the association of common SNCA variants with age at onset (AAO) or any clinical feature attributed to PD in patients with idiopathic PD. Fifty-eight studies were included in the review that investigated the association between SNCA polymorphisms and a broad range of outcomes, including motor and cognitive impairment, sleep disorders, mental health, hyposmia, or AAO. The most reproducible findings were with the REP1 polymorphism or rs356219 and an earlier AAO, but no clear associations were identified with an SNCA polymorphism and any individual clinical outcome. The results of this comprehensive summary suggest that, while there is evidence that genetic variance in the SNCA region may have a small impact on clinical outcomes in PD, the mechanisms underlying the association of SNCA polymorphisms with PD risk may not be a major factor driving clinical heterogeneity in PD.

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Section: Resultsmentioning

confidence: 99%

A systematic review of associations between common SNCA variants and clinical heterogeneity in Parkinson’s disease

Pedersen

Lange

Førland

et al. 2021

npj Parkinsons Dis.

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show abstract

“…Indeed, it has been shown that telomere length may influence the occurrence of dementia in PD patients [ 22 ]. Additionally, several studies have argued for the existence of genetic modifiers of PD clinical presentation, such as TMEM106B [ 23 ], SCNA [ 24 ], and COMT [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

Phenotypic Heterogeneity among GBA p.R202X Carriers in Lewy Body Spectrum Disorders

et al. 2022

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We describe the clinical and neuropathologic features of patients with Lewy body spectrum disorder (LBSD) carrying a nonsense variant, c.604C>T; p.R202X, in the glucocerebrosidase 1 (GBA) gene. While this GBA variant is causative for Gaucher’s disease, the pathogenic role of this mutation in LBSD is unclear. Detailed neuropathologic evaluation was performed for one index case and a structured literature review of other GBA p.R202X carriers was conducted. Through the systematic literature search, we identified three additional reported subjects carrying the same GBA mutation, including one Parkinson’s disease (PD) patient with early disease onset, one case with neuropathologically-verified LBSD, and one unaffected relative of a Gaucher’s disease patient. Among the affected subjects carrying the GBA p.R202X, all males were diagnosed with Lewy body dementia, while the two females presented as PD. The clinical penetrance of GBA p.R202X in LBSD patients and families argues strongly for a pathogenic role for this variant, although presenting with a striking phenotypic heterogeneity of clinical and pathological features.

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“…Genetic variables included individual APOE genotype, MAPT haplotype and the SNPs rs12411216 38 , rs356181 39 and rs3910105 40 . GBA mutation status was included as a binary factor for the presence of any non-synonymous coding mutations present within the GBA region.…”

Section: Methodsmentioning

confidence: 99%

Machine learning-based prediction of cognitive outcomes in de novo Parkinson’s disease

Harvey

Reijnders

Cavill

et al. 2022

Preprint

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Cognitive impairment is a debilitating symptom in Parkinson's disease (PD). We aimed to establish an accurate multivariate machine learning (ML) model to predict cognitive outcome in newly diagnosed PD cases from the Parkinson's Progression Markers Initiative (PPMI). Annual cognitive assessments over an eight-year time span were used to define two cognitive outcomes of i) cognitive impairment, and ii) dementia conversion. Selected baseline variables were organized into three subsets of clinical, biofluid and genetic/epigenetic measures and tested using four different ML algorithms. Irrespective of the ML algorithm used, the models consisting of the clinical variables performed best and showed better prediction of cognitive impairment outcome over dementia conversion. We observed a marginal improvement in the prediction performance when clinical, biofluid, and epigenetic/genetic variables were all included in one model. Several cerebrospinal fluid measures and an epigenetic marker showed high predictive weighting in multiple models when included alongside clinical variables.

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Cortical Thinning Associated with Age and CSF Biomarkers in Early Parkinson’s Disease Is Modified by the SNCA rs356181 Polymorphism

Cited by 7 publications

References 23 publications

A systematic review of associations between common SNCA variants and clinical heterogeneity in Parkinson’s disease

A systematic review of associations between common SNCA variants and clinical heterogeneity in Parkinson’s disease

Phenotypic Heterogeneity among GBA p.R202X Carriers in Lewy Body Spectrum Disorders

Machine learning-based prediction of cognitive outcomes in de novo Parkinson’s disease

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