SynthesisBrain : a journal of neurology2023
Association between the LRP1B and APOE loci and the development of Parkinson's disease dementia.
Synthesis in Brain : a journal of neurology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 2 syntheses or guidelines pooled it, 57 citations in OpenAlex.
- Prognosis in Parkinson's Disease: An Individual Patient Data Meta-Analysis of Six European Incidence Cohorts.Movement disorders : official journal of the Movement Disorder Society · 2026Pooled it
- Mapping the research landscape of Mild Cognitive Impairment in Parkinson's disease: a bibliometric and visualization analysis.Frontiers in aging neuroscience · 2025Pooled it
- Co- and Multi-Pathologies in Parkinson's Disease: An International Parkinson and Movement Disorder Society Scientific Issues Committee Review.Movement disorders : official journal of the Movement Disorder Society · 2026Review
- Advances in biomarkers for Parkinson's disease: from molecular pathology to precision diagnostics.Journal of Zhejiang University. Science. B · 2026Review
- Understanding the genetic imperfections of Lewy body dementia.Molecular neurodegeneration · 2026Review
- Using iPSC models to examine neuron-glia interactions in neurodegenerative diseases.Bioscience reports · 2026Review
- Multi-locus genetic dosage shapes cognitive disease progression in Parkinson's patients: 15-year meta-analysis of 24 cohorts.NPJ Parkinson's disease · 2026Article
- How does type 2 diabetes modify the risk of Alzheimer's disease?Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- APOE, Aβ42, and tau differentially impact cognitive decline in Sporadic, GBA1 and LRRK2 Parkinson's disease.NPJ Parkinson's disease · 2026Article
- Genetic Modifiers of Parkinson's Disease: A Case-Control Study.Annals of clinical and translational neurology · 2025Observational
- Neuropathology of Lewy body dementia: Lewy-related pathology, α-synuclein oligomers, and comorbid pathologies.Molecular neurodegeneration · 2025Review
- Tackling a disease on a global scale, the Global Parkinson's Genetics Program, GP2: A new generation of opportunities.American journal of human genetics · 2025Review
- APOE ε4 carriers share immune-related proteomic changes across neurodegenerative diseases.Nature medicine · 2025Article
- Review
- Crosstalk Between the Nervous System and Colorectal Cancer.Neuroscience bulletin · 2025Review
- Mitochondrial dysfunction, cause or consequence in neurodegenerative diseases?BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- The role ofFrontiers in neuroscience · 2025Review
- Neuropsychiatric disorders in Parkinson's disease.Therapeutic advances in neurological disorders · 2025Review
- Association of CSF α-synuclein seed amplification assay positivity with disease progression and cognitive decline: A longitudinal Alzheimer's Disease Neuroimaging Initiative study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Mutational landscape of risk variants in comorbid depression and obesity: a next-generation sequencing approach.Molecular psychiatry · 2024Article
Corrections and comments
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Authors and funding
21 authors at 12 institutions in 6 countries.
Funding
Abstract
Parkinson's disease is one of the most common age-related neurodegenerative disorders. Although predominantly a motor disorder, cognitive impairment and dementia are important features of Parkinson's disease, particularly in the later stages of the disease. However, the rate of cognitive decline varies among Parkinson's disease patients, and the genetic basis for this heterogeneity is incompletely understood. To explore the genetic factors associated with rate of progression to Parkinson's disease dementia, we performed a genome-wide survival meta-analysis of 3923 clinically diagnosed Parkinson's disease cases of European ancestry from four longitudinal cohorts. In total, 6.7% of individuals with Parkinson's disease developed dementia during study follow-up, on average 4.4 ± 2.4 years from disease diagnosis. We have identified the APOE ε4 allele as a major risk factor for the conversion to Parkinson's disease dementia [hazard ratio = 2.41 (1.94-3.00), P = 2.32 × 10-15], as well as a new locus within the ApoE and APP receptor LRP1B gene [hazard ratio = 3.23 (2.17-4.81), P = 7.07 × 10-09]. In a candidate gene analysis, GBA variants were also identified to be associated with higher risk of progression to dementia [hazard ratio = 2.02 (1.21-3.32), P = 0.007]. CSF biomarker analysis also implicated the amyloid pathway in Parkinson's disease dementia, with significantly reduced levels of amyloid β42 (P = 0.0012) in Parkinson's disease dementia compared to Parkinson's disease without dementia. These results identify a new candidate gene associated with faster conversion to dementia in Parkinson's disease and suggest that amyloid-targeting therapy may have a role in preventing Parkinson's disease dementia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.