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Record W4308709381 · doi:10.1101/2022.11.06.22281991

Impact of <i>APOE</i> genotype on cognition in idiopathic and genetic forms of Parkinson’s disease

2022· preprint· en· W4308709381 on OpenAlexaboutno aff
Christos Koros, Kathrin Brockmann, Athina-Maria Simitsi, Anastasia Bougea, Hui Liu, Ann‐Kathrin Hauser, Claudia Schulte, Stefanie Lerche, Ioanna Pachi, Nikolaos Papagiannakis, Roubina Antonelou, Athina Zahou, Isabel Wurster, Efthymia Efthymiopoulou, Ion Beratis, Matina Maniati, Marina Moraitou, Helen Michelakakis, Sokratis G. Papageorgiou, Constantin Potagas, Dimitra Papadimitriou, Maria Bozi, María Stamelou, Thomas Gasser, Leonidas Stefanis

Bibliographic record

VenuemedRxiv · 2022
Typepreprint
Languageen
FieldMedicine
TopicParkinson's Disease Mechanisms and Treatments
Canadian institutionsnot available
FundersHorizon 2020 Framework ProgrammeMichael J. Fox Foundation for Parkinson's Research
KeywordsApolipoprotein EParkinson's diseaseGenotypeCohortMedicineInternal medicineCognitionMontreal Cognitive AssessmentCognitive declineDiseaseOncologyPsychologyPsychiatryCognitive impairmentGeneticsDementiaBiologyGene

Abstract

fetched live from OpenAlex

Abstract Background Apolipoprotein E-ε4 ( APOE ε4) genotype may be associated with the development of cognitive decline in idiopathic Parkinson’s disease i(PD), however its effect in genetic PD is understudied. Objectives In the current work we aimed to assess the impact of APOE genotype on cognition in iPD as well as in genetic PD with mutations in the Alpha-synuclein ( SNCA ) and Glycocerebrosidase ( GBA1 ) genes. Methods Two independent PD cohorts were analyzed: The first cohort (Athens) included 50 iPD patients, 35 patients with the p.A53T SNCA mutation and 59 patients with GBA1 mutations (13 mild /46 severe). The second cohort (Tübingen) included 292 patients with GBA1 mutations (170 risk/ 52 mild/ 70 severe). All patients underwent cognitive testing and were genotyped for APOE . Results In the iPD subgroup, carriers of at least one APOE ε4 exhibited lower Montreal Cognitive Assessment test (MoCA) score as compared to non-carriers (p=0.044). Notably, in the p.A53T SNCA subgroup, APOE ε4 carriers also had lower MoCA scores compared to non-carriers (p=0.039). There were no APOE ε4-related differences in the two GBA1 subgroups (Athens, p=0.729; Tübingen p=0.585). Conclusions We confirm the impact of APOE ε4 on cognitive decline in iPD and for the first time report a similar effect in p.A53T SNCA mutation carriers, who represent the prototypical genetic synucleinopathy. Contrary, the lack of such an effect in two independent cohorts of GBA1 mutation carriers, who are thought to also manifest a predominant alpha-synuclein-driven cognitive decline, suggests differences in factors associated with cognitive dysfunction between different genetic forms of synucleinopathies.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.006
Threshold uncertainty score0.012

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.001
Bibliometrics0.0010.001
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.022
GPT teacher head0.291
Teacher spread0.269 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations0
Published2022
Admission routes1
Has abstractyes

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