Evidence map›Paper›PMID 40392924›Full record

ArticlePloS one2025

Amphetamine use and Parkinson's disease: integration of artificial intelligence prediction, clinical corroboration, and mechanism of action analyses.

Maria P Gorenflo, Zhenxiang Gao, Pamela B Davis, David Kaelber, Rong Xu

Abstract read
In one paragraph

Article in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors.

Maria P GorenfloCenter for Artificial Intelligence in Drug Discovery, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America.ORCID 0000-0003-1145-6823
Zhenxiang GaoCenter for Artificial Intelligence in Drug Discovery, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America.
Pamela B DavisCenter for Community Health Integration, Case Western Reserve University School of Medicine, Euclid Avenue, Cleveland, Ohio, United States of America.
David KaelberCenter for Clinical Informatics Research and Education, The MetroHealth System, MetroHealth Drive, Cleveland, Ohio, United States of America.ORCID 0000-0001-7855-9515
Rong XuCenter for Artificial Intelligence in Drug Discovery, School of Medicine, Case Western Reserve University, Cleveland, Ohio, United States of America.ORCID 0000-0003-3127-4795

Funding

Clinical and Translational Science Collaborative of ClevelandUL1TR002548 · NCATS · CASE WESTERN RESERVE UNIVERSITY · PI MCCOMSEY, GRACE A · 2018 to 2022
$35.5M
Collision of Alzheimers disease and COVID-19 pandemic in the United States: risks, outcomes, disparities and treatmentsRF1AG076649 · NIA · CASE WESTERN RESERVE UNIVERSITY · PI DAVIS, PAMELA B, XU, RONG · 2022 to 2022
$2.3M
Characterize multifaceted interactions between COVID-19 and alcohol use disorder based on real-time analysis of electronic health records of 62 million adult patientsR01AA029831 · NIAAA · CASE WESTERN RESERVE UNIVERSITY · PI DAVIS, PAMELA B, XU, RONG · 2021 to 2023
$1.1M
NCATS NIH HHS UL1 TR002548NIAAA NIH HHS R01 AA029831NIA NIH HHS RF1 AG076649
6 · The paper itself

Abstract

Parkinson's disease (PD) is an increasingly prevalent neurologic condition for which symptomatic, but not preventative, treatment is available. Drug repurposing is an innovate drug discovery method that uncovers existing therapeutics to treat or prevent conditions for which they are not currently indicated, a method that could be applied to incurable diseases such as PD. A knowledge graph artificial intelligence prediction system was used to select potential drugs that could be used to treat or prevent PD, and amphetamine was identified as the strongest candidate. Retrospective cohort analysis on a large, electronic health record database of deidentified patients with attention deficit hyperactive disorder (the main diagnosis for which amphetamine is prescribed) revealed a significantly reduced hazard of developing PD in patients prescribed amphetamine versus patients not prescribed amphetamine at 2, 4, and 6 years: Hazard Ratio (95% Confidence Interval) = 0.59 (0.36, 0.98), 0.63 (0.42, 0.93), and 0.55 (0.38, 0.79). Pathway enrichment analysis confirmed that amphetamine targets many of the biochemical processes implicated in PD, such as dopaminergic synapses and neurodegeneration. Together, these observational findings suggest that therapeutic and legal amphetamine use may reduce the risk of developing PD, in contrast to previous work that found the inverse relationship in patients using amphetamine recreationally.

Indexed as

AmphetamineArtificial IntelligenceParkinson DiseaseAgedAttention Deficit Disorder with HyperactivityDrug RepositioningFemaleHumansMaleMiddle AgedRetrospective StudiesAmphetamine

Identifiers

PMID40392924
PMCPMC12091834

What OpenQuestion holds

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Registered trials

None linked

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.