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Quantitative Autonomic Testing
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Phenoconversion in Pure Autonomic Failure: A Systematic Review and Meta-Analysis.

Sasivimol Virameteekul1,2, Ilenia Bonini3, Nicole Campese3,4

  • 1Centre for Preventive Neurology, Wolfson Institute of Population Health, Queen Mary University of London, London, United Kingdom.

JAMA Neurology
|May 4, 2026
PubMed
Summary
This summary is machine-generated.

Pure autonomic failure (PAF) can precede Parkinson disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA). Clinical predictors like RBD and hyposmia aid early diagnosis for these α-synucleinopathies.

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Area of Science:

  • Neurology
  • Neuroscience
  • Clinical Medicine

Background:

  • Pure autonomic failure (PAF) is increasingly recognized as a potential prodromal stage for α-synucleinopathies.
  • The phenoconversion rates and clinical predictors for progression from PAF to Parkinson disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA) require systematic evaluation.

Purpose of the Study:

  • To estimate the phenoconversion rates of PAF to MSA, PD, and DLB individually and as a group of central α-synucleinopathies.
  • To identify clinical predictors associated with phenoconversion in individuals diagnosed with PAF.

Main Methods:

  • A systematic review and meta-analysis were conducted using data from PubMed and Embase databases up to June 2025.
  • Included were longitudinal studies reporting on the incidence and/or predictors of phenoconversion in patients with confirmed PAF.
  • Data extraction and synthesis followed PRISMA guidelines, employing random-effects models for meta-analysis of incidence rates and predictors.

Main Results:

  • Nine studies involving 900 individuals with PAF were analyzed. Over a mean follow-up of 6.4 years, 30% phenoconverted to a central α-synucleinopathy.
  • The pooled incidence rate for phenoconversion to any central α-synucleinopathy was 5.09 per 100 person-years. MSA phenoconversion was highest early on, while DLB and PD showed more constant rates.
  • Hyposmia was a predictor for distinguishing PD/DLB from MSA, while rapid eye movement sleep behavior disorder (RBD) and subtle motor signs predicted phenoconversion to any central α-synucleinopathy.

Conclusions:

  • PAF represents a significant prodromal stage for PD, DLB, and MSA, with phenoconversion rates comparable to those of RBD.
  • Combining clinical indicators (RBD, motor signs, hyposmia) with emerging biomarkers can enhance early diagnosis and intervention strategies for individuals with PAF.
  • These findings highlight the potential for early identification and management of neurodegenerative diseases originating from PAF.