Brain-first forms of Parkinson's disease are over-represented in patients with non-responsive resting tremor

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Abstract

Motor subtypes in Parkinson's Disease (PD) are unstable over time, limiting mechanistic insights and biomarker discovery. We focused on Rest Tremor (RT) as a symptom to test for phenotype stability and link it to specific circuits and disease mechanisms. Using the PPMI cohort data over 5 years we found that RT is more stable than classical Tremor-Dominant definitions, a stability also seen for RT response to therapy. At time of diagnosis, the population of therapy-resistant RT patients was enriched with a brain-first PD profile as predicted by a-Synuclein origin site and connectome (SOC) model. Resistant-RT patients have lower gastrointestinal and cardiovascular symptoms, lower prevalence of probable REM-Sleep behaviour disorder, and higher dopaminergic asymmetry compared to therapy-responsive or no tremor patients. Treating RT as a distinct phenomenon revealed a relative phenotypic stability with treatment response being linked to different patterns of disease progression.

Original languageEnglish
Article number106691
JournalNeurobiology of Disease
Volume201
DOIs
Publication statusPublished - 15 Oct 2024

Keywords

  • Brain-first
  • Circuits
  • Dopamine
  • Parkinson's disease
  • Phenotype
  • Rest tremor

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