Neurobiology of Disease (Oct 2024)

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

  • Marcelo D. Mendonça,
  • Pedro Ferreira,
  • Raquel Barbosa,
  • Joaquim Alves da Silva

Journal volume & issue
Vol. 201
p. 106691

Abstract

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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.

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