TY - JOUR
T1 - Brain-first forms of Parkinson's disease are over-represented in patients with non-responsive resting tremor
AU - Mendonça, Marcelo D.
AU - Ferreira, Pedro
AU - Barbosa, Raquel
AU - da Silva, Joaquim Alves
N1 - Publisher Copyright:
© 2024 The Authors
PY - 2024/10/15
Y1 - 2024/10/15
N2 - 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.
AB - 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.
KW - Brain-first
KW - Circuits
KW - Dopamine
KW - Parkinson's disease
KW - Phenotype
KW - Rest tremor
UR - http://www.scopus.com/inward/record.url?scp=85205919085&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2024.106691
DO - 10.1016/j.nbd.2024.106691
M3 - Article
AN - SCOPUS:85205919085
SN - 0969-9961
VL - 201
JO - Neurobiology of Disease
JF - Neurobiology of Disease
M1 - 106691
ER -