Movement disorders : official journal of the Movement Disorder Society · 2026
Striatal Dopaminergic Reserve Shapes the Longitudinal Impact of Peripheral Immune Activation on Motor Progression in Parkinson's Disease.
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Kahveci Osman, Ay Ulaş, Demiralp Tamer
Аннотация
BACKGROUND: Peripheral immune dysregulation has been implicated in Parkinson's disease (PD) progression, but whether motor deterioration reflects accelerated nigrostriatal degeneration or residual dopaminergic reserve remains unclear.
OBJECTIVES: To examine whether baseline and time-varying neutrophil-to-lymphocyte ratio (NLR) relate to motor progression and striatal dopamine transporter (DAT) decline, and whether baseline DAT modifies the NLR-motor relationship.
METHODS: We analyzed 7 years of Parkinson's Progression Markers Initiative (PPMI) data from 335 drug-naive patients with PD and 305 healthy controls. Linear mixed-effects models assessed NLR trajectories, longitudinal Unified Parkinson's Disease Rating Scale-Part III (UPDRS-III) and DAT associations, and moderation by baseline DAT; follow-up motor assessments were ON-medication.
RESULTS: NLR remained higher in PD than controls (P < 0.001). A 1 SD higher baseline NLR was associated with an additional 0.350 UPDRS-III points/year (P < 0.001), while higher-than-usual visit-wise NLR was associated with higher concurrent motor severity (β = 0.352, P = 0.041). Neither baseline nor time-varying NLR was consistently associated with DAT decline. Higher baseline DAT binding moderated NLR-related motor progression in the left caudate (β = 0.326, P < 0.001), right caudate (β = 0.183, P = 0.036), and left putamen (β = 0.168, P = 0.023); within the DAT-imaging interval, moderation persisted in the left caudate (β = 0.314, P = 0.044) and left putamen (β = 0.223, P = 0.047).
CONCLUSIONS: Higher baseline NLR predicted faster treated-state motor worsening, while visit-wise NLR tracked concurrent severity. These associations were not accompanied by clear evidence of accelerated DAT decline, supporting a reserve-dependent relationship between peripheral inflammation and motor progression. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
OBJECTIVES: To examine whether baseline and time-varying neutrophil-to-lymphocyte ratio (NLR) relate to motor progression and striatal dopamine transporter (DAT) decline, and whether baseline DAT modifies the NLR-motor relationship.
METHODS: We analyzed 7 years of Parkinson's Progression Markers Initiative (PPMI) data from 335 drug-naive patients with PD and 305 healthy controls. Linear mixed-effects models assessed NLR trajectories, longitudinal Unified Parkinson's Disease Rating Scale-Part III (UPDRS-III) and DAT associations, and moderation by baseline DAT; follow-up motor assessments were ON-medication.
RESULTS: NLR remained higher in PD than controls (P < 0.001). A 1 SD higher baseline NLR was associated with an additional 0.350 UPDRS-III points/year (P < 0.001), while higher-than-usual visit-wise NLR was associated with higher concurrent motor severity (β = 0.352, P = 0.041). Neither baseline nor time-varying NLR was consistently associated with DAT decline. Higher baseline DAT binding moderated NLR-related motor progression in the left caudate (β = 0.326, P < 0.001), right caudate (β = 0.183, P = 0.036), and left putamen (β = 0.168, P = 0.023); within the DAT-imaging interval, moderation persisted in the left caudate (β = 0.314, P = 0.044) and left putamen (β = 0.223, P = 0.047).
CONCLUSIONS: Higher baseline NLR predicted faster treated-state motor worsening, while visit-wise NLR tracked concurrent severity. These associations were not accompanied by clear evidence of accelerated DAT decline, supporting a reserve-dependent relationship between peripheral inflammation and motor progression. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.