Frontiers in neurology · 2026
Evidence for exponential progression in advanced Parkinson's disease: retrospective analysis of a prospective cohort study.
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Yener Sophie Merve, Ding Catherine, Ganesvaran Ganga, Alty Jane E, Clissold Benjamin G, McColl Craig D, Reardon Katrina A, Schiff Mark, Kempster Peter A
Аннотация
INTRODUCTION: While prospective cohort research in Parkinson's disease (PD) suggests a linear increase in motor disability, there is some clinico-pathological evidence for exponential progression in the final disease stage.
METHODS: Thirty-four patients with PD composed a long-term cohort. Defined off state with levodopa test dose motor scoring on a modified Webster disability scale and Mini-Mental State Examination (MMSE) were conducted every 3 years. Twenty-four patients had 2 or more assessments. For each progression segment, defined as the interval between consecutive assessments, motor progression was calculated as the annual percentage increase of maximum disability score. The entire disease duration is now known for all members of this cohort. Serial motor scores were aligned with time of death, permitting late and earlier observations to be separated for analysis. Progression segments were classified in 3 ways to capture the advanced stage of PD-i) the final segment for each participant; ii) any segment that concluded within 5 years of death; iii) any segment that concluded with a MMSE score < 24. Each advanced category was compared with all other segments from the cohort.
RESULTS: Median age at death was 78.4. Mean disease duration was 14.5 years. Late off scores progressed twice as fast, and on scores three times as fast, as earlier disease segments (p < 0.001 for all comparisons). Classification by presence of cognitive impairment had the strongest effect.
DISCUSSION: Progression of motor disability accelerates in advanced PD. It is possible that the entire disease course has an exponential character.
METHODS: Thirty-four patients with PD composed a long-term cohort. Defined off state with levodopa test dose motor scoring on a modified Webster disability scale and Mini-Mental State Examination (MMSE) were conducted every 3 years. Twenty-four patients had 2 or more assessments. For each progression segment, defined as the interval between consecutive assessments, motor progression was calculated as the annual percentage increase of maximum disability score. The entire disease duration is now known for all members of this cohort. Serial motor scores were aligned with time of death, permitting late and earlier observations to be separated for analysis. Progression segments were classified in 3 ways to capture the advanced stage of PD-i) the final segment for each participant; ii) any segment that concluded within 5 years of death; iii) any segment that concluded with a MMSE score < 24. Each advanced category was compared with all other segments from the cohort.
RESULTS: Median age at death was 78.4. Mean disease duration was 14.5 years. Late off scores progressed twice as fast, and on scores three times as fast, as earlier disease segments (p < 0.001 for all comparisons). Classification by presence of cognitive impairment had the strongest effect.
DISCUSSION: Progression of motor disability accelerates in advanced PD. It is possible that the entire disease course has an exponential character.