Distinct progression patterns across Parkinson disease clinical subtypes

Abstract

Objective To examine specific symptom progression patterns and possible disease staging in Parkinson disease clinical subtypes. Methods We recently identified Parkinson disease clinical subtypes based on comprehensive behavioral evaluations, “Motor Only,” “Psychiatric & Motor,” and “Cognitive & Motor,” which differed in dementia and mortality rates. Parkinson disease participants (“Motor Only”: n = 61, “Psychiatric & Motor”: n = 17, “Cognitive & Motor”: n = 70) and controls (n = 55) completed longitudinal, comprehensive motor, cognitive, and psychiatric evaluations (average follow‐up = 4.6 years). Hierarchical linear modeling examined group differences in symptom progression. A three‐way interaction among time, group, and symptom duration (or baseline age, separately) was incorporated to examine disease stages. Results All three subtypes increased in motor dysfunction compared to controls. The “Motor Only” subtype did not show significant cognitive or psychiatric changes compared to the other two subtypes. The “Cognitive & Motor” subtype’s cognitive dysfunction at baseline further declined compared to the other two subtypes, while also increasing in psychiatric symptoms. The “Psychiatric & Motor” subtype’s elevated psychiatric symptoms at baseline remained steady or improved over time, with mild, steady decline in cognition. The pattern of behavioral changes and analyses for disease staging yielded no evidence for sequential disease stages. Interpretation Parkinson disease clinical subtypes progress in clear, temporally distinct patterns from one another, particularly in cognitive and psychiatric features. This highlights the importance of comprehensive clinical examinations as the order of symptom presentation impacts clinical prognosis.

Two distinct trajectories of clinical and neurodegeneration events in Parkinson’s disease

“…Great efforts to identify subtypes of PD have been made, from the initial classification based on a single motor symptom, to classification based on multidomain phenotypes including motor and non-motor symptoms, neuroimaging data, and biochemical markers [3][4][5][6][7][8] . Owing to the poor reliability and difficulty in characterizing disease heterogeneity, empirical classification methods have lost favor and have been replaced by data-driven methods without a priori hypotheses [9][10][11][12][13][14] .…”

Genetic architecture of Parkinson’s disease subtypes – Review of the literature

“…Previous studies consistently demonstrated that different motor subtypes vary in disease progression and the burden of non-dopaminergic (e.g., cognitive decline, dysautonomia, RBD) symptoms. The TD subtype is considered the phenotype with a lower risk of cognitive decline, slower progression, and lesser impact of non-dopaminergic symptoms compared to GD and AR subtypes ( Marras et al, 2020 ; Ren et al, 2020 , 2021 ; Kohat et al, 2021 ; Myers et al, 2021 ; Lee et al, 2022 ). Lastly, the PD subtyping is relevant for clinical trials, as some protocols include the presence of specific phenotypes in the inclusion or exclusion criteria.…”

Paroxysmal Slow-Wave Events Are Uncommon in Parkinson’s Disease

“…Parkinson’s disease (PD) is defined primarily as a motor disorder; however, in recent years PD has been increasingly recognized as a heterogeneous multisystem disorder with a wide variety of non-motor symptoms [ 1 , 2 ]. The progression of PD-related pathology from specific subcortical sites to cortical regions supports this wide involvement of motor and non-motor symptoms [ 3 ].…”