Parkinson disease clinical subtypes: key features & clinical milestones

Abstract

Objectives Based on multi‐domain classification of Parkinson disease (PD) subtypes, we sought to determine the key features that best differentiate subtypes and the utility of PD subtypes to predict clinical milestones. Methods Prospective cohort of 162 PD participants with ongoing, longitudinal follow‐up. Latent class analysis (LCA) delineated subtypes based on score patterns across baseline motor, cognitive, and psychiatric measures. Discriminant analyses identified key features that distinguish subtypes at baseline. Cox regression models tested PD subtype differences in longitudinal conversion to clinical milestones, including deep brain stimulation (DBS), dementia, and mortality. Results LCA identified distinct subtypes: “motor only” (N = 63) characterized by primary motor deficits; “psychiatric & motor” (N = 17) characterized by prominent psychiatric symptoms and moderate motor deficits; “cognitive & motor” (N = 82) characterized by impaired cognition and moderate motor deficits. Depression, executive function, and apathy best discriminated subtypes. Since enrollment, 22 had DBS, 48 developed dementia, and 46 have died. Although there were no subtype differences in rate of DBS, dementia occurred at a higher rate in the “cognitive & motor” subtype. Surprisingly, mortality risk was similarly elevated for both “cognitive & motor” and “psychiatric & motor” subtypes compared to the “motor only” subtype (relative risk = 3.15, 2.60). Interpretation Psychiatric and cognitive features, rather than motor deficits, distinguish clinical PD subtypes and predict greater risk of subsequent dementia and mortality. These results emphasize the value of multi‐domain assessments to better characterize clinical variability in PD. Further, differences in dementia and mortality rates demonstrate the prognostic utility of PD subtypes.

Clinical Phenotypes of Parkinson’s Disease Associate with Distinct Gut Microbiota and Metabolome Enterotypes

“…PD is associated with a heterogeneity of clinical changes, suggesting the existence of different subtypes, characterized by both motor and non-motor dysfunctions [ 2 , 3 ]. Although it remains to be established whether the different subtypes represent distinct disorders or different disease stages [ 4 ], a current classification based on motor signs suggests two main subtypes of tremor dominant (TD) and non-tremor dominant (non-TD) [ 2 , 5 ]. Typically, in the TD subtype tremors are the main motor feature [ 6 , 7 , 8 ].…”

Functional genomic analyses uncover APOE-mediated regulation of brain and cerebrospinal fluid beta-amyloid levels in Parkinson disease

“…PD is a heterogeneous disorder with different identifiable clinical-pathological subtypes based on symptom severity and predominance [15]. It is conceivable that more homogeneous PD subtypes could be defined using biomarker-driven, clinical-molecular phenotyping approaches.…”

Distinct progression patterns across Parkinson disease clinical subtypes

“…PD participants were categorized into one of three subtypes, previously described in detail in Campbell et al. (2020) 10 . Briefly, a latent class analysis (LCA) 36 identified clinical subtypes within PD.…”

“…We recently identified three distinct PD clinical subtypes 10 : “Motor Only,” featuring mild motor deficits, “Psychiatric & Motor,” featuring increased psychiatric symptoms, and “Cognitive & Motor,” featuring decreased cognitive function. While cognitive and psychiatric features distinguished the subtypes and prior longitudinal studies demonstrate that cognitive, 9 , 11 , 12 , 13 motor, 12 , 13 and psychiatric function 14 , 15 worsen over time in PD, the rate of decline and pattern of symptom progression among PD clinical subtypes have not been thoroughly explored.…”