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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.

SUBMITTER: Campbell MC

PROVIDER: S-EPMC7448190 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Parkinson disease clinical subtypes: key features & clinical milestones.

Campbell Meghan C MC Myers Peter S PS Weigand Alexandra J AJ Foster Erin R ER Cairns Nigel J NJ Jackson Joshua J JJ Lessov-Schlaggar Christina N CN Perlmutter Joel S JS

Annals of clinical and translational neurology 20200629 8

<h4>Objectives</h4>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.<h4>Methods</h4>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 ...[more]

PMID: 32602253

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Project description:ImportanceClinical subtyping of Parkinson disease at diagnosis is useful in estimating disease course and survival. Severity and rate of progression of neuropathologies are important determinants of clinical Parkinson subtypes.ObjectiveTo provide longitudinal clinical disease-course data and neuropathologic correlation for newly proposed Parkinson disease subtypes.Design, setting, and participantsRetrospective cohort study of consecutive patients with autopsy-confirmed Parkinson disease who were regularly seen throughout their disease course by hospital specialists in the United Kingdom and donated their brain at death to the Queen Square Brain Bank between January 2009 and December 2017. Patients with additional neuropathologic diagnoses, monogenic forms of parkinsonism, or insufficiently detailed clinical information were excluded. Based on severity of motor symptoms, rapid eye movement sleep behavior disorder, and autonomic and cognitive function at diagnosis, patients were classified adapting a subtyping classification into mild-motor predominant, intermediate, or diffuse malignant subtypes.Main outcomes and measuresTime from diagnosis to disease milestones (recurrent falls, wheelchair dependence, dementia, and care home placement) and death were compared between subtypes, and their risk was estimated using Cox hazard regression models. Severity and distribution of Lewy pathology and Alzheimer disease-related pathology were assessed using staging systems.ResultsFrom a total of 146 patients, 111 patients were included (67 men [60.4%]; mean [SD] age at diagnosis, 62.5 [11.5] years). The diffuse malignant subtype had earlier development of milestones and reduced survival. Cox proportional hazard regression showed an increased adjusted risk of any disease milestone (hazard ratio, 10.90; 95% CI, 5.51-21.58; P < .001) and death (hazard ratio, 3.65; 95% CI, 1.98-6.75; P < .001) in the diffuse malignant group. Age at diagnosis was the only additional variable with statistical significance (adjusted hazard ratio for death, 1.14; 95% CI, 1.11-1.17; P <.001). Staging of Lewy pathology and Alzheimer disease-related pathology did not differ between subtypes, although they showed different rates of progression, and the latter was associated with age at death.Conclusions and relevanceParkinson clinical subtypes at diagnosis may estimate disease course and survival, which may be useful in providing a more accurate prognosis in individual patients in clinical practice and helping to stratify subgroups in clinical trials. Different severity and progression of neuropathologies are important determinants of Parkinson subtypes, and age at diagnosis should be included in future subtype classifications.

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Parkinson disease clinical subtypes: key features & clinical milestones.

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Parkinson disease clinical subtypes: key features & clinical milestones.

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