New Clinical Subtypes of Parkinson Disease and Their Longitudinal Progression

Abstract

IMPORTANCE There is increasing evidence that Parkinson disease (PD) is heterogeneous in its clinical presentation and prognosis. Defining subtypes of PD is needed to better understand underlying mechanisms, predict disease course, and eventually design more efficient personalized management strategies.OBJECTIVES To identify clinical subtypes of PD, compare the prognosis and progression rate between PD phenotypes, and compare the ability to predict prognosis in our subtypes and those from previously published clustering solutions. DESIGN, SETTING, AND PARTICIPANTS Prospective cohort study. The cohorts were from 2 movement disorders clinics in Montreal, Quebec, Canada (patients were enrolled during the period from 2005 to 2013). A total of 113 patients with idiopathic PD were enrolled. A comprehensive spectrum of motor and nonmotor features (motor severity, motor complications, motor subtypes, quantitative motor tests, autonomic and psychiatric manifestations, olfaction, color vision, sleep parameters, and neurocognitive testing) were assessed at baseline. After a mean follow-up time of 4.5 years, 76 patients were reassessed. In addition to reanalysis of baseline variables, a global composite outcome was created by merging standardized scores for motor symptoms, motor signs, cognitive function, and other nonmotor manifestations. MAIN OUTCOMES AND MEASURESChanges in the quintiles of the global composite outcome and its components were compared between different subtypes. RESULTSThe best cluster solution found was based on orthostatic hypotension, mild cognitive impairment, rapid eye movement sleep behavior disorder (RBD), depression, anxiety, and Unified Parkinson's Disease Rating Scale Part II and Part III scores at baseline. Three subtypes were defined as mainly motor/slow progression, diffuse/malignant, and intermediate. Despite similar age and disease duration, patients with the diffuse/malignant phenotype were more likely to have mild cognitive impairment, orthostatic hypotension, and RBD at baseline, and at prospective follow-up, they showed a more rapid progression in cognition (odds ratio [OR], 8.

Facial emotion recognition in Parkinson's disease: A review and new hypotheses

“…Patients with the same disease duration/severity may have different patterns of neuronal loss in striatal, limbic, and cortical regions 82, 83. Thus, to examine the link between disease severity and FER deficit in PD, it might be useful to employ more sensitive markers (neuroimaging) of disease progression or subtype 84. Furthermore, FER deficit could also be linked to motor asymmetries in PD, but the question of whether patients with left‐dominant motor symptoms (LPD) showing relatively greater neural degeneration in the right hemisphere have a more severe deficit than patients with right‐dominant motor symptoms remains open.…”

“…It starts with awareness of the patients' difficulties in decoding, expressing, and mimicking emotions, along with their attendant social consequences. Research on these issues could also improve medical management, as therapeutic strategies can be adapted to patients' symptoms, especially knowing that there are several PD subtypes with 3 separate phenotypes: mainly motor/slow progression, intermediate, and diffuse/malignant 84. Patients with the latter are more likely to exhibit nonmotor symptoms, including cognitive and mood disorders, but patients with the main motor form may also develop emotional impairments as a consequence of impaired facial mimicry.…”

Prevalence and determinants of rapid eye movement sleep behavior disorder in the general population

“…This surprising finding suggests that RBD has a unique epidemiology, which is different from that of PD. There have been many studies suggesting that RBD marks a specific subtype of PD, with high risk of dementia, motor worsening, and autonomic dysfunction, termed the "diffuse-malignant" subtype [41]. If so, its environmental risk factors may also differ.…”

The dementia-associated APOE ε4 allele is not associated with rapid eye movement sleep behavior disorder

“…With long term follow-up, more than 80% of individuals with idiopathic RBD developed either Parkinson's disease (PD), dementia with Lewy bodies (DLB) or multiple system atrophy (MSA) ,Schenck, et al, 2013. It was suggested that RBD may define a subtype of PD patients (Fereshtehnejad, et al, 2015,Gagnon, et al, 2004 with cognitive decline (Gagnon, et al, 2009,Vendette, et al, 2007, dementia (Anang, et al, 2014), hallucinations (Sixel-Doring, et al, 2011) and autonomic dysfunction (Postuma, et al, 2008), as compared to PD patients without RBD. In addition, pathological studies in brains of PD patients with and without RBD demonstrated a more widespread -synuclein accumulation in those associated with RBD .…”