Dementia Predictors in Parkinson Disease: A Validation Study.

In a prospective study, we recently discovered 8 clinical predictors of dementia in Parkinson's disease. Here, we validate these dementia predictors using two additional prospective cohorts (n = 134). After a 3.6-year follow-up, 35/134 developed dementia (7.2% per year). When confirming individual variables, 5/8 were significantly associated with dementia in the validation cohort. These included age, male sex, baseline RBD, orthostatic hypotension, and MCI. Bilateral onset, hallucinations and falls/freezing did not significantly predict dementia; however, point estimates of OR were all >1. In all cohorts, the strongest determinant for dementia development was the co-existence of RBD, MCI and orthostatic hypotension at baseline.

Risk Factor Profile in Parkinson's Disease Subtype with REM Sleep Behavior Disorder.

BACKGROUND: Numerous large-scale studies have found diverse risk factors for Parkinson's disease (PD), including caffeine non-use, non-smoking, head injury, pesticide exposure, and family history. These studies assessed risk factors for PD overall; however, PD is a heterogeneous condition. One of the strongest identifiers of prognosis and disease subtype is the co-occurrence of rapid eye movement sleep behavior disorder (RBD).In previous studies, idiopathic RBD was associated with a different risk factor profile from PD and dementia with Lewy bodies, suggesting that the PD-RBD subtype may also have a different risk factor profile. OBJECTIVE: To define risk factors for PD in patients with or without associated RBD. METHODS: In a questionnaire, we assessed risk factors for PD, including demographic, medical, environmental, and lifestyle variables of 189 PD patients with or without associated polysomnography-confirmed RBD. The risk profile of patients with vs. without RBD was assessed with logistic regression, adjusting for age, sex, and disease duration. RESULTS: PD-RBD patients were more likely to have been a welder (OR = 3.11 (1.05-9.223), and to have been regular smokers (OR = 1.96 (1.04-3.68)). There were no differences in use of caffeine or alcohol, other occupations, pesticide exposure, rural living, or well water use. Patients with RBD had a higher prevalence of the combined family history of both dementia and parkinsonism (13.3% vs. 5.5% , OR = 3.28 (1.07-10.0). CONCLUSION: The RBD-specific subtype of PD may also have a different risk factor profile.

New Clinical Subtypes of Parkinson Disease and Their Longitudinal Progression: A Prospective Cohort Comparison With Other Phenotypes.

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 MEASURES: Changes in the quintiles of the global composite outcome and its components were compared between different subtypes. RESULTS: The 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], 8.7 [95% CI, 4.0-18.7]; P < .001), other nonmotor symptoms (OR, 10.0 [95% CI, 4.3-23.2]; P < .001), motor signs (OR, 4.1 [95% CI, 1.8-9.1]; P = .001), motor symptoms (OR, 2.9 [95% CI, 1.3-6.2]; P < .01), and the global composite outcome (OR, 8.0 [95% CI, 3.7-17.7]; P < .001). CONCLUSIONS AND RELEVANCE: It is recommended to screen patients with PD for mild cognitive impairment, orthostatic hypotension, and RBD even at baseline visits. These nonmotor features identify a diffuse/malignant subgroup of patients with PD for whom the most rapid progression rate could be expected.

Predictors of dementia in Parkinson disease: a prospective cohort study.

OBJECTIVE: We investigated an array of possible markers of early dementia in Parkinson disease. METHODS: We performed a comprehensive assessment of autonomic, sleep, psychiatric, visual, olfactory, and motor manifestations in 80 patients with Parkinson disease who were dementia-free at baseline. After 4.4 years' follow-up, patients were evaluated for dementia. Predictive variables were assessed using logistic regression adjusting for disease duration, follow-up duration, age, and sex. RESULTS: Of 80 patients, 27 (34%) developed dementia. Patients destined to develop dementia were older and more often male (odds ratio [OR] = 3.64, p = 0.023). Those with baseline mild cognitive impairment had increased dementia risk (OR = 22.5, p < 0.001). REM sleep behavior disorder at baseline dramatically increased dementia risk (OR = 49.7, p = 0.001); however, neither daytime sleepiness nor insomnia predicted dementia. Higher baseline blood pressure increased dementia risk (OR = 1.37 per 10 mm Hg, p = 0.032). Orthostatic blood pressure drop was strongly associated with dementia risk (OR = 1.84 per 10 mm Hg, p < 0.001); having a systolic drop of >10 mm Hg increased dementia odds 7-fold (OR = 7.3, p = 0.002). Abnormal color vision increased dementia risk (OR = 3.3, p = 0.014), but olfactory dysfunction did not. Among baseline motor variables, proportion of gait involvement (OR = 1.12, p = 0.023), falls (OR = 3.02, p = 0.042), and freezing (OR = 2.63, p = 0.013), as well as the Purdue Pegboard Test (OR = 0.67, p = 0.049) and alternate tap test (OR = 0.97, p = 0.033) predicted dementia. CONCLUSION: Cardiovascular autonomic dysfunction, REM sleep behavior disorder, color discrimination ability, and gait dysfunction strongly predict development of dementia in Parkinson disease.

Rapid eye movement sleep behavior disorder and subtypes of Parkinson's disease.

Numerous studies have explored the potential relationship between rapid eye movement sleep behavior disorder (RBD) and manifestations of PD. Our aim was to perform an expanded extensive assessment of motor and nonmotor manifestations in PD to identify whether RBD was associated with differences in the nature and severity of these manifestations. PD patients underwent polysomnography (PSG) to diagnose the presence of RBD. Participants then underwent an extensive evaluation by a movement disorders specialist blinded to PSG results. Measures of disease severity, quantitative motor indices, motor subtypes, therapy complications, and autonomic, psychiatric, visual, and olfactory dysfunction were assessed and compared using regression analysis, adjusting for disease duration, age, and sex. Of 98 included patients, 54 had RBD and 44 did not. PD patients with RBD were older (P = 0.034) and were more likely to be male (P < 0.001). On regression analysis, the most consistent links between RBD and PD were a higher systolic blood pressure (BP) change while standing (-23.9 ± 13.9 versus -3.5 ± 10.9; P < 0.001), a higher orthostatic symptom score (0.89 ± 0.82 versus 0.44 ± 0.66; P = 0.003), and a higher frequency of freezing (43% versus 14%; P = 0.011). A systolic BP drop >10 could identify PD patients with RBD with 81% sensitivity and 86% specificity. In addition, there was a probable relationship between RBD and nontremor predominant subtype of PD (P = 0.04), increased frequency of falls (P = 0.009), and depression (P = 0.009). Our results support previous findings that RBD is a multifaceted phenomenon in PD. Patients with PD who have RBD tend to have specific motor and nonmotor manifestations, especially orthostatic hypotension.