Autonomic symptoms (AS) are an important feature of Parkinson disease (PD) and increase with age, disease severity, and medication use. The prominent presence of AS warrants increased clinical awareness and highlights the need for efficacious therapies for the wide spectrum of problems related to this domain of PD.

The clinical variability between patients with Parkinson's disease (PD) may point at the existence of subtypes of the disease. Identification of subtypes is important, since a focus on homogeneous groups may enhance the chance of success of research on mechanisms of disease and may also lead to tailored treatment strategies. Cluster analysis (CA) is an objective method to classify patients into subtypes. We systematically reviewed the methodology and results of CA studies in PD to gain a better understanding of the robustness of identified subtypes. We found seven studies that fulfilled the inclusion criteria. Studies were limited by incomplete reporting and methodological limitations. Differences between studies rendered comparisons of the results difficult. However, it appeared that studies which applied a comparable design identified similar subtypes. The cluster profiles "old age-at-onset and rapid disease progression" and "young age-at-onset and slow disease progression" emerged from the majority of studies. Other cluster profiles were less consistent across studies. Future studies with a rigorous study design that is standardized with respect to the included variables, data processing, and CA technique may advance the knowledge on subtypes in PD.

Cognition is an important domain of the clinical spectrum of PD and poorer cognitive performance is associated with greater impairment in motor and non-motor domains in PD. The difference in cognitive scores between PIGD dominant patients and tremor dominant patients likely reflects more advanced disease.

The clinical heterogeneity of Parkinson's disease (PD) may point at the existence of subtypes. Because subtypes likely reflect distinct underlying etiologies, their identification may facilitate future genetic and pharmacotherapeutic studies. Aim of this study was to identify subtypes by a data-driven approach applied to a broad spectrum of motor and nonmotor features of PD. Data of motor and nonmotor PD symptoms were collected in 802 patients in two different European prevalent cohorts. A model-based cluster analysis was conducted on baseline data of 344 patients of a Dutch cohort (PROPARK). Reproducibility of these results was tested in data of the second annual assessment of the same cohort and validated in an independent Spanish cohort (ELEP) of 357 patients. The subtypes were subsequently characterized on clinical and demographic variables. Four similar PD subtypes were identified in two different populations and are largely characterized by differences in the severity of nondopaminergic features and motor complications: Subtype 1 was mildly affected in all domains, Subtype 2 was predominantly characterized by severe motor complications, Subtype 3 was affected mainly on nondopaminergic domains without prominent motor complications, while Subtype 4 was severely affected on all domains. The subtypes had largely similar mean disease durations (nonsignificant differences between three clusters) but showed considerable differences with respect to their association with demographic and clinical variables. In prevalent disease, PD subtypes are largely characterized by the severity of nondopaminergic features and motor complications and likely reflect complex interactions between disease mechanisms, treatment, aging, and gender.

Objective Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS patients carrying ANG variants also showed signs of Parkinson disease (PD). Furthermore, relatives of ALS patients have an increased risk to develop PD, and the prevalence of concomitant motor neuron disease in PD is higher than expected based on chance occurrence. We therefore investigated whether ANG variants could predispose to both ALS and PD. Methods We reviewed all previous studies on ANG in ALS and performed sequence experiments on additional samples, which allowed us to analyze data from 6,471 ALS patients and 7,668 controls from 15 centers (13 from Europe and 2 from the USA). We sequenced DNA samples from 3,146 PD patients from 6 centers (5 from Europe and 1 from the USA). Statistical analysis was performed using the variable threshold test, and the Mantel-Haenszel procedure was used to estimate odds ratios. Results Analysis of sequence data from 17,258 individuals demonstrated a significantly higher frequency of ANG variants in both ALS and PD patients compared to control subjects (p = 9.3 × 10−6 for ALS and p = 4.3 × 10−5 for PD). The odds ratio for any ANG variant in patients versus controls was 9.2 for ALS and 6.7 for PD. Interpretation The data from this multicenter study demonstrate that there is a strong association between PD, ALS, and ANG variants. ANG is a genetic link between ALS and PD.