Clinical Patterns of Nonmotor Features Occur in Early Parkinson’s Disease

WASHINGTON, DC—Nonmotor features are prominent early in Parkinson’s disease and are intrinsic to parkinsonism with dopaminergic deficits, according to a presentation at the American Academy of Neurology’s 67th Annual Meeting. “To our knowledge, this is the first description of nonmotor clinical patterns and underlying biomarkers in early Parkinson’s disease,” said Samay Jain, MD, Assistant Professor of Neurology at the University of Pittsburgh.

Although parkinsonism is a constellation of motor features, in most cases its nonmotor features (eg, cognitive, autonomic, sleep disturbances) contribute more to quality of life, health care costs, and institutionalization rates. According to Dr. Jain, such features are under-recognized and undertreated.

Hypothesizing that clinical patterns of nonmotor features occur in early, medication-naïve Parkinson’s disease, Dr. Jain and colleagues conducted an observational study of Parkinson’s disease—the Parkinson’s Progression Marker Initiative (PPMI). Clinical, neuroimaging (striatal dopamine transporter binding ratio), and CSF biomarkers (α-synuclein, tau phosphorylated at threonine 181, total tau, and β-amyloid 1-42) were obtained. Group comparisons of patients with Parkinson’s disease, controls, and participants with parkinsonian motor features but scans without evidence of dopaminergic deficits (SWEDDs) were done with ANOVA F-tests, chi-square tests, and post-hoc pairwise tests. Within the Parkinson’s disease group (excluding SWEDDs), cluster analyses were performed with k-means using nonmotor or motor features, or both.

Results revealed that α-synuclein and tau-related markers were lower in patients with Parkinson’s disease than in controls. The SWEDDs group had the most severe autonomic, sleep-related, and impulsive or compulsive symptoms. Four nonmotor Parkinson’s disease patterns were observed: impulsive, sleep-autonomic, cognitive-olfactory, and mild. Four motor patterns also were observed: tremor plus bradykinesia, tremor without bradykinesia, postural instability, and no tremor. Five combined motor–nonmotor patterns were observed: tremor with bradykinesia, tremor without bradykinesia, no tremor and mild non-motor features, postural instability with sleep-autonomic disturbances, and oldest onset cognitive-olfactory. Tau-related markers were higher in patterns with severe cognitive deficits.

“While several studies have reported lower concentrations of α-synuclein in CSF in Parkinson’s disease, our results suggest that this occurs early in parkinsonism with dopaminergic deficits, prior to the initiation of antiparkinsonian medications,” Dr. Jain and colleagues said. “The fact that nonmotor features are prominent in a medication-naïve cohort provides strong evidence that such phenomena can be intrinsic to parkinsonism, [thus] demonstrating the need for treatment strategies which encompass both motor and nonmotor features to begin at diagnosis.”

WASHINGTON, DC—Nonmotor features are prominent early in Parkinson’s disease and are intrinsic to parkinsonism with dopaminergic deficits, according to a presentation at the American Academy of Neurology’s 67th Annual Meeting. “To our knowledge, this is the first description of nonmotor clinical patterns and underlying biomarkers in early Parkinson’s disease,” said Samay Jain, MD, Assistant Professor of Neurology at the University of Pittsburgh.

Although parkinsonism is a constellation of motor features, in most cases its nonmotor features (eg, cognitive, autonomic, sleep disturbances) contribute more to quality of life, health care costs, and institutionalization rates. According to Dr. Jain, such features are under-recognized and undertreated.

Hypothesizing that clinical patterns of nonmotor features occur in early, medication-naïve Parkinson’s disease, Dr. Jain and colleagues conducted an observational study of Parkinson’s disease—the Parkinson’s Progression Marker Initiative (PPMI). Clinical, neuroimaging (striatal dopamine transporter binding ratio), and CSF biomarkers (α-synuclein, tau phosphorylated at threonine 181, total tau, and β-amyloid 1-42) were obtained. Group comparisons of patients with Parkinson’s disease, controls, and participants with parkinsonian motor features but scans without evidence of dopaminergic deficits (SWEDDs) were done with ANOVA F-tests, chi-square tests, and post-hoc pairwise tests. Within the Parkinson’s disease group (excluding SWEDDs), cluster analyses were performed with k-means using nonmotor or motor features, or both.

Results revealed that α-synuclein and tau-related markers were lower in patients with Parkinson’s disease than in controls. The SWEDDs group had the most severe autonomic, sleep-related, and impulsive or compulsive symptoms. Four nonmotor Parkinson’s disease patterns were observed: impulsive, sleep-autonomic, cognitive-olfactory, and mild. Four motor patterns also were observed: tremor plus bradykinesia, tremor without bradykinesia, postural instability, and no tremor. Five combined motor–nonmotor patterns were observed: tremor with bradykinesia, tremor without bradykinesia, no tremor and mild non-motor features, postural instability with sleep-autonomic disturbances, and oldest onset cognitive-olfactory. Tau-related markers were higher in patterns with severe cognitive deficits.

“While several studies have reported lower concentrations of α-synuclein in CSF in Parkinson’s disease, our results suggest that this occurs early in parkinsonism with dopaminergic deficits, prior to the initiation of antiparkinsonian medications,” Dr. Jain and colleagues said. “The fact that nonmotor features are prominent in a medication-naïve cohort provides strong evidence that such phenomena can be intrinsic to parkinsonism, [thus] demonstrating the need for treatment strategies which encompass both motor and nonmotor features to begin at diagnosis.”

WASHINGTON, DC—Nonmotor features are prominent early in Parkinson’s disease and are intrinsic to parkinsonism with dopaminergic deficits, according to a presentation at the American Academy of Neurology’s 67th Annual Meeting. “To our knowledge, this is the first description of nonmotor clinical patterns and underlying biomarkers in early Parkinson’s disease,” said Samay Jain, MD, Assistant Professor of Neurology at the University of Pittsburgh.

Although parkinsonism is a constellation of motor features, in most cases its nonmotor features (eg, cognitive, autonomic, sleep disturbances) contribute more to quality of life, health care costs, and institutionalization rates. According to Dr. Jain, such features are under-recognized and undertreated.

Hypothesizing that clinical patterns of nonmotor features occur in early, medication-naïve Parkinson’s disease, Dr. Jain and colleagues conducted an observational study of Parkinson’s disease—the Parkinson’s Progression Marker Initiative (PPMI). Clinical, neuroimaging (striatal dopamine transporter binding ratio), and CSF biomarkers (α-synuclein, tau phosphorylated at threonine 181, total tau, and β-amyloid 1-42) were obtained. Group comparisons of patients with Parkinson’s disease, controls, and participants with parkinsonian motor features but scans without evidence of dopaminergic deficits (SWEDDs) were done with ANOVA F-tests, chi-square tests, and post-hoc pairwise tests. Within the Parkinson’s disease group (excluding SWEDDs), cluster analyses were performed with k-means using nonmotor or motor features, or both.

Results revealed that α-synuclein and tau-related markers were lower in patients with Parkinson’s disease than in controls. The SWEDDs group had the most severe autonomic, sleep-related, and impulsive or compulsive symptoms. Four nonmotor Parkinson’s disease patterns were observed: impulsive, sleep-autonomic, cognitive-olfactory, and mild. Four motor patterns also were observed: tremor plus bradykinesia, tremor without bradykinesia, postural instability, and no tremor. Five combined motor–nonmotor patterns were observed: tremor with bradykinesia, tremor without bradykinesia, no tremor and mild non-motor features, postural instability with sleep-autonomic disturbances, and oldest onset cognitive-olfactory. Tau-related markers were higher in patterns with severe cognitive deficits.

“While several studies have reported lower concentrations of α-synuclein in CSF in Parkinson’s disease, our results suggest that this occurs early in parkinsonism with dopaminergic deficits, prior to the initiation of antiparkinsonian medications,” Dr. Jain and colleagues said. “The fact that nonmotor features are prominent in a medication-naïve cohort provides strong evidence that such phenomena can be intrinsic to parkinsonism, [thus] demonstrating the need for treatment strategies which encompass both motor and nonmotor features to begin at diagnosis.”