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Using non-motor features to define clinical and biomarker patterns of early drug-naïve Parkinsonism

Jain, S; Young Park, S; Comer, D
AAN: Washington, DC
Download Presentation: Jain-poster-clustering-AAN-2015.pdf
OBJECTIVE: We hypothesized clinical patterns of non-motor features occur in early, medication-naïve Parkinsonism.

BACKGROUND: Although Parkinsonism is a constellation of motor features, in most Parkinsonian cases, non-motor features (e.g., cognitive, autonomic, sleep disturbances) contribute more to quality of life, healthcare costs, and institutionalization rates. Such features are under-recognized and undertreated. Non-motor features may be either intrinsic to Parkinsonian disorders or due in part to medication side effects.

METHODS: Clinical, neuroimaging (striatal dopamine transporter binding ratio (SBR)), and cerebrospinal fluid (CSF) biomarkers (? -synuclein (?-syn), tau phosphorylated at threonine 181, total tau, and ?-amyloid 1-42) were
obtained in an ongoing observational study of Parkinsonism - the
Parkinson?s Progression Marker Initiative (PPMI). Group comparisons of
Parkinsonism with dopaminergic deficits (PDD), controls, and participants
with Parkinsonian motor features but scans without evidence of
dopaminergic deficits (SWEDD?s) were done with ANOVA F-tests, chi-square tests, and post-hoc pairwise tests. Within the PDD group, cluster analyses were performed with k-means using non-motor or motor features, or both.

- ?-syn and tau-related markers were lower in PDD than controls
- SWEDD?s had the most severe autonomic, sleep-related, and
impulsive/compulsive symptoms.
- Within the PDD group, four non-motor patterns were observed:
- Impulsive: presence of impulsive/compulsive behaviors
- Sleep-autonomic: most severe non-motor (MDS-UPDRS Part 1),
autonomic (SCOPA-AUT) and REM sleep disorder symptoms
- Cognitive-olfactory: performed worst on all cognitive tests and had
low UPSIT scores
- Mild: no impulsive/compulsive behaviors and the best UPSIT
- Within the PDD group, four motor patterns were observed
- Tremor plus bradykinesia: tremor and bradykinesia at the time of diagnosis
- Tremor without bradykinesia: tremor and no bradykinesia at the time of diagnosis
- Postural instability: postural instability at the time of diagnosis
- No tremor: no tremor at the time of diagnosis
- Within the PDD group, five combined motor/non-motor patterns were
- Tremor with bradykinesia
- Tremor without bradykinesia
- No tremor and mild non-motor features: no tremor at diagnosis and lower severity for several non-motor features
- Postural instability with sleep and autonomic disturbances: postural
instability at the time of diagnosis and the most severe sleep and autonomic symptoms
- Oldest onset cognitive-olfactory: the oldest age of onset of PDD with the worst cognitive and olfactory performance

CONCLUSIONS: To our knowledge, this is the first description of non-motor clinical patterns and underlying biomarkers in early medication naïve Parkinsonism. In the PDD group, most are Parkinson disease. However other Parkinsonian disorders, could, in part, account for clinical patterns observed.
While several studies have reported lower concentrations of ?-synuclein in CSF in Parkinson Disease, our results suggest this occurs early in PDD, prior to the initiation of anti-Parkinsonian medications. The fact that non-motor features are prominent in a medication-naïve cohort provides strong evidence that such phenomena can be intrinsic to PDD. Several non-motor symptoms are treatable, including sleep disturbances, autonomic dysfunction, cognitive impairment, and psychiatric disorders. This
demonstrates the need for treatment strategies which encompass both motor and non-motor features to begin at diagnosis.