Evaluation of progression markers in the premotor phase of Parkinson's disease: the progression markers in the premotor phase study.
BACKGROUND
The clinical diagnosis of Parkinson's disease (PD) is proposed to be too late for the application of beneficial neuroprotective treatment. Thus, it is important to identify and follow individuals at risk for PD in order to gain knowledge about the prodromal course of the disease. Substantia nigra hyperechogenicity (SN+) has been confirmed as a risk factor for PD and appears promising as a predictor of PD, particularly in combination with other putative PD markers. We present the design and initial data of a 2-year longitudinal investigation of subjects proposed to be at high risk of developing PD (HRPD), compared to early PD patients and control subjects. The aim of the presented study is to monitor progression of the neurodegenerative process to motor PD.


METHODS
In total, 40 HRPD, 16 PD and 41 control individuals were recruited. The HRPD subjects had SN+ and additionally either 1 cardinal PD motor sign or 2 further risk (e.g. positive family history) or prodromal markers (e.g. hyposmia). In this cohort, motor function, olfaction, mood and blood markers will be evaluated every 6 months, complemented by a comprehensive clinical, imaging and electrophysiological assessment.


RESULTS
PD, HRPD and control subjects did not differ significantly regarding age, but the HRPD group consisted mainly of males (72.5% of HRPD subjects vs. 43.9% of controls; p = 0.013). Mean disease duration in PD patients was 31 months (range 15-56). HRPD subjects were predominantly recruited according to the occurrence of slight motor signs (HRPD 77.5%, PD 100%, p = 0.05; controls 0%, HRPD vs. controls, p < 0.017). The Unified Parkinson's Disease Rating Scale motor score (mean, range) indicated that the HRPD group (4, 0-12) had values between those of controls (0, 0-2; p < 0.017) and PD subjects (26, 9-55; p < 0.017). Among nonmotor symptoms, hyposmia was more common in both HRPD (47.5%) and PD subjects (75%) than in controls (5.1%; p < 0.017 for both comparisons).


CONCLUSIONS
Here, we describe the recruitment of a highly enriched-risk cohort and a promising study design to assess progression to motor PD. Whether the HRPD group indeed suffers from early, PD-specific neurodegeneration remains to be verified in the ongoing follow-up examinations.
Department of Neurodegeneration, Center of Neurology, Hertie Institute for Clinical Brain Research, Tübingen, Germany.
Inga
I
Liepelt-Scarfone
Katharina
K
Gauss
Walter
W
Maetzler
Katharina
K
Müller
Christian
C
Bormann
Monika
M
Fruhmann Berger
Maarten
M
Timmers
Johannes
J
Streffer
Daniela
D
Berg
D000368:Aged; D000369:Aged, 80 and over; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies / Q000379:methods; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000175:diagnosis*; D062706:Prodromal Symptoms; D011446:Prospective Studies; D012307:Risk Factors