Objective: To verify if non-affected siblings (Sibs) of PD patients share candidate PD biomarkers in comparison with de-novo PD patients (PD) and healthy controls (HC).

Background: PD originates from a complex interplay of genetics and environment [1]. Moreover, PD progressively develops over years, during which non-motor symptoms (NMS) can precede the appearance of motor dysfunction [2]. Scarce is evidence on how these non-motor markers interweave into the increased “familial” risk of PD siblings sharing both a common genetic and environmental background with PD patients.

Method: Within the PROPAG-AGEING Phase 2 project, a large multicentric cohort of 340 siblings of PD patients, diagnosed according to UKBBC criteria [3], from Bologna, Kassel and Seville, underwent a clinical and neurological evaluation including demographics, comorbidities, motor examination (MDS-UPDRS III) and non-motor symptoms such as RBD (RBDSQ and nocturnal polysomnography), hyposmia (Sniffin’ Sticks Screening – SSS), cognitive impairment (MoCA), and symptoms of dysautonomia. The cohort was compared with de-novo PD patients and matched healthy controls from the Kassel DeNoPa cohort [4] [Figure 1].

Results: Siblings were younger than DeNoPa PD patients (p=0.003) [Table 1]. The mean age difference with their siblings with PD was of -1.09 ± 6.46 years. Compared to PD and HC, Sibs showed the lowest prevalence of hypertension and dyslipidemia (p<0.001) and the lowest presence of presumed, clinical RBD. PD presented more frequently with the non-motor symptoms olfactory and cognitive impairment (p<0.001), compared with HC and Sibs. The 109 Sibs abnormal at MoCA scored more similarly to PD than to HC, especially in visuo-executive functions. Sibs were significantly more constipated and tended to present more sexual dysfunctions than HC, but less than PD. Regarding motor score, Sibs presented an MDS-UPDRS part III score 3-fold higher than HC (p<0.001). Exploring predictive markers for mild motor signs in Sibs (MDS-UPDRS III≥6 without action/postural tremor), the combination of MDS-UPDRS I, MoCA visuo-executive and SSS score reached an AUC of 0.809 (95% confidence interval 0.736-0.882) [Figure 2].

Conclusion: Our multinational study represents the largest described cohort of PD siblings. Sibs showed several non-motor symptoms discretely predicting underlying mild motor signs. These preliminary results have to be confirmed by further analyses.

References: 1. Kalia LV, Lang AE. Parkinson’s disease. Lancet 2015;386(9996):896-912. 2. Berg D, Postuma RB, Adler CH, et al. MDS research criteria for prodromal Parkinson’s disease. Mov Disord 2015;30(12):1600-1611. 3. Hughes AJ, Daniel SE, Blankson S, Lees AJ. A clinicopathologic study of 100 cases of Parkinson’s disease. Arch Neurol 1993;50(2):140-148. 4. Mollenhauer B, Trautmann E, Sixel-Doring F, et al. Nonmotor and diagnostic findings in subjects with de novo Parkinson disease of the DeNoPa cohort. Neurology 2013;81(14):1226-1234.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/familial-imprint-of-parkinson-disease-the-siblings-cohort-of-propag-ageing/