Quality of Life in Newly Diagnosed Patients With Parkin-Related Parkinson's Disease

Abstract

Introduction: Mutations in the Parkin gene are the most common cause of autosomal recessive early-onset Parkinson's disease (PD). However, little is known about the quality of life (QoL) in Parkin-related PD. Here, we investigated the patterns of QoL in newly diagnosed Parkin-related PD patients.Methods: Newly diagnosed PD patients (diagnosis made within 12 months) who had an age of onset (AOO) below 40 and underwent a PD-related genetic testing, were recruited (n = 148). Among them, 24 patients carried bi-allelic variants in Parkin (PD-Parkin) and 24 patients did not have any known causative PD mutations, or risk variants (GU-EOPD). The clinical materials, relevant factors and determinants of QoL were analyzed.Results: PD-Parkin patients had a younger AOO (p = 0.003) and longer disease duration (p = 0.005). After adjustment for AOO and disease duration, more dystonia (p = 0.034), and worse scores of non-motor symptoms including Beck depression inventory (BDI, p = 0.035), Epworth sleepiness scale (ESS, p = 0.044), and subdomains of depression/anxiety (p = 0.015) and sleep disorders (p = 0.005) in Non-motor symptoms questionnaire, were found in PD-Parkin comparing with GU-EOPD. PD-Parkin patients had poorer QoL (adjusted p = 0.045), especially in the mobility (adjusted p = 0.025), emotional well-being (adjusted p = 0.015) and bodily discomfort dimensions (adjusted p = 0.016). BDI scores (p = 0.005) and ESS scores (p = 0.047) were significant determinants of QoL in PD-Parkin.Conclusion: Newly diagnosed PD-Parkin patients showed worse QoL. More depression and excessive daytime sleepiness predicted worse QoL. For clinicians, management of depression and excessive daytime sleepiness is suggested to better improve QoL in patients with Parkin mutations.

Genetic heterogeneity on sleep disorders in Parkinson’s disease: a systematic review and meta-analysis

“…1). Twelve studies were included to compare patients with and without heterozygous GBA carriers [5,[14][15][16][17][18][19][20][21][22][23][24], 17 studies to compare patients with and without heterozygous LRRK2 carriers [15,16,[20][21][22][25][26][27][28][29][30][31][32][33][34][35][36] and seven studies to compare patients with and without homozygous or compound heterozygous PRKN carriers [7,8,15,[37][38][39][40]. Six studies comparing asymptomatic heterozygous GBA carriers with non-carrier HCs were selected [9,10,20,[41][42][43], and 11 studies compared asymptomatic heterozygous LRRK2 carriers with non-carrier HCs [9, 20, 29-31, 42, 44-48].…”

Recent advances in the pathology of prodromal non-motor symptoms olfactory deficit and depression in Parkinson’s disease: clues to early diagnosis and effective treatment

“…It has been reported that monogenic PD patients with mutations in the α-synuclein, LRRK2, VPS35, Parkin, PINK1, DJ-1 and GBA genes exhibit psychiatric disturbances such as depression and anxiety (Liu et al 2020b ). In particular, PD patients carrying parkin, PINK1 and GBA mutations have more severe depression compared with idiopathic PD (Ephraty et al 2007 ; Thaler et al 2018 ; Zhou et al 2020 ). Currently, there are no guidelines or recommendations for selective treatment of depression associated with PD, so patients with PD are not receiving the optimal treatment for depression (Weintraub et al 2003 ).…”

Transcriptome datasets of neural progenitors and neurons differentiated from induced pluripotent stem cells of healthy donors and Parkinson's disease patients with mutations in the PARK2 gene

“… The transcriptomic datasets generated are useful for identifying genes involved in the PD pathogenesis and determining mechanisms of PD onset associated with mutations in PARK2. PARK2 was selected for analysis as mutations in this gene have been shown to cause autosomal recessive early onset PD [2] , [3] . These data are valuable for researchers who investigate gene network in the process of neuronal differentiation and molecular mechanisms involved in PD development.…”

“…The transcriptomic datasets generated are useful for identifying genes involved in the PD pathogenesis and determining mechanisms of PD onset associated with mutations in PARK2. PARK2 was selected for analysis as mutations in this gene have been shown to cause autosomal recessive early onset PD [2] , [3] .…”