Role of genetics in amyotrophic lateral sclerosis: a large cohort study in Chinese mainland population.

BACKGROUND: A large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers. METHODS: A total of 1587 patients, including 64 familial ALS (FALS) and 1523 sporadic ALS (SALS), and 1866 in-house controls were analysed by whole-exome sequencing and/or testing for G4C2 repeats in C9orf72. Forty-one ALS-associated genes were analysed. FINDINGS: 155 patients, including 26 (40.6%) FALS and 129 (8.5%) SALS, carrying rare pathogenic/likely pathogenic (P/LP) variants of ALS causative genes were identified. SOD1 was the most common mutated gene, followed by C9orf72, FUS, NEK1, TARDBP and TBK1. By burden analysis, rare variants in SOD1, FUS and TARDBP contributed to the collective risk for ALS (p<2.5e-6) at the gene level, but at the allelic level TARDBP p.Gly294Val and FUS p.Arg521Cys and p.Arg521His were the most important single variants causing ALS. Clinically, P/LP variants in TARDBP and C9orf72 were associated with poor prognosis, in FUS linked with younger age of onset, and C9orf72 repeats tended to affect cognition. CONCLUSIONS: Our data provide essential information for understanding the genetic and clinical features of ALS in China and for optimal design of genetic testing and evaluation of disease prognosis.

Genetic factors for survival in amyotrophic lateral sclerosis: an integrated approach combining a systematic review, pairwise and network meta-analysis.

BACKGROUND: The time of survival in patients with amyotrophic lateral sclerosis (ALS) varies greatly, and the genetic factors that contribute to the survival of ALS are not well studied. There is a lack of a comprehensive study to elucidate the role of genetic factors in the survival of ALS. METHODS: The published studies were systematically searched and obtained from PubMed, EMBASE, and the Cochrane Library without any language restrictions from inception to Oct 27, 2021. A network meta-analysis for ALS causative/risk genes and a systematic review and pairwise meta-analysis for other genetic modifiers were conducted. The PROSPERO registration number: CRD42022311646. RESULTS: A total of 29,764 potentially relevant references were identified, and 71 papers were eligible for analysis based on pre-decided criteria, including 35 articles in network meta-analysis for 9 ALS causative/risk genes, 17 articles in pairwise meta-analysis for four genetic modifiers, and 19 articles described in the systematic review. Variants in three genes, including ATXN2 (HR: 3.6), C9orf72 (HR: 1.6), and FUS (HR:1.8), were associated with short survival of ALS, but such association was not identified in SOD1, TARDBP, TBK1, NEK1, UBQLN2, and CCNF. In addition, UNC13A rs12608932 CC genotype and ZNF521B rs2275294 C allele also caused a shorter survival of ALS; however, APOE ε4 allele and KIFAP3 rs1541160 did not be found to have any effect on the survival of ALS. CONCLUSIONS: Our study summarized and contrasted evidence for prognostic genetic factors in ALS and would help to understand ALS pathogenesis and guide clinical trials and drug development.

The mutation spectrum of Parkinson-disease-related genes in early-onset Parkinson's disease in ethnic Chinese.

BACKGROUND AND PURPOSE: Recent genetic progress has shown many causative/risk genes linked to Parkinson's disease (PD), mainly in patients of European ancestry. The study aimed to investigate the PD-related genes and determine the mutational spectrum of early-onset PD in ethnic Chinese. METHODS: In this study, whole-exome sequencing and/or gene dosage analysis were performed in 704 early-onset PD (EOPD) patients (onset age ≤45 years) and 1866 controls. Twenty-six PD-related genes and 20 other genes linked to neurodegenerative and lysosome diseases were analysed. RESULTS: Eighty-two (11.6%, 82/704) EOPD patients carrying rare pathogenic/likely pathogenic variants in PD-related genes were identified. The mutation frequency in autosomal recessive inheritance EOPD (42.9%, 27/63) was much higher than that in autosomal dominant inheritance EOPD (0.9%, 12/110) or sporadic EOPD (8.1%, 43/531). Bi-allelic mutations in PRKN were the most frequent, accounting for 5.1% of EOPD cases. Three common pathogenic variants, p.A53V in SNCA, p.G284R in PRKN and p.P53Afs*38 in CHCHD2, occur exclusively in Asians. The putative damaging variants from GBA, PRKN, DJ1, PLA2G6 and GCH1 contributed to the collective risk for EOPD. Notably, the protein-truncating variants in CHCHD2 were enriched in EOPD, especially for p.P53Afs*38, which was also found in three patients from an independent cohort of patients with late-onset PD (n = 1300). Functional experiments confirmed that truncated CHCHD2 variants cause loss of function and are linked to mitochondrial dysfunction. CONCLUSIONS: Our study reveals that the genetic spectrum of EOPD in Chinese, which may help develop genetic scanning strategies, provided more evidence supporting CHCHD2 in PD.

Genome-wide genetic links between amyotrophic lateral sclerosis and autoimmune diseases.

BACKGROUND: Epidemiological and clinical studies have suggested comorbidity between amyotrophic lateral sclerosis (ALS) and autoimmune disorders. However, little is known about their shared genetic architecture. METHODS: To examine the relation between ALS and 10 autoimmune diseases, including asthma, celiac disease (CeD), Crohn's disease (CD), inflammatory bowel disease (IBD), multiple sclerosis (MS), psoriasis, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), and ulcerative colitis (UC), and identify shared risk loci, we first estimated the genetic correlation using summary statistics from genome-wide association studies, and then analyzed the genetic enrichment leveraging the conditional false discovery rate statistical method. RESULTS: We identified a significant positive genetic correlation between ALS and CeD, MS, RA, and SLE, as well as a significant negative genetic correlation between ALS and IBD, UC, and CD. Robust genetic enrichment was observed between ALS and CeD and MS, and moderate enrichment was found between ALS and UC and T1D. Thirteen shared genetic loci were identified, among which five were suggestively significant in another ALS GWAS, namely rs3828599 (GPX3), rs3849943 (C9orf72), rs7154847 (G2E3), rs6571361 (SCFD1), and rs9903355 (GGNBP2). By integrating cis-expression quantitative trait loci analyses in Braineac and GTEx, we further identified GGNBP2, ATXN3, and SLC9A8 as novel ALS risk genes. Functional enrichment analysis indicated that the shared risk genes were involved in four pathways including membrane trafficking, vesicle-mediated transport, ER to Golgi anterograde transport, and transport to the Golgi and subsequent modification. CONCLUSIONS: Our findings demonstrate a specific genetic correlation between ALS and autoimmune diseases and identify shared risk loci, including three novel ALS risk genes. These results provide a better understanding for the pleiotropy of ALS and have implications for future therapeutic trials.

Camptocormia in patients with multiple system atrophy at different disease durations: frequency and related factors.

BACKGROUND: Camptocormia is common in patients with multiple system atrophy (MSA). The current study was aimed at assessing the frequency of camptocormia and its related factors in MSA patients with different disease durations. Also, the impact of camptocormia on disability was evaluated. METHODS: A total of 716 patients were enrolled in the study. They were classified into three groups based on disease duration (≤ 3, 3-5, ≥ 5 years). Specific scales were used to evaluate the motor and non-motor symptoms. Disease severity was assessed using the Unified Multiple System Atrophy Rating Scale (UMSARS). The binary logistic regression model was used to explore the factors related to camptocormia. To analyze the impact of camptocormia on disability in patients with disease duration less than 5 years, propensity score matching (PSM) and stratified Cox regression analysis were used. RESULTS: In the current study, we found that the frequency of camptocormia was 8.9, 19.7 and 19.2% when the disease duration was ≤3, 3-5, ≥ 5 years, respectively. In the disease duration ≤3 years group, we found that MSA-parkinsonian subtype (MSA-P) (OR = 2.043, P = 0.043), higher total UMSARS score (OR = 1.063, P < 0.001), older age of onset (OR = 1.047, P = 0.042), and lower score on the frontal assessment battery (FAB) (OR = 0.899, P = 0.046) were associated with camptocormia. Only greater disease severity was associated with camptocormia in the group of patients with disease duration 3-5 years (OR = 1.494, P = 0.025) and in the group of patients with disease duration ≥5 years (OR = 1.076, P = 0.005). There was no significant impact of camptocormia on disability in patients with a disease duration of < 5 years (HR = 0.687, P = 0.463). CONCLUSION: The frequency of camptocormia increased with prolonged disease duration. Disease severity was related to camptocormia at different stages of the disease. The MSA-P subtype, older age of onset, and lower FAB score were associated with camptocormia in the early stage of the disease.

Coding mutations in NUS1 contribute to Parkinson's disease.

Whole-exome sequencing has been successful in identifying genetic factors contributing to familial or sporadic Parkinson's disease (PD). However, this approach has not been applied to explore the impact of de novo mutations on PD pathogenesis. Here, we sequenced the exomes of 39 early onset patients, their parents, and 20 unaffected siblings to investigate the effects of de novo mutations on PD. We identified 12 genes with de novo mutations (MAD1L1, NUP98, PPP2CB, PKMYT1, TRIM24, CEP131, CTTNBP2, NUS1, SMPD3, MGRN1, IFI35, and RUSC2), which could be functionally relevant to PD pathogenesis. Further analyses of two independent case-control cohorts (1,852 patients and 1,565 controls in one cohort and 3,237 patients and 2,858 controls in the other) revealed that NUS1 harbors significantly more rare nonsynonymous variants (P = 1.01E-5, odds ratio = 11.3) in PD patients than in controls. Functional studies in Drosophila demonstrated that the loss of NUS1 could reduce the climbing ability, dopamine level, and number of dopaminergic neurons in 30-day-old flies and could induce apoptosis in fly brain. Together, our data suggest that de novo mutations could contribute to early onset PD pathogenesis and identify NUS1 as a candidate gene for PD.

Altered oligomeric states in pathogenic ALS2 variants associated with juvenile motor neuron diseases cause loss of ALS2-mediated endosomal function.

Familial amyotrophic lateral sclerosis type 2 (ALS2) is a juvenile autosomal recessive motor neuron disease caused by the mutations in the ALS2 gene. The ALS2 gene product, ALS2/alsin, forms a homophilic oligomer and acts as a guanine nucleotide-exchange factor (GEF) for the small GTPase Rab5. This oligomerization is crucial for both Rab5 activation and ALS2-mediated endosome fusion and maturation in cells. Recently, we have shown that pathogenic missense ALS2 mutants retaining the Rab5 GEF activity fail to properly localize to endosomes via Rac1-stimulated macropinocytosis. However, the molecular mechanisms underlying dysregulated distribution of ALS2 variants remain poorly understood. Therefore, we sought to clarify the relationship between intracellular localization and oligomeric states of pathogenic ALS2 variants. Upon Rac family small GTPase 1 (Rac1) activation, all mutants tested moved from the cytosol to membrane ruffles but not to macropinosomes and/or endosomes. Furthermore, most WT ALS2 complexes were tetramers. Importantly, the sizes of an ALS2 complex carrying missense mutations in the N terminus of the regulator of chromosome condensation 1-like domain (RLD) or in-frame deletion in the pleckstrin homology domain were shifted toward higher molecular weight, whereas the C-terminal vacuolar protein sorting 9 (VPS9) domain missense mutant existed as a smaller dimeric or trimeric smaller form. Furthermore, in silico mutagenesis analyses using the RLD protein structure in conjunction with a cycloheximide chase assay in vitro disclosed that these missense mutations led to a decrease in protein stability. Collectively, disorganized higher structures of ALS2 variants might explain their impaired endosomal localization and the stability, leading to loss of the ALS2 function.

Genome-wide association study of Parkinson's disease in East Asians.

Genome-wide association studies (GWAS) on Parkinson's disease (PD) have mostly been done in Europeans and Japanese. No study has been done in Han Chinese, which make up nearly a fifth of the world population. We conducted the first Han Chinese GWAS analysing a total of 22,729 subjects (5,125 PD cases and 17,604 controls) from Singapore, Hong Kong, Malaysia, Korea, mainland China and Taiwan. We performed imputation, merging and logistic regression analyses of 2,402,394 SNPs passing quality control filters in 779 PD cases, 13,227 controls, adjusted for the first three principal components. 90 SNPs with association P < 10-4 were validated in 9 additional sample collections and the results were combined using fixed-effects inverse-variance meta-analysis. We observed strong associations reaching genome-wide significance at SNCA, LRRK2 and MCCC1, confirming their important roles in both European and Asian PD. We also identified significant (P < 0.05) associations at 5 loci (DLG2, SIPA1L2, STK39, VPS13C and RIT2), and observed the same direction of associations at 9 other loci including BST1 and PARK16. Allelic heterogeneity was observed at LRRK2 while European risk SNPs at 6 other loci including MAPT and GBA-SYT11 were non-polymorphic or very rare in our cohort. Overall, we replicate associations at SNCA, LRRK2, MCCC1 and 14 other European PD loci but did not identify Asian-specific loci with large effects (OR > 1.45) on PD risk. Our results also demonstrate some differences in the genetic contribution to PD between Europeans and Asians. Further pan-ethnic meta-analysis with European GWAS cohorts may unravel new PD loci.

Functional links between SQSTM1 and ALS2 in the pathogenesis of ALS: cumulative impact on the protection against mutant SOD1-mediated motor dysfunction in mice.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by a selective loss of motor neurons in the brain and spinal cord. Multiple toxicity pathways, such as oxidative stress, misfolded protein accumulation, and dysfunctional autophagy, are implicated in the pathogenesis of ALS. However, the molecular basis of the interplay between such multiple factors in vivo remains unclear. Here, we report that two independent ALS-linked autophagy-associated gene products; SQSTM1/p62 and ALS2/alsin, but not antioxidant-related factor; NFE2L2/Nrf2, are implicated in the pathogenesis in mutant SOD1 transgenic ALS models. We generated SOD1H46R mice either on a Nfe2l2-null, Sqstm1-null, or Sqstm1/Als2-double null background. Loss of SQSTM1 but not NFE2L2 exacerbated disease symptoms. A simultaneous inactivation of SQSTM1 and ALS2 further accelerated the onset of disease. Biochemical analyses revealed that loss of SQSTM1 increased the level of insoluble SOD1 at the intermediate stage of the disease, whereas no further elevation occurred at the end-stage. Notably, absence of SQSTM1 rather suppressed the mutant SOD1-dependent accumulation of insoluble polyubiquitinated proteins, while ALS2 loss enhanced it. Histopathological examinations demonstrated that loss of SQSTM1 accelerated motor neuron degeneration with accompanying the preferential accumulation of ubiquitin-positive aggregates in spinal neurons. Since SQSTM1 loss is more detrimental to SOD1H46R mice than lack of ALS2, the selective accumulation of such aggregates in neurons might be more insulting than the biochemically-detectable insoluble proteins. Collectively, two ALS-linked factors, SQSTM1 and ALS2, have distinct but additive protective roles against mutant SOD1-mediated toxicity by modulating neuronal proteostasis possibly through the autophagy-endolysosomal system.

Impact of sleep-related breathing disorder on motor and non-motor symptoms in multiple system atrophy.

INTRODUCTION: Although several studies suggested that sleep-related breathing disorder (SRBD) is a frequent symptom of multiple system atrophy (MSA), whether SRBD has influence on the motor and non-motor symptoms of MSA is unknown. METHODS: A total of 40 MSA patients and 40 healthy volunteers (HVs) underwent video-polysomnography (PSG) in the current study. All the MSA individuals were assessed using the Epworth Sleepiness Scale (ESS), Unified Multiple-System Atrophy Rating Scale (UMSARS), Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale, Frontal assessment battery (FAB), Parkinson's Disease Questionnaire-39 (PDQ-39), and the Montreal Cognitive Assessment (MoCA). RESULTS: We found apnea-hypopnea index (AHI) of the MSA patients recorded by PSG was 16.4 ± 20.2. SRBD was found in 65% of the MSA patients (26/40), which was significantly higher than HVs (8/40, 20%) (p = 0.0001). Compared to the MSA patients without SRBD, MSA individuals with SRBD showed higher total UMSARS, UMSARS-II, FAB, and HAMD scores, more frequent occurrence of excessive daytime sleepiness, hypopneas, longer mean times for hypopneas, and obstructive sleep apnea (OSA), as well as longer time for OSA. This study suggested that SRBD is frequently seen in MSA patients. CONCLUSION: MSA individuals with SRBD are prone to be severe motor deficits, depression, frontal lobe dysfunction, and excessive daytime sleepiness.

White matter microstructure damage in tremor-dominant Parkinson's disease patients.

PURPOSE: Resting tremor is one of the cardinal motor features of Parkinson's disease (PD). Several lines of evidence suggest resting tremor may have different underlying pathophysiological processes from those of bradykinesia and rigidity. The current study aims to identify white matter microstructural abnormalities associated with resting tremor in PD. METHODS: We recruited 60 patients with PD (30 with tremor-dominant PD and 30 with nontremor-dominant PD) and 26 normal controls. All participants underwent clinical assessment and diffusion tensor MRI. We used tract-based spatial statistics to investigate white matter integrity across the entire white matter tract skeleton. RESULTS: Compared with both healthy controls and the nontremor-dominant PD patients, the tremor-dominant PD patients were characterized by increased mean diffusivity (MD) and axial diffusivity (AD) along multiple white matter tracts, mainly involving the cerebello-thalamo-cortical (CTC) pathway. The mean AD value in clusters with significant difference was correlated with resting tremor score in the tremor-dominant PD patients. There was no significant difference between the nontremor-dominant PD patients and controls. CONCLUSION: Our results support the notion that resting tremor in PD is a distinct condition in which significant microstructural white matter changes exist and provide evidence for the involvement of the CTC in tremor genesis of PD.

C9ORF72 repeat expansions in Chinese patients with Parkinson's disease and multiple system atrophy.

The hexanucleotide repeat expansions in the C9ORF72 gene has been found in some patients with atypical Parkinsonism. A number of hexanucleotide repeats were examined in a Chinese population, including 619 patients with Parkinson's disease (PD), 381 patients with multiple system atrophy (MSA), and 632 healthy controls. We did not identify any pathogenic repeat expansions in either patients or controls, and any associations between repeats number and disease risk. C9ORF72 expansions are not involved the wider spectrum of Parkinsonism.

Assessment of a multiple biomarker panel for diagnosis of amyotrophic lateral sclerosis.

BACKGROUND: The aim of the study was to assess a panel of promising biomarkers for their ability to improve diagnosis of sporadic amyotrophic lateral sclerosis (ALS). METHODS: Forty patients with sporadic ALS and 40 controls with other neurological diseases were evaluated. Levels of phosphorylated neurofilament heavy chain (pNfH), S100-ß, cystatin C, and chitotriosidase (CHIT) in cerebrospinal fluid were assayed using two-site solid-phase sandwich ELISA. RESULTS: Patients with sporadic ALS showed higher levels of pNfH and CHIT than controls, but lower levels of cystatin C. Multivariate logistic regression that adjusted for patient age and sex identified significant associations between sporadic ALS and levels of pNfH, CHIT and cystatin C. Levels of pNfH correlated positively with rate of progression and decline based on the Amyotrophic Lateral Sclerosis Functional Rating Scale - Revised. Based on receiver operating curve analysis, a pNfH cut-off of 437 ng/L discriminated patients from controls with a sensitivity of 97.3 % and specificity of 83.8 %. A CHIT cut-off of 1593.779 ng/L discriminated patients from controls with a sensitivity of 83.8 % and specificity of 81.1 %. Combining the two biomarkers gave a sensitivity of 83.8 % and specificity of 91.9 %. CONCLUSIONS: Levels of pNfH in cerebrospinal fluid may be a reliable biomarker for diagnosing ALS, and combining this biomarker with levels of CHIT may improve diagnostic accuracy.

Association analysis of the GRN rs5848 and MAPT rs242557 polymorphisms in Parkinson's disease and multiple system atrophy: a large-scale population-based study and meta-analysis.

BACKGROUND: Previous studies have found an association between the granulin gene rs5848 and microtubule-associated protein tau gene (MAPT) rs242557 polymorphisms and susceptibility to Parkinson's disease (PD). However, the results of association studies between the two polymorphisms and PD have been inconsistent. Given the overlap in clinical and pathological characteristics of PD and multiple system atrophy (MSA), we examined the associations of these two polymorphisms with PD and MSA in a subset of the Chinese population. METHODS: In total, 1270 PD patients, 360 MSA patients and 830 healthy controls (HCs) were included in the study. All subjects were genotyped for the two polymorphisms using Sequenom iPLEX Assay technology. After combining our results with the available published data, a meta-analysis was conducted to investigate the association between MAPT rs242557 and the risk of PD. RESULTS: The minor allele "T" of GRN rs5848 decreased the risk for PD (p = 0.0309, odds radio [OR], 0.86; 95% CI, 0.76-0.99). No differences in the genotype distributions and minor allele frequency (MAF) of MAPT rs242557 were observed between the PD and the HCs in our Chinese population. Our meta-analysis revealed an association between MAPT rs242557 and PD in Caucasian and Asian population in a recessive model (p = 0.049 and p = 0.046, respectively). However, no significant differences in the genotype distributions and MAFs of the two polymorphisms were found between the MSA patients and HCs. CONCLUSION: Our results indicate that GRN rs5458 may decrease the risk of PD in Chinese individuals, and the MAPT rs242557 is marginally associated with PD.

The trajectory of disturbed resting-state cerebral function in Parkinson's disease at different Hoehn and Yahr stages.

OBJECTIVE: We aim to investigate the disturbance of neural network associated with the different clinical stages of Parkinson's disease (PD). METHOD: We recruited 80 patients at different H&Y stages of PD (28 at H&Y stage I, 28 at H&Y stage II, 24 at H&Y stage III) and 30 normal controls. All participants underwent resting-state fMRI scans on a 3-T MR system. The amplitude of low-frequency fluctuation (ALFF) of blood oxygen level-dependent signals was used to characterize regional cerebral function. Functional integration across the brain regions was evaluated by a seed voxel correlation approach. RESULTS: PD patients had decreased regional activities in left occipital and lingual regions; these regions show decreased functional connection pattern with temporal regions, which is deteriorating as H&Y stage ascending. In addition, PD patients, especially those at stage II, exhibit increased regional activity in the posterior regions of default mode network (DMN), increased anticorrelation between posterior cingulate cortex (PCC) and cortical regions outside DMN, and higher temporal coherence within DMN. Those indicate more highly functioned DMN in PD patients at stage II. CONCLUSIONS: Our study demonstrated the trajectories of resting-state cerebral function disturbance in PD patients at different H&Y stages. Impairment in functional integration of occipital-temporal cortex might be a promising measurement to evaluate and potentially track functional substrates of disease evolution of PD.

Assessment of TREM2 rs75932628 association with Parkinson's disease and multiple system atrophy in a Chinese population.

Although rs75932628 in triggering receptor expressed on myeloid cells 2 (TREM2) was shown to increase the risk for Alzheimer's disease, there is no agreement on the association between this variant and the risk for Parkinson's disease (PD). Considering the overlapping of clinical manifestation and pathologic characteristics of PD and multiple system atrophy (MSA), we conducted a large-sample study to investigate the associations between this variant and these two neurodegenerative diseases in a Chinese population. A total of 1216 PD, 406 MSA patients, and 869 healthy controls were included. All cases were genotyped for the Single Nucleotide Polymorphisms (SNP) using Sequenom iPLEX Assay technology. The rs75932628-T variant of the TREM2 gene was not identified in PD patients and controls. The genotype frequency of rs75932628-T SNP in MSA patients was 0.25% (1/406). However, no significant correlation was identified between this variant and the risk for MSA. TREM2 rs75932628 is unlikely to play a major role in the pathogenesis of these neurodegenerative diseases. Our findings argue against a generalized immune dysfunction triggered by the variant in the TREM2 gene.

Impact of Frontal Lobe Function and Behavioral Changes on Health-Related Quality of Life in Patients with Parkinson's Disease: A Cross-Sectional Study from Southwest China.

BACKGROUND: Cognitive impairment may negatively impact the health-related quality of life (HRQoL) in patients with Parkinson's disease (PD). However, information on the effects of frontal lobe function and behavior changes on the HRQoL of the Chinese PD population is limited. Studies on the associations among frontal lobe function, behavioral changes and the HRQoL may help optimize the treatment and improve the HRQoL of PD patients. METHODS: A total of 309 PD patients were evaluated using the Frontal Assessment Battery, the Frontal Behavioral Inventory (FBI) and the PD Questionnaire 39-item version (PDQ-39). RESULTS: Patients with worse frontal lobe function were older (p < 0.001), had longer disease durations (p = 0.002), higher Unified Parkinson's Disease Rating Scale part III (UPDRS-III) scores (p < 0.001) and higher Hoehn and Yahr (H-Y) stages (p = 0.001), and exhibited significantly higher PDQ-39 summary index (SI; p = 0.001) compared with those who had better frontal lobe function. In addition, the disease duration (p = 0.008), UPDRS-III scores (p < 0.001), H-Y stage (p < 0.001), PDQ-39 SI and scores for each domain of the PDQ-39 (p < 0.001) were higher as the severity of frontal behavioral changes increased. The total FBI score (p < 0.001) was positively correlated with the PDQ-39 SI. CONCLUSIONS: Frontal behavioral changes were closely associated with poor HRQoL in Chinese PD patients.

The serum lipid profile of Parkinson's disease patients: a study from China.

BACKGROUND: The association between the fasting levels of serum lipids and Parkinson's disease (PD) in Chinese populations remains largely unknown. METHODS: This study enrolled 555 sporadic PD patients and 555 age-, gender- and body mass index (BMI)-matched controls. The fasting serum lipid concentrations of all subjects, including total cholesterol, low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C) and triglycerides (TG), were measured. RESULTS: Total cholesterol, LDL-C, HDL-C and TG were significantly lower in PD patients than in controls. The prevalence of PD is significantly lower in subjects with the second, third and fourth quartiles of total cholesterol than in those with the first quartile of total cholesterol, regardless of gender. The prevalence of PD is significantly lower in subjects with the third and fourth quartiles of LDL-C than in those with the first quartile of LDL-C, regardless of gender. Negative correlations were found between UPDRS part III score and level of total cholesterol/LDL-C. CONCLUSIONS: PD patients are with lower levels of total cholesterol, LDL-C, HDL-C and TG than controls. Lipids may be a marker of PD severity.