Pathological tau accumulates in the cerebral cortex of Parkinson's disease (PD), resulting in cognitive deterioration. Positron emission tomography (PET) can be used for
imaging of tau protein. ...Therefore, we conducted a systematic review and meta-analysis of tau protein burden in PD cognitive impairment (PDCI), PD dementia (PDD), and other neurodegenerative diseases and explored the potential of the tau PET tracer as a biomarker for the diagnosis of PDCI.
PubMed, Embase, the Cochrane Library, and Web of Science databases were systematically searched for studies published till 1 June 2022 that used PET imaging to detect tau burden in the brains of PD patients. Standardized mean differences (SMDs) of tau tracer uptake were calculated using random effects models. Subgroup analysis based on the type of tau tracers, meta-regression, and sensitivity analysis was conducted.
A total of 15 eligible studies were included in the meta-analysis. PDCI patients (
= 109) had a significantly higher tau tracer uptake in the inferior temporal lobe than healthy controls (HCs) (
= 237) and had a higher tau tracer uptake in the entorhinal region than PD with normal cognition (PDNC) patients (
= 61). Compared with progressive supranuclear palsy (PSP) patients (
= 215), PD patients (
= 178) had decreased tau tracer uptake in the midbrain, subthalamic nucleus, globus pallidus, cerebellar deep white matter, thalamus, striatum, substantia nigra, dentate nucleus, red nucleus, putamen, and frontal lobe. Tau tracer uptake values of PD patients (
= 178) were lower than those of patients with Alzheimer's disease (AD) (
= 122) in the frontal lobe and occipital lobe and lower than those in patients with dementia with Lewy bodies (DLB) (
= 55) in the occipital lobe and infratemporal lobe.
imaging studies with PET could reveal region-specific binding patterns of the tau tracer in PD patients and help in the differential diagnosis of PD from other neurodegenerative diseases.
https://www.crd.york.ac.uk/PROSPERO/.
4 Additionally, total cholesterol (TC)/high-density lipoprotein (HDL), low-density lipoprotein (LDL)/HDL, and apolipoprotein (Apo) B/Apo A1 are defined as predictive indicators of ...dyslipidemia-related disease risk with a greater informative value than that of isolated lipid parameters, especially for the risk of cardiovascular diseases (CVDs). According to the results, although a statistically significant difference in the mean levels of triglycerides (TG) was found between the SMA and control groups (1.07 ± 0.54 mmol/L vs. 0.82 ± 0.39 mmol/L; P <0.001) Table 1, they both remained within the normal reference range. Serum lipid profiles* SMA (n = 91) Control (n = 91) t† P values MD (95% CI‡) TG (mmol/L) 1.07 ± 0.54 0.82 ± 0.39 3.705 <0.001 0.25 (0.12, 0.38) TC (mmol/L) 4.34 ± 1.25 4.51 ± 0.77 –1.153 0.252 –0.17 (–0.45, 0.12) Lp(a) (mg/L) 53 (23, 130) 75 (38, 133) –0.771§ 0.440 0.21 (NA) HDL (g/L) 1.16 ± 0.29 1.39 ± 0.25 –6.075 <0.001 –0.23 (–0.30, 0.15) LDL (g/L) 2.65 ± 0.77 2.75 ± 0.54 –0.992 0.324 –0.09 (–0.28, 0.09) Apo Al (mmol/L) 1.20 ± 0.21 1.40 ± 0.14 –8.452 <0.001 –0.20 (–0.25, 0.15) Apo B (mmol/L) 0.74 ± 0.23 0.78 ± 0.16 –1.385 0.170 –0.04 (–0.10, 0.02) TC/HDL 3.98 ± 1.88 3.29 ± 0.53 3.707 <0.001 0.69 (0.32, 1.07) LDL/HDL 2.41 ± 0.90 2.01 ± 0.43 4.166 <0.001 0.40 (0.21, 0.59) Apo B/Apo A1 0.63 ± 0.22 0.56 ± 0.12 2.830 0.006 0.07 (0.02, 0.12) Data are shown as mean ± standard deviation, and median (Q1, Q3).*TG elevation is defined as TG >1.70 mmol/L; TC elevation is defined as TC >5.20 mmol/L; Lp(a) elevation is defined as Lp(a) >500 mg/L; HDL cholesterol decrease is defined as HDL <1.04 mmol/L; low-density lipoprotein (LDL) cholesterol elevation is defined as LDL >3.38 mmol/L; Apo A1 decrease is defined as Apo A1 <1.20 g/L; and Apo B elevation is defined as Apo B >0.90 g/L. The reference risk levels by gender for these three ratios in primary/secondary prevention of cardiovascular diseases were defined as follows: the TC/HDL >5.0/4.0 for males or >4.5/3.5 for females; the LDL/HDL >3.5/3.0 for males or >3.0/2.5 for females; and the Apo B/Apo A1 >1.0/0.8 for males or >0.9/0.7 for females. †t is referred to as the test statistic of the paired-samples t-test. ‡95% CI is referred to as the confidence interval of the mean level of the differences between each paired sample of the SMA and control groups.§ Here the –0.771 is referred to the test statistic Z of the Wilcoxon rank sum test.
Evidence has shown that the CUB and Sushi Multiple Domains (CSMD1) gene is an inhibitor of the complement activation pathway and is also involved in central nervous system inflammation. Previous ...studies have revealed that the CSMD1 gene is related to familial Parkinson’s disease. This study aimed to investigate the relationship between CSMD1 gene and susceptibility to Parkinson’s disease in population of northern China. A case-control study was performed on 423 Parkinson’s disease patients and 465 healthy controls matched for age and sex. DNA from enrolled subjects were extracted from the peripheral blood, and single nucleotide polymorphisms (SNPs) rs12681349 (C＞T), rs10503253 (C＞A), and rs1983474 (T＞G) within CSMD1 gene were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Genotype frequency of rs10503253 (CA versus CC : OR = 1.554, 95% CI = 1.169–2.066, p=0.002) and rs1983474 (GG versus TT : OR = 0.599, 95% CI = 0.401–0.895, p=0.012) was significantly different between PD cases and controls, but not for rs12681349. Comprehensive and subgroup analysis indicated that rs10503252 showed significant statistical differences in the dominant model (AA + CA versus CC : OR = 0.677, 95% CI = 0.517–0.886, p=0.004), late-onset cohort (CA versus CC : OR = 1.570, 95% CI = 1.159–2.126, p=0.004), and the female cohort (CA versus CC : OR = 0.687, 95% CI = 0.497–0.952, p=0.023), compared with the matched control group. The difference of recessive model of rs1983474 (GG versus TT + TG : OR = 1.837, 95% CI = 1.287–2.620, p=0.001) was significant in Parkinson’s disease. According to the subgroup analysis, results indicated that late-onset cohort (GG versus TT : OR = 0.643, 95% CI = 0.420–0.985, p=0.042), male cohort (TG versus TT : OR = 2.160, 95% CI = 1.162–4.016, p=0.015), and female group (GG versus TT : OR = 0.418, 95% CI = 0.234–0.746, p=0.003) of rs1983474 were significantly associated with Parkinson’s disease susceptibility. In both genotype and subgroup analysis, we failed to find any relationship between rs12681349 polymorphism and Parkinson’s disease risk. Our results indicate that the rs10503253 and rs1983474 gene polymorphism may be associated with idiopathic Parkinson’s disease susceptibility in Chinese population. Nevertheless, these conclusions need to be further verified by more studies.
Introduction
Spinal muscular atrophy (SMA) can cause multiple system dysfunction, especially lipid metabolic disorders, for which management strategies are currently lacking. Microbes are related to ...metabolism and the pathogenesis of neurological diseases. This study aimed to preliminarily explore the alterations in the gut microbiota in SMA and the potential relationship between altered microbiota and lipid metabolic disorders.
Methods
Fifteen patients with SMA and 17 gender- and age-matched healthy controls were enrolled in the study. Feces and fasting plasma samples were collected. 16S ribosomal RNA sequencing and nontargeted metabolomics analysis were performed to explore the correlation between microbiota and differential lipid metabolites.
Results
No significant difference was found in microbial diversity (α- and β-diversity) between the SMA and control groups, with both groups having a relatively similar community structure. However, compared to the control group, the SMA group showed an increased relative abundance of the genera
Ruminiclostridium
,
Gordonibacter
,
Enorma
,
Lawsonella
,
Frisingicoccus
, and
Anaerofilum
and a decreased abundance of the genera
Catabacter
,
Howardella
,
Marine_Methylotrophic_Group_3
, and
Lachnospiraceae_AC2044_group
. The concurrent metabolomic analysis showed that the SMA group had 56 different kinds of lipid metabolite levels than did the control group. Additionally, the Spearman correlation suggested a correlation between the altered differential lipid metabolites and the above-mentioned altered microbiota.
Conclusions
The gut microbiome and lipid metabolites differed between the patients with SMA and the control subjects. The altered microbiota may be related with the lipid metabolic disorders in SMA. However, further study is necessary to clarify the mechanism of lipid metabolic disorders and develop management strategies to improve the related complications in SMA.
Objectives
To evaluate the difference of tau burden between patients with progressive supranuclear palsy (PSP) and healthy controls (HCs) or other neurodegenerative diseases using tau-positron ...emission tomography (PET) imaging.
Methods
A systematic search on PubMed, Embase, and Web of Science databases was performed for tau-PET studies in PSP patients, up to April 1, 2022. Standardized mean differences (SMDs) of tau tracer uptake were calculated using random-effects models. Subgroup analysis based on the type of tau tracers, meta-regression, and sensitivity analysis were conducted.
Results
Twenty-seven studies comprising 553 PSP, 626 HCs, and 406 other neurodegenerative diseases were included. Compared with HCs, PSP patients showed elevated tau binding in basal ganglia, midbrain, dentate nucleus, cerebellar white matter, and frontal lobe with decreasing SMD (SMD: 0.390–1.698). Compared with Parkinson’s disease patients, increased tau binding was identified in the midbrain, basal ganglia, dentate nucleus, and frontal and parietal lobe in PSP patients with decreasing SMD (SMD: 0.503–1.853). PSP patients showed higher tau binding in the subthalamic nucleus (SMD = 1.351) and globus pallidus (SMD = 1.000), and lower binding in the cortex and parahippocampal gyrus than Alzheimer’s disease patients (SMD: − 2.976 to − 1.018). PSP patients showed higher midbrain tau binding than multiple system atrophy patients (SMD = 1.269).
Conclusion
Tau PET imaging indicates different topography of tau deposition between PSP patients and HCs or other neurodegenerative disorders. The affinity and selectivity of tracers for 4R-tau and the off-target binding of tracers should be considered when interpreting the results.
The risk of relapse in major depressive disorder (MDD) is associated with high worldwide disease burden. Cognitive behavioral therapy (CBT) and its modifications might be effective in relapse ...prevention. The aim of this review was to evaluate the efficacy of these treatments for reducing relapse of MDD.
The retrieval was performed in the databases of MEDLINE via Pubmed, EMBASE and PsycINFO via OVID, The Cochrane Library and four Chinese databases. Clinical trials registry platforms and references of relevant articles were retrieved as well. Hazard ratio (HR) and corresponding 95% confidence interval (CI) were used to pool evidences.
A total of 16 eligible trials involving 1945 participants were included. In the first 12 months, CBT was more efficacious than control in reducing the risk of developing a new episode of depression for MDD patients in remission (HR:0.50, 95%CI:0.35-0.72, I
= 11%). Mindfulness-based cognitive therapy (MBCT) was more efficacious than control only among patients with 3 or more previous depressive episodes (HR:0.46, 95%CI:0.31-0.70, I
= 38%). Besides, compared with maintenance antidepressant medication (m-ADM), MBCT was a more effective intervention (HR:0.76, 95%CI:0.58-0.98, I
= 0%). These positive effects might be only maintained at two and nearly 6 years follow up for CBT.
The use of CBT for MDD patients in remission might reduce risk of relapse. Besides, the effect of MBCT was moderated by number of prior episodes and MBCT might only be effective for MDD patients with 3 or more previous episodes. Further exploration for the influence of previous psychological intervention is required.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
•Our study is to verify the relationship between the polymorphism of SORL1 gene and PD in Han Chinese population.•Three single nucleotide polymorphisms (SNPs) of SORL1 gene (rs1010159, rs1629493 and ...rs2298813) were genotyped in a Han Chinese cohort.•Variations of rs1010159 and rs2298813 on SORL1 gene may be both risk factors for PD.•No significant correlation between rs1629493 and PD was found.
There is increasing evidence that lysosomal pathway dysfunction is closely linked to the pathogenesis of Parkinson's disease (PD). Considering the relationship between sortilin-related receptor 1 (SORL1) and lysosomal dysfunction, the abnormal aggregation of misfolded proteins in neurodegenerative disorders, especially in PD, and that glial cell-derived neurotrophic factor (GDNF) is the most effective neurotrophic factor affecting the activity of the dopamine system, and that SORL1 may induce PD by affecting GDNF, we investigated the correlation between three genetic variants (rs1010159, rs1629493, and rs2298813) of SORL1 gene polymorphisms and the risk of PD in the northern Chinese population in order to broaden the perspective for PD therapy.
Three single-nucleotide polymorphisms (SNPs) of SORL1 genes (rs1010159, rs1629493, and rs2298813) were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) on the DNA of 400 patients with PD and 400 healthy controls matched by age and gender. The chi-square test was used to analyze the statistical differences in genotypic and allelic polymorphism frequency between PD patients and healthy controls. Logistic regression analysis was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to estimate potential correlations.
The frequencies of the T allele of rs1010159 and the A allele of rs2298813 in patients with PD were much higher than those in the controls (P = 0.003, P = 0.042, respectively). For rs1010159, subgroup analysis showed statistical changes in the frequency of the T allele in all subgroups (P = 0.021, P = 0.036, P = 0.001, P = 0.030, respectively); however, genotypic frequency distributions were statistically significant only between male patients with PD and matched healthy male controls (P = 0.001), and between early onset PD (EOPD) and late-onset PD (LOPD) and controls (P = 0.001, P = 0.001). For rs2298813, the explicit model showed that the GA + AA genotype had an increased risk of PD compared with the GG genotype (P = 0.020, OR = 1.518, 95% CI = 1.065–2.162), and the additive model showed that GA was also associated with a higher trend in PD compared with the GG genotype (P = 0.037, OR = 1.475, 95% CI = 1.024–2.125), and the allelic and genotypic frequencies of the LOPD were statistically different from those of the healthy group (P = 0.013, P = 0.044; respectively). No distinct correlation was found between rs1629493 and PD risk. The GAT haplotype, together with the AGT haplotype, was associated with PD susceptibility.
The rs1010159 and rs2298813 polymorphisms of the SORL1 gene rather than the rs1629493 polymorphism may be implicated in the susceptibility to PD in the northern Chinese population. Studies in different ethnicities and larger populations are indispensable for understanding the intrinsic correlation between the SORL1 gene and PD pathogenesis.
•PGLYRP2 gene rs892145, rs3813135 and rs733731 polymorphisms were examined in a Chinese Han cohort.•The rs892145 AT heterozygote in PGLYRP2 gene is a risk factor for PD and early-onset PD.•The ...rs3813135 C allele in PGLYRP2 gene might be a risk factor for PD.•No association was found between genotype or allele in rs733731 polymorphism and PD.
Gut inflammation is increasingly corroborated to take part in the pathogenesis of Parkinson’s disease (PD). The PGLYRP2 gene has been proven to increase susceptibility to inflammatory bowel disease (IBD). The present study aimed to explore the genetic relationship between single nucleotide polymorphism (SNP) of the PGLYRP2 gene and the risk of sporadic PD in the Han population of northern China. The genotypes of the rs3813135 T/C, rs733731 C/T and rs892145 A/T polymorphisms of the PGLYRP2 gene in 400 Chinese Han patients with PD and 400 healthy age-and sex-matched individuals were identified by the Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR–RFLP) method. The results showed that the frequency of the rs892145 AT heterozygote significantly differed between the PD and control groups (OR = 1.459, 95%CI = 1.459–1.039, P = 0.029), as well as the early-onset PD and control groups (P = 0.024). The rs3813135 polymorphism yielded only one significant result: C allele was more common in the male PD group than in the male control group (P = 0.045). Conversely, no significant difference in the genotype frequency of rs733731 was found between the PD and control groups. Five common haplotypes were assessed, of which the TTA and TCA haplotypes were related to PD susceptibility. In summary, our results indicated that the PGLYRP2 gene is associated with sporadic PD in the Chinese Han population, in which the rs892145 AT heterozygote might increase the risk of PD and possibly the risk of early-onset PD. Moreover, linkage disequilibrium (LD) analysis showed these three PGLYRP2 polymorphisms has a strong linkage in causing mutations.
•NEK1 gene polymorphisms may be associated with sporadic Parkinson’s disease in the Chinese Northern Han population.•NEK1 rs66509122 T allele may be a protective factor for Parkinson’s disease.•The ...rs4563461 C allele was significantly associated with sleep disorders in Parkinson’s disease.•The rs66509122 C allele was associated with diabetes in female patients and depression in the early-onset of Parkinson’s disease.
Parkinson’s disease (PD) has been identified as a genetically influenced disease linked to various genetic loci. Previous studies have suggested that neurodegenerative illnesses, including PD, Alzheimer’s disease, and Amyotrophic lateral sclerosis (ALS), may share certain genetic loci. Recently, the NEK1 gene was identified as overlapping between PD and ALS. We therefore wanted to explore the potential association between the NEK1 gene single nucleotide polymorphisms (SNPs) and the clinical features and pathophysiology of sporadic PD in a northern Chinese population.
A total of 510 sporadic PD patients and 510 age- and sex-matched healthy controls (HCs) were included in this study. Two SNPs (rs4563461 and rs66509122) of the NEK1 gene were genotyped using polymerase chain reaction (PCR). And we analyzed the association between NEK1 gene polymorphisms and clinical manifestations.
Allele T (C vs. T, P = 0.018) and genotype TT (CC vs. TT: P = 0.021) of rs66509122 among PD group and HCs were significantly different. In addition, we discovered that the rs66509122 genotype TT was associated with depression in early-onset PD (EOPD) (P = 0.031) and diabetes in female PD (P = 0.032). Unfortunately, no distinct correlation of rs4563461 polymorphisms with sporadic PD susceptibility was found in either the overall group (C vs. T, P = 0.086) or other subgroups. However, the T allele of rs4563461 was significantly correlated with sleep disorders in the PD group, especially in the late-onset PD (LOPD) group and male PD group.
This study found that the NEK1 rs66509122 polymorphism was associated with a lower risk of sporadic PD, while T allele of rs66509122 may be a protective factor for PD. The NEK1 rs4563461 and rs66509122 polymorphisms both showed correlations with some non-motor symptoms in sporadic PD patients. Further research with a larger sample and varied ethnic groups is needed to investigate the role of NEK1 gene polymorphisms in the pathophysiology of PD.
Background and purpose
Axial postural abnormalities, mainly involving the spinal deformities, are disabling symptoms of Parkinson’s disease (PD). However, the prevalence of axial postural ...abnormalities in PD and their clinical correlates remain unclear. The present study aimed to conduct a systematic review and meta-analysis of the prevalence of overall and subtypes of axial postural abnormalities in PD.
Methods
PubMed, Embase, Web of Science and Cochrane databases were searched up to 31st March, 2022. We identified studies that reported the prevalence of axial postural abnormalities in PD. The pooled estimate of prevalence was calculated using a random effect model. Subgroup analysis and meta-regression were performed.
Results
There were 19 studies met the inclusion criteria. The overall prevalence of axial postural abnormalities in PD was 22.1% (95% CI 19.7–24.5%). The prevalence of each subtype of axial postural abnormalities was 19.6% for scoliosis (95% CI 10.6–28.7%), 10.2% for camptocormia (95% CI 7.7–12.7%), 8% for Pisa syndrome (95% CI 4.7–11.4%), and 7.9% for antecollis (95% CI 3.9–11.9%). Subgroup analysis showed that the measuring method of axial postural abnormalities exerted significant effects on prevalence estimates. Axial postural abnormalities in PD were associated with older age, longer disease duration, higher H-Y stage, greater levodopa equivalent daily dose, more severe motor symptoms, motor fluctuations, and akinetic-rigid subtype.
Conclusions
Axial postural abnormalities, which include scoliosis, camptocormia, Pisa syndrome, and antecollis, are not uncommon in patients with PD. Future research on axial postural abnormalities should be based on uniform diagnostic criteria and measuring methods.
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