Emerging evidence has suggested a close correlation between COVID-19 and neurodegenerative disorders. However, whether there exists a causal association and the effect direction remains unknown. To examine the causative role of COVID-19 in the risk of neurodegenerative disorders, we estimated their genetic correlation, and then conducted a two-sample Mendelian randomization analysis using summary statistics from genome-wide association studies of susceptibility, hospitalization, and severity of COVID-19, as well as six major neurodegenerative disorders including Alzheimer’s disease (AD), amyotrophic lateral sclerosis, frontotemporal dementia, Lewy body dementia, multiple sclerosis, and Parkinson’s disease. We identified a significant and positive genetic correlation between hospitalization of COVID-19 and AD (genetic correlation: 0.23,P = 8.36E–07). Meanwhile, hospitalization of COVID-19 was significantly associated with a higher risk of AD (OR: 1.02, 95% CI: 1.01–1.03,P: 1.19E–03). Consistently, susceptibility (OR: 1.05, 95% CI: 1.01–1.09,P: 9.30E–03) and severity (OR: 1.01, 95% CI: 1.00–1.02,P: 0.012) of COVID-19 were nominally associated with higher risk of AD. The results were robust under all sensitivity analyses. These results demonstrated that COVID-19 could increase the risk of AD. Future development of preventive or therapeutic interventions could attach importance to this to alleviate the complications of COVID-19.

The survival time of amyotrophic lateral sclerosis (ALS) is greatly variable and protective or risk effects of the potential survival predictors are controversial. Thus, we aim to undertake a comprehensive meta-analysis of studies investigating non-genetic prognostic and survival factors in patients with ALS. A search of relevant literature from PubMed, Embase, Cochrane library and other citations from 1^st January 1966 to 1^st December 020 was conducted. Random-effects models were conducted to pool the multivariable or adjusted hazard ratios (HR) by Stata MP 16.0. PROSPERO registration number: CRD42021256923. A total of 5717 reports were identified, with 115 studies meeting pre-designed inclusion criteria involving 55,169 ALS patients. Five dimensions, including demographic, environmental or lifestyle, clinical manifestations, biochemical index, therapeutic factors or comorbidities were investigated. Twenty-five prediction factors, including twenty non-intervenable and five intervenable factors, were associated with ALS survival. Among them, NFL (HR:3.70, 6.80, in serum and CSF, respectively), FTD (HR:2.98), ALSFRS-R change (HR:2.37), respiratory subtype (HR:2.20), executive dysfunction (HR:2.10) and age of onset (HR:1.03) were superior predictors for poor prognosis, but pLMN or pUMN (HR:0.32), baseline ALSFRS-R score (HR:0.95), duration (HR:0.96), diagnostic delay (HR:0.97) were superior predictors for a good prognosis. Our results did not support the involvement of gender, education level, diabetes, hypertension, NIV, gastrostomy, and statins in ALS survival. Our study provided a comprehensive and quantitative index for assessing the prognosis for ALS patients, and the identified non-intervenable or intervenable factors will facilitate the development of treatment strategies for ALS. This study was supported by the National Natural Science Fund of China (Grant No. 81971188), the 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (Grant No. 2019HXFH046), and the Science and Technology Bureau Fund of Sichuan Province (No. 2019YFS0216).

Background: Parkinson's disease (PD) and sarcopenia are two common diseases in aging people. To date, the prevalence of sarcopenia in PD patients and the relationship between clinical features and sarcopenia in PD patients are not clear. The aim of the study was to (1) assess the prevalence of sarcopenia in PD patients and (2) reveal the clinical features between PD patients with and without sarcopenia.Method: A systematic review was carried out through screening PubMed, EMBASE, and Cochrane database in May 2020. All study designs (case–control, cohort, and cross-sectional studies) were eligible for meta-analysis. Data of patients' characteristics, sarcopenia criteria, sarcopenia prevalence, and sarcopenia measures were retrieved. The primary outcome was estimated prevalence of sarcopenia by a pooled prevalence (%) and its 95% confidence interval (CI), using a random-effects model. The secondary outcome was the differences in clinical features between PD patients with and without sarcopenia by meta-analysis. Included articles were assessed for risk of bias. Potential sources of variation were investigated by using subgroup analyses and meta-regression.Result: Ten studies were included in the review. Among them, nine were cross-sectional studies, and one was a prospective cohort study. Age of participants with PD in the studies ranged from 51.1 to 80.7 years. The estimated prevalence of sarcopenia ranged from 6 to 55.5%. The random-effects pooled prevalence was 29% (95% CIs: 0.18–0.40). When only studies at low risk of bias were considered, pooled prevalence decreased to 17% (95% CIs: 0.02–0.33), with still high heterogeneity. The incidence of falls in PD patients with sarcopenia was higher than that in PD patients without sarcopenia. There was no difference in sex ratio between PD patients with and without sarcopenia.Conclusion: Sarcopenia seems to be common in patients with PD. Early assessment of sarcopenia should be implemented in PD to avoid fall and disability.

By detecting spontaneous low-frequency fluctuations (LFF) of blood oxygen level–dependent (BOLD) signals, resting-state functional magnetic resonance imaging (rfMRI) measurements are believed to reflect spontaneous cerebral neural activity. Previous fMRI studies were focused on the examination of motor-related areas and little is known about the functional changes in the extra-motor areas in amyotrophic lateral sclerosis (ALS) patients. The aim of this study is to investigate functional cerebral abnormalities in ALS patients on a whole brain scale. Twenty ALS patients and twenty age- and sex-matched healthy volunteers were enrolled. Voxel-based analysis was used to characterize the alteration of amplitude of low frequency fluctuation (ALFF). Compared with the controls, the ALS patients showed significantly decreased ALFF in the visual cortex, fusiform gyri and right postcentral gyrus; and significantly increased ALFF in the left medial frontal gyrus, and in right inferior frontal areas after grey matter (GM) correction. Taking GM volume as covariates, the ALFF results were approximately consistent with those without GM correction. In addition, ALFF value in left medial frontal gyrus was negatively correlated with the rate of disease progression and duration. Decreased functional activity observed in the present study indicates the underlying deficits of the sensory processing system in ALS. Increased functional activity points to a compensatory mechanism. Our findings suggest that ALS is a multisystem disease other than merely motor dysfunction and provide evidence that alterations of ALFF in the frontal areas may be a special marker of ALS.