Abstract Background Previous studies have found a correlation between coronavirus disease 2019 (COVID-19) and changes in brain structure and cognitive function, but it remains unclear whether COVID-19 causes brain structural changes and which specific brain regions are affected. Herein, we conducted a Mendelian randomization (MR) study to investigate this causal relationship and to identify specific brain regions vulnerable to COVID-19. Methods Genome-wide association study (GWAS) data for COVID-19 phenotypes (28,900 COVID-19 cases and 3,251,161 controls) were selected as exposures, and GWAS data for brain structural traits (cortical thickness and surface area from 51,665 participants and volume of subcortical structures from 30,717 participants) were selected as outcomes. Inverse-variance weighted method was used as the main estimate method. The weighted median, MR-Egger, MR-PRESSO global test, and Cochran’s Q statistic were used to detect heterogeneity and pleiotropy. Results The genetically predicted COVID-19 infection phenotype was nominally associated with reduced cortical thickness in the caudal middle frontal gyrus ( β = − 0.0044, p = 0.0412). The hospitalized COVID-19 phenotype was nominally associated with reduced cortical thickness in the lateral orbitofrontal gyrus ( β = − 0.0049, p = 0.0328) and rostral middle frontal gyrus ( β = − 0.0022, p = 0.0032) as well as with reduced cortical surface area of the middle temporal gyrus ( β = − 10.8855, p = 0.0266). These causal relationships were also identified in the severe COVID-19 phenotype. Additionally, the severe COVID-19 phenotype was nominally associated with reduced cortical thickness in the cuneus ( β = − 0.0024, p = 0.0168); reduced cortical surface area of the pericalcarine ( β = − 2.6628, p = 0.0492), superior parietal gyrus ( β = − 5.6310, p = 0.0408), and parahippocampal gyrus ( β = − 0.1473, p = 0.0297); and reduced volume in the hippocampus ( β = − 15.9130, p = 0.0024). Conclusions Our study indicates a suggestively significant association between genetic predisposition to COVID-19 and atrophy in specific functional regions of the human brain. Patients with COVID-19 and cognitive impairment should be actively managed to alleviate neurocognitive symptoms and minimize long-term effects.
The Chinese population has been aging rapidly and the country's economy has experienced exponential growth during the past three decades. The goal of this study was to estimate the changes in the prevalence of dementia, Alzheimer's disease (AD), and vascular dementia (VaD) among elderly Chinese individuals and to analyze differences between urban and rural areas.For the years 2008 to 2009, we performed a population-based cross-sectional survey with a multistage cluster sampling design. Residents aged 65 years and older were drawn from 30 urban (n = 6096) and 45 rural (n = 4180) communities across China. Participants were assessed with a series of clinical examinations and neuropsychological measures. Dementia, AD, and VaD were diagnosed according to established criteria via standard diagnostic procedures.The prevalence of dementia, AD, and VaD among individuals aged 65 years and older were 5.14% (95% CI, 4.71-5.57), 3.21% (95% CI, 2.87-3.55), and 1.50% (95% CI, 1.26-1.74), respectively. The prevalence of dementia was significantly higher in rural areas than in urban ones (6.05% vs. 4.40%, P < .001). The same regional difference was also seen for AD (4.25% vs. 2.44%, P < .001) but not for VaD (1.28% vs. 1.61%, P = .166). The difference in AD was not evident when the sample was stratified by educational level. Moreover, the risk factors for AD and VaD differed for urban and rural populations.A notably higher prevalence of dementia and AD was found in rural areas than in urban ones, and education might be an important reason for the urban-rural differences.
Vascular cognitive impairment, no dementia (VCIND) refers to cognitive deficits associated with underlying vascular causes that fall short of a dementia diagnosis. There is currently no treatment for VCIND. Computerized cognitive training, which has significantly improved cognitive function in healthy older adults and patients with cognitive impairment has not yet been applied to VCIND. The proposed study is a three-center, double-blinded, randomized controlled trial that will include 60 patients with VCIND. The patients will be randomized to either a training or a control group. The intervention is internet-based cognitive training performed for 30 min over 35 sessions. Neuropsychological assessment and functional and structural MRI will be performed before and after 7 weeks training. Primary outcomes are global cognitive function and executive function. Secondary outcome measures are neuroplasticity changes measured by functional and structural MRI. Applying an internet-based, multi-domain, adaptive program, this study aims to assess whether cognitive training improves cognitive abilities and neural plasticity in patients with subcortical VCIND. In addition to the comprehensive assessment of the participants by neuropsychological tests, cerebrovascular risk factors and apolipoprotein E genotyping, neuroplasticity will be used as an evaluation outcome in this study for, to our knowledge, the first time. The combination of functional and structural MRI and neuropsychological tests will have strong sensitivity in evaluating the effects of cognitive training and will also reveal the underlying mechanisms at work. ClinicalTrials.gov NCT02640716 . Retrospectively registered on 21 December 2015.
Recently, transcranial alternating current stimulation (tACS), which can interact with ongoing neuronal activity, has emerged as a potentially effective and promising treatment for Alzheimer's disease (AD), and the 40 Hz gamma frequency was suggested as a suitable stimulation frequency for AD.The TRANSFORM-AD study is a double-blind, randomized-controlled trial that will include 40 individuals with mild AD. Eligible patients need to have amyloid β (Aβ) loads examined by Pittsburgh compound B (PiB) positron emission tomography (PET) or decreased Aβ level in cerebrospinal fluid. Participants will be randomized into either a 40 Hz tACS group or a sham stimulation group. Both groups will undergo 30 one-hour sessions across 3 weeks (21 days). The outcome measures will be assessed at baseline, at the end of the intervention, and 3 months after the first session. The primary outcome is global cognitive function, assessed by the 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog), and the secondary outcomes include changes in other neuropsychological assessments and in PiB-PET, structural magnetic resonance imaging (MRI), resting electroencephalography (EEG), and simultaneous EEG-functional MRI (EEG-fMRI) results.The trial is currently ongoing, and it is anticipated that recruitment will be completed in June 2021.This trial will evaluate the efficacy and safety of 40 Hz tACS in patients with AD, and further explore the potential mechanisms by analyzing amyloid deposits using PiB-PET, brain volume and white matter integrity by structural MRI, and neural activity by EEG and EEG-fMRI.
Differences in cortical morphology have been reported in individuals with Parkinson's disease (PD). However, the pathophysiological mechanism of transcriptomic vulnerability in local brain regions remains unclear.
As an ill-defined syndrome consisting of heterogeneous neurological symptoms and high serum antithyroid antibody titers, Hashimoto's encephalopathy typically responds to steroids. More serial clinical studies are required to characterize the clinical, laboratory and imaging features and outcomes.We analyzed retrospectively the clinical, laboratory, and imaging features and outcomes of 15 consecutive patients with Hashimoto's encephalopathy diagnosed at our hospital from 2005 to 2011.Cognitive impairment (11/15) and psychiatric symptoms (5/15) were the most frequent manifestations. Seizure (4/15) and myoclonus (1/15) were less common than previously described. Three (3/15) patients showed abnormal signals in hippocampus or temporal lobe related to memory disorders. Among 10 patients on steroid therapy, there were recovery (n = 5), improvement with residual deficits (n = 2) and relapse or no effect (n = 3). Among 5 patients on non-steroid, there were stable remission with antiepileptic drugs or general neurotrophic therapy (n = 3) and continuous deterioration (n = 2).Most patients respond well to steroids while someone improves without steroid therapy. In light of its reversible course, we recommend that Hashimoto's encephalopathy should always be considered in the differential diagnosis while evaluating disorders of central nervous system, even disorders those without manifestations of encephalopathy.
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