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Cerebral small vessel disease (CSVD) is common among older people and it could lead to dementia. Whether anti-platelet therapy (APT) could retard the cognitive decline of CSVD is unclear. The aim of the study was to evaluate, in newly diagnosed CSVD patients without dementia, the association between the APT and dementia during follow-up.
We conducted a nested case-control study within a CSVD cohort. Dementia cases, such as vascular dementia (VaD), Alzheimer's disease (AD), and unspecified dementia (UD), were individually matched (11) to controls by age, sex, and follow-up time. Conditional logistic regression models were used to estimate the odds ratios (
s) between APT and dementia.
Of 9,991 patients in a cohort screened from January 2009 to December 2019 and followed-up until November 2020, 131 dementia cases were finally included and successfully matched to 131 controls. Among 262 patients with CSVD, the mean [standard deviation (SD)] age was 73.9 (7.9) years and 126 (48.1%) were men. The median [interquartile range (IQR)] follow-up periods were 4.73 (2.70-6.57) years in the control group and 2.94 (1.34-4.89) years in the case group. According to MRI at baseline, the case group showed higher CSVD burden in lacune(s) (
= 0.001), moderate-to-severe white matter hyperintensities (WMHs) (
= 0.015), enlarged perivascular spaces (EPVSs) in basal ganglia (
= 0.005), and brain atrophy (
< 0.001). The APT was associated with the lower overall dementia risk and the matched
was statistically significant (a
0.15, 95%
0.05-0.45,
= 0.001), and clopidogrel showed protective effects on overall dementia (a
0.30, 95%
0.14-0.62,
= 0.001).
Among newly diagnosed CSVD patients without dementia, APT was associated with a lower risk of dementia and clopidogrel might be an appropriate candidate in preventing dementia.
Among newly diagnosed CSVD patients without dementia, APT was associated with a lower risk of dementia and clopidogrel might be an appropriate candidate in preventing dementia.The number of older adults is increasing globally. Aging is associated with cognitive and sensory decline. Additionally, declined auditory performance and cognitive function affect the quality of life of older adults. Therefore, it is important to develop an intervention method to improve both auditory and cognitive performances. LLY-283 PRMT inhibitor The current study aimed to investigate the beneficial effects of auditory and cognitive training on auditory ability and cognitive functions in healthy older adults. Fifty healthy older adults were randomly divided into four training groups-an auditory-cognitive training group (AC training; n = 13), an auditory training group (A training; n = 13), a cognitive training group (C training; n = 14), and an active control group (n = 12). During the training period, we reduced the sound intensity level in AC and A training groups and increase training task difficulty in AC, A, and C training groups based on participants' performance. Cognitive function measures [digit-cancelation test (D-CTFGs (the A training group and active control group). Therefore, the auditory training factor and cognitive training factor would be useful in enhancing the quality of life of older adults. The current AC training study, the plasticity of the brain structure was observed after 4 weeks of training.
Frailty is considered a major public health challenge of the 21st century, characterized by the decline of multiform body functions. Physical activity may be the most effective intervention to delay frailty. This study aims to verify the effect of remotely supervised physical activity on health profile in community-dwelling frail older adults.
This is a multicenter, three-blind, two-arm, and cohort randomized controlled study.
The intelligent exercise rehabilitation management system (IERMS) is an integrated digital platform that involves evaluation, guidance, monitoring, and feedback. A total of 120 participants aged ≥ 65 years and diagnosed as frailty on the FRAIL scale will be recruited and randomly divided into two groups. Group 1 will receive a 12-week IERMS-based intervention, and Group 2 will receive the usual care. Data will be collected at baseline, 12 and 24 weeks. The primary outcome is the physical function, and secondary outcomes include gait parameters, psychology, and cognition measurements. Analyses will be performed using DSS statistics, version 25.
< 0.05 will be considered statistically significant.
We believe that intervention plays a positive role in delaying the frailty. If our program is effective, we will provide a viable means to promote healthy aging in primary healthcare.
ChiCTR2100052286; Pre-results.
ChiCTR2100052286; Pre-results.Parkinson's disease is a complex neurodegenerative disorder resulting in a multifaceted clinical presentation which includes bradykinesia combined with either rest tremor, rigidity, or both, as well as many non-motor symptoms. The motor features of the disorder are associated with the pathological form of alpha synuclein aggregates and fibrils in Lewy bodies and loss of dopaminergic neurons in the substantia nigra. Parkinson's disease is increasingly considered as a group of underlying disorders with unique genetic, biological, and molecular abnormalities that are likely to respond differentially to a given therapeutic approach. For this reason, it is clinically challenging to treat and at present, no therapy can slow down or arrest the progression of Parkinson's disease. There is a clear unmet clinical need to develop reliable diagnostic and prognostic biomarkers. When disease-modifying treatments become available, prognostic biomarkers are required to support a definitive diagnosis and clinical intervention during the long prodromal period as no clinical implications or symptoms are observed. Robust diagnostic biomarkers would also be useful to monitor treatment response. Potential biomarkers for the sporadic form of Parkinson's disease have mostly included synuclein species (monomer, oligomer, phosphorylated, Lewy Body enriched fraction and isoforms). In this review, we consider the analysis of synuclein and its proteoforms in biological samples using proteomics techniques (immunoassay and mass spectrometry) applied to neurodegenerative disease research.
Current treatments for Alzheimer's disease (AD) modulate global neurotransmission but are neither specific nor anatomically directed. Tailored stimulation of target nuclei will increase treatment efficacy while reducing side effects. We report the results of the first directional deep brain stimulation (dDBS) surgery and treatment of a patient with AD in an attempt to slow the progression of the disease in a woman with multi-domain, amnestic cognitive status.
We aimed to assess the safety of dDBS in patients with AD using the fornix as stimulation target (primary objective) and the clinical impact of the stimulation (secondary objective). In a registered clinical trial, a female patient aged 81 years with a 2-year history of cognitive decline and diagnoses of AD underwent a bilateral dDBS surgery targeting the fornix. Stimulation parameters were set between 3.9 and 7.5 mA, 90 μs, 130 Hz for 24 months, controlling stimulation effects by 18F-fluoro-2-deoxy-D-glucose (18F-FDG) scans (baseline, 12 and 24 mont.
[https//clinicaltrials.gov/ct2/show/NCT03290274], identifier [NCT03290274].
[https//clinicaltrials.gov/ct2/show/NCT03290274], identifier [NCT03290274].Alzheimer's disease (AD) is an irreversible brain disorder associated with slow, progressive loss of brain functions mostly in older people. The disease processes start years before the symptoms are manifested at which point most therapies may not be as effective. In the hippocampus, the key proteins involved in the JAK2/STAT3 signaling pathway, such as p-JAK2-Tyr1007 and p-STAT3-Tyr705 were found to be elevated in various models of AD. In addition to neurons, glial cells such as astrocytes also play a crucial role in the progression of AD. Without having a significant effect on tau and amyloid pathologies, the JAK2/STAT3 pathway in reactive astrocytes exhibits a behavioral impact in the experimental models of AD. Cholinergic atrophy in AD has been traced to a trophic failure in the NGF metabolic pathway, which is essential for the survival and maintenance of basal forebrain cholinergic neurons (BFCN). In AD, there is an alteration in the conversion of the proNGF to mature NGF (mNGF), in addition to an increafer a better understanding of novel signaling pathways associated with neural and glial mechanisms involved in AD, elaborate potential links between vascular dysfunction and AD, and recent developments in "omics"-based biomarkers in AD.We undertook longitudinal β-amyloid positron emission tomography (Aβ-PET) imaging as a translational tool for monitoring of chronic treatment with the peroxisome proliferator-activated receptor gamma (PPARγ) agonist pioglitazone in Aβ model mice. We thus tested the hypothesis this treatment would rescue from increases of the Aβ-PET signal while promoting spatial learning and preservation of synaptic density. Here, we investigated longitudinally for 5 months PS2APP mice (N = 23; baseline age 8 months) and App NL-G-F mice (N = 37; baseline age 5 months) using Aβ-PET. Groups of mice were treated with pioglitazone or vehicle during the follow-up interval. We tested spatial memory performance and confirmed terminal PET findings by immunohistochemical and biochemistry analyses. Surprisingly, Aβ-PET and immunohistochemistry revealed a shift toward higher fibrillary composition of Aβ-plaques during upon chronic pioglitazone treatment. Nonetheless, synaptic density and spatial learning were improved in transgenic mice with pioglitazone treatment, in association with the increased plaque fibrillarity. These translational data suggest that a shift toward higher plaque fibrillarity protects cognitive function and brain integrity. Increases in the Aβ-PET signal upon immunomodulatory treatments targeting Aβ aggregation can thus be protective.
To study
gray matter (GM) volumes of the nucleus basalis of Meynert (nbM) in different parkinsonian syndromes and assess their relationship with clinical variables.
T1-weighted magnetic resonance images from patients with progressive supranuclear palsy (PSP,
= 43), multiple system atrophy (MSA,
= 23), Parkinson's disease (PD,
= 26), and healthy controls (HC,
= 29) were included. T1-weighted images were analyzed using a voxel-based morphometry approach implemented in the VBM8 toolbox, and nbM volumes were extracted from the spatially normalized GM images using a cyto-architectonically-defined nbM mask in stereotactic standard space. NbM volumes were compared between groups, while controlling for intracranial volume. Further, within each group correlation analyses between nbM volumes and the Mini Mental Status Examination (MMSE), Hoehn and Yahr stage, PSP Rating Scale, Unified Parkinson's Disease Rating Scale part III and Frontal Assessment Battery scores were performed.
Significantly lowerfunction in PSP patients.
This study investigates the topological properties of brain functional networks in patients with isolated rapid eye movement sleep behavior disorder (iRBD).
A total of 21 patients with iRBD (iRBD group) and 22 healthy controls (HCs) were evaluated using resting-state functional MRI (rs-fMRI) and neuropsychological measures in cognitive and motor function. Data from rs-fMRI were analyzed using graph theory, which included small-world properties, network efficiency, network local efficiency, nodal shortest path, node efficiency, and network connectivity, as well as the relationship between behavioral characteristics and altered brain topological features.
Rey-Osterrieth complex figure test (ROCFT-copy), symbol digital modalities test (SDMT), auditory verbal learning test (AVLT)-N1, AVLT-N2, AVLT-N3, and AVLT-N1-3 scores were significantly lower in patients with iRBD than in HC (
< 0.05), while trail making test A (TMT-A), TMT-B, and Unified Parkinson's Disease Rating Scale Part-III (UPDRS-III) scores were higher in patients with iRBD (
< 0.
My Website: https://www.selleckchem.com/products/lly-283.html
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