Cerebral microbleeds and cognitive decline in a hemodialysis patient: Case report and review of literature

Cerebral microbleeds (CMBs) are small hemosiderin deposits indicative of prior cerebral microscopic hemorrhage and previously thought to be clinically silent. Recent population‐based cross‐sectional studies and prospective longitudinal cohort studies have revealed association between CMB and cognitive dysfunction. In the general population, CMBs are associated with age, hypertension, and cerebral amyloid angiopathy. In the chronic kidney disease (CKD) population, diminished estimated glomerular filtration rate has been found to be an independent risk factor for CMB, raising the possibility that a uremic milieu may predispose to microbleeds. In the end‐stage renal disease (ESRD) population on hemodialysis, the incidence of microbleeds is significantly higher compared with a control group without history of CKD or stroke. We present an ESRD patient on chronic hemodialysis with a history of gradual cognitive decline and progressive CMBs. Through this case and literature review, we illustrate the need to develop detection and prediction models to treat this frequent development in ESRD patients.     

Skeletal Muscle Health and Cognitive Function: A Narrative Review

Sarcopenia is the loss of skeletal muscle mass and function with advancing age. It involves both complex genetic and modifiable risk factors, such as lack of exercise, malnutrition and reduced neurological drive. Cognitive decline refers to diminished or impaired mental and/or intellectual functioning. Contracting skeletal muscle is a major source of neurotrophic factors, including brain-derived neurotrophic factor, which regulate synapses in the brain. Furthermore, skeletal muscle activity has important immune and redox effects that modify brain function and reduce muscle catabolism. The identification of common risk factors and underlying mechanisms for sarcopenia and cognition may allow the development of targeted interventions that slow or reverse sarcopenia and also certain forms of cognitive decline. However, the links between cognition and skeletal muscle have not been elucidated fully. This review provides a critical appraisal of the literature on the relationship between skeletal muscle health and cognition. The literature suggests that sarcopenia and cognitive decline share pathophysiological pathways. Ageing plays a role in both skeletal muscle deterioration and cognitive decline. Furthermore, lifestyle risk factors, such as physical inactivity, poor diet and smoking, are common to both disorders, so their potential role in the muscle–brain relationship warrants investigation.     

Neuroticism and depressive symptoms among spouse caregivers: Do health behaviors mediate this relationship?

This study examined the mediating role of health behaviors in the relationship between neuroticism and depressive symptoms among spouse caregivers. Path analysis was used to test a model of the caregiver stress process among 233 caregivers of people with dementia. Results indicate that neuroticism has a significant direct effect on depressive symptoms and also indirectly influences depressive symptoms through health behaviors and perceived stress. When individual health behaviors were examined in the path model, only physical activity served a significant mediating role. These findings suggest that neuroticism may lead to depressive symptoms among caregivers partly through declines in physical activity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

What does the object decision task measure? Reflections on the basis of evidence from semantic dementia.

The authors investigated the impact of semantic knowledge on visual object analysis by assessing the performance of patients with semantic dementia on a different-views object matching test and on 2 object decision tests differing, for example, in whether the nonreal items were nonsense objects or chimeras of 2 real objects. On average, the patients scored normally on both the object matching and the object decision test including nonsense objects but were impaired on the object decision test including chimeras; this latter was also the only visual object test that correlated significantly with degree of semantic impairment. These findings demonstrate that object decision is not a single task or ability and that it is not necessarily independent of conceptual knowledge. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Question hard, answer simply: A comment on Storms et al. (2003).

It seems clear that, for whatever reasons, the dementia of the Alzheimer type patient group (as well as other patient groups) exhibits behavior that is different from the normal control group. G. Storms, T. Dirikx, J. Saerens, S. Verstraeten, and P. P. De Deyn (2003) rightfully argue that the observed behavior (similarity judgments) does not tell us the source (cause) of the differences between the 2 groups. Rather, the focus of the study should be placed more on finding the ways the 2 groups are different. They also point out various methodological problems in some of the previous attempts to characterize the nature of the differences. Further methodological issues in G. Storms et al.'s study are examined. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

调理心肾中药对拟痴呆大鼠脑组织中M和GABA受体功能的影响

以~3H-QNB和~3H-GABA为放射性配基,用受体放射性配基结合分析法,测出拟痴呆模型大鼠大脑皮层和海马组织中的M受体和小脑组织中的GABA受体的R_t值明显降低;M受体的K_D值在大脑皮层中明显减少,在海马中略有升高。小脑中GABA受体的K_D值显著降低。调理心肾中药及喜德镇(Hydergin,为国外常用抗老年痴呆药)能使降低的M受体和GABA受体的R_t值均明显升高,接近正常水平。对K_D值则有不同程度的调整作用。     

Genetic Architecture and Molecular,Imaging and Prodromic Markers in Dementia with Lewy Bodies: State of the Art,Opportunities and Challenges

Dementia with Lewy bodies (DLB) is one of the most common causes of dementia and belongs to the group of α-synucleinopathies. Due to its clinical overlap with other neurodegenerative disorders and its high clinical heterogeneity, the clinical differential diagnosis of DLB from other similar disorders is often difficult and it is frequently underdiagnosed. Moreover, its genetic etiology has been studied only recently due to the unavailability of large cohorts with a certain diagnosis and shows genetic heterogeneity with a rare contribution of pathogenic mutations and relatively common risk factors. The rapid increase in the reported cases of DLB highlights the need for an easy, efficient and accurate diagnosis of the disease in its initial stages in order to halt or delay the progression. The currently used diagnostic methods proposed by the International DLB consortium rely on a list of criteria that comprises both clinical observations and the use of biomarkers. Herein, we summarize the up-to-now reported knowledge on the genetic architecture of DLB and discuss the use of prodromal biomarkers as well as recent promising candidates from alternative body fluids and new imaging techniques.     

An Engineered sgsh Mutant Zebrafish Recapitulates Molecular and Behavioural Pathobiology of Sanfilippo Syndrome A/MPS IIIA

Mucopolysaccharidosis IIIA (MPS IIIA, Sanfilippo syndrome type A), a paediatric neurological lysosomal storage disease, is caused by impaired function of the enzyme N-sulfoglucosamine sulfohydrolase (SGSH) resulting in impaired catabolism of heparan sulfate glycosaminoglycan (HS GAG) and its accumulation in tissues. MPS IIIA represents a significant proportion of childhood dementias. This condition generally leads to patient death in the teenage years, yet no effective therapy exists for MPS IIIA and a complete understanding of the mechanisms of MPS IIIA pathogenesis is lacking. Here, we employ targeted CRISPR/Cas9 mutagenesis to generate a model of MPS IIIA in the zebrafish, a model organism with strong genetic tractability and amenity for high-throughput screening. The sgsh^Δex5−6 zebrafish mutant exhibits a complete absence of Sgsh enzymatic activity, leading to progressive accumulation of HS degradation products with age. sgsh^Δex5−6 zebrafish faithfully recapitulate diverse CNS-specific features of MPS IIIA, including neuronal lysosomal overabundance, complex behavioural phenotypes, and profound, lifelong neuroinflammation. We further demonstrate that neuroinflammation in sgsh^Δex5−6 zebrafish is largely dependent on interleukin-1β and can be attenuated via the pharmacological inhibition of Caspase-1, which partially rescues behavioural abnormalities in sgsh^Δex5−6 mutant larvae in a context-dependent manner. We expect the sgsh^Δex5−6 zebrafish mutant to be a valuable resource in gaining a better understanding of MPS IIIA pathobiology towards the development of timely and effective therapeutic interventions.     

Advances in Applying Computer-Aided Drug Design for Neurodegenerative Diseases

Neurodegenerative diseases (NDs) including Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease are incurable and affect millions of people worldwide. The development of treatments for this unmet clinical need is a major global research challenge. Computer-aided drug design (CADD) methods minimize the huge number of ligands that could be screened in biological assays, reducing the cost, time, and effort required to develop new drugs. In this review, we provide an introduction to CADD and examine the progress in applying CADD and other molecular docking studies to NDs. We provide an updated overview of potential therapeutic targets for various NDs and discuss some of the advantages and disadvantages of these tools.