Intellectual Disability Modifies Gender Effects on Disruptive Behaviors

In typically developing children, boys are more commonly diagnosed than girls with disruptive behavior disorders, namely, attention-deficit/hyperactivity disorder, conduct disorder, and oppositional defiant disorder. For children with intellectual disability (ID), the evidence for this gender effect is less clear. In this report we examine gender effects on disruptive behavior in the Australian Child to Adult Development Study, a cohort of children and adolescents with ID, assessed in 4 waves. Items from the Developmental Behaviour Checklist were selected for their similarity to Diagnostic and Statistical Manual of Mental Disorders, 4th edition (American Psychiatric Association, 1994 American Psychiatric Association. 1994. Diagnostic and statistical manual of mental disorders, 4th, Washington, DC: Author.  [Google Scholar]) criteria and their frequency compared for boys and girls after taking age and severity of ID into account, both individually and as a composite score. On 14 items, there were no significant gender differences. On 3 items, boys had significantly higher scores than girls, whereas for 1 item, girls scored higher. The extent of these differences was smaller than that reported in typically developing children. On a composite scale of all items, there was no significant effect of gender. We discuss possible explanations for the lesser effect of gender in children with ID.     

SHORT COMMUNICATION: Apolipoprotein E genotype and Cognition in Bipolar Disorder

Apolipoprotein E (APOE) has been extensively studied as a risk factor for sporadic and late onset Alzheimer's Disease (AD). APOE allele*3, the most frequent variant, is not associated to cognitive dysfunction (CD) or to increased AD risk. Differently, the *4 allele is a well‐established risk factor for CD, while the *2 allele is associated with survival and longevity. CD is an important feature of Bipolar Disorder (BD) and recent data suggest that CD may be one of its endophenotypes, although controversial results exist. The aim of this research is to study the association of APOE genotype (APOE) and neurocognitive function in a sample of drug free young BD‐type I patients. Sample consisted of 25 symptomatic BD (type I) patients (age 18–35 years old). They were submitted to an extensive neuropsychological evaluation and genotyped for APOE. Subjects with allele*2 presented better cognitive performance. The presence of allele*4 was associated with worse performance in a few executive tasks. APOE*3*3 was associated with overall severe dysfunction on cognitive performance. In young individuals with nontreated BD‐type I, APOE may predict cognitive performance. Further and larger studies on APOE and cognition in BD are required to clarify whether APOE is a BD cognitive endophenotype.     

Apolipoprotein E and Subjective Symptomatology Following Brain Injury Rehabilitation

The Apolipoprotein E (APOE) allele ?4 has been repeatedly demonstrated to be related to the development of Alzheimer's disease. We have investigated its potential significance in stroke and traumatic brain injury as reflected in outcome following neuropsychological rehabilitation of 39 brain injured adults (mean age at injury 33.3 years, range 16–56). Outcome was evaluated by rating scales derived from a questionnaire completed by each brain injured subject and by a close relative. The questionnaire scales covered physical, cognitive, emotional, and social functioning. Ten of the subjects were found to carry the APOE-epsilon4 gene and the remaining 29 did not. There were no differences between these two groups on the questionnaire scales at the time of entry into the rehabilitation programme. At follow-up, however, on average more than 1 year after completing the rehabilitation programme, scale scores for the APOE-non epsilon4 group showed significant improvements in functioning whereas the APOE-?4 showed deterioration, the two groups differing on a global scale by 0.87 standard deviations. A battery of attention and memory tests, administered and readministered over a shorter test-retest interval, showed no such deterioration. Within the constraints of the time interval and small sample sizes involved, these findings would suggest that the presence of the APOE-epsilon4 may be associated with poorer outcome following neuropsychological rehabilitation.     

Deep Brain Stimulation for Disorders of Memory and Cognition

The next several decades will see an exponential rise in the number of patients with disorders of memory and cognition, and of Alzheimer’s disease in particular. Impending demographic shifts, an absence of effective treatments, and the significant burden these conditions place on patients, caregivers, and society, mean there is an urgent need to develop novel therapies. Deep brain stimulation (DBS) is a neurosurgical procedure that is a standard-of-care for many patients with treatment-refractory Parkinson’s disease, dystonia, and essential tremor. DBS has proven to be an effective means of modulating activity in disrupted motor circuitry, and has shown promise as a modulator of other dysfunctional circuits, including for mood and anxiety disorders. The deficits in Alzheimer’s disease and other disorders of memory and cognition are also beginning to be thought of as arising from dysfunction in neural circuits. Such dysfunction may be amenable to modulation using focal brain stimulation. A global experience is now emerging for the use of DBS for these conditions, targeting key nodes in the memory circuit, including the fornix and nucleus basalis of Meynert. Such work holds promise as a novel therapeutic approach for one of medicine’s most urgent priorities.     

甘露醇与尼莫地平联合应用对大鼠创伤性脑水肿以及水通道蛋白-4表达的影响

目的观察甘露醇与尼莫地平联合应用对大鼠挫裂伤脑组织水通道蛋白-4（AQP-4）表达的影响。方法成年Wistar大鼠54只,随机分为挫裂伤组、甘露醇治疗组、甘露醇与尼莫地平联合治疗组。采用文献报告的方法制作大鼠左顶叶皮层局限性脑挫裂伤模型。各组分别于脑挫裂伤后24、48、72h取挫伤区脑组织,检测其含水量以及AQP-4的表达。结果随着伤后时间的增加;各组脑组织含水量增加,AQP-4mRNA和AQP-4蛋白的表达均逐渐增高（P〈0．0．5）;与挫裂伤组相比较,甘露醇治疗组伤后各时间点脑组织含水量、AQP-4mRNA和AQP-4蛋白的表达均明显增加（P〈0．05）;甘露醇与尼莫地平联合治疗组伤后各时间点与前两组相比,脑组织含水量及AQP-4mRNA和AQP-4蛋白的表达均明显降低（P〈0．05）。结论脑挫裂伤后,AQP-4mRNA和AQP-4蛋白的表达增加;脯组织含水增加,甘露醇联合应用尼莫地平后,能够下调AQP-4mRNA和AQP-4蛋白的表达,有效缓解创伤性脑水肿。     

Effect of Cardiac Function on Cognition and Brain Structural Changes in Dementia

Background and Purpose

Cardiovascular risk factors are considered to also be risk factors for dementia. Recent studies have shown that the prevalence of cognitive dysfunction is high in patients with cardiac diseases. However, few studies have investigated the influence of cardiac function on cognition and brain structural changes in dementia. The aims of this study were to determine the relationship between cardiac and cognitive function, and to characterize any structural changes in the brain that could be caused by cardiac function in patients with dementia.

Methods

Dementia patients (n=93) were recruited prospectively with checking for the presence of vascular risk factors such as hypertension. Cognitive function was measured by the Mini-Mental State Examination, modified Mini-Mental State test, and Korean version of the Dementia Rating Scale. Brain magnetic resonance imaging was conducted to evaluate the cerebral white-matter changes (WMC), ventricular dilation, and cortical and hippocampal atrophy. Cardiac function was evaluated using two-dimensional echocardiography. We divided the patients into two groups according to the presence (+) or absence (-) of WMC.

Results

In the entire cohort, the size of the left atrium (LA) was positively correlated with the degree of WMC, irrespective of age (p<0.05). The LA was larger in the WMC (+) group (n=42) than in the WMC (-) group. General cognitive function was significantly lower in the WMC (+) group than in the WMC (-) group. Subjects with an enlarged LA tended to exhibit lower cognitive function and more-severe cerebral WMC.

Conclusions

Cardiac dysfunction represented by LA enlargement could be related to cognitive decline and WMC of the brain resulting from impairment of the cerebral hemodynamic process in dementia.     

Effects of Long-Term Rice Bran Extract Supplementation on Survival,Cognition and Brain Mitochondrial Function in Aged NMRI Mice

Aging represents a major risk factor for the development of neurodegenerative diseases like Alzheimer’s disease (AD). As mitochondrial dysfunction plays an important role in brain aging and occurs early in the development of AD, the prevention of mitochondrial dysfunction might help to slow brain aging and the development of neurodegenerative diseases. Rice bran extract (RBE) contains high concentrations of vitamin E congeners and γ-oryzanol. We have previously shown that RBE increased mitochondrial function and protected from mitochondrial dysfunction in vitro and in short-term in vivo feeding studies. To mimic the use of RBE as food additive, we have now investigated the effects of a long-term (6 months) feeding of RBE on survival, behavior and brain mitochondrial function in aged NMRI mice. RBE administration significantly increased survival and performance of aged NMRI mice in the passive avoidance and Y-maze test. Brain mitochondrial dysfunction found in aged mice was ameliorated after RBE administration. Furthermore, data from mRNA and protein expression studies revealed an up-regulation of mitochondrial proteins in RBE-fed mice, suggesting an increase in mitochondrial content which is mediated by a peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α)-dependent mechanism. Our findings suggest that a long-term treatment with a nutraceutical containing RBE could be useful for slowing down brain aging and thereby delaying or even preventing AD.     

Apolipoprotein E Isoform-Specific Effects on Lipoprotein Receptor Processing

Recent findings indicate an isoform-specific role for apolipoprotein E (apoE) in the elimination of beta-amyloid (Aβ) from the brain. ApoE is closely associated with various lipoprotein receptors, which contribute to Aβ brain removal via metabolic clearance or transit across the blood–brain barrier (BBB). These receptors are subject to ectodomain shedding at the cell surface, which alters endocytic transport and mitigates Aβ elimination. To further understand the manner in which apoE influences Aβ brain clearance, these studies investigated the effect of apoE on lipoprotein receptor shedding. Consistent with prior reports, we observed an increased shedding of the low-density lipoprotein receptor (LDLR) and the LDLR-related protein 1 (LRP1) following Aβ exposure in human brain endothelial cells. When Aβ was co-treated with each apoE isoform, there was a reduction in Aβ-induced shedding with apoE2 and apoE3, while lipoprotein receptor shedding in the presence of apoE4 remained increased. Likewise, intracranial administration of Aβ to apoE-targeted replacement mice (expressing the human apoE isoforms) resulted in an isoform-dependent effect on lipoprotein receptor shedding in the brain (apoE4 > apoE3 > apoE2). Moreover, these results show a strong inverse correlation with our prior work in apoE transgenic mice in which apoE4 animals showed reduced Aβ clearance across the BBB compared to apoE3 animals. Based on these results, apoE4 appears less efficient than other apoE isoforms in regulating lipoprotein receptor shedding, which may explain the differential effects of these isoforms in removing Aβ from the brain.