Does apolipoprotein E influence learning and memory in the nondemented oldest old?

The objective of this study was to analyze the relationship of the apolipoprotein E (apoE) epsilon4 and epsilon2 alleles to learning and memory performances in the nondemented oldest old. Forty-six nondemented persons aged 85 years or over from a randomly selected group of 128 subjects in Vantaa, Finland, were studied. ApoE genotyping was performed using the minisequencing technique. A structured clinical examination and interview were carried out. The test variables studied were learning and memory scores (from the Fuld Object-Memory Evaluation), verbal fluency, and conceptualization (the Similarities subtest of the WAIS-R). We compared apoE-epsilon4 carriers to noncarriers and apoE-epsilon2 carriers to noncarriers. No statistically significant differences were found in any of the test variables. The results failed to confirm the hypotheses that poor cognitive performance is associated with the apoE-epsilon4 allele and good performance with the apoE-epsilon2 allele in the oldest old. This suggests that the apoE alleles do not have a detectable relationship to learning and memory in nondemented very elderly people.     

Bariatric surgery in adolescents: what's the rationale? what's rational?

Rates of obesity in adolescents continue to rise, and available lifestyle and pharmacological interventions have had limited success in reducing excess weight and risk for comorbid health issues. However, ongoing health risks, psychosocial issues, and increased risk of mortality place these adolescents in jeopardy and warrant ongoing investigation for available treatments. Bariatric surgery for adults has had positive medical and psychological outcomes. However, bariatric surgery is a relatively new option for adolescents. Initial findings suggest positive results for excess weight loss and psychosocial improvements, but not without possible risks. Selection of appropriate candidates is essential in the process, specifically considering developmental maturity, family support, and resultant disease burden without surgery. Surgery is not a panacea for the obesity epidemic. Outcome studies are limited and long-term results are unknown, but for extremely obese adolescents, bariatric surgery is promising and should be considered a viable option for appropriate adolescent candidates.     

AIDS and the brain: is there a chemokine connection?

Many HIV-1-positive individuals suffer from a variety of neurological problems known collectively as the HIV-1-related cognitive-motor complex. However, the molecular mechanisms that underlie HIV-1-induced neuropathology are unclear. They might include a combination of indirect effects, which result from the release of neurotoxins from activated astrocytes and microglia, and the direct effects of HIV-1-related proteins, such as gp120, on neurons. As the interaction of gp120 with immune cells has been shown to require the participation of chemokine receptors, this article explores the possibility that such receptors participate in the events underlying HIV-1-induced neuropathology. It is now clear that many types of cell in the brain possess chemokine receptors, including microglia, glia and neurons, and the interaction of gp120 with neuronal chemokine receptors initiates apoptotic death of neurons in vitro. Such effects might be modified by the actions of chemokines that act at these same receptors. However, the importance of this direct interaction with neurons in vivo and its relevance in the pathogenesis of AIDS-related dementia still needs to be established. Furthermore, the existence of chemokine receptors on neurons suggests that chemokines might regulate neuronal functions physiologically.     

Does apolipoprotein E genotype modify the clinical expression of ALS?

Background: The presence of the apolipoprotein E (ApoE) 4 genotype is associated with an earlier age of onset for Alzheimer’s disease (AD) and several other neurodegenerative disorders. The objective of this study was to investigate the effect of ApoE genotypes on the clinical course of amyotrophic lateral sclerosis (ALS). Methods: Eight hundred and fifty‐two consecutive patients with sporadic ALS evaluated at a tertiary care center were investigated for the effect of ApoE genotype on age of onset, rate of motor disease progression, cognitive functioning, and survival in ALS. Results: The frequencies of individual ApoE genotypes did not differ between patients with ALS and ALS‐free Caucasian populations. Patients with different ApoE genotypes did not differ in the age of onset for ALS (years) (ApoE2 = 57.8 ± 13.7, ApoE3 = 57.3 ± 13.7, ApoE4 = 57.7 ± 13.2; P = 0.97), the rate of disease progression (Appel ALS score/month) (ApoE2 = 2.91 ± 2.66, ApoE3 = 2.67 ± 2.66, ApoE4 = 2.61 ± 2.47; P = 0.89), cognitive status (% cognitively impaired) (ApoE2 = 31.7, ApoE3 = 26.8, ApoE4 = 34.3, P = 0.28), or survival in years (ApoE2 = 3.79 ± 3.70, ApoE3 = 3.17 ± 2.27, ApoE4 = 3.05 ± 1.75; P = 0.85). Conclusions: Our results suggest that ApoE genotype does not modify clinical course of sporadic ALS, in stark contrast to the influence of ApoE genotype on the disease course of AD and other neurodegenerative disorders.     

Reward or reinforcement: what's the difference?

The histories of the terms "reward" and "reinforcement" are reviewed to show the difference in their origins. Reward refers to the fact that certain environmental stimuli have the property of eliciting approach responses. Evidence suggests that the ventral striatum (nucleus accumbens area) is central to the mediation of this behavior. Reinforcement refers to the tendency of certain stimuli to strengthen learned stimulus-response tendencies. The dorsolateral striatum appears to be central to the mediation of this behavior. Neuroanatomical and neurochemical data are adduced suggesting that reward may be mediated by a neural circuit including the neostriatal patch system, together with the hippocampus, limbic system (amygdala, prefrontal cortex) and ventral pallidum. The evidence also suggests that reinforcement, in the form of dopamine release in the striatal matrix, acts to promote the consolidation of sensori-motor associations. Thus, the matrix may mediate stimulus-response memory as part of a circuit including the cerebral cortex, substantia nigra pars reticulata and its projections to thalamic and brainstem motor areas.     

Lack of association between schizophrenia and the apolipoprotein E ε4 allele

The association between the 4 allele of the apolipoprotein E (APOE) gene and Alzheimer's disease (AD) has been reported. In order to examine if the 4 allele may play a role also in schizophrenia, another mental disorder, patients (n=87) and control subjects (n=57) were genotyped for APOE. No significant difference was found between the groups. The data indicate that the APOE gene is not of major importance for the genesis of schizophrenia.     

How preferential is the preferential encoding of threatening stimuli? Working memory biases in specific anxiety and the Attentional Blink

Temporal visual working memory (VWM) biases in spider anxiety were studied with an Attentional Blink paradigm. In Experiment 1, participants viewed pictures sequentially presented at rates of 80 ms and were instructed to memorize two target pictures. We varied time between targets and valence of the second target (neutral: mushroom, positive: blossom, negative: spider). In Experiment 2, spider fearfuls and non-anxious controls (both without snake anxiety) participated. Here we tested two negative targets: disorder-related spiders and disorder-irrelevant snakes. Both positive and negative items were memorized more successfully than neutral targets. Spiders were preferentially recalled by spider fearfuls compared to non-anxious controls, implying temporal VWM biases in spider anxiety. This advantage for threat was not related to a disruption of the encoding of non-threatening targets presented before the threat item.     

Working memory in Down syndrome: is there a dual task deficit?

Background Recent studies have shown that individuals with Down syndrome (DS) are poorer than controls in performing verbal and visuospatial dual tasks. The present study aims at better investigating the dual task deficit in working memory in individuals with DS. Method Forty‐five individuals with DS and 45 typically developing children matched for verbal mental age completed a series of verbal and visuospatial working memory tasks, involving conditions that either required the combination of two tasks in the same modality (verbal or visual) or of cross‐modality pairs of tasks. Results and conclusions Two distinct deficits were found in individuals with DS: impairment in verbal tasks and further impairment in all dual task conditions. The results confirm the hypothesis of a central executive impairment in individuals with DS.     

Polymorphism of apolipoprotein E gene and post-stroke vascular dementia

INTRODUCTIONRecent researches indicate that the incidence rate of vascular de- mentia after stroke is about 25%[1]. Though vascular dimension can be caused by various factors, such as the site, number and size of stroke, etc. [2], there are arguments in t…     

γ-Secretase, apolipoprotein E and cellular cholesterol metabolism

Genetic studies demonstrate that the 4 allele of the apolipoprotein (apo) E is a risk factor for late onset Alzheimer's disease (AD). Apo E is the major component of lipoprotein particles in the brain that mediate transport of cholesterol and other lipids between neurons and glial cells, indicating an implication of cerebral lipid metabolism in the pathogenesis of AD. In addition, apo E is also involved in the metabolism and aggregation of the amyloid β-peptide (Aβ) that derives from proteolytic processing of the amyloid precursor protein (APP) and is found in plaques of AD brains. The generation of Aβ involves sequential cleavages of APP by proteases called β- and γ-secretase. γ-Secretase is a high molecular weight protein complex containing presenilins as catalytically active subunits. Importantly, mutations in the genes of APP and the two homologous PS proteins are a major cause of familial early onset AD, indicating that the metabolism of APP and generation of Aβ play critical roles in the initiation of the disease. This review focuses on the functional relation of γ-secretase complexes and the metabolism of lipoproteins in the brain. It is hypothesized that γ-secretase activity is critically involved in cellular lipid homeostasis and that impaired lipid metabolism contributes to the pathogenesis of AD.