The COMT Val158 Met polymorphism as an associated risk factor for Alzheimer disease and mild cognitive impairment in APOE 4 carriers

Background: The aim of this study is to examine the influence of the catechol-O-methyltranferase (COMT) gene (polymorphism Val158 Met) as a risk factor for Alzheimer's disease (AD) and mild cognitive impairment of amnesic type (MCI), and its synergistic effect with the apolipoprotein E gene (APOE). A total of 223 MCI patients, 345 AD and 253 healthy controls were analyzed. Clinical criteria and neuropsychological tests were used to establish diagnostic groups. The DNA Bank of the University of the Basque Country (UPV-EHU) (Spain) determined COMT Val158 Met and APOE genotypes using real time polymerase chain reaction (rtPCR) and polymerase chain reaction (PCR), and restriction fragment length polymorphism (RFLPs), respectively. Multinomial logistic regression models were used to determine the risk of AD and MCI. Results: Neither COMT alleles nor genotypes were independent risk factors for AD or MCI. The high activity genotypes (GG and AG) showed a synergistic effect with APOE epsilon 4 allele, increasing the risk of AD (OR = 5.96, 95% CI 2.74-12.94, p < 0.001 and OR = 6.71, 95% CI 3.36-13.41, p < 0.001 respectivily). In AD patients this effect was greater in women. In MCI patients such as synergistic effect was only found between AG and APOE epsilon 4 allele (OR = 3.21 95% CI 1.56-6.63, p = 0.02) and was greater in men (OR = 5.88 95% CI 1.69-20.42, p < 0.01). Conclusion: COMT (Val158 Met) polymorphism is not an independent risk factor for AD or MCI, but shows a synergistic effect with APOE epsilon 4 allele that proves greater in women with AD.

Structural Integrity of the Contralesional Hemisphere Predicts Cognitive Impairment in Ischemic Stroke at Three Months

After stroke, white matter integrity can be affected both locally and distally to the primary lesion location. It has been shown that tract disruption in mirror's regions of the contralateral hemisphere is associated with degree of functional impairment. Fourteen patients suffering right hemispheric focal stroke (S) and eighteen healthy controls (HC) underwent Diffusion Weighted Imaging (DWI) and neuropsychological assessment. The stroke patient group was divided into poor (SP; n = 8) and good (SG; n = 6) cognitive recovery groups according to their cognitive improvement from the acute phase (72 hours after stroke) to the subacute phase (3 months post-stroke). Whole-brain DWI data analysis was performed by computing Diffusion Tensor Imaging (DTI) followed by Tract Based Spatial Statistics (TBSS). Assessment of effects was obtained computing the correlation of the projections on TBSS skeleton of Fractional Anisotropy (FA) and Radial Diffusivity (RD) with cognitive test results. Significant decrease of FA was found only in right brain anatomical areas for the S group when compared to the HC group. Analyzed separately, stroke patients with poor cognitive recovery showed additional significant FA decrease in several left hemisphere regions; whereas SG patients showed significant decrease only in the left genu of corpus callosum when compared to the HC. For the SG group, whole brain analysis revealed significant correlation between the performance in the Semantic Fluency test and the FA in the right hemisphere as well as between the performance in the Grooved Pegboard Test (GPT) and theTrail Making Test-part A and the FA in the left hemisphere. For the SP group, correlation analysis revealed significant correlation between the performance in the GPT and the FA in the right hemisphere. Palabras clave

Structural Integrity of the Contralesional Hemisphere Predicts Cognitive Impairment in Ischemic Stroke at Three Months

After stroke, white matter integrity can be affected both locally and distally to the primary lesion location. It has been shown that tract disruption in mirror's regions of the contralateral hemisphere is associated with degree of functional impairment. Fourteen patients suffering right hemispheric focal stroke (S) and eighteen healthy controls (HC) underwent Diffusion Weighted Imaging (DWI) and neuropsychological assessment. The stroke patient group was divided into poor (SP; n = 8) and good (SG; n = 6) cognitive recovery groups according to their cognitive improvement from the acute phase (72 hours after stroke) to the subacute phase (3 months post-stroke). Whole-brain DWI data analysis was performed by computing Diffusion Tensor Imaging (DTI) followed by Tract Based Spatial Statistics (TBSS). Assessment of effects was obtained computing the correlation of the projections on TBSS skeleton of Fractional Anisotropy (FA) and Radial Diffusivity (RD) with cognitive test results. Significant decrease of FA was found only in right brain anatomical areas for the S group when compared to the HC group. Analyzed separately, stroke patients with poor cognitive recovery showed additional significant FA decrease in several left hemisphere regions; whereas SG patients showed significant decrease only in the left genu of corpus callosum when compared to the HC. For the SG group, whole brain analysis revealed significant correlation between the performance in the Semantic Fluency test and the FA in the right hemisphere as well as between the performance in the Grooved Pegboard Test (GPT) and theTrail Making Test-part A and the FA in the left hemisphere. For the SP group, correlation analysis revealed significant correlation between the performance in the GPT and the FA in the right hemisphere.

Pretreatment with Resveratrol Prevents Neuronal Injury and Cognitive Deficits Induced by Perinatal Hypoxia-Ischemia in Rats

Despite advances in neonatal care, hypoxic-ischemic brain injury is still a serious clinical problem, which is responsible for many cases of perinatal mortality, cerebral palsy, motor impairment and cognitive deficits. Resveratrol, a natural polyphenol with important anti-oxidant and anti-inflammatory properties, is present in grapevines, peanuts and pomegranates. The aim of the present work was to evaluate the possible neuroprotective effect of resveratrol when administered before or immediately after a hypoxic-ischemic brain event in neonatal rats by analyzing brain damage, the mitochondrial status and long-term cognitive impairment. Our results indicate that pretreatment with resveratrol protects against brain damage, reducing infarct volume, preserving myelination and minimizing the astroglial reactive response. Moreover its neuroprotective effect was found to be long lasting, as behavioral outcomes were significantly improved at adulthood. We speculate that one of the mechanisms for this neuroprotection may be related to the maintenance of the mitochondrial inner membrane integrity and potential, and to the reduction of reactive oxygen species. Curiously, none of these protective features was observed when resveratrol was administered immediately after hypoxia-ischemia.

Plasma brain-derived neurotrophic factor levels, learning capacity and cognition in patients with first episode psychosis

Background: Cognitive impairments are seen in first psychotic episode (FEP) patients. The neurobiological underpinnings that might underlie these changes remain unknown. The aim of this study is to investigate whether Brain Derived Neurotrophic Factor (BDNF) levels are associated with cognitive impairment in FEP patients compared with healthy controls. Methods: 45 FEP patients and 45 healthy controls matched by age, gender and educational level were selected from the Basque Country area of Spain. Plasma BDNF levels were assessed in healthy controls and in patients. A battery of cognitive tests was applied to both groups, with the patients being assessed at 6 months after the acute episode and only in those with a clinical response to treatment. Results: Plasma BDNF levels were altered in patients compared with the control group. In FEP patients, we observed a positive association between BDNF levels at six months and five cognitive domains (learning ability,immediate and delayed memory, abstract thinking and processing speed) which persisted after controlling for medications prescribed, drug use, intelligence quotient (IQ) and negative symptoms. In the healthy control group, BDNF levels were not associated with cognitive test scores. Conclusion: Our results suggest that BDNF is associated with the cognitive impairment seen after a FEP. Further investigations of the role of this neurotrophin in the symptoms associated with psychosis onset are warranted.

Behavioral profile of adults with Prader-Willi syndrome : correlations with individual and environmental variables

Background: Maladaptive behavior has been reported as a phenotypical feature in Prader–Willi syndrome (PWS). It severely limits social adaptation and the quality of life of children and adults with the syndrome. Different factors have been linked with the intensity and form of these behavioral disturbances but there is no consensus about the cause. Consequently, there is still controversy regarding management strategies and there is a need for new data. Methods: The behavior of 100 adults with PWS attending a dedicated center was assessed using the Developmental Behavior Checklist for Adults (DBC-A) and the PWS-specific Hyperphagia Questionnaire. The DBC-A was completed separately by trained caregivers at the center and relatives or caregivers in a natural setting. Genotype, gender, age, degree of obesity and cognitive impairment were analyzed as variables with a hypothetical influence on behavioral features. Results: Patients showed a relatively high rate of behavioral disturbances other than hyperphagia. Disruptive and social relating were the highest scoring DBC-A subscales whereas anxiety/antisocial and self-absorbed were the lowest. When hospital caregiver and natural caregiver scores were compared, scores for the latter were higher for all subscales except for disruptive and anxiety/antisocial. These effects of institutional management were underlined. In the DBC-A, 22 items have descriptive indications of PWS behavior and were used for further comparisons and correlation analysis. In contrast to previous reports, rates of disturbed behavior were lower in patients with a deletion genotype. However, the behavioral profile was similar for both genotypes. No differences were found in any measurement when comparing type I and type II deletions. The other analyzed variables showed little relevance. Conclusions: Significant rates of behavioral disorders were highlighted and their typology described in a large cohort of adults with PWS. The deletion genotype was related to a lower severity of symptoms. Some major behavioral problems, such as hyperphagia, may be well controlled if living circumstances are adapted to the specific requirements of individuals with PWS.

Efficacy of a cognitive and behavioural psychotherapy applied by primary care psychologists in patients with mixed anxiety-depressive disorder: a research protocol

Background: In contrast with the recommendations of clinical practice guidelines, the most common treatment for anxiety and depressive disorders in primary care is pharmacological. The aim of this study is to assess the efficacy of a cognitive-behavioural psychological intervention, delivered by primary care psychologists in patients with mixed anxiety-depressive disorder compared to usual care. Methods/Design: This is an open-label, multicentre, randomized, and controlled study with two parallel groups. A random sample of 246 patients will be recruited with mild-to-moderate mixed anxiety-depressive disorder, from the target population on the lists of 41 primary care doctors. Patients will be randomly assigned to the intervention group, who will receive standardised cognitive-behavioural therapy delivered by psychologists together with usual care, or to a control group, who will receive usual care alone. The cognitive-behavioural therapy intervention is composed of eight individual 60-minute face-to face sessions conducted in eight consecutive weeks. A follow-up session will be conducted over the telephone, for reinforcement or referral as appropriate, 6 months after the intervention, as required. The primary outcome variable will be the change in scores on the Short Form-36 General Health Survey. We will also measure the change in the frequency and intensity of anxiety symptoms (State-Trait Anxiety Inventory) and depression (Beck Depression Inventory) at baseline, and 3, 6 and 12 months later. Additionally, we will collect information on the use of drugs and health care services. Discussion: The aim of this study is to assess the efficacy of a primary care-based cognitive-behavioural psychological intervention in patients with mixed anxiety-depressive disorder. The international scientific evidence has demonstrated the need for psychologists in primary care. However, given the differences between health policies and health services, it is important to test the effect of these psychological interventions in our geographical setting.