Dementia and cancer: a review of the literature and current practice

Age is a risk factor for dementia, and also for most cancers. Surprisingly, rates of cancer appear to be lower in individuals with dementia and vice versa. Genetic mechanisms could underpin this inverse relationship and are outlined, but underdiagnosis must also be taken into account. Individuals with cancer and dementia pose unique challenges to healthcare professionals owing to the potential for impaired decision-making capacity, poor communication and difficulties following medication regimes. Mild cognitive impairment and ‘chemo brain’ should be differentiated from progressive neurodegeneration.

Dominant β-catenin mutations cause intellectual disability with recognizable syndromic features

The recent identification of multiple dominant mutations in the gene encoding β-catenin in both humans and mice has enabled exploration of the molecular and cellular basis of β-catenin function in cognitive impairment. In humans, β-catenin mutations that cause a spectrum of neurodevelopmental disorders have been identified. We identified de novo β-catenin mutations in patients with intellectual disability, carefully characterized their phenotypes, and were able to define a recognizable intellectual disability syndrome. In parallel, characterization of a chemically mutagenized mouse line that displays features similar to those of human patients with β-catenin mutations enabled us to investigate the consequences of β-catenin dysfunction through development and into adulthood. The mouse mutant, designated batface (Bfc), carries a Thr653Lys substitution in the C-terminal armadillo repeat of β-catenin and displayed a reduced affinity for membrane-associated cadherins. In association with this decreased cadherin interaction, we found that the mutation results in decreased intrahemispheric connections, with deficits in dendritic branching, long-term potentiation, and cognitive function. Our study provides in vivo evidence that dominant mutations in β-catenin underlie losses in its adhesion-related functions, which leads to severe consequences, including intellectual disability, childhood hypotonia, progressive spasticity of lower limbs, and abnormal craniofacial features in adults

Factors contributing to fecal incontinence in older people and outcome of routine management in home, hospital and nursing home settings

Objective: Fecal loading, cognitive impairment, loose stools, functional disability, comorbidity and anorectal incontinence are recognized as factors contributing to loss of fecal continence in older adults. The objective of this project was to assess the relative distribution of these factors in a variety of settings along with the outcome of usual management. Methods: One hundred and twenty adults aged 65 years and over with fecal incontinence recruited by convenience sampling from four different settings were studied. They were either living at home or in a nursing home or receiving care on an acute or rehabilitation elderly care ward. A structured questionnaire was used to elicit which factors associated with fecal incontinence were present from subjects who had given written informed consent or for whom assent for inclusion in the study had been obtained. Results: Fecal loading (Homes 6 [20%]; Acute care wards 17 [57%]; Rehabilitation wards 19 [63%]; Nursing homes 21 [70%]) and functional disability (Homes 5 [17%]; Acute care wards 25 [83%]; Rehabilitation wards 25 [83%]; Nursing homes 20 [67%]) were significantly more prevalent in the hospital and nursing home settings than in those living at home (P < 0.01). Loose stools were more prevalent in the hospital setting than in the other settings (Homes 11 [37%]; Acute care wards 20 [67%]; Rehabilitation wards 17 [57%]; Nursing homes 6 [20%]) (P < 0.01). Cognitive impairment was significantly more common in the nursing home than in the other settings (Nursing homes 26 [87%], Homes 5 [17%], Acute care wards 13 [43%], Rehabilitation wards 14 [47%]) (P < 0.01). Loose stools were the most prevalent factor present at baseline in 13 of the 19 (68%) subjects whose fecal incontinence had resolved at 3 months. Conclusion: The distribution of the factors contributing to fecal incontinence in older people living at home differs from those cared for in nursing home and hospital wards settings. These differences need to be borne in mind when assessing people in different settings. Management appears to result in a cure for those who are not significantly disabled with loose stools as a cause for their fecal incontinence, but this would need to be confirmed by further research.

Advanced feature selection methods in multinominal dementia classification from structural MRI data

Recent studies showed that features extracted from brain MRIs can well discriminate Alzheimer’s disease from Mild Cognitive Impairment. This study provides an algorithm that sequentially applies advanced feature selection methods for findings the best subset of features in terms of binary classification accuracy. The classifiers that provided the highest accuracies, have been then used for solving a multi-class problem by the one-versus-one strategy. Although several approaches based on Regions of Interest (ROIs) extraction exist, the prediction power of features has not yet investigated by comparing filter and wrapper techniques. The findings of this work suggest that (i) the IntraCranial Volume (ICV) normalization can lead to overfitting and worst the accuracy prediction of test set and (ii) the combined use of a Random Forest-based filter with a Support Vector Machines-based wrapper, improves accuracy of binary classification.

Towards the computer-aided diagnosis of dementia based on the geometric and network connectivity of structural MRI data

We present an intuitive geometric approach for analysing the structure and fragility of T1-weighted structural MRI scans of human brains. Apart from computing characteristics like the surface area and volume of regions of the brain that consist of highly active voxels, we also employ Network Theory in order to test how close these regions are to breaking apart. This analysis is used in an attempt to automatically classify subjects into three categories: Alzheimer’s disease, mild cognitive impairment and healthy controls, for the CADDementia Challenge.

Standardized evaluation of algorithms for computer-aided diagnosis of dementia based on structural MRI: The CADDementia challenge

Algorithms for computer-aided diagnosis of dementia based on structural MRI have demonstrated high performance in the literature, but are difficult to compare as different data sets and methodology were used for evaluation. In addition, it is unclear how the algorithms would perform on previously unseen data, and thus, how they would perform in clinical practice when there is no real opportunity to adapt the algorithm to the data at hand. To address these comparability, generalizability and clinical applicability issues, we organized a grand challenge that aimed to objectively compare algorithms based on a clinically representative multi-center data set. Using clinical practice as the starting point, the goal was to reproduce the clinical diagnosis. Therefore, we evaluated algorithms for multi-class classification of three diagnostic groups: patients with probable Alzheimer's disease, patients with mild cognitive impairment and healthy controls. The diagnosis based on clinical criteria was used as reference standard, as it was the best available reference despite its known limitations. For evaluation, a previously unseen test set was used consisting of 354 T1-weighted MRI scans with the diagnoses blinded. Fifteen research teams participated with a total of 29 algorithms. The algorithms were trained on a small training set (n = 30) and optionally on data from other sources (e.g., the Alzheimer's Disease Neuroimaging Initiative, the Australian Imaging Biomarkers and Lifestyle flagship study of aging). The best performing algorithm yielded an accuracy of 63.0% and an area under the receiver-operating-characteristic curve (AUC) of 78.8%. In general, the best performances were achieved using feature extraction based on voxel-based morphometry or a combination of features that included volume, cortical thickness, shape and intensity. The challenge is open for new submissions via the web-based framework: http://caddementia.grand-challenge.org.

Oxidative variables and antioxidant enzymes activities in the mdx mouse brain

Dystrophin is a protein found at the plasmatic membrane in muscle and postsynaptic membrane of some neurons, where it plays an important role on synaptic transmission and plasticity. Its absence is associated with Duchenne`s muscular dystrophy (DMD), in which cognitive impairment is found. Oxidative stress appears to be involved in the physiopathology of DMD and its cognitive dysfunction. In this regard, the present study investigated oxidative parameters (lipid and protein peroxidation) and antioxidant enzymes activities (superoxide dismutase and catalase) in prefrontal cortex, cerebellum, hippocampus, striatum and cortex tissues from male dystrophic mdx and normal C57BL10 mice. We observed (I) reduced lipid peroxidation in striatum and protein peroxidation in cerebellum and prefrontal cortex; (2) increased superoxide dismutase activity in cerebellum, prefrontal cortex, hippocampus and striatum: and (3) reduced catalase activity in striatum. It seems by our results, that the superoxide dismutase antioxidant mechanism is playing a protective role against lipid and protein peroxidation in mdx mouse brain. (C) 2009 Elsevier Ltd. All rights reserved.

Neuropsychological Assessment of Current and Past Crack Cocaine Users

Background: Cognitive changes due to crack cocaine consumption remain unclear Methods: For clarification, 55 subjects were assigned to three groups: control group, crack cocaine current users, and ex-users. Participants were submitted to Mini-Mental State Examination (MMSE) and tasks evaluating executive functioning and verbal memory Mood state was also measured. Intergroup comparisons were carried out. Results: Control group performance on the MMSE was better than that of users and ex-users. Verbal memory performance for logical memory of users was impaired. Ex-users scored lower on DSST and Trail Making Test (Part B). Conclusion: Chronic crack cocaine use seems to disrupt general cognitive functioning (MMSE), verbal memory, and attentional resources, but findings suggest that some of these effects could be reversed by abstinence.

Evidence that OGG1 glycosylase protects neurons against oxidative DNA damage and cell death under ischemic conditions

7,8-Dihydro-8-oxoguanine DNA glycosylase (OGG1) is a major DNA glycosylase involved in base-excision repair (BER) of oxidative DNA damage to nuclear and mitochondrial DNA (mtDNA). We used OGG1-deficient (OGG1(-/-)) mice to examine the possible roles of OGG1 in the vulnerability of neurons to ischemic and oxidative stress. After exposure of cultured neurons to oxidative and metabolic stress levels of OGG1 in the nucleus were elevated and mitochondria exhibited fragmentation and increased levels of the mitochondrial fission protein dynamin-related protein 1 (Drp1) and reduced membrane potential. Cortical neurons isolated from OGG1(-/-) mice were more vulnerable to oxidative insults than were OGG1(+/+) neurons, and OGG1(-/-) mice developed larger cortical infarcts and behavioral deficits after permanent middle cerebral artery occlusion compared with OGG1(+/+) mice. Accumulations of oxidative DNA base lesions (8-oxoG, FapyAde, and FapyGua) were elevated in response to ischemia in both the ipsilateral and contralateral hemispheres, and to a greater extent in the contralateral cortex of OGG1(-/-) mice compared with OGG1(+/+) mice. Ischemia-induced elevation of 8-oxoG incision activity involved increased levels of a nuclear isoform OGG1, suggesting an adaptive response to oxidative nuclear DNA damage. Thus, OGG1 has a pivotal role in repairing oxidative damage to nuclear DNA under ischemic conditions, thereby reducing brain damage and improving functional outcome. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 680-692; doi:10.1038/jcbfm.2010.147; published online 25 August 2010

Influência de fatores biopsicossociais sobre a mortalidade de idosos no município de Santa Cruz/RN: um estudo prospectivo

The aging process if characterizes for a complex events network, from multidimensional nature, that encloses biological, social, psychic and functional aspects. The alteration of one or more aspects can speed up the aging process, anticipating limitations and until the death in the aged. For an adjusted confrontation of this question is necessary an interdisciplinary vision, in which the some areas of the knowledge can interact and with this to intervenes of the best possible form. Then, information derived from studies of aspects related to incidence, morbidity-mortality and transition patterns, involved in the health-illness process can more accurately identify risk groups thereby establishing links between social factors, illness, incapacity and death. Thus, this study aimed to identify, by a multidimensional vision, the risk factors of mortality in a coorth of elderly in a city in the interior of the state of Rio Grande do Norte (RN), Brazil. A prospective study carried out in Santa Cruz RN, where 310 elderly were randomly selected to form a baseline. The follow-up was 53 months. The predictive variables were divided into sociodemographic, physical health, neuropsychiatric and functional capacity. The statistical analysis carried out by bivariate analysis, survival analysis, followed by binary logistic regression and Cox regression, in the multivariate analysis, considering significant levels p < 0.05 and confidence interval (CI) of 95%. A total of 60 (19.3%) elderly died during the follow-up, where cardiovascular disease was the main cause. The survival was approximately 24.8 months. The study of general survival showed, at 12, 24, 36, and 48 months of observation, a survival rate of 97%, 54%, 31%, and 5% respectively, with a statistical difference in survival only observed for the variables of cognitive function and Basic Activities of Daily Living. In the logistic regression analysis, the risk factors identified were cognitive deficits (OR = 8.74), poor perception of health (OR = 3.89) and dependence for Basic Activities of Daily Living (OR = 3.96). In the Cox analysis, as well as dependence for Basic Activities of Daily Living (HR = 3.17), cognitive deficit (HR = 4.30) and stroke (CVA) (HR = 3.49) continued as independent risk factors for death. The risk factors found in the study can be interpreted as the primary predictors for death among elderly members of the community. Therefore, improvements in health conditions, with actions towards sustaining an autonomous life with special attention for elderly with cognitive impairment, could mean additional healthy quality of life, resulting in the reduction of premature mortality in this population

Influência do método pilates na força e atividade elétrica dos músculos respiratórios de idosas - ensaio clínico controlado randomizado

The reduction of physiological capacity present in the process of aging causes a marked decline in lung function. The exercise does promote several positive changes in the physical health of people and protect the cardiorespiratory function. The aim of this study was to investigate the effects of a program of Pilates exercices on the strengh and electrical activity of respiratory muscles of elderly. This is a randomized, controlled clinical trial, evaluating 33 elderly aged 65 and 80 (70.88 ± 4.32), healthy, sedentary, without cognitive impairment and able the practice physical activity. The sample was divided into two groups, one experimental group with 16 elderly women who did Pilates exercises and a control group (17) that was not submitted to the exercises, but received educational booklets on aging and health care. The elderly were evaluated initially and after a period of three months, taking into account the Maximal Inspiratory Pressure (MIP) and Maximal Expiratory Pressure (MEP), obtained by Manovacuometry and intensity of EMG activity was measured using the values of Root Mean Square (RMS) for the diaphragm and rectus abdominis muscles, during the course of diaphragmatic breathing and MIP maneuver. Data were analyzed using SPSS version 17.0. For all tests, we used a significance level or p value < 0.05 and confidence interval 95%. RMS in diaphragm and rectus abdominis muscles in both tests increased, but the data were significant for the rectus abdominis during diaphragmatic breathing (p = 0.03) and the diaphragm during the MIP maneuver (p = 0.01). There was no significant variation of the MIP and MEP. Pilates exercises were responsible for increasing the electrical activation of the diaphragm and rectus abdominis muscles in a group of healthy elderly, but had no influence on changes in strength of respiratory muscles

Características sociodemográficas, hábitos de sono, estado cognitivo e funcional após acidente vascular cerebral

ABSTRACT Introduction: The cerebrovascular accident (CVA) is an important cause of neurological impairment. Few data about the factors associated with morbidity of cerebrovascular accident are found in Brazil. Objectives: Evaluate sociodemographic characteristics, sleep habits, cognitive and functional status of patients with cerebrovascular accident. Methods: The patients evaluated through questionnaire Step 1 to survey the sociodemographic characteristics and Modified Rankin Scale for functional assessment. The neurological degree was evaluated by the National Institutes of Health Stroke Scale (NIHSS), the sleep Habits questionnaire for sleep and cognitive status by the Mini-Examination of the Mental State (MEMS). The data were analyzed using the chi-square test to determine differences in proportions of variables and linear regression analysis. Results: 305 patients were evaluated and the larger number of subjects was between 50 and 69 years (40%), most patients had no formal education (40.3%) and had ischemic type of cerebrovascular accident (72.5%). In the analysis of the functionality it was found that most patients had moderate impairment (55.1%). The results of the sleep habits showed that 63,6% of patients had one more person in the bedroom,12,3% complained about too much noise in the 11 room and 35% of too much light. From these patients 5,8% were smokers, 7,8% and 70,1% drank coffee drinkers, 28,6% had difficulty in initiate to sleep and woke up 37,6% in the middle of the night. Were showed complaints about nightmares (11%), feeling of suffocation (37,7%) and 35% felt very sleepy during the day. In addition, 95% were unemployed, 80,5% did not perform physical activities and 95,4% did not perform mental activities. The cognitive screening conducted a determined association of cognitive status with age and education level and neurological status. Conclusion: The study showed a high frequency of cases of cerebrovascular accident with functional dependence in a moderate degree, identified that many patients do not follow hygienic measures of sleep and found that the assessment of cognitive deficits must take into consideration the age, educational level and degree of neurological patients. We suggest the need for programs of assistance to victims of cerebrovascular accident patients, with a multidimensional approach including the rehabilitation team, the role of sleep medicine and Neuropsychology, so that patients have access to a more appropriate functional rehabilitation, develop a lifestyle that ensures a good sleep quality and are evaluated and rehabilitated with regard to cognitive impairment

Avaliação do padrão do ciclo sono-vigília e a cognição em estudantes de medicina com diferentes esquemas de horários de aulas

The sleep patterns of students entering the university, is accompanied by many factors that can lead to changes in sleep habits, such as academic demands, new social opportunities, reduced parental care and irregular teaching schedules. The irregular pattern of sleep-wake cycle is usually accompanied by several daytime consequences, for example, reduced levels of motivation, performance, concentration, alertness and mood as well as increased fatigue and sleepiness.Thus, there are numerous reasons to support the fact that these students may suffer damage in their academic performance. The aim of this study was to evaluate the sleep-wake cycle (SWC) and cognition in medical students with different schemes teaching schedules. One group started classes at 08am, while the other started at 07am. We analyzed the data from 88 volunteers, 39 from each group. However, only those who participated in both stages of the study (n = 78) underwent cognitive testing. For subjective evaluation of the SWC was used questionnaires to check the quality of sleep, chronotype, daytime sleepiness and sleep habits. For objective evaluation was used actigraphy. For cognitive assessment was used the test MoCA (Montreal Cognitive Assessment). The results indicate that the group has class earlier had a greater irregularity of the SWC and a worse performance in cognitive testing. There was a difference between the schedules the week and weekend in the subjective variables, bedtime, wake up and sleep duration in both groups. The objective variables, time in bed showed difference between the schedules the week and weekend to the group started class at 08am and the variables bedtime, get up time, actual sleep time, time in bed and wake bouts in the class at 07am. In the cognitive test, there were differences between the groups in overall score and in the areas of executive function and memory recall. Thus, it is suggested that the class starting time may cause irregularity of the SWC and the irregularity may cause mild cognitive impairment. Moreover, cognitive testing MoCA was sensitive to detect differences among students, although the difference between the schedules is small

Álcool e comportamento: efeitos na aprendizagem e memória

Excessive alcohol consumption is responsible for many harmful effects on individuals and society. Despite years of research, the mechanisms by which alcohol affects neurological functions and the exact causes of cognitive impairment related to long-term use are unknown. In this sense, this master study proposed to observe how different doses of alcohol affect the addiction response and the learning ability of two fish species: Betta splendens and Danio rerio, the latter a commonly model due to organizational and functional characteristics shared with mammals. For this, different concentrations of ethanol (0%, 0.1%, 0.25%, 1% and 1.5%) were used in acute, chronic and withdrawal treatments. We tested the fish in three experimental protocols: 1) alcohol addiction potential using conditioned place preference, 2) associative conditioning using light as unconditioned stimulus and food as conditioned stimulus and 3) spatial learning using a maze without cues. For the alcohol addiction potential, preference between two different places in a shuttle box was tested before and after alcohol exposure (chronic and acute). In this test, the animals intoxicated by 0.1% did not change behavior, while animals receiving 1% and 1.5% alcohol changed the initial preference to the side where they received alcohol For the associative conditioning, the results show that the groups undergoing low dose (0.1%), both in chronic and withdrawal treatment, learned the task faster than control; groups under 0.25 and 1% alcohol withdrawal learned the task after control; groups chronically intoxicated with these doses did not learn the task. For the spatial learning test, fish submitted to acute and chronic treatments decreased the time to exit the maze; there were significant differences in the animal s performance in a dose-dependent pattern. This difference was not observed for the withdrawal treatment. Given these results, we conclude that the effects of alcohol on learning are dependent on the dosage. Furthermore, low doses of alcohol seem to maximize animal performance on learning tasks and do not alter their seeking behavior, while higher doses induced addition and hinder learning

Maior nível de atividade física associa-se a melhor função cognitiva em renais crônicos em hemodiálise

INTRODUÇÃO: Pacientes com doença renal crônica (DRC) apresentam menor tolerância ao exercício e baixa capacidade funcional, o que os torna, via de regra, sedentários. Outra alteração importante encontrada na DRC é a disfunção cognitiva. O sedentarismo tem sido associado à disfunção cognitiva na população geral, porém, poucos estudos avaliaram essa associação na DRC. OBJETIVOS: Verificar associação entre o nível de atividade física e a função cognitiva de pacientes com DRC que realizam hemodiálise (HD). MÉTODOS: Foram avaliados 102 pacientes que realizam HD. Os participantes responderam o Questionário Internacional de Atividade Física, que avalia o nível de atividade física e o Mini Exame do Estado Mental, utilizado para o rastreamento cognitivo. Os pacientes foram divididos em três grupos conforme a classificação do nível de atividade física (GI: ativos/GII: irregularmente ativos/GIII: sedentários). Foi aplicada análise de regressão logística adotando-se como variável desfecho a presença de disfunção cognitiva e preservando como variáveis independentes aquelas com probabilidade estatística de diferença entre os grupos inferior a 0,1. Foi considerado estatisticamente significante o valor de p inferior a 0,05. RESULTADOS: Os grupos foram semelhantes quanto à idade, tempo de HD, escolaridade e tabagismo. Apresentaram diferença estatisticamente significante quanto à raça, índice de massa corporal, presença de diabetes mellitus, doença de base e grau de déficit cognitivo. Quanto aos dados laboratoriais, os grupos diferiram quanto à creatinina, glicemia, hemoglobina e hematócrito. Houve associação entre o nível de atividade física e função cognitiva, mesmo ajustando-se para as variáveis de confusão. CONCLUSÃO: O maior nível de atividade física associou-se a melhor função cognitiva em renais crônicos em HD, independentemente das variáveis de confusão avaliadas.