Rehabilitación neuropsicológica en un caso de trastorno límite de la personalidad / Neuropsychological rehabilitation in a case of borderline personality disorder

La rehabilitación neuropsicológica es una terapia que busca mejorar la independencia y autonomía en pacientes que presentan dificultades cognitivas. El objetivo de la investigación fue determinar la eficacia de un programa de rehabilitación neuropsicológica en una paciente con diagnóstico de trastorno neurocognitivo leve, tipo ejecutivo, asociado a trastorno límite de la personalidad, mediante el fortalecimiento de la atención y de los procesos ejecutivos implicados en la memoria, bajo los principios de sustitución y restitución. Los instrumentos para establecer línea base y para medir el efecto del tratamiento fueron la escala de trastornos de la memoria y la escala de criterios del trastorno límite de la personalidad (TLP) basados en el DSM-V; estos instrumentos se le aplicaron a la paciente y también a su informador para comparar los datos. Los resultados arrojaron una mejoría estadística en las puntuaciones de la escala de trastornos de la memoria y de la escala de criterios para el TLP-DSM-V; pasando de tener una puntuación en memoria de 36 en línea base a 16 después de la intervención, también pasó de tener 3 criterios para impulsividad a 1 criterio después de la intervención. Finalmente se establece la eficacia de la rehabilitación neuropsicológica en los pacientes con TLP, no solo se evidencia mejoría en los síntomas cognitivos asociados a las dificultades en la memoria, sino que también se muestra disminución en los síntomas psiquiátricos asociados con el control de los impulsos.

Neuropsychological rehabilitation is a therapy that seeks to improve independence and autonomy in patients with cognitive difficulties. The objective of the investigation was to determine the efficacy of a neuropsychological rehabilitation program in a patient diagnosed with a mild neurocognitive disorder, executive type, associated with borderline disorder personality, by strengthening attention and executive processes involved in memory, under the principles of substitution and restitution. The instruments to establish a baseline and to measure the effect of treatment were the memory disorders scale and the DSM-V-based borderline personality disorder (BPD) criteria scale; these instruments were applied to the patient and also to her informant to compare the data. The results showed a statistical improvement in the scores of the memory disorders scale and the criteria scale for the BPD-DSM-V; going from having a memory score of 36 at baseline to 16 after the intervention, it also went from having three criteria for impulsivity to one criterion after the intervention. Finally, the efficacy of neuropsychological rehabilitation in patients with BPD is established, not only is there an improvement in the cognitive symptoms associated with memory difficulties, but also a decrease in the psychiatric symptoms associated with impulse control.

Memory and language impairments are associated with anxiety disorder severity in childhood

Abstract Introduction Children with anxiety disorders have been suggested to possess deficits in verbal fluency, shifting and attention, with inconsistent results regarding working memory and its subcomponents. This study extends previous findings by analyzing the performance of children with anxiety disorders in a wide range of neuropsychological functions. Methods We evaluated 54 children with a primary diagnosis of an anxiety disorder according to diagnostic criteria from the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) using subtests of a neuropsychological battery. The severity of anxiety disorders was assessed using the Pediatric Anxiety Rating Scale (PARS). We calculated the frequency of neuropsychological impairments (-1.5 standard deviation of the normative sample). Comparisons between groups were performed based on the severity of anxiety symptoms, as well as in the presence of one vs. more diagnoses of anxiety disorder. Results We found higher impairment in visuospatial working memory (23.1%), semantic memory (27.8%), oral language (35.4%) and word writing (44.4%) in anxious children. Moreover, children with higher anxiety severity presented lower performance in visuospatial working memory, inferential processing, word reading, writing comprehension, copied writing, and semantic verbal fluency (d = 0.49 to 0.96 [Cohen's d]). The higher the number of anxiety diagnoses, the lower the performance in episodic memory and oral and written language (d = 0.56 to 0.77). Conclusion Our data suggested the presence of memory (visuospatial working memory and semantic memory) and language deficits (oral and writing) in some children with an anxiety disorder. Severity and number of anxiety diagnoses were associated with lower performance in memory and language domains in childhood.

Características clínicas del trastorno de déficit atencional e hiperactividad en epilepsia / Clinical features of the attentional deficit and hyperactivity disorder in epilepsy

La epilepsia y el trastorno por déficit de atención e hiperactividad (TDAH) son condiciones frecuentes en pediatría y suelen presentarse asociadas en muchos pacientes. Su relación es compleja y comparten comorbilidad psiquiátrica. Los pacientes con ambas condiciones conjuntas, epilepsia y TDAH, se presentan con igual frecuencia en ambos géneros, predominando la presentación inatenta. El déficit cognitivo incrementa el riesgo de asociar TDAH en pacientes con epilepsia. No hay evidencia suficiente para otros factores de riesgo, sin embargo, se puede anticipar su presencia en pacientes con algunos tipos de epilepsia y con modelos neuropsicológicos que evidencian la disfunción de redes subyacentes. Se revisa la relación con el control de crisis, las alteraciones electroencefalográficas y los fármacos antiepilépticos (FAEs). Se describen las recomendaciones para reducir efectos adversos de FAEs. El diagnóstico de TDAH en pacientes con epilepsia debe partir por la sospecha, a través de instrumentos clínicos y valoraciones de funcionamiento cognitivo. El tratamiento multimodal es recomendado para pacientes con TDAH con y sin epilepsia. Los psicoestimulantes se pueden usar con seguridad. La calidad de vida se afecta en pacientes y sus familias, por lo que la educación, pesquisa precoz y referencia para rehabilitación, están encaminadas a resolver las dificultades de estos pacientes. En caso contrario, se generan consecuencias negativas escolares, sociales y emocionales, que pueden ser relevantes y persistentes.

Epilepsy and attention deficit and hyperactivity disorder (ADHD) are frequent conditions in pediatrics. Their association is frequent and complex, often sharing psychiatric comorbidity. Patients who present epilepsy and ADHD, show equal frequency in both genders, with the inattentive type, as predominant presentation. Cognitive deficit increases the risk of associating ADHD in patients with epilepsy. There is not enough evidence for other risk factors, however there is enough information that allows to ant icipate its presence in some types of epilepsy, with neuropsychological models that evidence the underlying network dysfunction. The relationship with frequency and seizure control, electroencephalographic alterations and antiepileptic drugs (AEDs) is also reviewed. Recommendations to reduce adverse effects of AEDs are described. The diagnosis must therefore be based on suspicion, through clinical instruments and assessments of cognitive functioning. Multimodal treatment is also recommended in patients with ADHD with and without epilepsy. Psych stimulants can be used safely. The quality of life of the patients and their families is affected, so it is advisable for them to be supported by a specialized team that could provide education, early assessment and therapy. If they are omitted, the consequences can be negative at school, social environment and emotional development, which could be relevant and become persistent.

Rehabilitación multidisciplinaria para pacientes adultos con accidente cerebrovascular / Multidisciplinary rehabilitation for adult patients with stroke

Se estima que dos tercios de las personas que han sufrido un accidente cerebrovascular (ACV) tienen secuelas que condicionan su calidad de vida. La rehabilitación del ACV es un proceso complejo, que requiere de un equipo multidisciplinario de profesionales especializados (médicos, kinesiólogos, enfermeros, terapistas ocupacionales, fonoaudiólogos, neuropsicólogos y nutricionistas). Actualmente, las prácticas realizadas en rehabilitación son consecuencia de la combinación de evidencia y consenso, siendo la mayoría aportadas a través de guías internacionales de rehabilitación en ACV. El objetivo de esta revisión es ajustar las recomendaciones internacionales sobre rehabilitación a lo aplicado a la práctica diaria, a fin de unificar criterios en las recomendaciones y reducir la variabilidad de las prácticas empleadas. En este trabajo, se realizó una revisión de la literatura sobre las guías de rehabilitación en ACV realizadas en los últimos 10 años y cada apartado fue supervisado por distintos profesionales especializados en dichas áreas. Se analizaron los tiempos y organización necesaria para desarrollarla, las recomendaciones para la rehabilitación motora, cognitiva y visual, el tratamiento de la disfagia y nutrición, de las comorbilidades (trombosis venosa, úlceras cutáneas, dolor, trastornos psiquiátricos, osteoporosis) y las tareas necesarias para favorecer el retorno a las actividades de la vida diaria.

It is estimated that two thirds of people who have suffered a stroke have sequels that condition their quality of life. The rehabilitation of the stroke is a complex process, which requires the multidisciplinary approach of specialized professionals (doctors, kinesiologists, nurses, occupational therapists, phonoaudiologists, neuropsychologists and nutritionists). Currently, the practices carried out are a consequence of the combination of evidence and consensus, most of them through international stroke rehabilitation guides. The objective of this review is to adjust the international recommendations on stroke rehabilitation to what is applied to daily practice, in order to unify the criteria of the recommendations and to reduce the variability of the practices carried out. This work is a review of the literature on stroke rehabilitation guides developed in the last 10 years. Each section was supervised by different professionals specialized in these areas. We analyze the time and organization necessary to develop rehabilitation, recommendations for motor, cognitive and visual rehabilitation, the management of dysphagia and nutrition, the approach of comorbidities (venous thrombosis, skin ulcers, pain, psychiatric disorders and osteoporosis) and the necessary tasks to favor the return to the activities of daily life.

Voxel-wise meta-analysis of structural changes in gray matter of Parkinsons disease patients with mild cognitive impairment

Evidence from previous voxel-based morphometry (VBM) studies indicates that widespread brain regions are involved in Parkinson's disease with mild cognitive impairment (PD-MCI). However, the spatial localization reported for gray matter (GM) abnormalities is heterogeneous. The aim of the present study was to quantitatively integrate studies on GM abnormalities observed in PD-MCI in order to determine whether a pattern exists. Eligible whole-brain VBM studies were identified by a systematic search of articles in PubMed and EMBASE databases spanning from 1995 to January 1, 2019. A meta-analysis was performed to investigate regional GM abnormalities in PD-MCI. The anisotropic effect size version of seed-based d mapping (AES-SDM) meta-analysis was conducted to explore the GMV differences of PD-MCI compared with PD patients with normal cognitive function (PD-NC). A total of 12 studies comprising 243 PD-MCI patients and 326 PD-NC were included in the meta-analysis. PD-MCI patients showed a robust GM decrease in the left insula and left superior temporal gyrus. Moreover, meta-regression analysis demonstrated that age, PD duration and stage, and Unified Parkinson's Disease Rating Scale III and Mini-Mental State Examination scores might be partly correlated with the GM abnormalities observed in PD-MCI patients. The convergent findings of this quantitative meta-analysis revealed a characteristic neuroanatomical pattern in PD-MCI. The findings provide some evidence that MCI in PD may result in the breakdown of the insula and temporal gyrus, which may serve as specific regions of interest for further investigations.

Reserva cognitiva y demencias: Limitaciones del efecto protector en el envejecimiento y el deterioro cognitivo / Limited protective effects of cognitive reserve on the progression of cognitive impairment

Aging constitutes a series of physical, physiological and cognitive changes, affecting independence in the activities of daily living. During this stage, neurodegenerative diseases and cognitive impairment are common. Cognitive Reserve allows to face neuropathological changes and maintain cognitive function in the presence of brain damage. However, there are cases where a high cognitive reserve fails to attenuate and delay the effects of neuropathology, allowing the progression of cognitive damage to advanced stages. The objective of this systematic review is to identify evidence where high cognitive reserve does not limit the effects of cognitive impairment. Results indicate that the protective effect of cognitive reserve occurs only in the presence of minimal cognitive impairment, but not at later stages.

Alzheimer's disease and sleep disturbances: a review / Doença de Alzheimer e distúrbios do sono: uma revisão

ABSTRACT The association between Alzheimer's disease (AD) and sleep disturbances has received increasing scientific attention in the last decades. However, little is known about the impact of sleep and its disturbances on the development of preclinical AD stages, such as mild cognitive impairment. This review describes the evolution of knowledge about the potential bidirectional relationships between AD and sleep disturbances exploring recent large prospective studies and meta-analyses and studies of the possible mechanisms through which sleep and the neurodegenerative process could be associated. The review also makes a comprehensive exploration of the sleep characteristics of older people, ranging from cognitively normal individuals, through patients with mild cognitive impairment, up to the those with dementia with AD.

RESUMO A associação entre Doença de Alzheimer (DA) e distúrbios do sono vem recebendo atenção crescente nas últimas décadas. No entanto, pouco se sabe sobre o impacto do sono e suas alterações no desenvolvimento de estágios pré-clínicos da doença, como é o caso do Comprometimento Cognitivo Leve (CCL). Esta revisão descreve a evolução do conhecimento sobre as relações potencialmente bidirecionais entre DA e distúrbios do sono, explorando grandes estudos prospectivos e meta-análises, assim como estudos dos possíveis mecanismos da associação entre o sono e as doenças neurodegenerativas. Também revisamos amplamente as características do sono de pessoas idosas, incluindo indivíduos cognitivamente normais, com CCL e com demência por DA.

¿Cuál es la asociación entre el tiempo destinado a dormir y el desarrollo de deterioro cognitivo en adultos mayores chilenos? / Association between sleep duration and cognitive impairment in older people

Background Sleep duration may be a risk factor for cognitive impairment. Aim To investigate the association between sleep duration and cognitive function in Chilean older adults. Material and Methods We analyzed information from 1,384 participants aged > 60 years participating in the National Health Survey 2009-2010 who were assessed with the Mini Mental State Examination (MMSE) and self-reported their average daily sleep hours. Logistic regression analysis was performed to investigate the association between MMSE and sleep duration. Results Compared to those participants who reported sleeping 7 hours per day, those that reported sleeping < 5 hours had a higher odd for cognitive impairment (Odds ratio (OR): 3.66 [95% confidence intervals (CI: 1.69; 7.95], p < 0.01). Similarly, those who reported sleeping > 8 hours per day also showed a higher odd for cognitive impairment (OR: 2.56 [95% CI: 1.32; 4.95], p < 0.01). This association was even stronger for people who reported more than 10 hours of sleep per day (OR: 4.46 [95% CI: 1.32; 4.95], p < 0.01). Conclusions Long and short sleep duration is associated with cognitive impairment in older adults in Chile independent of major confounding factors.

Actividad física y tiempo sedente se asocian a sospecha de deterioro cognitivo en población adulta mayor chilena / Physical activity and sedentary behaviours are associated with cognitive impairment in Chilean older adults

Background: Lifestyle factors could promote healthy ageing. Aim: To investigate the association between physical activity (PA), sedentary behavior and cognitive impairment in Chilean older adults. Material and Methods: We included 1,390 participants from the National Health Survey (2009-2010). The Mini-Mental State Examination was used to diagnose cognitive impairment. Physical activity and sedentary behavior were assessed with the Global Physical Activity Questionnaire (GPAQ). Logistic regression was performed to investigate the associations. Results: Compared with older adults with lower levels of PA (< 48 min/day), those with middle (48-248 min/day) and higher (>248 min/day) levels of PA had lower odds for cognitive impairment (Odds ratio (OR): 0.57 [95% confidence intervals (CI): 0.33; 0.82], p < 0.01 and 0.58 [95% CI: 0.32; 0.83], p < 0.01, respectively). Participants who reported spending more than 8 hours/day sitting had a high odds for cognitive impairment compared to those who spent < 4 hours/day (OR: 3.70 [95% CI: 1.37; 6.03], p = 0.01). Conclusions: Both PA and sedentary behavior were independently associated with cognitive decline independent of major confounding factors in Chilean older adults.

Decreased plasmatic spermidine and increased spermine in mild cognitive impairment and Alzheimer's disease patients

Abstract Background Current evidence suggests that upregulation of polyamines system plays a role both in cognitive deficit and synaptic loss observed in Alzheimer's disease (AD). Objective The aim of this study was to determine the plasmatic concentration of polyamines in mild cognitive impairment (MCI) and AD patients in comparison with healthy controls (HC). Methods Plasmatic polyamines were quantified using the AbsoluteIDQ® p180 and liquid chromatography coupled to tandem mass spectrometry (LC/MS-MS). Results The study group comprised 34 AD patients, 20 MCI and 25 HC. All individuals were followed for 4 years. During this period 8 amnestic MCI patients (40% of the MCI sample at baseline) converted to AD. Spermidine level was lower in both patient groups (AD; MCI) compared to HC (p = 0.007). Plasma levels of spermine were higher in the MCI group (p < 0.001), but decreased in the sub-sample of MCI patients who converted to AD (p = 0.043). No statistically significant differences were found in ornithine and putrescine levels (p = 0.056 and p = 0.126, respectively). Discussion Our results suggest dynamic changes in the expression of polyamines in the MCI-AD continuum.

Exploratory analysis of rare and novel variants in Mexican patients diagnosed with schizophrenia and dementia

Abstract Background Schizophrenia (SCZ) and dementia, often related, are two of the most common neuropsychiatric diseases; epidemiological studies have shown that SCZ patients present a 2-fold increased risk for dementia compared to non-schizophrenic individuals. We explored the presence of rare and novel damaging gene variants in patients diagnosed with late-onset dementia of Alzheimer’s type (DAT) or SCZ. Methods We included 7 DAT and 12 SCZ patients and performed high-depth targeted sequencing of 184 genes. Results We found novel and rare damaging variants in 18 genes in these Mexican patients. Carriers of these variants showed extreme phenotypes, including, treatment-resistant SCZ or cognitive decline. Furthermore, we found a variation on ABCC1 as a possible link between psychosis and cognitive impairment. Discussion As an exploratory analysis, we report some interesting variations that should be corroborated in larger sample size studies.

Memory impairment: an intermediate clinical syndrome symptom in HTLV-1-infected patients? / Comprometimento da memória: um sintoma de síndrome clínica intermediária em pacientes infectados pelo HTLV-1?

Background Although classical human T-cell lymphocyte virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis syndrome is the most frequent HTLV-1-associated neurological disorder, some "minor" neurological disorders can be seen in "asymptomatic" carriers. These disorders, including cognitive alterations already described in clinical cases and studies, may constitute an intermediate syndrome (IMS) between the asymptomatic state and myelopathy. The aim of this study was to investigate the presence of cognitive deficits in patients with HTLV-1 virus, who usually are diagnosed as asymptomatic. Methods A total of 54 HTLV-1-infected patients were evaluated, 35 asymptomatic and 19 with minor neurological alterations (evaluated by a neurologist); 25 HTLV-1-seronegative individuals served as controls. The instruments used were: Beck's Depression Inventory, Lawton's Daily Life Activity Scale, and a complete neuropsychological battery. The application of these evaluation instruments was performed blindly, with the evaluator neuropsychologist not knowing the clinical condition of the patient. Results Most of the participants in this cohort, including seronegative controls, were female (n = 57, 72.21%), their mean age was 52.34 years (SD = 14.29) and their average schooling was 9.70 years (SD = 4.11). Discussion Participants classified with IMS had lower gross scores when compared with both the patients classified as asymptomatic and with the control group, and when tested for auditory episodic memory of immediate (p < 0.01), and late (p = 0.01), recall. Conclusion Patients with IMS presented with memory impairment when compared with asymptomatic patients and seronegative individuals; this is one of the symptoms that aids in the classification of the syndrome.

RESUMO Apesar da síndrome de HAM / TSP clássica ser a perturbação neurológica mais atribuída, alguns distúrbios neurológicos denominados "menores" são vistos em portadores "assintomáticos" de HTLV-1. Esses distúrbios, incluindo alterações cognitivas já observadas em descrições de casos clínicos e estudos, podendo constituir uma verdadeira síndrome clínica intermediária (SI) entre o estado assintomático e mielopatia. O objetivo deste estudo foi investigar a presença de déficits cognitivos em pacientes portadores do vírus HTLV-1 diagnosticados classicamente como assintomáticos. Métodos Foram avaliadas 54 pessoas, sendo 35 assintomáticos, 19 com alterações neurológicas menores (avaliados por um neurologista) e 25 HTLV-1 negativo. Os instrumentos utilizados foram: Inventário Beck de Depressão, Escala de Atividades de Vida Diária de Lawton e uma completa bateria neuropsicológica. A aplicação destes instrumentos de avaliação foi realizada de forma cega, ou seja, a avaliadora não sabia a condição clinica do paciente. Resultados A maioria dos participantes era do sexo feminino (n = 57, 72,21%), com idade média de 52.34 anos (DP = 14,29) e escolaridade média de 9.70 anos (DP = 4,11). Discussão Avaliando o desempenho cognitivo nos três grupos, foi possível observar que os participantes classificados com SI, apresentaram menores escores brutos, quando comparados, com os pacientes com classificação assintomática e grupo controle e, em relação à memória episódica auditiva de evocação imediata (p < 0,01) (p = 0,01) e tardia. Conclusão Diante dos resultados foi possível concluir que os pacientes com SI apresentam comprometimento de memória quando comparado com os outros grupos, sendo possível, ser este um dos sintomas para auxiliar na classificação da síndrome.

Non-pharmacological motor-cognitive treatment to improve the mental health of elderly adults

SUMMARY OBJECTIVE: To propose a program of physical-cognitive dual task and to measure its impact in Chilean institutionalized elderly adults. METHOD: Experimental design study with pre and post-intervention evaluations, measuring the cognitive and depressive levels by means of the Pfeiffer test and the Yesavage scale, respectively. The program was applied for 12 weeks to adults between 68 and 90 years old. The statistical analysis was based on the nonparametric Wilcoxon test for paired samples and was contrasted with its parametric version. The statistical software R was used. RESULTS: Statistically significant differences were obtained in the cognitive level (p-value < 0.05) and highly significant (p-value < 0.001) in the level of depression with both tests (parametric and nonparametric). CONCLUSION: Due to the almost null evidence of scientific interventions of programs that integrate physical activity and cognitive tasks together in Chilean elderly adults, a program of physical-cognitive dual task was proposed as a non-pharmacological treatment, easy to apply and of low cost to benefit their integral health, which improves significantly the cognitive and depressive levels of institutionalized elderly adults.

RESUMO OBJETIVO: Propor um programa físico-cognitivo e medir seu impacto em idosos institucionalizados chilenos. MÉTODO: Estudo de planejamento experimental com avaliações pré e pós-intervenção, medindo os níveis cognitivo e depressivo por meio do teste de Pfeiffer e da escala de Yesavage, respectivamente. O programa foi aplicado por 12 semanas a idosos entre 68 e 90 anos de idade. A análise estatística foi baseada no teste não paramétrico de Wilcoxon para amostras pareadas e foi contrastada com sua versão paramétrica. O software estatístico R foi utilizado. RESULTADOS: Diferenças estatisticamente significantes foram obtidas no nível cognitivo (p < 0,05) e altamente significante (p < 0,001) no nível de depressão com ambos os testes (paramétrico e não paramétrico). CONCLUSÃO: Porque quase não existe evidência científica de programas de intervenções que integram a atividade física e tarefas cognitivas em chilenos idosos, um programa físico-cognitivo foi proposto como tratamento não farmacológico, fácil de implementar e de baixo custo, para beneficiar a sua saúde integral, melhorando significativamente os níveis cognitivos e depressivos de idosos institucionalizados.

Egocentric and allocentric spatial memory in healthy aging: performance on real-world tasks

Although normal aging has been related to several cognitive difficulties, other processes have been studied less, such as spatial memory. Our aim was to compare egocentric and allocentric memory in an elderly population using ecological tasks. Twenty-eight cognitively unimpaired participants performed Egocentric and Allocentric Spatial Memory Tasks, as well as Spatial Span from CANTAB, Benton's Judge of Line Orientation test (JoLO), and Montreal Cognitive Assessment test (MoCA). The results revealed that younger participants showed better performance than older participants on both the Egocentric and Allocentric Spatial Memory Tasks, although only the Egocentric test was able to discriminate between younger, middle, and older elderly participants. Learning effect was found in Allocentric Spatial Memory Task in younger and older groups, but not in the middle group. Allocentric and egocentric performance was not related to other visuospatial neuropsychological scores and gender did not influence performance in any task. Egocentric and Allocentric Spatial Memory Tasks may be useful tools in early screening for cognitive decline, as they are able to detect age differences in the cognitive unimpaired elderly population.

A study on changes of the resting-state brain function network in patients with amnestic mild cognitive impairment

This study aimed to explore the structural and functional characteristics of the neural network of resting-state brain activities in patients with amnestic mild cognitive impairment (aMCI) by functional magnetic resonance imaging (fMRI) technology. Resting state fMRI scanning was performed on 10 clinically diagnosed aMCI patients and 10 healthy volunteers, and the difference in the resting-state brain activities between aMCI patients and healthy volunteers was compared using the brain function network regional homogeneity (ReHo) analysis method. Results of the ReHo analysis of aMCI patients and healthy volunteers revealed that the ReHo value significantly increased in the posterior cingulate gyrus region, medial frontal lobe, medial cortex of the prefrontal lobe, and part of the parietal lobe. Compared with the normal elderlies, ReHo decreased in aMCI patients in the left temporal lobe (middle temporal gyrus and inferior temporal gyrus), left parahippocampal gyrus, occipital lobe, lingual gyrus, precuneus, and other regions while ReHo increased in regions of the right frontal lobe (inferior frontal gyrus), left superior temporal gyrus, precentral gyrus (frontal lobe), right thalamus, left fusiform gyrus, and other regions. In the resting state, there may be regional abnormalities in brain functional areas in aMCI patients, which may be associated with cognitive impairment.

Oxiracetam ameliorates cognitive deficits in vascular dementia rats by regulating the expression of neuronal apoptosis/autophagy-related genes associated with the activation of the Akt/mTOR signaling pathway

Oxiracetam (ORC) is a commonly used nootropic drug for improving cognition and memory impairments. The therapeutic effect and underlying mechanism of ORC in vascular dementia (VaD) treatment remain unknown. In this study, 3-month-old male Sprague-Dawley rats with permanent bilateral common carotid artery occlusion-induced VaD were treated orally with low (100 mg/kg) or high (200 mg/kg) dose ORC once a day for 4 weeks. The results of the Morris water maze test and Nissl staining showed that ORC treatment significantly alleviated learning and memory deficits and neuronal damage in rats with VaD. Mechanistically, the protein levels of a panel of genes associated with neuronal apoptosis (Bcl-2, Bax) and autophagy (microtubule-associated protein 1 chain 3, Beclin1, p62) were significantly altered by ORC treatment compared with VaD, suggesting a protective role of ORC against VaD-induced neuronal apoptosis and autophagy. Moreover, the Akt/mTOR pathway, which is known to be the upstream signaling governing apoptosis and autophagy, was found to be activated in ORC-treated rats, suggesting an involvement of Akt/mTOR activation in ORC-rendered protection in VaD rats. Taken together, this study demonstrated that ORC may alleviate learning and memory impairments and neuronal damage in VaD rats by altering the expression of apoptosis/autophagy-related genes and activation of the Akt/mTOR signaling pathway in neurons.

BsmI polymorphism in the vitamin D receptor gene is associated with 25-hydroxy vitamin D levels in individuals with cognitive decline / Polimorfismo BsmI no gene do receptor de vitamina D está associado aos níveis de 25-hidroxi vitamina D em indivíduos com declínio cognitivo

ABSTRACT Elderly people are at a high risk of developing vitamin D (VitD) deficiency due to both decreased intake and cutaneous synthesis. Most of the biological actions of VitD are mediated by the vitamin D receptor (VDR), which is present in neurons and glial cells of the hippocampus, and in the cortex and subcortical nuclei, essential areas for cognition. It is known that VDR gene polymorphisms may decrease the VDR affinity for VitD. Objective: The present study aimed to investigate the influence of VitD levels on cognitive decline in patients with dementia due to Alzheimer's disease (AD, n = 32) and mild cognitive impairment (MCI, n = 15) compared to cognitively healthy elderly (n = 24). We also evaluated the association of VDR gene polymorphisms with cognitive disturbance. Methods: Four polymorphisms on the VDR gene were studied, namely, BsmI, ApaI, FokI and TaqI, by polymerase chain reaction-restriction fragment length polymorphism. Serum levels of 25-hydroxy vitamin D (25(OH)D) were determined by high performance liquid chromatography. Results: No significant difference in 25(OH)D levels or genotypic/allelic frequencies was observed between the groups. Deficiency of 25(OH)D was more frequently observed in women. The AA/AG genotypes of the BsmI polymorphism was associated with sufficient 25(OH)D levels, while the GG genotype of this same polymorphism was associated to insufficient levels in the cognitively-impaired group (individuals with AD or MCI). Conclusions: The data obtained do not confirm the relationship between reductions of VitD levels, polymorphisms in the VDR gene, and altered cognitive function in this sample. However, the data indicate that BsmI polymorphism in the VDR gene is associated with the VitD levels in individuals with cognitive decline.

RESUMO Idosos apresentam risco elevado de desenvolverem deficiência de Vitamina D (VitD) devido à diminuição da ingestão e da síntese na pele. A maioria das ações biológicas da VitD é mediada pelo receptor da vitamina D (VDR), que está presente nos neurônios e células gliais do hipocampo, e no córtex e em núcleos subcorticais, áreas essenciais para a cognição. Sabe-se que polimorfismos do gene VDR podem diminuir a afinidade do VDR pela VitD. Objetivo: O presente estudo teve como objetivo investigar a influência dos níveis de VitD no declínio cognitivo em pacientes com demência devida à doença de Alzheimer (DA, n = 32) e comprometimento cognitivo leve (CCL, n = 15) em comparação a um grupo de idosos cognitivamente saudáveis (n = 24). Nós também avaliamos a associação entre polimorfimos no gene do receptor de VitD e as alterações cognitivas. Métodos: Quatro polimorfismos no gene VDR foram estudados, sendo BsmI, ApaI, FokI e TaqI, por PCR-RFLP. Os níveis séricos de 25-hidroxi vitamina D (25(OH)D) foram determinados por HPLC. Resultados: Não houve diferença significativa nos níveis de 25(OH)D ou nas frequências genotípicas / alélicas entre os grupos. Níveis deficientes de 25(OH)D foram mais frequentes nas mulheres. Os genótipos AA / AG do polimorfismo BsmI foram associados a níveis suficientes de 25(OH)D, enquanto o genótipo GG deste mesmo polimorfismo foi associado a níveis insuficientes no grupo com comprometimento cognitivo (em indivíduos com DA ou CCL). Conclusões: Os resultados obtidos não confirmam a relação entre redução dos níveis de VitD, polimorfismos no gene VDR e função cognitiva alterada nesta amostra. No entanto, os dados indicam que o polimorfismo BsmI no gene VDR está associado aos níveis de VitD em indivíduos com declínio cognitivo.

Twenty-five years since the identification of the first SCA gene: history, clinical features and perspectives for SCA1 / Vinte e cinco anos desde a identificação do primeiro gene das SCAs: história, aspectos clínicos e perspectivas para a SCA1

ABSTRACT Spinocerebellar ataxias (SCA) are a clinically and genetically heterogeneous group of monogenic diseases that share ataxia and autosomal dominant inheritance as the core features. An important proportion of SCAs are caused by CAG trinucleotide repeat expansions in the coding region of different genes. In addition to genetic heterogeneity, clinical features transcend motor symptoms, including cognitive, electrophysiological and imaging aspects. Despite all the progress in the past 25 years, the mechanisms that determine how neuronal death is mediated by these unstable expansions are still unclear. The aim of this article is to review, from an historical point of view, the first CAG-related ataxia to be genetically described: SCA 1.

RESUMO As ataxias espinocerebelares (SCA) são um grupo clínico e geneticamente heterogêneo de doenças monogênicas que compartilham ataxia e herança autossômica dominante como características principais. Uma proporção importante de SCAs é causada por expansões de repetição de trinucleotídeos CAG na região de codificação de diferentes genes. Além da heterogeneidade genética, os aspectos clínicos transcendem os sintomas motores, incluindo aspectos cognitivos, eletrofisiológicos e de imagem. Apesar de todo o progresso feito nos últimos 25 anos, os mecanismos que determinam como se dá a morte neuronal mediada por essas expansões instáveis ainda não estão claros. O objetivo deste artigo é revisar, de um ponto de vista histórico, a primeira ataxia geneticamente relacionada com o CAG descrita: SCA 1.

Performances on the Timed Up and Go Test and subtasks between fallers and non-fallers in older adults with cognitive impairment / Performances no teste Timed Up and Go e subtarefas em idosos com comprometimento cognitivo, caidores e não caidores

ABSTRACT This work aimed to compare performances on the Timed Up and Go (TUG) test and its subtasks between faller and non-faller older adults with mild cognitive impairment (MCI) and mild Alzheimer's disease (AD). A prospective study was conducted, with 38 older adults with MCI and 37 with mild AD. Participants underwent an assessment at baseline (the TUG and its subtasks using the Qualisys ProReflex system) and the monitoring of falls at the six-month follow up. After six months, 52.6% participants with MCI and 51.3% with AD fell. In accordance with specific subtasks, total performance on the TUG distinguished fallers from non-fallers with AD, fallers from non-fallers with MCI and non-fallers with MCI from non-fallers with AD. Although no other difference was found in total performances, non-fallers with MCI and fallers with AD differed on the walking forward, turn and turn-to-sit subtasks; and fallers with MCI and non-fallers with AD differed on the turn-to-sit subtask.

RESUMO O objetivo deste trabalho foi comparar o desempenho do Timed up and go test (TUG) e suas subtarefas entre idosos caidores e não caidores com comprometimento cognitivo leve (CCL) e doença de Alzheimer (DA) leve. Um estudo prospectivo foi conduzido, com 38 idosos com CCL e 37 com DA leve. Foi realizada uma avaliação inicial (TUG e subtarefas por meio do sistema Qualisys Pro Reflex) e um monitoramento de quedas por 6 meses. Após 6 meses, 52.6% pessoas com CCL e 51.3% com DA caíram. Em concordância com subtarefas específicas, a performance total do TUG distinguiu caidores de não caidores com DA, caidores de não caidores com CCL e não caidores com CCL de não caidores com DA. Embora nenhuma outra diferença foi encontrada na performance total do TUG, não caidores com CCL e caidores com DA apresentaram diferenças nas performances das subtarefas marcha ida, retornar e virar-se para sentar; e caidores com CCL e não caidores com DA diferiram na subtarefa virar-se para sentar.

Normative values of the Brief Repeatable Battery of Neuropsychological Tests in a Brazilian population sample: discrete and regression-based norms / Valores normativos da Brief Repeatable Battery of Neuropsychological Tests (BRB-N) em uma amostra da população Brasileira: dados discretos e contínuos

ABSTRACT Objective Cognitive dysfunction is common in multiple sclerosis. The Brief Repeatable Battery of Neuropsychological Tests (BRB-N) was developed to assess cognitive functions most-frequently impaired in multiple sclerosis. However, normative values are lacking in Brazil. Therefore, we aimed to provide continuous and discrete normative values for the BRB-N in a Brazilian population sample. Methods We recruited 285 healthy individuals from the community at 10 Brazilian sites and applied the BRB-N version A in 237 participants and version B in 48 participants. Continuous norms were calculated with multiple-regression analysis. Results Mean raw scores and the 5th percentile for each neuropsychological measure are provided, stratified by age and educational level. Healthy participants' raw scores were converted to scaled scores, which were regressed on age, sex and education, yielding equations that can be used to calculate predicted scores. Conclusion Our normative data allow a more widespread use of the BRB-N in clinical practice and research.

RESUMO Objetivo Disfunção cognitiva é comum em pacientes com esclerose múltipla. Por isto, a Brief Repeatable Battery of Neuropsychological Tests (BRB-N) foi desenvolvida para avaliar as funções cognitivas mais frequentemente alteradas na doença. Entretanto, estão faltando dados normativos desta bateria no Brasil. Assim, nosso objetivo foi fornecer valores normativos contínuos e discretos da BRB-N para a população brasileira. Métodos Foram recrutados 285 indivíduos sadios da comunidade em 10 centros do Brasil e aplicada a versão A em 237 e a versão B em 48 sujeitos. Normas contínuas foram calculadas com análise de regressão múltipla. Resultados Escores brutos médios e 5°percentil para cada subteste são fornecidos, estratificados por idade e nível educacional. Os escores brutos dos sujeitos sadios foram convertidos em escores de escalas e postos em regressão quanto a idade, sexo e educação, fornecendo equações que podem ser usadas para calcular escores previsíveis. Conclusão Nossos dados normativos permitem um uso mais amplo da BRB-N na prática clínica e na pesquisa, fornecendo normas para dados discretos e contínuos. Normas para dados discretos deveriam ser usadas com cuidado e escores demograficamente ajustados são geralmente preferidos quando interpretando dados neuropsicológicos.