Presenilin-1 mutation position influences amyloidosis, small vessel disease, and dementia with disease stage.

INTRODUCTION: Amyloidosis, including cerebral amyloid angiopathy, and markers of small vessel disease (SVD) vary across dominantly inherited Alzheimer's disease (DIAD) presenilin-1 (PSEN1) mutation carriers. We investigated how mutation position relative to codon 200 (pre-/postcodon 200) influences these pathologic features and dementia at different stages. METHODS: Individuals from families with known PSEN1 mutations (n = 393) underwent neuroimaging and clinical assessments. We cross-sectionally evaluated regional Pittsburgh compound B-positron emission tomography uptake, magnetic resonance imaging markers of SVD (diffusion tensor imaging-based white matter injury, white matter hyperintensity volumes, and microhemorrhages), and cognition. RESULTS: Postcodon 200 carriers had lower amyloid burden in all regions but worse markers of SVD and worse Clinical Dementia Rating® scores compared to precodon 200 carriers as a function of estimated years to symptom onset. Markers of SVD partially mediated the mutation position effects on clinical measures. DISCUSSION: We demonstrated the genotypic variability behind spatiotemporal amyloidosis, SVD, and clinical presentation in DIAD, which may inform patient prognosis and clinical trials. HIGHLIGHTS: Mutation position influences Aß burden, SVD, and dementia. PSEN1 pre-200 group had stronger associations between Aß burden and disease stage. PSEN1 post-200 group had stronger associations between SVD markers and disease stage. PSEN1 post-200 group had worse dementia score than pre-200 in late disease stage. Diffusion tensor imaging-based SVD markers mediated mutation position effects on dementia in the late stage.

Sex and Socioeconomic Disparities in Dementia Risk: A Population Attributable Fractions Analysis in Argentina.

INTRODUCTION, twelve modifiable risk factors (RF) account for 40% of dementia cases worldwide. However, limited data exists on such factors in middle- and low-income countries. We aimed to estimate the population-attributable fractions (PAFs) for the 12 RF in Argentina, assessing changes over a decade, and exploring socioeconomic and sex influences. METHODS, we conducted cross-sectional analyses of the 12 RF from Argentinian surveys conducted in 2009, 2015, and 2018, including 96,321 people. We calculated PAFs, and stratified estimates based on sex and income. RESULTS, we estimated an overall PAF of 59.6%(95%CI=58.9%-60.3%). The largest PAFs were hypertension=9.3%(8.7%-9.9%), physical inactivity=7.4%(6.8%-8.2%), and obesity=7.4%(6.8%-7.9%). Men were more impacted by excessive alcohol, while women by isolation and smoking. Lower income linked to higher PAFs in education, hypertension, and obesity. DISCUSSION, Argentina has a higher PAF for dementia than the world population, with distinct RF distribution. PAF varied by sex and economic status, advocating tailored prevention strategies.

Etiology of White Matter Hyperintensities in Autosomal Dominant and Sporadic Alzheimer Disease.

Importance: Increased white matter hyperintensity (WMH) volume is a common magnetic resonance imaging (MRI) finding in both autosomal dominant Alzheimer disease (ADAD) and late-onset Alzheimer disease (LOAD), but it remains unclear whether increased WMH along the AD continuum is reflective of AD-intrinsic processes or secondary to elevated systemic vascular risk factors. Objective: To estimate the associations of neurodegeneration and parenchymal and vessel amyloidosis with WMH accumulation and investigate whether systemic vascular risk is associated with WMH beyond these AD-intrinsic processes. Design, Setting, and Participants: This cohort study used data from 3 longitudinal cohort studies conducted in tertiary and community-based medical centers-the Dominantly Inherited Alzheimer Network (DIAN; February 2010 to March 2020), the Alzheimer's Disease Neuroimaging Initiative (ADNI; July 2007 to September 2021), and the Harvard Aging Brain Study (HABS; September 2010 to December 2019). Main Outcome and Measures: The main outcomes were the independent associations of neurodegeneration (decreases in gray matter volume), parenchymal amyloidosis (assessed by amyloid positron emission tomography), and vessel amyloidosis (evidenced by cerebral microbleeds [CMBs]) with cross-sectional and longitudinal WMH. Results: Data from 3960 MRI sessions among 1141 participants were included: 252 pathogenic variant carriers from DIAN (mean [SD] age, 38.4 [11.2] years; 137 [54%] female), 571 older adults from ADNI (mean [SD] age, 72.8 [7.3] years; 274 [48%] female), and 318 older adults from HABS (mean [SD] age, 72.4 [7.6] years; 194 [61%] female). Longitudinal increases in WMH volume were greater in individuals with CMBs compared with those without (DIAN: t = 3.2 [P = .001]; ADNI: t = 2.7 [P = .008]), associated with longitudinal decreases in gray matter volume (DIAN: t = -3.1 [P = .002]; ADNI: t = -5.6 [P < .001]; HABS: t = -2.2 [P = .03]), greater in older individuals (DIAN: t = 6.8 [P < .001]; ADNI: t = 9.1 [P < .001]; HABS: t = 5.4 [P < .001]), and not associated with systemic vascular risk (DIAN: t = 0.7 [P = .40]; ADNI: t = 0.6 [P = .50]; HABS: t = 1.8 [P = .06]) in individuals with ADAD and LOAD after accounting for age, gray matter volume, CMB presence, and amyloid burden. In older adults without CMBs at baseline, greater WMH volume was associated with CMB development during longitudinal follow-up (Cox proportional hazards regression model hazard ratio, 2.63; 95% CI, 1.72-4.03; P < .001). Conclusions and Relevance: The findings suggest that increased WMH volume in AD is associated with neurodegeneration and parenchymal and vessel amyloidosis but not with elevated systemic vascular risk. Additionally, increased WMH volume may represent an early sign of vessel amyloidosis preceding the emergence of CMBs.

Effectiveness of cognitive rehabilitation on mild cognitive impairment using teleneuropsychology / A eficácia da reabilitação cognitiva no comprometimento cognitivo leve usando tele neuropsicologia

ABSTRACT The COVID-19 pandemic has affected the continuity of cognitive rehabilitation worldwide. However, the use of teleneuropsychology to provide cognitive rehabilitation has contributed significantly to the continuity of the treatment. Objectives: To measure the effects of cognitive telerehabilitation on cognition, neuropsychiatric symptoms, and memory strategies in a cohort of patients with mild cognitive impairment. Methods: A sample of 60 patients with mild cognitive impairment according to Petersen's criteria was randomly divided into two groups: 30 treatment cases and 30 controls (waiting list group). Subjects were matched by age, sex, and Montreal Cognitive Assessment. The treatment group received ten cognitive telerehabilitation sessions of 45 minutes duration once a week. Pre-treatment (week 0) and post-treatment (week 10) measures were assessed for both groups. Different linear mixed models were estimated to test treatment effect (cognitive telerehabilitation vs. controls) on each outcome of interest over time (pre/post-intervention). Results: A significant group (control/treatment) x time (pre/post) interaction revealed that the treatment group at week 10 had better scores in cognitive variables: memory (RAVLT learning trials p=0.030; RAVLT delayed recall p=0.029), phonological fluency (p=0.001), activities of daily living (FAQ p=0.001), satisfaction with memory performance (MMQ satisfaction p=0.004) and use of memory strategies (MMQ strategy p=0.000), as well as, and a significant reduction of affective symptomatology: depression (GDS p=0.000), neuropsychiatric symptoms (NPI-Q p=0.045), forgetfulness (EDO-10 p=0.000), and stress (DAS stress p=0.000). Conclusions: Our study suggests that CTR is an effective intervention.

RESUMO A pandemia do COVID-19 afetou a continuidade da reabilitação cognitiva em todo o mundo. No entanto, o uso de tele neuropsicologia para a reabilitação cognitiva tem contribuído significativamente para a continuidade do tratamento. Objetivos: Medir os efeitos da tele reabilitação cognitiva na cognição, nos sintomas neuropsiquiátricos e nas estratégias de memória em uma coorte de pacientes com comprometimento cognitivo leve. Métodos: Uma amostra de 60 pacientes com comprometimento cognitivo leve de acordo com os critérios de Petersen foi dividida aleatoriamente em dois grupos: 30 casos de tratamento e 30 controles (grupo de lista de espera). Os assuntos foram pareados por idade, sexo e Avaliação Cognitiva de Montreal. O grupo de tratamento recebeu dez sessões de tele reabilitação cognitiva de 45 minutos de duração uma vez por semana. As medidas pré-tratamento (semana 0) e pós-tratamento (semana 10) foram avaliadas para ambos os grupos. Diferentes modelos lineares mistos foram estimados para testar o efeito do tratamento (tele reabilitação cognitiva vs. controles) em cada desfecho de interesse ao longo do tempo (pré-/pós-intervenção). Resultados: Uma interação significativa grupo (controle/tratamento) x tempo (pré/pós) revelou que o grupo de tratamento teve melhores pontuações em variáveis cognitivas na semana 10: memória (ensaios de aprendizagem RAVLT p = 0,030; RAVLT recordação tardia p=0,029), fluência fonológica (p=0,001), atividades da vida diária (FAQ p=0,001), satisfação com o desempenho da memória (satisfação MMQ p=0,004) e uso de estratégias de memória (estratégia MMQ p=0,000), bem como uma significativa redução da sintomatologia afetiva: depressão (GDS p=0,000), sintomas neuropsiquiátricos (NPI-Q p=0,045), esquecimento (EDO-10 p=0,000) e estresse (DAS estresse p=0,000). Conclusões: Nosso estudo sugere que a CTR é uma intervenção eficaz.

El funcionamiento cognitivo como endofenotipo de la anorexia nerviosa. Estudio en familiares no afectados por la enfermedad / Cognitive functioning as an endophenotype of anorexia nervosa. A study in first-degree relatives unaffected by the disease

Resumen El perfil cognitivo de los pacientes con anorexia nerviosa se caracteriza por dificultades en la flexibilidad mental y en la coherencia central. El objetivo de este trabajo fue analizar si los familiares de primer grado no afectados de los pacientes presentan estas dificultades cognitivas, que podrían representar rasgos endofenotípicos de la enfermedad. Fueron estudiadas 34 mujeres: 17 familiares de primer grado (madres y hermanas) de pacientes con anorexia nerviosa y 17 controles sanos agrupados por edad y escolaridad. Se consideraron el índice de masa corporal, la ansiedad, la depresión, los síntomas obsesivo-compulsivos y los relacionados con los trastornos alimentarios. Se evaluó la coherencia central, mediante la copia de la Figura Compleja de Rey, y la flexibilidad mental, mediante el test de Stroop, el test de los trazos B y el test de fluencia fonológica. Los familiares de pacientes con anorexia nerviosa presentaron un menor rendimiento en las medidas de coherencia central (p < .05) y en fluencia fonológica (p < .05) que los controles sanos. Se observó una correlación entre el test de Stroop y los síntomas de depresión y trastornos alimentarios (p < .05). Los familiares de primer grado no afectados de pacientes con anorexia nerviosa presentaron dificultades en la coherencia central y, en menor grado, en la flexibilidad mental. Los resultados en los familiares indican que este perfil podría ser mediado genéticamente, constituyendo un rasgo característico de la anorexia nerviosa y, por ende, un posible candidato a endofenotipo neuropsicológico de esta enfermedad.

Abstract The cognitive profile of patients with anorexia nervosa is characterized by difficulties in central coherence and mental flexibility. Central coherence is defined by the ability to integrate incoming information in its own context, and weakness in central coherence is characterized by poor overall processing and superior detail processing. Mental flexibility is defined by the ability to change the course of a thought or action according to the demands of the environment. Alterations in this cognitive domain generate rigid and inflexible behavior. An open question in the literature is whether these cognitive characteristics are a transient state derived from the disease or whether they are stable traits associated with anorexia nervosa and endophenotypical features of this disease. The concept of endophenotype refers to the internal phenotype that is not clinically appreciable but can be observed indirectly through deficits that arise in the performance of certain neuropsychological tests. In recent years the search for endophenotypes has been renewed in the field of psychiatry as they would constitute an important route for the understanding of the biological and genetic bases of mental illnesses, constituting markers that allow a diagnosis before the onset of clinical symptomatology. For a cognitive marker to be considered an endophenotype it must meet a series of characteristics such as being measurable, inherited, found in patients with and without active disease and in first-degree relatives not affected by the disease. The aim of the present study was to assess whether difficulties in central coherence and mental flexibility are shared by unaffected first-degree relatives of patients with anorexia nervosa and thus constitute an endophenotypical feature of this disease. This is a cross-sectional, descriptive-comparative study in which 34 women participated: 17 unaffected first-degree relatives of patients with anorexia nervosa (mothers and sisters) and 17 healthy controls matched by age and education. For the study of central coherence the copy of Rey's Complex Figure was used and to assess set-shifting the Stroop test, the Trail Making Test B and the Phonological Fluency test were used. Demographic and clinical aspects such as age, educational level, body mass index, anxiety, depression, obsessive-compulsive and eating disorder related symptoms were also evaluated. First-degree relatives of patients with anorexia nervosa showed lower performance on measures of central coherence (p < .05) and phonological fluency (p < .05) than healthy controls. A correlation was observed between the Stroop test and depression and eating disorders symptoms (p < .05). The results of this study show that unaffected first-degree relatives of patients with anorexia nervosa presented alterations in central coherence and, to a lesser degree, in mental flexibility. These results, in addition to previous research in which difficulties persisted even after recovery, indicate that these alterations could be genetically mediated, constituting a characteristic trait of anorexia nervosa and therefore a possible candidate for neuropsychological endophenotype of this disease. Regarding practical implications of the study, the findings reinforce the importance of cognitive remediation treatments not only for patients with anorexia nervosa but also emphasize that they could be useful for unaffected family members. Taking into account that family intervention is a widely used tool in the psychological treatment of anorexia, improving the perception of the patient and his relatives about cognitive biases, could contribute to raising awareness of the disease, something that patients with anorexia nervosa do not usually have, and generate a positive impact on the response to treatment as a whole.

Autosomal dominant and sporadic late onset Alzheimer's disease share a common in vivo pathophysiology.

The extent to which the pathophysiology of autosomal dominant Alzheimer's disease corresponds to the pathophysiology of 'sporadic' late onset Alzheimer's disease is unknown, thus limiting the extrapolation of study findings and clinical trial results in autosomal dominant Alzheimer's disease to late onset Alzheimer's disease. We compared brain MRI and amyloid PET data, as well as CSF concentrations of amyloid-ß42, amyloid-ß40, tau and tau phosphorylated at position 181, in 292 carriers of pathogenic variants for Alzheimer's disease from the Dominantly Inherited Alzheimer Network, with corresponding data from 559 participants from the Alzheimer's Disease Neuroimaging Initiative. Imaging data and CSF samples were reprocessed as appropriate to guarantee uniform pipelines and assays. Data analyses yielded rates of change before and after symptomatic onset of Alzheimer's disease, allowing the alignment of the ∼30-year age difference between the cohorts on a clinically meaningful anchor point, namely the participant age at symptomatic onset. Biomarker profiles were similar for both autosomal dominant Alzheimer's disease and late onset Alzheimer's disease. Both groups demonstrated accelerated rates of decline in cognitive performance and in regional brain volume loss after symptomatic onset. Although amyloid burden accumulation as determined by PET was greater after symptomatic onset in autosomal dominant Alzheimer's disease than in late onset Alzheimer's disease participants, CSF assays of amyloid-ß42, amyloid-ß40, tau and p-tau181 were largely overlapping in both groups. Rates of change in cognitive performance and hippocampal volume loss after symptomatic onset were more aggressive for autosomal dominant Alzheimer's disease participants. These findings suggest a similar pathophysiology of autosomal dominant Alzheimer's disease and late onset Alzheimer's disease, supporting a shared pathobiological construct.

Spanish version of the frontotemporal dementia knowledge scale: adaptation and validation / Versión en español de la escala de conocimiento sobre demencia frontotemporal: adaptación y validación

ABSTRACT Background: Frontotemporal dementia (FTD) is a neurodegenerative disease and is one of the most common causes of dementia in people under 65. There is often a significant diagnostic delay, as FTD can be confused with other psychiatric conditions. A lack of knowledge regarding FTD by health professionals is one possible cause for this diagnostic confusion. Objectives: The aim of this study was to adapt and validate the Frontotemporal Dementia Knowledge Scale (FTDKS) in Spanish. Methods: A translation was done, following cross-cultural adaptation guidelines, which consisted of forward translation, blind back translation, and an analysis by a committee of experts. For the present study, 134 professionals from different health areas responded the Spanish version of the FTDKS. The statistical analysis was performed using R version 4.0.0 "Arbor day" and the Psych, sjPlot packages. Results: The Spanish version of the FTDKS had good reliability and internal consistency (Cronbach alpha 0.74.). The sample's mean score was 19.78 (range = 4-32, SD 6.3) out of a maximum of 36 points. Conclusions: The results obtained show that the Spanish version has good psychometric properties. The FTDKS is applicable in our environment and can be a useful tool to evaluate the knowledge of health professionals regarding frontotemporal dementia.

RESUMEN Antecedentes: La demencia frontotemporal (DFT) es una enfermedad neurodegenerativa y es una de las causas más comunes de demencia en personas menores de 65 años. A menudo existe un retraso significativo en el diagnóstico, ya que la FTD puede confundirse con otras afecciones psiquiátricas. La falta de conocimientos sobre la DFT por parte de los profesionales de salud es una posible causa de esta confusión diagnóstica. Objetivos: El presente estudio describe nuestros esfuerzos para adaptar y validar la Escala de Conocimiento de la Demencia Frontotemporal (FTDKS) en español. Métodos: Se realizó una traducción, siguiendo las pautas de adaptación transcultural, que consistió en una traducción directa, una traducción inversa ciega y un análisis por parte de un comité de expertos. Para el presente estudio, 134 profesionales de diferentes áreas de la salud respondieron la versión en español del FTDKS. El análisis estadístico se realizó utilizando la versión 4.0.0 de R "Arbor day" y los paquetes Psych, sjPlot. Resultados: La versión en español del FTDKS tiene una buena fiabilidad y consistencia interna (alfa de Cronbach 0,74.). La puntuación media de la muestra fue de 19,78 (rango = 4-32, SD 6,3) sobre un máximo de 36 puntos. Conclusiones: Los resultados obtenidos muestran que la versión española tiene buenas propiedades psicométricas. El FTDKS es aplicable en nuestro medio y puede ser una herramienta útil para evaluar los conocimientos de los profesionales sanitarios sobre la demencia frontotemporal.

Generation of a human induced pluripotent stem cell line from a familial Alzheimer's disease PSEN1 T119I patient.

Human induced pluripotent stem cells (hiPSC) line FLENIi001-A was reprogrammed from dermal fibroblasts using the lentiviral-hSTEMCCA-loxP vector. Fibroblasts were obtained from a skin biopsy of a 72-year-old Caucasian male familial Alzheimer's disease patient carrying the T119I mutation in the PSEN1 gene. PSEN1 genotype was maintained and stemness and pluripotency confirmed in the FLENIi001-A hiPSC line.

Environmental factors between normal and superagers in an Argentine cohort / Diferenças de fatores ambientais entre normais e superidosos em uma coorte argentina

ABSTRACT. Normal aging usually brings age-related cognitive decline. However, there is a group of aged individuals who have exceptional memory performance: the superagers. Objective: Our aim was to identify the environmental factors that could influence exceptional memory performance in a cohort of Argentine individuals. Methods: Forty healthy volunteers >80 years of age were classified into two groups, superagers (SA, n=20) and normal agers (NA, n=20), according to the Northwestern SuperAging Program criteria. Participants were neuropsychologically tested and evaluated on environmental aspects: working status, education, bilingualism, cognitive reserve, physical activity, social networking, clinical comorbidities, and longevity of parents and siblings. Results: Both groups were highly educated (NA=16.3±3 years; SA 15.85±2.6; p=0.6), 11.8% of the sample was still working without differences between groups. There were no differences in cognitive reserve inventory (p=0.7), physical activity engagement (p=0.423), or social network index (p=0.73). As for longevity, 44% of the siblings lived longer than 80 years of age (p=0.432) and maternal longevity was linked to SA (NA=46.7%; SA=80%; p=0.045). Conclusions: This study is a pilot approximation to the superaging population in Argentina. Our results suggest that environmental factors related to successful aging do not differentiate superaging. SA may depend on variables yet to be identified, probably of a genetic/metabolic order.

RESUMO. O envelhecimento normal geralmente traz declínio cognitivo relacionado à idade. No entanto, existe um grupo de idosos com desempenho excepcional de memória: os superidosos. Objetivo: Nosso objetivo foi identificar os fatores ambientais que podem influenciar o desempenho excepcional da memória em uma coorte de indivíduos argentinos. Métodos: Quarenta voluntários saudáveis com idade >80 anos foram classificados em dois grupos: superidosos (SI, n=20) e idosos normais (IN, n=20), de acordo com os critérios do Programa de Superidosos da Universidade Northwestern. Os participantes foram testados neuropsicologicamente e avaliados nos aspectos ambientais: situação de trabalho, escolaridade, bilinguismo, reserva cognitiva, atividade física e rede social, comorbidades clínicas e longevidade de pais e irmãos. Resultados: Ambos os grupos tinham alto nível de escolaridade (IN=16,3±3 anos; SI=15,85±2,6; p=0,6), 11,8% da amostra ainda trabalhava sem diferença entre os grupos. Não houve diferenças no inventário de reserva cognitiva (p=0,7), prática de atividade física (p=0,423) ou índice de rede social (p=0,73). Quanto à longevidade, 44% dos irmãos viviam mais de 80 anos (p=0,432) e a longevidade materna estava associada a SI (IN=46,7%; SI=80%; p=0,045). Conclusões: Este estudo é uma aproximação piloto ao super envelhecimento da população na Argentina. Nossos resultados sugerem que os fatores ambientais relacionados ao envelhecimento bem-sucedido não diferenciam os superidosos. Ser superidoso pode depender de variáveis ainda não identificadas, provavelmente de ordem genética/metabólica.

Moving from neurodegenerative dementias, to cognitive proteinopathies, replacing "where" by "what" / Passando de demências neurodegenerativas para proteinopatias cognitivas, substituindo "onde" por "o que"

ABSTRACT. Neurodegenerative dementias have been described based on their phenotype, in relation to selective degeneration occurring in a particular neuroanatomical system. More recently however, the term proteinopathy has been introduced to describe diseases in which one or more altered proteins can be detected. Neurodegenerative diseases can be produced by more than one abnormal protein and each proteinopathy can determine different clinical phenotypes. Specific biomarkers have now been linked to certain molecular pathologies in live patients. In 2016, a new biomarker-based classification, currently only approved for research in Alzheimer's disease, was introduced. It is based on the evaluation three biomarkers: amyloid (A) detected on amyloid-PET or amyloid- beta 42 assay in CSF; tau (T) measured in CSF as phosphorylated tau or on tau PET imaging; and neuronal injury/neurodegeneration (N), detected by total T-tau in CSF, FDG PET hypometabolism and on MRI brain scan. Results of clinical research using the ATN biomarkers at FLENI, a Neurological Institute in Buenos Aires, Argentina have, since 2011, contributed to ongoing efforts to move away from the concept of neurodegenerative dementias and more towards one of cognitive proteinopathies. Today, clinical diagnosis in dementia can only tell us "where" abnormal tissue is found but not "what" molecular mechanisms are involved.

RESUMO. As demências neurodegenerativas foram descritas com base em seu fenótipo, em relação à degeneração seletiva que ocorre em um sistema neuroanatômico específico. Mais recentemente, no entanto, o termo proteinopatia foi introduzido para descrever doenças nas quais uma ou mais proteínas alteradas podem ser detectadas. As doenças neurodegenerativas podem ser produzidas por mais de uma proteína anormal e cada proteinopatia pode determinar diferentes fenótipos clínicos. Biomarcadores específicos já foram associados a certas patologias moleculares em pacientes vivos. Em 2016, uma nova classificação baseada em biomarcadores, atualmente aprovada apenas para pesquisas na doença de Alzheimer, foi introduzida. É baseado na avaliação de três biomarcadores: amiloide (A) detectado no ensaio amiloide-PET ou amiloide-beta 42 no LCR; tau (T) medida no LCR como tau fosforilada ou em imagem de tau PET; e lesão/neurodegeneração neuronal (N), detectada por T-tau total no LCR, hipometabolismo FDG PET e pela ressonância magnética. Os resultados de pesquisas clínicas usando os biomarcadores ATN no FLENI, um Instituto Neurológico de Buenos Aires, Argentina, desde 2011, contribuíram para os esforços contínuos para se afastar do conceito de demência neurodegenerativa e mover-se mais em direção às proteinopatias cognitivas. Hoje, o diagnóstico clínico da demência só pode nos dizer "onde" o tecido anormal é encontrado, mas não "quais" mecanismos moleculares estão envolvidos.

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.

Diagnosis of Rapidly Progressive Dementia in a Referral Center in Argentina.

INTRODUCTION: Rapidly progressive dementia (RPD) is a broadly defined clinical syndrome. Our aim was to describe clinical and ancillary study findings in patients with RPD and evaluate their diagnostic performance for the identification of nonchronic neurodegenerative rapidly progressive dementia (ncnRPD). METHODS: We reviewed clinical records and ancillary methods of patients evaluated for RPD at our institution in Buenos Aires, Argentina from 2011 to 2017. We compared findings between chronic neurodegenerative RPD and ncnRPD and evaluated the diagnostic metrics using receiver operating characteristic curves. RESULTS: We included 104 patients with RPD, 29 of whom were chronic neurodegenerative RPD and 75 of whom were ncnRPD. The 6-month time to dementia cutpoint had a sensitivity of 89% and specificity of 100% for ncnRPD, with an area under the receiver operating characteristic curve of 0.965 (95% confidence interval=0.935-0.99; P<0.001). A decision tree that included time to dementia, brain magnetic resonance imaging, and cerebrospinal fluid analysis identified ncnRPD patients with a sensitivity of 100%, specificity of 79%, positive predictive value of 93%, and negative predictive value of 100% overall. DISCUSSION: RPD is a clinical syndrome that comprises different diagnoses, many of them for treatable diseases. Using the time to dementia, brain magnetic resonance imaging, and cerebrospinal fluid analysis when triaging these patients could help identify those diseases that need to be studied more aggressively.

Driving and Alzheimer's disease: A neuropsychological screening battery for the elderly / Condução e doença de alzheimer: uma bateria de triagem neuropsicológica para idosos

ABSTRACT As life expectancy increases, there is a marked increase in the elderly population eager to continue driving. A large proportion of these elderly drive safely, however, patients with mild dementia are high-risk drivers. Objective: to identify the cognitive tests that best predict driving ability in subjects with mild dementia. Methods: 28 drivers with mild dementia and 28 healthy elderly subjects underwent an extensive cognitive assessment (NACC Uniform Data Set Neuropsychological Battery), completed an adapted On Road Driving Test (ORDT) and a Driving Simulator assessment. Results: drivers with mild dementia made more mistakes on the ORDT and had slower responses in the simulator tasks. Cognitive tests correlated strongly with on road and simulator driving performance. Age, the Digit Symbol Modalities Test and Boston Naming Test scores were the variables that best predicted performance on the ORDT and were included in a logistic regression model. Conclusion: the strong correlation between driving performance and performance on specific cognitive tests supports the importance of cognitive assessment as a useful tool for deciding whether patients with mild dementia can drive safely. The algorithm including these three variables could be used as a screening tool for the detection of unsafe driving in elderly subjects with cognitive decline.

RESUMO À medida que aumenta a expectativa de vida, há um crescimento notável da população idosa ansiosa por continuar dirigindo. Uma grande proporção deles dirige com segurança, mas, pacientes com demência leve são condutores de alto risco. Objetivo: identificar os testes cognitivos que melhor predizem a capacidade de dirigir em indivíduos com demência leve. Métodos: 28 motoristas com demência leve e 28 idosos saudáveis foram submetidos a uma extensa avaliação cognitiva (Bateria Neuropsicológica de Conjunto de Dados Uniformes NACC), completaram um teste de condução real adaptado (TCRA) e uma avaliação do Simulador de Condução. Resultados: motoristas com demência leve cometeram mais erros no TCRA e tiveram respostas mais lentas nas tarefas do simulador. Os testes cognitivos correlacionaram-se fortemente com a condução na estrada e no simulador. A idade, o Teste de Modalidades do Símbolo Digit e o Teste de Nomeação de Boston foram as variáveis que melhor predisseram o desempenho no ORDT e foram incluídos em um modelo de regressão logística. Conclusão: a forte correlação entre o desempenho na direção e os testes cognitivos específicos apoia a importância da avaliação cognitiva como uma ferramenta útil para decidir se os pacientes com demência leve podem dirigir com segurança. O algoritmo que inclui essas três variáveis poderia ser usado como uma ferramenta de triagem para a detecção de condução de risco em idosos com declínio cognitivo.

Transient global amnesia: clinical features and prognostic factors suggesting recurrence / Amnesia global transitoria: características clínicas y factores pronósticos sugestivos de recurrencia

ABSTRACT The risk of recurrence of new amnesia events in patients having previously experienced transient global amnesia (TGA) ranges between 2.9-23.8%. Objective: Our objective was to search for recurrence predictors in TGA patients. Methods: Retrospective analysis to identify recurrence predictors in a cohort of 203 TGA patients from a single center in Buenos Aires, Argentina, diagnosed between January 2011 and March 2017 Clinical features and complementary studies (laboratory results, jugular vein Doppler ultrasound and brain MRI) were analyzed. Comparison between patients with recurrent versus single episode TGA was performed, applying a multivariate logistic regression model. Results: Mean age at presentation was 65 years (20-84); 52% were female. Median time elapsed between symptom onset and ER visit was two hours, with the average episode duration lasting four hours. Mean follow-up was 22 months. Sixty-six percent of patients referred to an identifiable trigger. Jugular reflux was present in 66% of patients; and 22% showed images with hippocampus restriction on diffusion-weighted MRI. Eight percent of patients had TGA recurrence. Patients with recurrent TGA had a more frequent history of migraine than patients without recurrence (37.5% vs. 14%; p = 0.03). None of the other clinical characteristics and complementary studies were predictors of increased risk of recurrence. Conclusions: Patients with migraine may have a higher risk of recurrent TGA. None of the other clinical characteristics evaluated allowed us to predict an increased risk of recurrence. Although the complementary studies allowed us to guide the diagnosis, they did not appear to have a significant impact on the prediction of recurrence risk.

RESUMEN El riesgo de recurrencia de nuevos eventos de amnesia en pacientes que han experimentado previamente Amnesia Global Transitoria (AGT) oscila entre el 2.9-23.8%. Objetivo: Nuestro objetivo fue buscar predictores de recurrencia en pacientes con AGT. Métodos: Análisis retrospectivo de una cohorte de 203 pacientes con AGT de un único centro en Buenos Aires, Argentina, diagnosticados entre enero-2011 y marzo-2017 Se analizaron las características clínicas y los estudios complementarios (laboratorio, Doppler de vena yugular y RM encéfalo). Se comparó el grupo de AGT recurrente versus episodio único, aplicando un modelo de regresión logística multivariada. Resultados: la edad promedio de presentación fue de 65 años (20-84); 52% mujeres. La mediana del tiempo transcurrido entre el inicio de los síntomas y la visita a la sala de emergencia fue de 2 horas, con una duración promedio del episodio de 4 horas. El seguimiento medio fue de 22 meses. 66% de los pacientes tuvieron un desencadenante identificable. El reflujo yugular estuvo presente en el 66% de los pacientes y el 22% mostró imágenes restrictivas en DWI a nivel hipocampal. 8% de los pacientes presentaron recurrencia. Los pacientes con AGT recurrente tuvieron un historial de migraña más frecuente (37.5% vs. 14%; p=0.03). Ninguna de las otras características clínicas y estudios complementarios fueron predictores de mayor riesgo de recurrencia. Conclusiones: los pacientes con migraña pueden tener un mayor riesgo de recurrencia de AGT. Ninguna de las otras características clínicas evaluadas nos permitió predecir un mayor riesgo de recurrencia. Aunque los estudios complementarios nos permitieron orientar el diagnóstico, no pareció tener un impacto significativo en la predicción del riesgo de recurrencia.

Longitudinal cognitive and biomarker changes in dominantly inherited Alzheimer disease.

OBJECTIVE: To assess the onset, sequence, and rate of progression of comprehensive biomarker and clinical measures across the spectrum of Alzheimer disease (AD) using the Dominantly Inherited Alzheimer Network (DIAN) study and compare these to cross-sectional estimates. METHODS: We conducted longitudinal clinical, cognitive, CSF, and neuroimaging assessments (mean of 2.7 [±1.1] visits) in 217 DIAN participants. Linear mixed effects models were used to assess changes in each measure relative to individuals' estimated years to symptom onset and to compare mutation carriers and noncarriers. RESULTS: Longitudinal ß-amyloid measures changed first (starting 25 years before estimated symptom onset), followed by declines in measures of cortical metabolism (approximately 7-10 years later), then cognition and hippocampal atrophy (approximately 20 years later). There were significant differences in the estimates of CSF p-tau181 and tau, with elevations from cross-sectional estimates preceding longitudinal estimates by over 10 years; further, longitudinal estimates identified a significant decline in CSF p-tau181 near symptom onset as opposed to continued elevations. CONCLUSION: These longitudinal estimates clarify the sequence and temporal dynamics of presymptomatic pathologic changes in autosomal dominant AD, information critical to a better understanding of the disease. The pattern of biomarker changes identified here also suggests that once ß-amyloidosis begins, additional pathologies may begin to develop less than 10 years later, but more than 15 years before symptom onset, an important consideration for interventions meant to alter the disease course.

Batería neuropsicológica Set de Datos Uniformes (UDS) para la evaluación de enfermedad de Alzheimer y deterioro cognitivo leve: Una revisión sistemática / Neuropsychological Battery Uniform Data Set (UDS) for the evaluation of Alzheimer's disease and mild cognitive impairment: A systematic review

Resumen La batería neuropsicológica UDS (del inglés Uniform Data Set), se usa a nivel mundial para homogeneizar las investigaciones de enfermedad de Alzheimer. Objetivo: Sintetizar cuantitativamente los resultados de las subpruebas de la UDS, para perfil cognitivo de controles, pacientes con deterioro cognitivo leve y demencia de tipo Alzheimer. Método: Se realizó una búsqueda sistemática avanzada y manual en bases de datos (PubMed/ MedLine, Web Of Science, Scopus, Lilacs, Science Direct, Cochrane Library, PsycINFO) para evaluar el rendimiento diagnóstico de la UDS. Resultados: La revisión sistemática, mostró una sintesís narrativa donde se analizaron 8 artículos que incluyeron 9260 sujetos, con un rango de edad entre 60 y 90 años. La síntesis cuantitativa utilizó 13 artículos con una muestra total de 2.884 participantes, con una edad promedio de 74 años y una media de 15 años de educación. Conclusión: Se describió una síntesis de las puntuaciones mediales, que generan puntos de corte para demencia tipo alzheimer (DTA), deterioro cognitivo leve (DCL) y controles cognitivamente normales, evidenciando una adecuada precisión diagnóstica.

Abstract The neuropsychological battery UDS (of the English Uniform Data Set), is used worldwide to homogenize the investigations of Alzheimer's disease. Objective: Quantitatively synthesize the results of the subtests of the UDS for the cognitive profile of controls, patients with mild cognitive impairment and dementia of the Alzheimer type. Method: An advanced and manual systematic search was performed in databases (PubMed / MedLine, Web of Science, Scopus, Lilacs, Science Direct, Cochrane Library, PsycINFO) evaluating the diagnostic performance of the UDS. Results: The systematic review showed a narrative synthesis where 8 articles were included that included 9260 subjects, with an age range between 60 and 90 years. The quantitative synthesis used 13 articles with a total sample of 2,884 participants, with an average age of 74 years and an average of 15 years of education. Conclusion: We described a synthesis of the medial scores, which generate cut-off points for Alzheimer's type dementia (DTA), mild cognitive impairment (MCI) and cognitively normal controls, evidencing an adequate diagnostic precession.

Hyper memory, synaesthesia, savants: Luria and Borges revisited / Hipermemória, sinestesia, savants: Luria e Borges revisitados

Abstract In this paper, we investigated two subjects with superior memory, or hyper memory: Solomon Shereshevsky, who was followed clinically for years by A. R. Luria, and Funes the Memorious, a fictional character created by J. L. Borges. The subjects possessed hyper memory, synaesthesia and symptoms of what we now call autistic spectrum disorder (ASD). We will discuss interactions of these characteristics and their possible role in hyper memory. Our study suggests that the hyper memory in our synaesthetes may have been due to their ASD-savant syndrome characteristics. However, this talent was markedly diminished by their severe deficit in categorization, abstraction and metaphorical functions. As investigated by previous studies, we suggest that there is altered connectivity between the medial temporal lobe and its connections to the prefrontal cingulate and amygdala, either due to lack of specific neurons or to a more general neuronal dysfunction.

Resumo Neste artigo, investigamos dois sujeitos com memória superior ou hipermemória: Solomon Shereshevsky, que foi seguido clinicamente por anos por A. R. Luria, e Funes o memorioso, um personagem fictício criado por J. L. Borges. Os sujeitos possuem hipermemória, sinestesia e sintomas do que hoje chamamos de transtorno do espectro autista (TEA). Vamos discutir interações dessas características e seu possível papel na hipermemória. Nosso estudo sugere que a hipermemória em nossos sujeitos sinestésicos pode ser devido às suas características de síndrome do TEA-savant. No entanto, esse talento foi acentuadamente diminuído pelo profundo déficit de categorização, abstração e funções metafóricas. Conforme investigado por estudos anteriores, sugerimos que há conectividade alterada entre o lobo temporal medial e suas conexões com o cingulado pré-frontal e amígdala, devido à falta de neurônios específicos ou a uma disfunção neuronal mais geral.

Relación entre actividades de tiempo libre y cognición en adultos mayores: una revisión de estudios argentinos e iberoamericanos / Relationship between leisure activities and cognition in elderly adults: a review of argentine and Iberoamerican studies

El envejecimiento poblacional implica un desafío para la salud pública por las patologías cuyos casos aumentan con la extensión de la vida. Se ha propuesto que ciertas actividades de la vida diaria (AVDs) avanzadas de tiempo libre poseen un efecto bené+co en la cognición de los adultos mayores. El objetivo de este trabajo fue relevar estudios empíricos presentando evidencia respecto a la relación entre dichas actividades y el funcionamiento cognitivo, para países iberoamericanos. Se incluyeron trabajos escritos en español, portugués e inglés, de enero de 2012 a mayo de 2017, involucrando a adultos de 60 y más años de edad no institucionalizados. Se hallaron 15 trabajos. Considerados en su conjunto, existiría evidencia de una relación entre las mencionadas actividades y el rendimiento cognitivo. Los trabajos de diseño prospectivo y los de intervención indicarían que la realización de dichas actividades avanzadas incide bene+ciosamente en el funcionamiento cognitivo.

Population aging implies a challenge to public health for the pathologies whose cases increase with the extension of life. It has been proposed that certain leisure advanced activities of daily living (ATLs) have a bene+cial effect on the cognition of the elderly. The objective of this work was to relieve empirical studies presenting evidence regarding the relationship between these activities and cognitive functioning, for Iberoamerican countries. Works written in Spanish, Portuguese and English were included from January 2012 to May 2017, involving non-institutionalized adults aged 60 and over. Fifteen papers were found. Considered as a whole, there would be evidence of a relationship between these activities and cognitive performance. Prospective design and interventional studies would indicate that such advanced activities has a bene+cial impact on cognitive functioning.

Argentina-Alzheimer's disease neuroimaging initiative (Arg-ADNI): neuropsychological evolution profile after one-year follow up / Argentina-Alzheimer's disease neuroimaging initiative (Arg-ADNI): evolução do perfil neuropsicológico depois de um ano de seguimento

ABSTRACT The Argentina-Alzheimer's disease neuroimaging initiative (Arg-ADNI) study is a longitudinal prospective cohort of 50 participants at a single institution in Buenos Aires, Argentina. Longitudinal assessments on a neuropsychological test battery were performed on 15 controls, 24 mild cognitive impairment (MCI) patients and 12 Alzheimer's disease (AD) dementia patients. In our study population, there was a high prevalence of positive AD biomarkers in the AD group, 92.3% (12/13); and a low prevalence in the normal controls, 20%; almost half (48%) of the patients diagnosed with MCI had positive amyloid detection. After a one year, the significant differences found at baseline on neuropsychological testing were similar at the follow-up assessment even though the AD group had significantly altered its functional performance (FAQ and CDR). The exception was semantic fluency, which showed greater impairment between the AD group and MCI and normal controls respectively. For these tests, the addition of AD biomarkers as a variable did not significantly alter the variations previously found for the established clinical group's model. Finally, the one-year conversion rate to dementia was 20% in the MCI cohort.

RESUMO El estudio de Argentina-Alzheimer's Disease Neuroimaging Initiative (Arg-ADNI) es una cohorte prospectiva de 50 pacientes seguidos en una misma institución. Fueron evaluados cognitivamente 15 controles normales (CN), 24 sujetos con deterioro cognitivo leve (DCL) y 12 con demencia tipo Alzheimer (DTA) leve. En los DTA, 92,3% tuvieron biomarcadores positivos para Alzheimer y 20% en los CN. Casi la mitad de los DCL presentaron biomarcadores positivos. Después de un año de seguimiento, la diferencias significativas halladas en la visita de inicio en las pruebas cognitivas fueron similares al año aunque los DTA tuvieron empeoramiento funcional medido en el FAQ y CDR. La excepción fue la fluencia semántica, la cual mostró mayor declinación entre DTA y los demás grupos. La incorporación de los biomarcadores como variable no alteró significativamente los hallazgos de grupo. La tasa de conversión a demencia anual fue del 20%.