Prevalence and Trajectories of Post-COVID-19 Neurological Manifestations: A Systematic Review and Meta-Analysis.

INTRODUCTION: The aim of this systematic review and meta-analysis was to evaluate the prevalence of thirteen neurological manifestations in people affected by COVID-19 during the acute phase and at 3, 6, 9 and 12-month follow-up time points. METHODS: The study protocol was registered with PROSPERO (CRD42022325505). MEDLINE (PubMed), Embase, and the Cochrane Library were used as information sources. Eligible studies included original articles of cohort studies, case-control studies, cross-sectional studies, and case series with ≥5 subjects that reported the prevalence and type of neurological manifestations, with a minimum follow-up of 3 months after the acute phase of COVID-19 disease. Two independent reviewers screened studies from January 1, 2020, to June 16, 2022. The following manifestations were assessed: neuromuscular disorders, encephalopathy/altered mental status/delirium, movement disorders, dysautonomia, cerebrovascular disorders, cognitive impairment/dementia, sleep disorders, seizures, syncope/transient loss of consciousness, fatigue, gait disturbances, anosmia/hyposmia, and headache. The pooled prevalence and their 95% confidence intervals were calculated at the six pre-specified times. RESULTS: 126 of 6,565 screened studies fulfilled the eligibility criteria, accounting for 1,542,300 subjects with COVID-19 disease. Of these, four studies only reported data on neurological conditions other than the 13 selected. The neurological disorders with the highest pooled prevalence estimates (per 100 subjects) during the acute phase of COVID-19 were anosmia/hyposmia, fatigue, headache, encephalopathy, cognitive impairment, and cerebrovascular disease. At 3-month follow-up, the pooled prevalence of fatigue, cognitive impairment, and sleep disorders was still 20% and higher. At six- and 9-month follow-up, there was a tendency for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache to further increase in prevalence. At 12-month follow-up, prevalence estimates decreased but remained high for some disorders, such as fatigue and anosmia/hyposmia. Other neurological disorders had a more fluctuating occurrence. DISCUSSION: Neurological manifestations were prevalent during the acute phase of COVID-19 and over the 1-year follow-up period, with the highest overall prevalence estimates for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache. There was a downward trend over time, suggesting that neurological manifestations in the early post-COVID-19 phase may be long-lasting but not permanent. However, especially for the 12-month follow-up time point, more robust data are needed to confirm this trend.

Systematic proteomics in Autosomal dominant Alzheimer's disease reveals decades-early changes of CSF proteins in neuronal death, and immune pathways.

Background: To date, there is no high throughput proteomic study in the context of Autosomal Dominant Alzheimer's disease (ADAD). Here, we aimed to characterize early CSF proteome changes in ADAD and leverage them as potential biomarkers for disease monitoring and therapeutic strategies. Methods: We utilized Somascan® 7K assay to quantify protein levels in the CSF from 291 mutation carriers (MCs) and 185 non-carriers (NCs). We employed a multi-layer regression model to identify proteins with different pseudo-trajectories between MCs and NCs. We replicated the results using publicly available ADAD datasets as well as proteomic data from sporadic Alzheimer's disease (sAD). To biologically contextualize the results, we performed network and pathway enrichment analyses. Machine learning was applied to create and validate predictive models. Findings: We identified 125 proteins with significantly different pseudo-trajectories between MCs and NCs. Twelve proteins showed changes even before the traditional AD biomarkers (Aß42, tau, ptau). These 125 proteins belong to three different modules that are associated with age at onset: 1) early stage module associated with stress response, glutamate metabolism, and mitochondria damage; 2) the middle stage module, enriched in neuronal death and apoptosis; and 3) the presymptomatic stage module was characterized by changes in microglia, and cell-to-cell communication processes, indicating an attempt of rebuilding and establishing new connections to maintain functionality. Machine learning identified a subset of nine proteins that can differentiate MCs from NCs better than traditional AD biomarkers (AUC>0.89). Interpretation: Our findings comprehensively described early proteomic changes associated with ADAD and captured specific biological processes that happen in the early phases of the disease, fifteen to five years before clinical onset. We identified a small subset of proteins with the potentials to become therapy-monitoring biomarkers of ADAD MCs. Funding: Proteomic data generation was supported by NIH: RF1AG044546.

Effectiveness of cognitive rehabilitation on mild cognitive impairment using teleneuropsychology.

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.

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.

Location of pathogenic variants in PSEN1 impacts progression of cognitive, clinical, and neurodegenerative measures in autosomal-dominant Alzheimer's disease.

Although pathogenic variants in PSEN1 leading to autosomal-dominant Alzheimer disease (ADAD) are highly penetrant, substantial interindividual variability in the rates of cognitive decline and biomarker change are observed in ADAD. We hypothesized that this interindividual variability may be associated with the location of the pathogenic variant within PSEN1. PSEN1 pathogenic variant carriers participating in the Dominantly Inherited Alzheimer Network (DIAN) observational study were grouped based on whether the underlying variant affects a transmembrane (TM) or cytoplasmic (CY) protein domain within PSEN1. CY and TM carriers and variant non-carriers (NC) who completed clinical evaluation, multimodal neuroimaging, and lumbar puncture for collection of cerebrospinal fluid (CSF) as part of their participation in DIAN were included in this study. Linear mixed effects models were used to determine differences in clinical, cognitive, and biomarker measures between the NC, TM, and CY groups. While both the CY and TM groups were found to have similarly elevated Aß compared to NC, TM carriers had greater cognitive impairment, smaller hippocampal volume, and elevated phosphorylated tau levels across the spectrum of pre-symptomatic and symptomatic phases of disease as compared to CY, using both cross-sectional and longitudinal data. As distinct portions of PSEN1 are differentially involved in APP processing by γ-secretase and the generation of toxic ß-amyloid species, these results have important implications for understanding the pathobiology of ADAD and accounting for a substantial portion of the interindividual heterogeneity in ongoing ADAD clinical trials.

Acute and subacute clinical markers after sport-related concussion in rugby union players.

OBJECTIVES: The purpose of this study was to investigate the relationship between on-field post-concussion symptoms reported by athletes, on-field neurological signs reported by a trainer or physician, and/or post-concussion symptoms 72 h after brain injury in male rugby players. DESIGN: Cross-sectional study in a Sports Concussion Clinic setting. METHODS: We enrolled 92 adult rugby union players, within the first 72 h after sport concussion. Four scales were measured. Immediate Concussion Sign Checklist (sideline); Immediate Concussion Symptom Checklist (24 h after concussion); Post-Concussion Symptoms Scale and Beck Depression Inventory (in-office 72 h after concussion). RESULTS: Odds ratios revealed that overtly symptomatic athletes were over 2.6 times more likely (p = 0.047) to exhibit post-traumatic amnesia than asymptomatic athletes. There were no differences in terms of on-field loss of consciousness or confusion. Immediate symptoms reported by athletes retrospectively were associated with symptoms reported on the Beck Depression Inventory (odds ratio 2.8; 95 % confidence interval 1.14-6.88), headache (odds ratio 4.9; 95 % confidence interval 1.92-12.79), memory concerns (odds ratio 3.15; 95 % confidence interval 1.06-9.34), pressure in the head (odds ratio 2.8; 95 % confidence interval 1.03-8.08), and visual disturbances (odds ratio 3.9; 95 % confidence interval 1.05-14.50) reported 72 h after sports concussion. CONCLUSIONS: Athletes who were overtly symptomatic after sports concussion were significantly more likely to experience post-traumatic amnesia and two or more on-field concussion signs relative to those athletes who were asymptomatic. Also, players with immediate symptoms reported higher depressive symptoms, somatic symptoms (headache and visual disturbances), and cognitive symptoms.

Utility of a Spanish version of Three Words-Three Shapes Test to detect memory impairment in primary progressive aphasia.

INTRODUCTION: Three Words-Three Shapes (3W3S) is a bedside test that assesses verbal and non-verbal memory and has proven useful in staging memory decline in amnestic disorders and primary progressive aphasia. Given its simple structure, the 3W3S can be easily adapted to other languages maintaining the original shapes and only modifying the words. We aim to validate a Spanish version of the 3W3S test and establish whether memory loss patterns present in amnesic disorders associated with Alzheimer's etiology and PPA were correctly characterized. METHOD: The translation and adaptation of the 3W3S were performed according to standardized guidelines and applied to a cohort of patients with Dementia of Alzheimer's type (DAT = 20), mild cognitive impairment (aMCI= 20), primary progressive aphasia (PPA = 20), and healthy controls (HC = 20). RESULTS: In verbal memory performance, PPA patients' score was lower than that of MCI and HC and similar to DAT's in the effortless encoding (p < 0.001), delayed recall (p < 0.001), and recognition (p < 0.012). For non-verbal performance, PPA patients performed better than DAT and similar to HC and MCI subjects (p < 0.001). CONCLUSIONS: Results show good applicability of 3W3S to determine memory function in PPA patients, independently from language ability. Visual and verbal components of memory are dissociated in PPA.

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.

Transient Global Amnesia Recurrence: Prevalence and Risk Factor Meta-analysis.

Background and Objectives: Transient global amnesia (TGA) is an acute amnestic disorder with unclear pathophysiology. Although considered a benign phenomenon, the possibility of a recurrence is a major concern for the patient. Our objective is to identify the prevalence and risk factors of relapse to help clinicians counsel patients about it. Methods: According to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidance, we screened 1,658 studies from MEDLINE, Lilacs, and Embase databases, published from 1985 to April 2021, in English or Spanish. We included 36 observational case-control and cohort studies that included patients with TGA according to the Caplan or Hodges and Warlow diagnostic criteria. We performed a meta-analysis with a random effect model for proportions and calculation of odds ratio (OR) for identified risk factors. Methodological quality was assessed according to the Newcastle-Ottawa scale. Results: We identified 4,514 TGA cases and 544 recurrence events (12.73%). A follow-up had no effect on its variance. We identified a statistically significant association between recurrence and sexual activity as a trigger, a personal history or current state of migraine and depression (OR 1,481 95% CI [1.0341-2.1222] p = 0.04; OR = 2.0795 95% CI [1.3892-3.1128] p = 0.003; and OR = 4.4871 95% CI [1.890-10.651] p = 0.0288, respectively). Discussion: The analysis showed that approximately 1 of 8 participants may experience recurrence, with an increased risk in the case of a history or current state of migraine, depression, or sexual intercourse before the event. A personal history of migraine and depression was associated with 2 and 4 times risk, respectively.

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.

Neuropsychological profile of Alzheimer's disease based on amyloid biomarker findings results from a South American cohort.

OBJECTIVE: Increased life expectancy and exponential growth of adults suffering from Alzheimer's disease (AD) worldwide, has led to biomarkers incorporation for diagnosis in early stages. Use of neuropsychological testing remains limited. This study aimed to identify which neuropsychological tests best indicated underlying AD pathophysiology. METHODS: One hundred and forty-one patients with MCI (Mild Cognitive Impairment) were studied. A neuropsychological test battery based on the Uniform Data Set (UDS) from the Alzheimer's Disease Centers program of the National Institute on Aging (NIA) was performed and amyloid markers recorded; according to presence or absence of amyloid identified by positive PIB-PET findings, or low CSF Aß42 levels, patients were separated into MCI amyloid-(n:58) and MCI amyloid + (n = 83) cases. RESULTS: Statistical differences were found in all memory tests between groups. Delayed recall score at thirty minutes on the Rey Auditory Verbal Learning Test (AVLT) was the best predictor of amyloid pathology presence (AUC 0.68), followed by AVLT total learning (AUC 0.66) and AVLT Recognition (AUC 0.59) scores, providing useful cut off values in the clinical setting. CONCLUSIONS: Use of neuropsychological testing, specifically AVLT scores with cutoff values, contributed to the correct diagnosis of MCI due to AD in this SouthAmerican cohort.

Spanish version of the Frontotemporal Dementia Knowledge Scale: adaptation and validation.

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.

Theory of mind, emotion recognition and emotional reactivity factors in early multiple sclerosis: Results from a South American cohort.

OBJECTIVES: To study different components of social cognition and quality of life in patients with early multiple sclerosis and low Expanded Disability Status Scale and to test the influence of cognitive performance, fatigue and neuropsychiatric symptoms on social cognition performance. METHODS: Thirty-four patients with relapsing-remitting MS, with ≤2 years of disease duration and scores ≤2 on the EDSS and 30 healthy controls underwent neuropsychological assessment with the Brief Repeatable Neuropsychological Test Battery. Components of social cognition, such as emotion recognition, theory of mind, empathy, and emotional reactivity, were assessed with the Reading the Mind in the Eyes test, the Faux Pas task, the International Affective Imagery System, and the Empathy Quotient. Anxiety, depression, fatigue and quality of life were measured. RESULTS: Patients showed significant differences in verbal memory, executive functions and social cognition, especially emotion recognition and ToM. Regarding emotional reactivity, patients showed a positive bias in the interpretation of the valence of neutral images. CONCLUSIONS: Patients with early MS showed impairments in several components of social cognition independent of cognitive performance, neuropsychiatric symptoms and fatigue. Social cognition deficits may be present in MS even in the early stages.

[Spanish Norms for Mini-SEA (Mini Social Cognition and Emotional Assessment) in adults in Buenos Aires]. / Baremos en español del Mini-SEA (Mini Social Cognition and Emotional Assessment) en adultos normales de Buenos Aires.

INTRODUCTION AND OBJECTIVE: The Mini-SEA is a quick and brief cognitive assessment test developed to study social cognition. It consists of a modified version of the faux pas Test and an emotional recognition test based on Ekman's faces. The objective of this work was to obtain the first Spanish Speaking norms for the Mini-SEA test. MATERIAL AND METHODS: 64 healthy volunteers, between 35 and 80 years old, were recruited and evaluated with the Mini-SEA by specialized neuropsychologists from the Cities of Buenos Aires and La Plata, both in the Province of Buenos Aires, Argentina. RESULTS: The total mean (M) of the Mini-SEA was 25 +/- 4. The M of the faux pas Score was 12.5 +/- 2.4 and the M of the Emotional Recognition Score was 12.8 +/- 1.5. The sample was divided into 4 age groups: Group 1 (<50 years), Group 2 (50-59 years), Group 3 (60-69 years) and Group 4 (more than 70 years). Differences were found in the age continuum in the Emotional Recognition score between group 1 and 4 (p <0.05) and between group 3 and 4 (p <0.01), but not in the Faux Pas Score. CONCLUSION: This study presents the first normative values of the Mini-SEA Social Cognition test for a Spanish-speaking population. The Mini-SEA, being a quick and easy to administer test, allows the study of social cognition in an adequate and precise way, especially in prodromal stages of neurodegenerative diseases.

Impact of Social Isolation on People with Dementia and Their Family Caregivers.

BACKGROUND: People with dementia and their family caregivers may face a great burden through social isolation due to the COVID-19 pandemic, which can be manifested as various behavioral and clinical symptoms. OBJECTIVE: To investigate the impacts of social isolation due to the COVID-19 pandemic on individuals with dementia and their family caregivers. METHODS: Two semi-structured questionnaires were applied via telephone to family caregivers of people diagnosed with dementia in three cities in Argentina, Brazil, and Chile, in order to assess clinical and behavioral changes in people with dementia and in their caregivers. RESULTS: In general, 321 interviews were conducted. A significant decline in memory function has been reported among 53.0%of people with dementia. In addition, 31.2%of individuals with dementia felt sadder and 37.4%had increased anxiety symptoms. These symptoms of anxiety were greater in individuals with mild to moderate dementia, while symptoms of agitation were greater in individuals with severe dementia. Moreover, compulsive-obsessive behavior, hallucinations, increased forgetfulness, altered appetite, and increased difficulty in activities of daily living were reported more frequently among individuals with moderate to severe dementia. Caregivers reported feeling more tired and overwhelmed during this period and these symptoms were also influenced by the severity of dementia. CONCLUSION: Social isolation during the COVID-19 pandemic triggered a series of negative behavioral repercussions, both for people with dementia and for their family caregivers in these three South American countries.

Environmental factors between normal and superagers in an Argentine cohort.

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.

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.

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" .

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.

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.

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.

Driving and Alzheimer's disease: A neuropsychological screening battery for the elderly.

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.

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.