Passando de demencias neurodegenerativas para proteinopatias cognitivas, substituindo ''onde'' por ''0 que''…

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.Fil: Allegri, Ricardo Francisco. Universidad de la Costa; Colombia. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Instituto de Neurociencias - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Neurociencias; Argentin

Cerebrolysin improves symptoms and delays progression in patients with alzheimer's disease and vascular dementia

Dementia is the result of various cerebral disorders, leading to an acquired loss of memory and impaired cognitive ability. The most common forms are Alzheimer´s disease(AD) and vascular dementia (VaD). Neurotrophic factors are essential for the survival and differentiation of developing neurons and protecting them against damage under pathologic conditions. Cerebrolysin is a peptide preparation that mimics the pleiotropic effects of neurotrophic factors Several clinical trials investigating the therapeutic efficacy of Cerebrolysin in AD and VaD have confirmed the proof of concept. The results of these trials have shown statistically significant and clinically relevant treatment effects of Cerebrolysin on cognitive, global and functional domains in mild to moderately severe stages of dementia. Doses of 10 and 30 mL were the most effective, but higher doses of up to 60 mL turned out to be most effective in improving neuropsychiatric symptoms, which become relevant at later stages of the disease. Combining treatment with cholinesterase inhibitors and Cerebrolysin indicated long-term synergistic treatment effects in mild to moderate AD. The efficacy of Cerebrolysin persisted for up to several months after treatment suggesting Cerebrolysin has not merely symptomatic benefits, but a disease-delaying potential. This paper reviews the clinical efficacy of Cerebrolysin in the treatment of dementia. Data were obtained from international, multicenter, randomized clinical trials performed in compliance with Good Clinical Practice and the principles of the Declaration of Helsinki (1964) and subsequent revisions.Fil: Allegri, Ricardo Francisco. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; ArgentinaFil: Guekht, A.. Russian National Research Medical University; Rusi

A systematic review and meta-analysis of the diagnostic accuracy of the Phototest for cognitive impairment and dementia

The recently developed Phototest is a simple, easy and very brief test for detecting cognitive impairment or dementia. Objective: To evaluate the diagnostic accuracy of the Phototest for detecting cognitive impairment or dementia. METHODS: We used a manually created database to search for studies evaluating the Phototest diagnostic yield and performed an initial meta-analysis to determine sensitivity (Sn) and specificity (Sp) of diagnostic parameters. We also performed a second meta-analysis of individual participant data. RESULTS: In total, 6 studies were included in the meta-analysis. For dementia, Sn was 0.85 (95% CI, 0.82-0.88) and Sp 0.87 (95% CI, 0.85-0.99); for cognitive impairment, Sn was 0.80 (95% CI, 0.77-0.92) and Sp 0.88 (95% CI, 0.86-0.90). In the individual data meta-analysis, 1565 subjects were included, where best cut-off points for dementia and for cognitive impairment were 26/27 (Sn=0.89 (95% CI 0.85-0.91), Sp=0.84 (95% CI, 0.82-0.91)) and 28/29 (Sn=0.79 (95% CI, 0.76-0.81), Sp=0.88 (95% CI, 0.86-0.90)), respectively. CONCLUSION: Phototest has good diagnostic accuracy for dementia and cognitive impairment. It is brief, simple and can be used in illiterate persons. This makes it suitable for use in primary care settings and/or in subjects with low educational level.Phototest é um teste simples, fácil e muito rápido para detecção de comprometimento cognitivo e demência recentemente desenvolvido. Objetivo: Avaliar a acurácia diagnostica do Phototest para detecção de comprometimento cognitivo e demência. MÉTODOS: Nós usamos um banco de dados manualmente criado para estudos que avaliassem a capacidade diagnóstica do Phototest e realizamos uma meta-análise para determinar a sensibilidade (Sn) e especificidade (Ep) dos parâmetros diagnósticos. Nós também realizamos uma segunda meta-análise dos dados individuais dos participantes. RESULTADOS: Um total de seis estudos foram incluídos na meta-análise. Para demência a Sn foi 0.85 (95% CI, 0,82-0,88) e Ep 0,87 (95% CI, 0,85-0,99); para comprometimento cognitivo a Sn foi 0,80 (95% CI, 0,77-0,92) e Sp 0,88 (95% CI, 0,86-0,90). Na meta-análise de dados individuais, 1565 foram incluídos, os melhores escores de corte para demência e para comprometimento cognitivo foram 26/27 (Sn=0,89 (95% CI 0,85-0,91), Ep=0,84 (95% CI, 0,82-0,91)) e 28/29 (Sn=0,79 (95% CI, 0,76-0,81), Ep=0,88 (95% CI, 0,86-0,90)), respectivamente. CONCLUSÃO: Photest tem boa acurácia diagnostica para demência e comprometimento cognitivo. É breve, simples e pode ser usado em pessoas analfabetas. Tornando-o apropriado para o uso em cuidados primários e/ou sujeitos com baixo nível educacional.Fil: Carnero Pardo, Cristobal. Hospital Universitario Virgen de Las Nieves; España. Fidyan Neurocenter; EspañaFil: Lopez Alcalde Samuel. Fidyan Neurocenter; España. Hospital Universitario Virgen de Las Nieves; EspañaFil: Allegri, Ricardo Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas ; ArgentinaFil: Russo, María Julieta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas ; Argentin

Neuropsychological Battery Uniform Data Set (UDS) for the evaluation of Alzheimer's disease and mild cognitive impairment: A systematic review

La batería neuropsicológica UDS (del inglés Uniform Data Set), se usa a nivel mundial para homogeneizar las investiga- ciones 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.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.Fil: Porto, Maria Fernanda. Universidad De La Costa; ColombiaFil: Russo, María Julieta. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Allegri, Ricardo Francisco. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad De La Costa; Colombi

Cognitive intervention in mild cognitive impairment: A review

Las intervenciones de entrenamiento, estimulación y rehabilitación cognitiva representan una opción no farmacológica de tratamiento para las diferentes causas de trastornos en las funciones mentales superiores y de demencia. El Deterioro Cognitivo Leve constituye un estadío intermedio entre el envejecimiento normal y la demencia y confiere un riesgo incrementado de progresión. Existen diferentes subtipos de Deterioro Cognitivo Leve en base a las funciones cognitivas comprometidas, siendo la variante amnésica la más frecuente. Se revisaron los trabajos que exploraron la utilidad y eficacia del entrenamiento, la estimulación y la rehabilitación cognitiva en el Deterioro Cognitivo Leve. Pese a la gran variabilidad en los diseños, en los tipos de intervenciones, en la duración de los tratamientos y en las variables consideradas, en la gran mayoría de las publicaciones se encontró un efecto beneficioso en diferentes medidas tenidas en cuenta. En ninguno de los trabajos se reportó una respuesta desfavorable. Resulta necesario profundizar el estudio de estas intervenciones mediante una metodología más homogénea para determinar el real grado de relevancia en la mejoría de los trastornos de los pacientes así como en el eventual retardo en la evolución a demencia en cada uno de los subtipos sindromáticos y etiológicos del Deterioro Cognitivo Leve.Cognitive intervention involves training, stimulation and rehabilitation of higher brain functions, and stands as a non pharmacological treatment option for patients with cognitive symptoms and dementia. Mild Cognitive Impairment is a syndrome that appears to capture a group of individuals in a transitional state between normal aging and dementia. Patients with Mild Cognitive Impairment have a higher risk of progression to dementia. There are different subtypes of Mild Cognitive Impairment taking in consideration the cognitive domains that are affected, being the amnestic subtype the most common. This review examines the publications that explored the utility and efficacy of cognitive intervention in patients with Mild Cognitive Impairment. Although there is great variability in the studies design, in the type of intervention, in the treatment length and in the outcome measures selected, the majority of the papers reviewed reported a beneficial effect of the intervention, and none of them found an unfavorable result. Further adequately designed studies of cognitive treatment interventions in the different Mild Cognitive Impairment subtypes are needed to evaluate their potential benefits in ameliorating the patients’ symptoms and in reducing the rate of progression to dementia.Fil: Demey, Ignacio. Instituto de Neurociencias Buenos Aires; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; ArgentinaFil: Allegri, Ricardo Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Neurociencias Buenos Aires; Argentina. Pontificia Universidad Católica Argentina "Santa María de los Buenos Aires"; Argentina. Centro de Educación Médica e Investigaciones Clínicas "Norberto Quirno"; Argentin

Background of the Sociedad Neurológica Argentina: Current state and concerns about neurologic education

Neurology in Argentina emerged toward the end of the 19th century, following the origin of the specialty in Europe. Its development can be divided into 3 periods. The first is the specialty of neurology as part of internal medicine. Doctoral theses and publication about neurologic topics are found early in the history of medicine, but merged into internal medicine. The second period is the foundation of clinical neurology under the typical European influence, mainly French, when the first neurologists appear. This period started in 1885 with the creation of the Hospital San Roque de Buenos Aires' first nervous diseases department. Its first chair was José María Ramos Mejía, MD. In 1887, 5 years after Jean-Martin Charcot was awarded the chair of neurology at the Salpêtrière in Paris, Ramos Mejía became the first professor of neurology in South America, at the University of Buenos Aires. The third period is the emergence of subspecialty practices. During the 1970s—reflecting the North American influence—there was a new paradigm favoring the division of different disciplines. Specialists in epilepsy, stroke, headache, dementia, and multiple sclerosis, among others, began to emerge.Fil: Correale, Jorge. Fundación Para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; ArgentinaFil: Allegri, Ricardo Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Centro Neurológico Tucumán. Departamento de Neurología; ArgentinaFil: Pelli Noble, Raúl Federico. Fundación Para la Lucha Contra las Enfermedades Neurológicas de la Infancia. Instituto de Investigaciones Neurológicas "Raúl Carrea"; Argentin

Estado del arte del proyecto

La Enfermedad de Alzheimer (EA), es pérdida paulatina de las funciones cognitivas que generan un deterioro significativo en las actividades de la vida diaria, el diagnóstico temprano determina el curso y evolución. La presente investigación pretende realizar una validación de la batería neuropsicológica Uniform Data set (UDS-3) en población colombiana con demencia tipo Alzheimer. La batería UDS, desarrollada por un grupo de NACC, está batería evalúa el cambio de las personas con deterioro cognitivo y los normales, el cual tiene como propósito detectar de manera temprano el deterioro cognitivo y unificar datos a nivel mundial, para contribuir con los datos internacionales de Alzheimer. Es un instrumento reconocido y comúnmente usado en investigaciones de biomarcadores, la versión 3 se inició a usar en el 2015, está incorpora los criterios NIA-AA para la demencia de Alzheimer, un diagnóstico de lesión cerebral vascular, así como una forma más detallada de historia familiar y una batería neuropsicológica actualizada. En este estudio con diseño instrumental participaran 384 personas, divididos en dos grupos 192 grupo control (sanos) y192 grupo de estudio (pacientes con Alzheimer, la proporción será 1:1 hombres-mujeres, con edades entre <60 y 90+,de 1 a más 19 años de formación académica. Se pretende establecer la validez, confiabilidad, especificad y sensibilidad de la prueba para población colombiana, así como la creación de un algoritmo clínico que determine el curso del Alzheimer en población colombiana, para evidenciar el curso presintomático de la enfermedad

Living with dementia: increased level of caregiver stress in times of COVID-19

COVID-19 pandemic has deeply affected the care that older adults with Alzheimer´s Disease(AD) and related disorders received in Argentina. Even though circulation for familycaregivers of subjects with dementia was one of the few exceptions allowed by thegovernment (Ministerio de la Nación, 2020), we observed that most family members decidedto stop visiting their relatives from fear of spreading the disease.COVID-19 epidemic is causing a radical change in the model of dementia care. Before thispandemic, engaging in social activities, performing cognitive and physical activities, andhaving a productive daily routine has been the mainstay therapy. (Austrom, M. G. et al.,2018). To relief caregiver stress, literature has shown that multicomponent strategies suchas avoiding isolation, attending family and group support meetings, sharing the burden ofcare with other family members were useful (Hughes, T.B. et al., 2014). Now, in times ofCOVID-19, we recommend the most strict social isolation, especially for older patients withdementia and other comorbidities who have the highest risk for severe COVID-19 diseaseand mortality. ( Emami et al., 2020).Previous quarantines in human history had a negative psychological impact on outcomessuch as anger, depression, and loneliness in the general population. (Brooks et al., 2020)but the effects on the wellbeing and standard care of subjects with dementia living in thecommunity is not well studied. The objective of our research was to study to what extendmandatory social isolation affected the stress and burden of care of family members caringfor subjects with dementia after the initial four weeks of quarantine and to study therelationship between the severity of the dementia, measured with the Clinical DementiaRating (CDR) (Hughes, C. et al. 1982) and the impact of the negative effects of quarantinein our setting.Fil: Cohen, Gabriela. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Russo, María Julieta. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Campos, Jorge A. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Allegri, Ricardo Francisco. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

COVID-19 Epidemic in Argentina: Worsening of Behavioral Symptoms in Elderly Subjects With Dementia Living in the Community

In Argentina, the quality of care that elderly subjects with dementia living in the community received has been deeply affected by COVID-19 epidemic. Our objective was to study to what extend mandatory quarantine imposed due to COVID-19 had affected behavioral symptoms in subjects with dementia after the first 8 weeks of quarantine. We invited family members to participate in a questionnaire survey. The sample consisted of family caregivers (n = 119) of persons with AD or related dementia living at home. We designed a visual analog scale to test the level of the burden of care of family members. Items inquired in the survey included type and setting (home or day care center) of rehabilitation services (physical/occupational/cognitive rehabilitation) and change in psychotropic medication and in behavioral symptoms that subjects with dementia experienced before and during the epidemic. Characteristics of people with dementia and their caregivers were analyzed with descriptive statistics using the chi-square tests, p < 0.01 was considered significant. Results: The sample included older adults with dementia. Mean age: 81.16 (±7.03), 35% of the subjects had more than 85 years of age. Diagnosess were 67% Alzheimer´s dementia and 26% mixed Alzheimer´s disease (AD). Stages were 34.5% mild cases, 32% intermediate stage, and 33% severe cases as per Clinical dementia Rating score. In 67% of the sample, a family member was the main caregiver. Important findings were increased anxiety (43% of the sample), insomnia (28% of the subjects), depression (29%), worsening gait disturbance (41%), and increase use of psychotropics to control behavioral symptoms. When we compared the frequency of behavioral symptoms within each dementia group category, we found that anxiety, depression, and insomnia were more prevalent in subjects with mild dementia compared to subjects with severe dementia. We analyzed the type and pattern of use of rehabilitation services before and during the isolation period, and we observed that, as a rule, rehabilitation services had been discontinued in most subjects due to the quarantine. We concluded from our analysis that during COVID-19 epidemic there was a deterioration of behavioral symptoms in our population of elderly dementia subjects living in the community. Perhaps, our findings are related to a combination of social isolation, lack of outpatient rehabilitation services, and increased stress of family caregivers. It is necessary to develop a plan of action to help dementia subjects deal with the increased stress that this epidemic imposed on them.Fil: Cohen, Gabriela. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Russo, María Julieta. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Campos Tapia, Jorge Andrés. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Allegri, Ricardo Francisco. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Changes in the Care of Neurological Diseases During the First Wave of the COVID-19 Pandemic: A Single Private Center Study in Argentina

Introduction: Healthcare systems are struggling to cope with the rapid evolution of the COVID-19 pandemic. In Argentina, the pandemic is advancing despite prolonged lockdown measures. We aim to analyze the impact of the easing of lockdown measures in the number of visits to the emergency department (ED), and outpatient consultations (OC) to a tertiary neurological center. Methods: We compared the number of ED visits with the social mobility overtime. We also compared the number of OC, and the geographic distribution of patients' addresses between 2019 and 2020. Results: ED visits decreased 48.33% (n = 14,697 in 2019 vs. n = 7,595 in 2020). At the beginning of the lockdown, the social mobility decreased in pharmacies/groceries, and workplaces, along with a reduction in the number of ED visits. With the easing of lockdown restrictions, the social mobility decreased in residential places, slightly increased in workplaces and almost return to normal in pharmacies/groceries. Variations in ED visits correlate better with social mobility in workplaces (coef. =0.75, p < 0.001) than in groceries/pharmacies (coef. =0.68, p < 0.001). OC decreased 43%. Fourteen percent of OC were tele consults. This was associated with an increase of the geographical area of influence of our center (standard distance of 109 km in 2019 and 127 km in 2020). Conclusions: Despite an increase in social mobility, the number of ED visits and OC to an Argentinian tertiary neurological center remain worrisomely low. The pandemic catalyzed the introduction of telemedicine in our country. This has also allowed patients from distant zones to gain access to specialized neurological care.Fil: Calandri, Ismael L.. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Hawkes, Maximiliano Alberto. University of Nebraska; Estados UnidosFil: Marrodan, Mariano. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Ameriso, Sebastian Francisco. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Correale, Jorge. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; ArgentinaFil: Allegri, Ricardo Francisco. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia. Instituto de Neurociencias - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Neurociencias; Argentin