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The Alzheimer's Disease Neuroimaging Initiative (ADNI) has fostered collaboration among researchers around the world, catalyzing innovation and accelerating progress in the field. In Latin America, this initiative advanced the validation and development of Alzheimer's disease biomarkers for the first time in our region. In 2011, as part of the international ADNI, Argentina-ADNI (Arg-ADNI) was founded. The following years were characterized by strong support from entities such as the Alzheimer's Association, transforming into the emergence of several multinational studies focusing on prevention and diagnosis, and treatment of dementias. These studies are heirs to the tradition of Arg-ADNI: the Dominantly Inherited Alzheimer Network, Latin American Initiative for Lifestyle Intervention to Prevent Cognitive Decline, Longitudinal Early-Onset Alzheimer's Disease Study, and Initiative for the Study of Down Syndrome and Alzheimer's Disease. These initiatives have contributed significantly to the development of regional research and serve as essential tools for health policy planning in Latin America. HIGHLIGHTS: In Latin America, the Alzheimer's Disease Neuroimaging Initiative (ADNI) advanced the validation and development of Alzheimer's disease biomarkers for the first time in our region. ADNI has been the basis that boosted several multinational studies focusing on both prevention and diagnosis, and treatment of dementias (Dominantly Inherited Alzheimer Network, LatAm-FINGER, LEADS). These initiatives with the support from the Alzheimer's Association have contributed significantly to the development of regional research This is an example of collaboration between high-income countries with low- and middle-income countries aimed at global scientific development and inclusion.

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PURPOSE: Neoadjuvant chemotherapy has recently become the standard of care for borderline resectable pancreatic ductal adenocarcinoma (PDAC), and there have even been numerous reports evaluating its potential benefits in resectable PDAC. However, neoadjuvant therapy first requires a histological or cytological diagnosis. This study aimed to analyze the safety and diagnostic yield of CT-guided core needle biopsy (CNB). MATERIAL AND METHODS: A retrospective analysis of patients with pancreatic tumor requiring a CNB during the period 2015 to 2023 were included. Biopsies were performed with an 18-20 G Tru-Core needle using a coaxial system and automatic biopsy gun. Demographics, procedural variables, postoperative outcomes, and histological results were analyzed. RESULTS: A total of 43 pancreatic biopsies were performed in 42 patients. The mean age was 60 years (35 to 81 y), and 24 (56%) were males. Tumors were more frequently localized in the head (42%) and body (42%) of the pancreas. The mean size of the pancreatic lesions was 53.77 mm (17 to 181 mm) and the mean number of samples per biopsy was 4 (1 to 12). Most procedures were performed via direct access (81%). No major complications were observed. Histological diagnosis was obtained in 40 (93%) patients, with a sensitivity of 93%, specificity of 100% and an overall accuracy rate of 93%. The probability of performing a molecular diagnostic test increased with the year of biopsy (OR 3.34, 95% CI 1.33-8.40, P=0.01). CONCLUSIONS: CNB is an efficient and safe method for obtaining high-quality material. This approach could be essential as molecular profiling continues to improve the diagnosis, prognosis, and treatment of PDAC.

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INTRODUCTION: While Latin America (LatAm) is facing an increasing burden of dementia due to the rapid aging of the population, it remains underrepresented in dementia research, diagnostics, and care. METHODS: In 2023, the Alzheimer's Association hosted its eighth satellite symposium in Mexico, highlighting emerging dementia research, priorities, and challenges within LatAm. RESULTS: Significant initiatives in the region, including intracountry support, showcased their efforts in fostering national and international collaborations; genetic studies unveiled the unique genetic admixture in LatAm; researchers conducting emerging clinical trials discussed ongoing culturally specific interventions; and the urgent need to harmonize practices and studies, improve diagnosis and care, and use affordable biomarkers in the region was highlighted. DISCUSSION: The myriad of topics discussed at the 2023 AAIC satellite symposium highlighted the growing research efforts in LatAm, providing valuable insights into dementia biology, genetics, epidemiology, treatment, and care.

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PURPOSE: Rectum sheath hematoma (RSH) is a rare and often misdiagnosed disease. We aimed to determine outcomes of patients affected by RSH and identify variables associated with the need of prompt intervention. METHODS: Patients diagnosed with RSH during the period 2012-2020 were retrospectively identified. Demographics, diagnostic, and therapeutic variables were evaluated. RSH was classified with computed tomography (CT) according to the Berna system. An artificial neural network (ANN) model including 12 variables was used to identify patients that might require a prompt endovascular or surgical treatment. RESULTS: A total of 20 patients were included for analysis; mean age was 69 (35-98) years and 14 (70%) were females. Iatrogenic injury and forceful contraction of the abdominal wall were the leading causes of RSH. Eleven (55%) patients were anticoagulated or antiaggregated. There were 3 (15%) grade 1, 5 (25%) grade 2, and 12 (60%) grade 3 RSH; 6 (30%) were treated conservatively, 10 (50%) with artery embolization, and 4 (20%) with surgery. Overall morbidity was 45% and there was no mortality in the series. According to the ANN, patients at high risk of requiring an invasive treatment were those with active extravasation on CT angiography, Berna grade III, age ≥ 65 years, hemodynamic instability, chronic use of corticosteroids, hematoma volume ≥ 1000 mL, and/or transfusion of ≥ 4 units of red blood cells. CONCLUSION: Conservative treatment might be effective in selected patients with RSH. Our artificial neural network analysis might help selecting patients who require endovascular or surgical treatment.

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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.

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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.

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Alzheimer's disease is, by far the first, cause of dementia and the more frequent neurodegenerative disease. Considered as a result of multifactorial causes, aging is the main risk factor for the classical form of the disease and because of global aging, a very significant increase in the prevalence is expected in the upcoming decades, especially in countries in development. Several drugs with different targets have been tried so far and, still with no success. Frenzied efforts seeking a new disease-modifying drug are constantly being pursued and innovative models of the clinical trials have emerged. The DIAN initiative studies individuals with known mutations in the deterministic genes of the disease. Au-tosomal Dominantly Alzheimer Disease (ADAD) showed to be a more predictable model in terms of whom and when will get the disease. This allows testing novel therapeutics agents by choosing the drug according to the biological mo-ment of the disease. But ADAD is also a uniquely human story full of courage and hope. The DIAN trial has started in Argentina and a new anti-tau age has begun as well.

La enfermedad de Alzheimer es por mucho, la primera causa de demencia y la enfermedad neurodegenerativa más frecuente. Considerada como resultado de causas multifactoriales, el envejecimiento sigue siendo el principal factor de riesgo en su forma clásica y debido al envejecimiento global, se espera un aumento muy significativo de la prevalencia en las próximas décadas, especialmente en los países en desarrollo. Hasta ahora se han probado numerosos fármacos con diferentes dianas aunque aún sin éxito. Constantemente se realizan descomunales estudios en busca de un nuevo fármaco que logre modificar el destino de la enfermedad y así han surgido innovadores modelos de ensayos clínicos. La iniciativa DIAN estudia individuos con mutaciones conocidas en los genes determinantes de la enfermedad. La en-fermedad de Alzheimer autosómica dominante (ADAD) demostró ser un modelo más predecible en términos de quién y cuándo contraerá la enfermedad. Esto permite probar nuevos agentes terapéuticos eligiendo el fármaco según el mo-mento biológico de la enfermedad. Pero ADAD es también una historia muy humana llena de coraje y esperanza. El ensayo DIAN ha comenzado en Argentina y también ha comenzado una nueva era anti-tau.

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RESUMEN Antecedentes: el dolor inguinal crónico posoperatorio representa una complicación que altera la ca lidad de vida después de la hernioplastia inguinal. Su incidencia es variable con informes de hasta el 16%. Objetivo: describir el tratamiento y los resultados en pacientes con dolor inguinal crónico luego de una hernioplastia inguinal con malla. Material y métodos: estudio descriptivo, observacional y retrospectivo. Se definió como dolor ingui nal crónico posoperatorio la presencia de dolor inguinal por daño nervioso o afectación del sistema somatosensorial tisular que persiste por más de 6 meses luego de la cirugía inicial. Se revisaron las historias clínicas de los pacientes que cursaban el posoperatorio de hernioplastia inguinal convencio nal y laparoscópica en el período 2010-2018. Se realizó la encuesta EuraHS Quality of life score antes y después del abordaje terapéutico multidisciplinario para evaluar cambios en el dolor y restricción de la actividad física. Los resultados fueron analizados y comparados. Resultados: se identificaron 8 pacientes con dolor inguinal crónico posoperatorio grave. El 100% fue evaluado por el Servicio de tratamiento del dolor y requirieron 3 o más fármacos para manejo del do lor. Posteriormente requirieron bloqueo guiado por tomografía computarizada a causa de la persisten cia de los síntomas. Se realizaron 3 (50%) exploraciones quirúrgicas con retiro de material protésico y 2 triples neurectomías. Se observó una disminución estadísticamente significativa (p < 0,05) en el dolor en reposo, dolor durante la actividad y dolor que experimentaron en la última semana. Conclusión: el abordaje multidisciplinario y escalonado permitiría seleccionar a los pacientes que se beneficiarán con el tratamiento quirúrgico.

ABSTRACT Background: Chronic postoperative inguinal pain represents a complication that alters the quality of life after inguinal hernioplasty. Its incidence is variable with reports of up to 16%. Objective: To describe the treatment and results in patients with chronic inguinal pain after an inguinal hernioplasty with mesh. Material and methods: Descriptive, observational and retrospective study. The postoperative chronic inguinal pain was defined as the presence of inguinal pain due to nerve damage or involvement of the somatosensory tissue system that persists for more than 6 months after the initial surgery. The medical records of patients in the postoperative period of conventional and laparoscopic inguinal hernioplasty in the period 2010-2018 were reviewed. The EuraHS Quality of life score pre and post multidisciplinary therapeutic approach was used to evaluate changes in pain and restriction of physical activity. The results were analyzed and compared. Results: 8 patients with severe chronic postoperative inguinal pain were identified. 100% were eva luated by the pain management service and required 3 or more drugs for pain management. Sub sequently, they required block guided by computed tomography due to persistence of symptoms. 3 (50%) surgical examinations were performed with removal of prosthetic material and 2 triple neurec tomies. A statistically significant decrease (p <0.05) was observed in pain at rest, pain during activity and pain experienced in the last week. Conclusion: The multidisciplinary and step up approach would allow selecting the patients who will benefit from the surgical treatment.

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PURPOSE: To describe results of the Amyloid, Tau, Neurodegeneration (ATN) research framework classification in the Argentine-Alzheimer's Disease Neuroimaging Initiative (arg-ADNI) cohort. METHODS: Twenty-three patients with mild cognitive impairment (MCI), 12 dementia of Alzheimer's type (DAT), and 14 normal controls were studied following the ADNI2 protocol. Patients were categorized according to presence or absence of the biomarkers for amyloid beta (Aß; A: amyloid positron emission tomography [PET] scan or cerebrospinal fluid [CSF] Aß42), tau (T: CSF phosphorylated-tau), and neurodegeneration (N: CSF total-tau, fluorodeoxyglucose [FDG]-PET scan, or structural magnetic resonance imaging [MRI] scan). RESULTS: A+T+N+ biomarker profile was identified at baseline in 91% of mild dementia patients, 20% of early MCI patients, 46% of late MCI patients, and 14% of control subjects. Suspected non-AD pathophysiology (SNAP, A-T-N+) was found in 8% of mild dementia, 20% of early MCI, 15% of late MCI, and 7% of control subjects. Conversion rates to dementia after 5-year follow-up were 85% in A+T+N+ MCI patients and 50% in A-T-N+ patients. CONCLUSIONS: We present initial 5-year follow-up results of a regional ADNI based on AD biomarkers and the ATN classification.

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Mutations in PSEN1 are the most common cause of early-onset Alzheimer's disease (AD). In this article, we present an Argentine family with autosomal dominant early- and late-onset AD. The proband and 6 family members were available for genetic testing and clinical and neuropsychological assessments. Cerebrospinal fluid biomarkers were analyzed in the proband and a cousin (mutation carrier), who also underwent positron emission tomography using F-18-2-fluoro-2-deoxy-D-glucose and Pittsburgh compound B. Exon sequencing of PSEN1, PSEN2, and APP revealed a novel heterozygous variant in PSEN1 (c.356C>T; p.T119I). Median age of onset in the family was 56 years. However, the proband's uncle showed initial symptoms at age 71. Although no DNA was available, he was an obligate carrier because his daughter (proband's cousin) carried the mutation. Both the proband and his cousin exhibited biomarker evidence (cerebrospinal fluid or imaging) of underlying Alzheimer's pathology. Overall, our results support that the PSEN1 p.T119I variant is likely pathogenic.

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Alzheimer disease (AD) is one of the major unresolved health burdens accompanying the increase in life expectancy. The great paradigm shift for this disease has resulted from finding amyloid deposition and neurobrillary degeneration 20 years and 10 years, respectively, prior to onset of the typical clinical memory loss symptoms. The advent of AD biomarkers has enabled a molecular definition of AD, making the clinical definition almost dispensable. Various types of AD biomarkers are available in our country. Each biomarker reflects a particular process and stage of the disease. Although costs restrict their use, the biomarker analysis may be justified in certain clinical scenarios, such as an early onset or an atypical presentation of the disease. Today, the usefulness of biomarkers in AD clinical research is beyond question. Furthermore, the introduction of biomarkers into medical practice has led to significant changes in therapeutic interventions, even in the absence of disease-modifying drugs.

La enfermedad de Alzheimer (EA) es uno de los mayores flagelos aún no resueltos que acompañan al aumento de la expectativa de vida. El gran cambio de paradigma en los últimos años fue consecuencia de descubrir que el depósito amiloideo se presenta hasta 20 años antes, y la degeneración neurofibrilar hasta 10 años antes, de que aparezca la sintomatología clínica típica de pérdida de memoria. La aparición de los biomarcadores permitió reestructurar el concepto de la EA, intentándose llegar a una definición molecular de la misma casi prescindiendo de la emblemática clínica. Existen distintos tipos de biomarcadores de EA disponibles en nuestro país. Cada uno nos habla de un proceso y un momento distinto de la enfermedad. Aunque su uso clínico aún se encuentra restringido por cuestiones de costos, existen escenarios particulares en donde sí se justifica, casi siempre en relación a presentaciones clínicas atípicas o de comienzo muy temprano. Sin embargo, hoy en día ya nadie discute que son imprescindibles en investigaciones clínicas sobre EA. La incorporación de biomarcadores en la práctica médica ha generado cambios significativos en la intervención terapéutica de los pacientes, incluso en un contexto en el que todavía no hay medicamentos modificadores de la enfermedad.

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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.

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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.

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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.

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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%.

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Frontotemporal lobar degeneration is a neuropathological disorder that causes a variety of clinical syndromes including frontotemporal dementia (FTD), progressive supranuclear palsy, and corticobasal syndrome (CBS). FTD associated with parkinsonism occurs frequently as a result of mutations in the C9orf72 gene and also in the genes coding for the protein associated with microtubule tau (MAPT) and progranulin (GRN) on chromosome 17 (FTDP-17). Herein, we report an Argentinean family, of Basque ancestry, with an extensive family history of behavioral variant of FTD. Twenty-one members over 6 generations composed the pedigree. An extensive neurologic and neurocognitive examination was performed on 2 symptomatic individuals and 3 nonsymptomatic individuals. Two different phenotypes were identified among affected members, CBS in the proband and FTD in his brother. DNA was extracted from blood for these 5 individuals and whole-exome sequencing was performed on 3 of them followed by Sanger sequencing of candidate genes on the other 2. In both affected individuals, a missense mutation (p.P301L; rs63751273) in exon 10 of the MAPT gene (chr17q21.3) was identified. Among MAPT mutations, p.P301L is the most frequently associated to different phenotypes: (1) aggressive, symmetrical, and early-onset Parkinsonism; (2) late parkinsonism associated with FTD; and (3) progressive supranuclear palsy but only exceptionally it is reported associated to CBS. This is the first report of the occurrence of the p.P301L-MAPT mutation in South America and supports the marked phenotypic heterogeneity among members of the same family as previously reported.

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PURPOSE: Argentina-Alzheimer's Disease Neuroimaging Initiative (Arg-ADNI) is the first ADNI study to be performed in Latin America at a medical center with the appropriate infrastructure. Our objective was to describe baseline characteristics and to examine whether biomarkers related to Alzheimer's disease (AD) physiopathology were associated with worse memory performance. PATIENTS AND METHODS: Fifteen controls and 28 mild cognitive impairment and 13 AD dementia subjects were included. For Arg-ADNI, all biomarker parameters and neuropsychological tests of ADNI-II were adopted. Results of positron emission tomography (PET) with fluorodeoxyglucose and 11C-Pittsburgh compound-B (PIB-PET) were available from all participants. Cerebrospinal fluid biomarker results were available from 39 subjects. RESULTS: A total of 56 participants were included and underwent baseline evaluation. The three groups were similar with respect to years of education and sex, and they differed in age (F=5.10, P=0.01). Mean scores for the baseline measurements of the neuropsychological evaluation differed significantly among the three groups at P<0.001, showing a continuum in their neuropsychological performance. No significant correlations were found between the principal measures (long-delay recall, C-Pittsburgh compound-B scan, left hippocampal volume, and APOEε4) and either age, sex, or education (P>0.1). Baseline amyloid deposition and left hippocampal volume separated the three diagnostic groups and correlated with the memory performance (P<0.001). CONCLUSION: Cross-sectional analysis of baseline data revealed links between cognition, structural changes, and biomarkers. Follow-up of a larger and more representative cohort, particularly analyzing cerebrospinal fluid and brain biomarkers, will allow better characterization of AD in our country.

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Pathologic expansion of the G4C2 repeat in C9orf72 is the main genetic cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). To evaluate the frequency of the G4C2 expansion in a Latin American cohort of FTD and ALS patients, we used a 2-step genotyping strategy. For FTD, we observed an overall expansion frequency of 18.2% (6 of 33 unrelated cases). Moreover, the C9orf72 expansion accounted for 37.5% of all familial FTD cases (6 of 16 families). The expansion frequency in sporadic ALS cases was 2% (1 of 47 unrelated patients), whereas we observed the expansion in 1 of 3 families with a positive history for ALS. Overall, the expansion frequency in our FTD group was similar to that reported for patients in Europe and North America, whereas the frequency in our sporadic ALS group was significantly lower. To our knowledge, this is the first report on the frequency of the C9orf72 expansion in a Latin American population.

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BACKGROUND: The purpose of this study was to investigate the relationship between cognitive reserve and concentration of Aß1-42 in the cerebrospinal fluid (CSF) of patients with mild cognitive impairment, those with Alzheimer's disease, and in control subjects. METHODS: Thirty-three participants from the Argentina-Alzheimer's Disease Neuroimaging Initiative database completed a cognitive battery, the Cognitive Reserve Questionnaire (CRQ), and an Argentinian accentuation reading test (TAP-BA) as a measure of premorbid intelligence, and underwent lumbar puncture for CSF biomarker quantification. RESULTS: The CRQ significantly correlated with TAP-BA, education, and Aß1-42. When considering Aß1-42 levels, significant differences were found in CRQ scores; higher levels of CSF Aß1-42 were associated with higher CRQ scores. CONCLUSION: Reduced Aß1-42 in CSF is considered as evidence of amyloid deposition in the brain. Previous results suggest that individuals with higher education, higher occupational attainment, and participation in leisure activities (cognitive reserve) have a reduced risk of developing Alzheimer's disease. Our results support the notion that enhanced neural activity has a protective role in mild cognitive impairment, as evidenced by higher CSF Aß1-42 levels in individuals with more cognitive reserve.