Effects of a dual intervention (motor and virtual reality-based cognitive) on cognition in patients with mild cognitive impairment: a single-blind, randomized controlled trial.

BACKGROUND: The increase in cases of mild cognitive impairment (MCI) underlines the urgency of finding effective methods to slow its progression. Given the limited effectiveness of current pharmacological options to prevent or treat the early stages of this deterioration, non-pharmacological alternatives are especially relevant. OBJECTIVE: To assess the effectiveness of a cognitive-motor intervention based on immersive virtual reality (VR) that simulates an activity of daily living (ADL) on cognitive functions and its impact on depression and the ability to perform such activities in patients with MCI. METHODS: Thirty-four older adults (men, women) with MCI were randomized to the experimental group (n = 17; 75.41 ± 5.76) or control (n = 17; 77.35 ± 6.75) group. Both groups received motor training, through aerobic, balance and resistance activities in group. Subsequently, the experimental group received cognitive training based on VR, while the control group received traditional cognitive training. Cognitive functions, depression, and the ability to perform activities of daily living (ADLs) were assessed using the Spanish versions of the Montreal Cognitive Assessment (MoCA-S), the Short Geriatric Depression Scale (SGDS-S), and the of Instrumental Activities of Daily Living (IADL-S) before and after 6-week intervention (a total of twelve 40-minutes sessions). RESULTS: Between groups comparison did not reveal significant differences in either cognitive function or geriatric depression. The intragroup effect of cognitive function and geriatric depression was significant in both groups (p < 0.001), with large effect sizes. There was no statistically significant improvement in any of the groups when evaluating their performance in ADLs (control, p = 0.28; experimental, p = 0.46) as expected. The completion rate in the experimental group was higher (82.35%) compared to the control group (70.59%). Likewise, participants in the experimental group reached a higher level of difficulty in the application and needed less time to complete the task at each level. CONCLUSIONS: The application of a dual intervention, through motor training prior to a cognitive task based on Immersive VR was shown to be a beneficial non-pharmacological strategy to improve cognitive functions and reduce depression in patients with MCI. Similarly, the control group benefited from such dual intervention with statistically significant improvements. TRIAL REGISTRATION: ClinicalTrials.gov NCT06313931; https://clinicaltrials.gov/study/NCT06313931 .

Human hippocampal astrocytes: Computational dissection of their transcriptome, sexual differences and exosomes across ageing and mild-cognitive impairment.

The role of astrocytes in Alzheimer's disease is often disregarded. Hence, characterization of astrocytes along their early evolution toward Alzheimer would be greatly beneficial. However, due to their exquisite responsiveness, in vivo studies are difficult. So public microarray data of hippocampal homogenates from (healthy) young, (healthy) elder and elder with mild cognitive impairment (MCI) were subjected to re-analysis by a multi-step computational pipeline. Ontologies and pathway analyses were compared after determining the differential genes that, belonging to astrocytes, have splice forms. Likewise, the subset of molecules exportable to exosomes was also determined. The results showed that astrocyte's phenotypes changed significantly. While already 'activated' astrocytes were found in the younger group, major changes occurred during ageing (increased vascular remodelling and response to mechanical stimulus, diminished long-term potentiation and increased long-term depression). MCI's astrocytes showed some 'rejuvenated' features, but their sensitivity to shear stress was markedly lost. Importantly, most of the changes showed to be sex biassed. Men's astrocytes are enriched in a type 'endfeet-astrocytome', whereas women's astrocytes appear close to the 'scar-forming' type (prone to endothelial dysfunction, hypercholesterolemia, loss of glutamatergic synapses, Ca+2 dysregulation, hypoxia, oxidative stress and 'pro-coagulant' phenotype). In conclusion, the computational dissection of the networks based on the hippocampal gene isoforms provides a relevant proxy to in vivo astrocytes, also revealing the occurrence of sexual differences. Analyses of the astrocytic exosomes did not provide an acceptable approximation to the overall functioning of astrocytes in the hippocampus, probably due to the selective cellular mechanisms which charge the cargo molecules.

Visual-spatial processing impairment in the occipital-frontal connectivity network at early stages of Alzheimer's disease.

Introduction: Alzheimer's disease (AD) is the leading cause of dementia worldwide, but its pathophysiological phenomena are not fully elucidated. Many neurophysiological markers have been suggested to identify early cognitive impairments of AD. However, the diagnosis of this disease remains a challenge for specialists. In the present cross-sectional study, our objective was to evaluate the manifestations and mechanisms underlying visual-spatial deficits at the early stages of AD. Methods: We combined behavioral, electroencephalography (EEG), and eye movement recordings during the performance of a spatial navigation task (a virtual version of the Morris Water Maze adapted to humans). Participants (69-88 years old) with amnesic mild cognitive impairment-Clinical Dementia Rating scale (aMCI-CDR 0.5) were selected as probable early AD (eAD) by a neurologist specialized in dementia. All patients included in this study were evaluated at the CDR 0.5 stage but progressed to probable AD during clinical follow-up. An equal number of matching healthy controls (HCs) were evaluated while performing the navigation task. Data were collected at the Department of Neurology of the Clinical Hospital of the Universidad de Chile and the Department of Neuroscience of the Faculty of Universidad de Chile. Results: Participants with aMCI preceding AD (eAD) showed impaired spatial learning and their visual exploration differed from the control group. eAD group did not clearly prefer regions of interest that could guide solving the task, while controls did. The eAD group showed decreased visual occipital evoked potentials associated with eye fixations, recorded at occipital electrodes. They also showed an alteration of the spatial spread of activity to parietal and frontal regions at the end of the task. The control group presented marked occipital activity in the beta band (15-20 Hz) at early visual processing time. The eAD group showed a reduction in beta band functional connectivity in the prefrontal cortices reflecting poor planning of navigation strategies. Discussion: We found that EEG signals combined with visual-spatial navigation analysis, yielded early and specific features that may underlie the basis for understanding the loss of functional connectivity in AD. Still, our results are clinically promising for early diagnosis required to improve quality of life and decrease healthcare costs.

Predictors of functional impairment and awareness in people with dementia, mild cognitive impairment and healthy older adults from a middle-income country.

Objective: To investigate the demographic, clinical and cognitive correlates of functional capacity and its awareness in people with dementia (PwD; n = 104), mild cognitive impairment (PwMCI; n = 45) and controls (healthy older adults; n = 94) in a sample from a middle-income country. Methods: Dementia and MCI were diagnosed, respectively, with DSM-IV and Petersen criteria. Performance in activities of daily living (ADL) at three different levels [basic (The Katz Index of Independence), instrumental (Lawton instrumental ADL scale) and advanced (Reuben's advanced ADL scale)], measured through self- and informant-report, as well as awareness (discrepancy between self- and informant-report), were compared between groups. Stepwise regression models explored predictors of ADL and their awareness. Results: PwD showed impairment in all ADL levels, particularly when measured through informant-report. No differences were seen between controls and PwMCI regardless of measurement type. PwD differed in awareness of instrumental and basic, but not of advanced ADL, compared to controls. Age, gender, education and fluency were the most consistent predictors for ADL. Diagnosis was a significant predictor only for instrumental ADL. Awareness of basic ADL was predicted by memory, and awareness of instrumental ADL was predicted by general cognitive status, educational level, and diagnosis. Conclusion: Results reinforce the presence of lack of awareness of ADL in PwD. Use of informant-reports and cognitive testing for fluency are suggested for the clinical assessment of ADL performance. Finally, assessment of instrumental ADL may be crucial for diagnostic purposes.

Textual Inference Comprehension in Mild Cognitive Impairment: The Influence of Semantic Processing and Verbal Episodic Memory.

Language complaints, especially in complex tasks, may occur in mild cognitive impairment (MCI). Various language measures have been studied as cognitive predictors of MCI conversion to Alzheimer's type dementia. Understanding textual inferences is considered a high-demanding task that recruits multiple cognitive functions and, therefore, could be sensitive to detect decline in the early stages of MCI. Thus, we aimed to compare the performance of subjects with MCI to healthy elderly in a textual inference comprehension task and to determine the best predictors of performance in this ability considering one verbal episodic memory and two semantic tasks. We studied 99 individuals divided into three groups: (1) 23 individuals with amnestic mild cognitive impairment (aMCI), (2) 42 individuals with non-amnestic mild cognitive impairment (naMCI), (3), and (4) 34 cognitively healthy individuals for the control group (CG). A reduced version of The Implicit Management Test was used to assess different types of inferential reasoning in text reading. MCI patients performed poorer than healthy elderly, and there were no differences between MCI subgroups (amnestic and non-amnestic). The best predictors for inference-making were verbal memory in the aMCI and semantic tasks in the naMCI group. The results confirmed that the failure to understand textual inferences can be present in MCI and showed that different cognitive skills like semantic knowledge and verbal episodic memory are necessary for inference-making.

Association between ApoE ε4 Carrier Status and Cardiovascular Risk Factors on Mild Cognitive Impairment among Mexican Older Adults.

Mild cognitive impairment (MCI) (amnestic or non-amnestic) has different clinical and neuropsychological characteristics, and its evolution is heterogeneous. Cardiovascular risk factors (CVRF), such as hypertension, diabetes, or dyslipidemia, and the presence of the Apolipoprotein E ε4 (ApoE ε4) polymorphism have been associated with an increased risk of developing Alzheimer's disease (AD) and other dementias but the relationship is inconsistent worldwide. We aimed to establish the association between the ApoE ε4 carrier status and CVRF on MCI subtypes (amnestic and non-amnestic) in Mexican older adults. Cross-sectional study including 137 older adults (n = 63 with normal cognition (NC), n = 24 with amnesic, and n = 50 with non-amnesic MCI). Multinomial logistic regression models were performed in order to determine the association between ApoE ε4 polymorphism carrier and CVRF on amnestic and non-amnestic-MCI. ApoE ε4 carrier status was present in 28.8% participants. The models showed that ApoE ε4 carrier status was not associated neither aMCI nor naMCI condition. The interaction term ApoE ε4 × CVRF was not statistically significant for both types of MCI. However, CVRF were associated with both types of MCI and the association remained statistically significant after adjustment by sex, age, and education level. The carrier status of the ApoE genotype does not contribute to this risk.

Gait and balance disturbances are common in young urbanites and associated with cognitive impairment. Air pollution and the historical development of Alzheimer's disease in the young.

To determine whether gait and balance dysfunction are present in young urbanites exposed to fine particular matter PM2.5 ≥ annual USEPA standard, we tested gait and balance with Tinetti and Berg tests in 575 clinically healthy subjects, age 21.0 ±â€¯5.7 y who were residents in Metropolitan Mexico City, Villahermosa and Reynosa. The Montreal Cognitive Assessment was also applied to an independent cohort n:76, age 23.3 ±â€¯9.1 y. In the 575 cohort, 75.4% and 34.4% had abnormal total Tinetti and Berg scores and high risk of falls in 17.2% and 5.7% respectively. BMI impacted negatively Tinetti and Berg performance. Gait dysfunction worsen with age and males performed worse than females. Gait and balance dysfunction were associated with mild cognitive impairment MCI (19.73%) and dementia (55.26%) in 57/76 and 19 cognitively intact subjects had gait and balance dysfunction. Seventy-five percent of urbanites exposed to PM2.5 had gait and balance dysfunction. For MMC residents-with historical documented Alzheimer disease (AD) and CSF abnormalities, these findings suggest Alzheimer Continuum is in progress. Early development of a Motoric Cognitive Risk Syndrome ought to be considered in city dwellers with normal cognition and gait dysfunction. The AD research frame in PM2.5 exposed young urbanites should include gait and balance measurements. Multicity teens and young adult cohorts are warranted for quantitative gait and balance measurements and neuropsychological and brain imaging studies in high vs low PM2.5 exposures. Early identification of gait and balance impairment in young air pollution-exposed urbanites would facilitate multidisciplinary prevention efforts for modifying the course of AD.

Alzheimer disease starts in childhood in polluted Metropolitan Mexico City. A major health crisis in progress.

Exposures to fine particulate matter (PM2.5) and ozone (O3) above USEPA standards are associated with Alzheimer's disease (AD) risk. Metropolitan Mexico City (MMC) youth have life time exposures to PM2.5 and O3 above standards. We focused on MMC residents ≤30 years and reviewed 134 consecutive autopsies of subjects age 20.03 ± 6.38 y (range 11 months to 30 y), the staging of Htau and ß amyloid, the lifetime cumulative PM2.5 (CPM 2.5) and the impact of the Apolipoprotein E (APOE) 4 allele, the most prevalent genetic risk for AD. We also reviewed the results of the Montreal Cognitive Assessment (MoCA) and the brainstem auditory evoked potentials (BAEPs) in clinically healthy young cohorts. Mobile sources, particularly from non-regulated diesel vehicles dominate the MMC pollutant emissions exposing the population to PM2.5 concentrations above WHO and EPA standards. Iron-rich,magnetic, highly oxidative, combustion and friction-derived nanoparticles (CFDNPs) are measured in the brain of every MMC resident. Progressive development of Alzheimer starts in childhood and in 99.25% of 134 consecutive autopsies ≤30 years we can stage the disease and its progression; 66% of ≤30 years urbanites have cognitive impairment and involvement of the brainstem is reflected by auditory central dysfunction in every subject studied. The average age for dementia using MoCA is 20.6 ± 3.4 y. APOE4 vs 3 carriers have 1.26 higher odds of committing suicide. PM2.5 and CFDNPs play a key role in the development of neuroinflammation and neurodegeneration in young urbanites. A serious health crisis is in progress with social, educational, judicial, economic and overall negative health impact for 25 million residents. Understanding the neural circuitry associated with the earliest cognitive and behavioral manifestations of AD is needed. Air pollution control should be prioritised-including the regulation of diesel vehicles- and the first two decades of life ought to be targeted for neuroprotective interventions. Defining paediatric environmental, nutritional, metabolic and genetic risk factor interactions is a multidisciplinary task of paramount importance to prevent Alzheimer's disease. Current and future generations are at risk.

Relationship of Neurofilament Light (NfL) and Cognitive Performance in a Sample of Mexican Americans with Normal Cognition, Mild Cognitive Impairment and Dementia.

INTRODUCTION: This study characterized the relationship between plasma NfL and cognition in a community-based sample of older Mexican Americans. METHODS: 544 participants completed a battery of neuropsychological tests and were diagnosed using clinical criteria. NfL was assayed using Simoa. NfL levels across groups and tests were analyzed. RESULTS: Difference in NfL was found between normal and impaired groups and was related to global cognition, processing speed, executive functions and a list of learning tasks with a significant negative effect for all diagnostic groups. NfL had a negative impact on processing speed, attention, executive functions and delayed and recognition memory for both normal and MCI groups. CONCLUSION: The research supports plasma NfL as a marker of cognitive impairment related to neurodegenerative processes in Mexican Americans and may be a marker of early changes in cognition in those with normal cognition and at risk for developing MCI.

Cut-off points of the Portuguese version of the Montreal Cognitive Assessment for cognitive evaluation in Parkinson's disease.

The Movement Disorder Society has published some recommendations for dementia diagnosis in Parkinson disease (PD), proposing the Montreal Cognitive Assessment (MOCA) as a cognitive screening tool in these patients. However, few studies have been conducted assessing the Portuguese version of this test in Brazil (MOCA-BR). OBJECTIVE: the aim of the present study was to define the cut-off points of the MOCA-BR scale for diagnosing Mild Cognitive Impairment (PD-MCI) and Dementia (PD-D) in patients with PD. METHODS: this was a cross-sectional, analytic field study based on a quantitative approach. Patients were selected after a consecutive assessment by a neurologist, after an extensive cognitive evaluation, and were classified as having normal cognition (PD-N), PD-MCI or PD-D. The MOCA-BR was then applied and 89 patients selected. RESULTS: on the cognitive assessment, 30.3% were PD-N, 41.6% PD-MCI and 28.1% PD-D. The cut-off score on the MOCA-Br to distinguish PD-N from PD-D was 22.50 (95% CI 0.748-0.943) for sensitivity of 85.5% and specificity of 71.1%. The cut-off for distinguishing PD-D from MCI was 17.50 (95% CI 0.758-0.951) for sensitivity of 81.6% and specificity of 76%.

A Movement Disorder Society publicou algumas recomendações para o diagnóstico de demência na doença de Parkinson (DP), propondo o Montreal Cognitive Assessment (MOCA) como ferramenta de triagem cognitiva nesses pacientes. Entretanto, poucos estudos foram aplicados à versão em português (MOCA-BR). OBJETIVO: o presente estudo tem o objetivo de definir os valores de corte na escala de MOCA-BR para diagnosticar o Comprometimento Cognitivo Leve (DP-CCL) e Demência (DP-D) em pacientes com DP. MÉTODOS: trata-se de um estudo transversal, analítico, com uma abordagem quantitativa. Os pacientes foram selecionados depois de avaliações consecutivas por um neurologista, após avaliação cognitiva extensa, e foram classificados como cognição normal (DP-N), DP-CCL e DP-D e então o MOCA-BR foi aplicado, sendo selecionados 89 pacientes. RESULTADOS: na avaliação cognitiva, foram encontrados 30.3% de DP-N, 41.6% de DP-CCL e 28.1% DP-D. O valor de corte no MOCA-BR para distinguir entre DP-N de DP-D foi 22.5 (IC 95%; 0.748-0.943), sensibilidade de 85.5% e especificidade de 71.1%. Para distinguir DP-P de CCL, o ponto de corte foi de 17.5 (IC 95%; 0.758-0.951), sensibilidade de 81.6% e especificidade de 76%.

Cut-off points of the Portuguese version of the Montreal Cognitive Assessment for cognitive evaluation in Parkinson's disease / Valores de corte da versão em português do "montreal cognitive assessment" para avaliação cognitiva na doença de parkinson

ABSTRACT. The Movement Disorder Society has published some recommendations for dementia diagnosis in Parkinson disease (PD), proposing the Montreal Cognitive Assessment (MOCA) as a cognitive screening tool in these patients. However, few studies have been conducted assessing the Portuguese version of this test in Brazil (MOCA-BR). Objective: the aim of the present study was to define the cut-off points of the MOCA-BR scale for diagnosing Mild Cognitive Impairment (PD-MCI) and Dementia (PD-D) in patients with PD. Methods: this was a cross-sectional, analytic field study based on a quantitative approach. Patients were selected after a consecutive assessment by a neurologist, after an extensive cognitive evaluation, and were classified as having normal cognition (PD-N), PD-MCI or PD-D. The MOCA-BR was then applied and 89 patients selected. Results: on the cognitive assessment, 30.3% were PD-N, 41.6% PD-MCI and 28.1% PD-D. The cut-off score on the MOCA-Br to distinguish PD-N from PD-D was 22.50 (95% CI 0.748-0.943) for sensitivity of 85.5% and specificity of 71.1%. The cut-off for distinguishing PD-D from MCI was 17.50 (95% CI 0.758-0.951) for sensitivity of 81.6% and specificity of 76%.

RESUMO. A Movement Disorder Society publicou algumas recomendações para o diagnóstico de demência na doença de Parkinson (DP), propondo o Montreal Cognitive Assessment (MOCA) como ferramenta de triagem cognitiva nesses pacientes. Entretanto, poucos estudos foram aplicados à versão em português (MOCA-BR). Objetivo: o presente estudo tem o objetivo de definir os valores de corte na escala de MOCA-BR para diagnosticar o Comprometimento Cognitivo Leve (DP-CCL) e Demência (DP-D) em pacientes com DP. Métodos: trata-se de um estudo transversal, analítico, com uma abordagem quantitativa. Os pacientes foram selecionados depois de avaliações consecutivas por um neurologista, após avaliação cognitiva extensa, e foram classificados como cognição normal (DP-N), DP-CCL e DP-D e então o MOCA-BR foi aplicado, sendo selecionados 89 pacientes. Resultados: na avaliação cognitiva, foram encontrados 30.3% de DP-N, 41.6% de DP-CCL e 28.1% DP-D. O valor de corte no MOCA-BR para distinguir entre DP-N de DP-D foi 22.5 (IC 95%; 0.748-0.943), sensibilidade de 85.5% e especificidade de 71.1%. Para distinguir DP-P de CCL, o ponto de corte foi de 17.5 (IC 95%; 0.758-0.951), sensibilidade de 81.6% e especificidade de 76%.

Deterioro Conductual Leve (MBI), Deterioro Cognitivo Leve (MCI) y desarrollo de la demencia: implicancias diagnósticas y clínicas / Mild Behavioral Impairment (MBI), Mild Cognitive Impairment (MCI) and development of dementia: diagnostic and clinical implications

Tanto el Deterioro Conductual Leve (MBI) y el Deterioro Cognitivo Leve (MCI) han sido identificados como estados o fases predemenciales. Estas entidades constituyen factores de riesgo para el desarrollo de las demencias y en muchos casos, una manifestación temprana de las mismas. En este contexto, los síntomas neuropsiquiátricos que caracterizan al MBI no solo podrían presentarse concurrentemente con el MCI, sino también antes de su aparición o incluso sin que este se llegara a presentar. Esta aparición selectiva del MBI sigue representando un gran desafío en términos de la comprensión de su etiología y el sustrato neurobiológico que podría compartir con el MCI. En este artículo se presentan las características centrales del MBI, los criterios que se emplean para su diagnóstico, las relaciones que guarda con el MCI y sus posibles biomarcadores, para discutir algunos aspectos relacionados con su diagnóstico clínico

CSF Aß1-42, but not p-Tau181, Predicted Progression from Amnestic MCI to Alzheimer's Disease Dementia.

The purpose of the study was to determine whether Aß1-42 and p-Tau181 cerebral spinal fluid (CSF) levels can predict progression from amnestic mild cognitive impairment (aMCI) to Alzheimer's disease dementia (ADD) in a 3-year follow-up study. All participants were evaluated blindly by a behavioral neurologist and a neuropsychologist, and classified according to the Petersen criteria for aMCI and according to the Clinical Dementia Rating (CDR) scale. Individuals were also submitted to lumbar puncture at baseline. Levels of Aß1-42 and p-Tau181 were measured by immunoenzymatic assay. Values were adjusted for age and sex. Thirty-one of 33 (93.9%) participants completed follow-up. Approximately 39% of aMCI individuals progressed to ADD. The relative risk of developing ADD in those with Aß1-42 CSF levels lower than 618.5 pg/mL was 17.4 times higher than in those whose levels were higher than 618.5 pg/mL (P = 0.003). p-Tau181 alone did not predict progression to ADD (P = 0.101). The relative risk in those with a p-Tau181/Aß1-42 ratio higher than 0.135 was 5.7 times greater (P < 0.001). Aß1-42 and p-Tau181 explained 40.1% of the verbal memory test subscore of the Consortium to Establish a Registry for Alzheimer's Disease (ΔCERADs) variance (P = 0.008). Aß1-42 strongly predicted progression from aMCI to ADD. p-Tau181 alone, or its relation to Aß1-42, was inferior than Aß1-42 alone as a predictor of progression to ADD.

Comparación de la respuesta inicial luego de la ablación con 30 mCi de 131I versus no ablación en pacientes con cáncer diferenciado de tiroides de bajo riesgo de recurrencia. Estudio prospectivo multicéntrico / Comparison of initial response to treatment after remnant ablation (RA) with 30 mCi of 131 I versus no RA in patients with differentiated thyroid cancer with low risk of recurrence. Multicentric prospective study

RESUMEN Material y métodos Estudio prospectivo multicéntrico. Se incluyeron 174 pacientes con CDT tratados consecutivamente desde junio 2014 hasta mayo 2015. Se los dividió en 2 grupos (ablacionados y no ablacionados) con 87 pacientes incluidos en cada uno. La respuesta inicial al tratamiento se determinó con la medición de tiroglobulina, anticuerpos anti-tiroglobulina y ecografía de cuello. Resultados Se compararon las características basales de ambos grupos y no se evidenciaron diferencias estadísticamente significativas: sexo femenino 84% y 88% (p = 0,5); edad promedio de 46,8 y 47,5 años (p = 0,7); carcinoma papilar variedad clásico 68% y 75,9% (p = 0,15), respectivamente. El resto de las características basales como tamaño tumoral, bilateralidad, multifocalidad, tiroiditis de Hashimoto y estadio tumoral tampoco mostraron diferencias significativas. La evaluación de la respuesta inicial al tratamiento se realizó en 64 pacientes del grupo ablacionado y en 76 del grupo no ablacionado. Se observó una respuesta excelente en 81% de pacientes ablacionados vs. 87% del grupo no ablacionado, con una frecuencia de respuesta estructural incompleta de 1,6% y 1,4%, respectivamente, (p = 0,9). Un 17% de los ablacionados y 12% de los no ablacionados presentaron una respuesta indeterminada. Conclusión: Los pacientes de bajo riesgo, ablacionados o no, presentan similares frecuencias de respuesta inicial excelente y estructural incompleta. El seguimiento a largo plazo podrá definir si estas respuestas iniciales se mantienen en el tiempo, lo que permitirá reducir la indicación de ablación con radioyodo en este grupo de pacientes con CDT.

ABSTRACT Patients and methods We included 174 patients; 87 patients in each group (ablated and nonablated). Assessment of the initial response to treatment was performed by measurement of thyroglobulin and anti-thyroglobulin antibodies and by neck ultrasonography. Results Baseline characteristics of both groups were compared, and no statistically significant differences were found: female sex 84% and 88,5%, respectively, (p = 0.5); mean age of 46.8 and 47.5 years, respectively (p = 0.7); papillary carcinoma classic variant 68% and 75.9%, respectively (p = 0.15). The remaining of the baseline characteristics such as tumor size, presence of bilaterality, multifocality, Hashimoto's thyroiditis and tumor stage were not statistically significant, either. The evaluation of the response to treatment was finally performed in 64 patients from the ablated group and in 76 from the non-ablated group. An excellent response to treatment was observed in 81% of ablated patients vs. 87% of the non-ablated group, with a frequency of structural incomplete response of 1.6% and 1.4%, respectively (p = 0.9). On the other hand, 17% and 12% of patients in each group had an indeterminate response. Conclusion Low-risk ablated and non-ablated patients have a similar frequency of excellent initial and structural incomplete response to treatment. Long-term follow-up is needed to establish whether these initial responses are maintained over time, and thus further refine the indications of RA in this group of patients with DTC.

PARP-1 and p53 Regulate the Increased Susceptibility to Oxidative Death of Lymphocytes from MCI and AD Patients.

Mild cognitive impairment (MCI) is a clinically detectable initial stage of cognitive deterioration with a high conversion rate to dementia. There is increasing evidence that some of the cerebral alterations present in Alzheimer type dementia can be found in peripheral tissues. We have previously shown that lymphocytes from Alzheimer's disease (AD) patients have increased susceptibility to hydrogen peroxide (H2O2)-induced death that depends on dementia severity. We here investigated whether lymphocytes from MCI patients show increased vulnerability to death, and explored the involvement of Poly [ADP-ribose] polymerase (PARP-1) and p53 in the regulation of this process. Lymphocytes from 16 MCI and 10 AD patients, and 15 healthy controls (HCs) were submitted to increasing concentrations of H2O2 for 20 h. Cell death was determined by flow cytometry, in the presence or absence of PARP-1 inhibitors (3-aminobenzamide (3-ABA) or Nicotinamide (NAM)), or the p53 inhibitor (nutlin-3) or stabilizer (pifithrin-α). PARP-1 and p53 mRNA levels were determined by quantitative PCR (qPCR). Lymphocytes from MCI patients showed increased susceptibility to death, attaining intermediate values between AD and controls. PARP inhibitors -3-ABA and NAM- markedly protected from H2O2-induced death, making the difference between MCI and controls disappear, but not the difference between AD and controls. PARP-1 mRNA expression was increased in MCI lymphocytes. Modulation of p53 with Nutlin-3 or pifithrin-α did not modify the H2O2-induced death of lymphocytes from MCI or AD patients, but augmented the death in control lymphocytes attaining levels similar to MCI and AD. Accordingly, p53 mRNA expression was increased in AD and MCI lymphocytes compared to controls. In all, these results show that increased oxidative death is present in lymphocytes at the MCI stage. PARP-1 has a preponderant role, with complete death protection achieved with PARP inhibition in MCI lymphocytes, but not in AD, suggesting that PARP-1 might have a protective role. In addition, deregulations of the p53 pathway seem to contribute to the H2O2-induced death in MCI and AD lymphocytes, which show increased p53 expression. The results showing a prominent protective role of PARP inhibitors opens the door to study the use of these agents to prevent oxidative death in MCI patients.

Evolución de la categorización semántica en adultos mayores con diagnóstico de DCL-A y DTA y sin patología neurológica / Evolution of semantic categorization in older adults with and without neurological disease

Tradicionalmente la memoria semántica ha sido definida como un tesoro mental que almacena información sobre las palabras, su significado, como así también la relación entre ellas, los hechos y los conceptos. Una de las vías principales para explicar cómo se organiza la información en la memoria semántica (MS) es a través de categorías. La demencia tipo Alzheimer (DTA) suele estar caracterizada por un deterioro en la memoria episódica. Sin embargo, se debate en torno al deterioro de la misma, en qué momento aparece, a qué se debe y si hay una pérdida diferencial en distintos momentos de la enfermedad. El objetivo del trabajo que se informa fue analizar los procesos de categorización semántica en adultos mayores sanos comparándolos con dos grupos de personas con patologías neurológicas: uno con diagnóstico de deterioro cognitivo leve (DCL) y otro con demencia tipo Alzheimer (DTA), emparejados por edad, nivel educativo y género. Para ello, se utilizaron tareas tradicionales para evaluar la memoria semántica y también un método novedoso, el DISTSEM, que permite evaluar las estimaciones que realizan las personas de las distancias semánticas entre los conceptos. Los resultados mostraron que el grupo de personas sin patología tuvo un rendimiento superior en todas las tareas en comparación con los grupos de personas con patología neurológica. Por otro lado, el grupo con DTA mostró un deterioro semántico afectando en primer lugar a la categoría seres vivos. El DCL preservó la estructura categorial sólo con pequeñas intrusiones. El DISTSEM mostró ser un instrumento adecuado para la discriminación entre sujetos sanos y DTA.(AU)

Traditionally, semantic memory has been defined as a mental trove that contains organized information about words and their meaning, as well as relationships between words, facts and concepts.There are different ways of explaining how the information in such memory system is represented and organized. One of the main ways of explaining this organization is through categories. Categorization starts the very moment that any sensorial perception is associated to an abstract category; it is the ability to organize information in equivalence classes, and it is very important because it allows us to summarize the information that we gather through our senses and thus facilitate its manipulation. Alzheimers disease (AD) is the main cause of dementia among older adults, and it is one of the most pressing sanitary, social and cultural problems of the present times. The main risk factor for the illness is age, for its prevalence augments exponentially from 65 to 85 years old, and due to the rise in life expectancy it is considered that it might be transformed into a world-wide epidemic in the coming years. The start of the illness is insidious and slowly progressing, and it is characterized by a loss of episodic memory from its beginnings. With respect to the deterioration of semantic memory in AD, a debate has arisen about its mode of presentation, its causes, and whether there is a differential loss of categories (live or non-live beings) in different moments of the illness. During the 90s, Petersen proposed the concept of mild cognitive impairment (MCI) to label the subjects with a functional cognitive impairment insufficient to diagnose a dementia syndrome. The importance of this syndrome is that between 8 to 15% of those who suffer it evolve to AD annually, while in the general population this evolution is only from 1 to 2%. However, there is a great controversy about the validity and scope of the term MCI, for its etiology can be very varied and it is very difficult to predict its evolution. There are different sub-kinds of MCI, and the amnesic form is the more likely to evolve into AD, for its main characteristic is the subjective deterioration of memory corroborated by standardized test by reference to normative data for the same age and educational level of the subject. The other cognitive functions not present alterations. The main objective of this work was to analyze the semantic categorization processes in healthy older adults comparing them with two groups of people with neurological pathologies, one with diagnosis of MCI and the other with AD, matched by age, educational level and gender. To evaluate this categorization process, two traditional tasks were used together with a novel method, the DISTSEM, which allows the evaluation of the estimation made by people about the semantic distance among a set of given concepts. The results showed that the group of people without pathologies had a superior performance in all the tasks in comparison with the groups of people with neurological pathologies. On the other hand, the group with AD showed a semantic impairment which affected in the first place the category of live beings, which was evident in the all the tasks. The MCI preserved the categorical structure with only minor intrusions. The DISTSEM has shown itself to be a valuable instrument that allows the discrimination between healthy subjects and those with AD. It is expected that this work can provide empirical evidence relevant to the debate surrounding semantic memory, for studies in patients with brain injury offer key information to examine the organizing models of such memory.(AU)

Evolución de la categorización semántica en adultos mayores con diagnóstico de DCL-A y DTA y sin patología neurológica / Evolution of semantic categorization in older adults with and without neurological disease

Tradicionalmente la memoria semántica ha sido definida como un tesoro mental que almacena información sobre las palabras, su significado, como así también la relación entre ellas, los hechos y los conceptos. Una de las vías principales para explicar cómo se organiza la información en la memoria semántica (MS) es a través de categorías. La demencia tipo Alzheimer (DTA) suele estar caracterizada por un deterioro en la memoria episódica. Sin embargo, se debate en torno al deterioro de la misma, en qué momento aparece, a qué se debe y si hay una pérdida diferencial en distintos momentos de la enfermedad. El objetivo del trabajo que se informa fue analizar los procesos de categorización semántica en adultos mayores sanos comparándolos con dos grupos de personas con patologías neurológicas: uno con diagnóstico de deterioro cognitivo leve (DCL) y otro con demencia tipo Alzheimer (DTA), emparejados por edad, nivel educativo y género. Para ello, se utilizaron tareas tradicionales para evaluar la memoria semántica y también un método novedoso, el DISTSEM, que permite evaluar las estimaciones que realizan las personas de las distancias semánticas entre los conceptos. Los resultados mostraron que el grupo de personas sin patología tuvo un rendimiento superior en todas las tareas en comparación con los grupos de personas con patología neurológica. Por otro lado, el grupo con DTA mostró un deterioro semántico afectando en primer lugar a la categoría seres vivos. El DCL preservó la estructura categorial sólo con pequeñas intrusiones. El DISTSEM mostró ser un instrumento adecuado para la discriminación entre sujetos sanos y DTA.

Traditionally, semantic memory has been defined as a mental trove that contains organized information about words and their meaning, as well as relationships between words, facts and concepts.There are different ways of explaining how the information in such memory system is represented and organized. One of the main ways of explaining this organization is through categories. Categorization starts the very moment that any sensorial perception is associated to an abstract category; it is the ability to organize information in equivalence classes, and it is very important because it allows us to summarize the information that we gather through our senses and thus facilitate its manipulation. Alzheimer's disease (AD) is the main cause of dementia among older adults, and it is one of the most pressing sanitary, social and cultural problems of the present times. The main risk factor for the illness is age, for its prevalence augments exponentially from 65 to 85 years old, and due to the rise in life expectancy it is considered that it might be transformed into a world-wide epidemic in the coming years. The start of the illness is insidious and slowly progressing, and it is characterized by a loss of episodic memory from its beginnings. With respect to the deterioration of semantic memory in AD, a debate has arisen about its mode of presentation, its causes, and whether there is a differential loss of categories (live or non-live beings) in different moments of the illness. During the 90s, Petersen proposed the concept of mild cognitive impairment (MCI) to label the subjects with a functional cognitive impairment insufficient to diagnose a dementia syndrome. The importance of this syndrome is that between 8 to 15% of those who suffer it evolve to AD annually, while in the general population this evolution is only from 1 to 2%. However, there is a great controversy about the validity and scope of the term MCI, for its etiology can be very varied and it is very difficult to predict its evolution. There are different sub-kinds of MCI, and the amnesic form is the more likely to evolve into AD, for its main characteristic is the subjective deterioration of memory corroborated by standardized test by reference to normative data for the same age and educational level of the subject. The other cognitive functions not present alterations. The main objective of this work was to analyze the semantic categorization processes in healthy older adults comparing them with two groups of people with neurological pathologies, one with diagnosis of MCI and the other with AD, matched by age, educational level and gender. To evaluate this categorization process, two traditional tasks were used together with a novel method, the DISTSEM, which allows the evaluation of the estimation made by people about the semantic distance among a set of given concepts. The results showed that the group of people without pathologies had a superior performance in all the tasks in comparison with the groups of people with neurological pathologies. On the other hand, the group with AD showed a semantic impairment which affected in the first place the category of live beings, which was evident in the all the tasks. The MCI preserved the categorical structure with only minor intrusions. The DISTSEM has shown itself to be a valuable instrument that allows the discrimination between healthy subjects and those with AD. It is expected that this work can provide empirical evidence relevant to the debate surrounding semantic memory, for studies in patients with brain injury offer key information to examine the organizing models of such memory.

Doença de Alzheimer prodrômica. MCI, biomarcadores, prevenção e novas drogas / Alzheimer´s disease prodromal AD, mild cognitive impairment, prevention and new drugs

Este artigo discute dois novos conceitos: doença de Alzheimer prodrômica (DAp) e deficiência cognitiva leve / mild cognitive impairment (MCI). Aborda a questão dos biomarcadores e da perspectiva futura de tratamentos e prevenção.

Puntuaciones del MoCA y el MMSE en pacientes con deterioro cognitivo leve y demencia en una clínica de memoria en Bogotá / MoCA and MMSE scores in patients with mild cognitive impairment and dementia in a memory clinic in Bogotá

Introducción. Diferentes pruebas neuropsicológicas permiten explorar las funciones cognitivas del adulto mayor, en un tiempo corto. En Colombia se dispone de pocos estudios sobre puntuaciones y puntos de corte para el MMSE y para el MoCA en relación al diagnóstico de deterioro cognitivo. Objetivo. Describir la distribución de las puntuaciones del MMSE y el MoCA y los puntos de corte con mejor discriminación, para el diagnóstico de deterioro cognitivo leve y demencia, en una muestra de pacientes de Bogotá. Material y métodos. Se evaluaron 248 pacientes por un equipo multidisciplinario, que consultaron a la Clínica de Memoria del HIUSJ entre 2009-2012, siguiendo un protocolo establecido. Se identificaron las puntuaciones del MoCA y MMSE, que permitieron obtener el mayor porcentaje de pacientes correctamente clasificados. Resultados. En el 70% de los pacientes con DCL y en el 69 % de los sujetos normales, se encontraron puntuaciones del MMSE inferiores o iguales a 28. En 91% de pacientes con DCL y 84% de los sujetos normales, se presentaron puntuaciones del MoCA inferiores o iguales a 25. Los pacientes con cualquier tipo de demencia, presentaron puntuaciones del MMSE inferiores o iguales a 27 e inferiores o iguales a 24 en el MoCA. Conclusión. Según el presente estudio, el tamizaje de funciones cognitivas, utilizando el MoCA, clasifica de manera más acertada que el MMSE, a los sujetos con deterioro cognitivo. Creemos que en atención primaria, estos puntos de corte del MoCA, pueden ser considerados por ahora, cuando se trate especialmente de sujetos con alta escolaridad.

Introduction. Some cognitive tests allow the evaluation of cognitive functions on the elderly in a short period of time. There are few studies in Colombia about cut-off point for the MMSE and the MoCA test. Objectives. To describe the distribution on scores on MMSE and MoCA test and the cut-off point with a better discrimination criteria for the diagnosis of mild cognitive impairment and dementia, in a sample of patients from Bogotá. Materials and methods. Two hundred forty eight patients were included in this study, being evaluated by a multidisciplinary team that followed an established protocol, on patients who attended to the Memory Clinic of HIUSJ between 2009-2012. MoCA test and MMSE scores that allow higher percentages of correctly classified patients were identified. Results. Seventy percent of patients with mild cognitive impairment and 69% of normal individuals had scores on MMSE below or equal to 28. Ninety-one percent of patients with MCI and 89% of normal patients, had scores below or equal to 25. Patients with any type of dementia had scores on MMSE below or equal to 27 and below or equal to 24 in MoCA test. Conclusion. According to the study, the screening of cognitive functions, using MoCA test, is more accurate than MMSE in patients with cognitive decline. The cut-off points, identified in our study, can be considered useful until now in primary attention, in patients with a high level of education.