Mild cognitive impairment: Follow-up of ten patients Deterioro cognitivo leve: Seguimiento de 10 casos

36 patients who presented with mild cognitive impairment (MCI) (memory loss and a Minimental test de Folstein (MMT) of 25-30) had previously been followed up for 31 months: 15 developed Alzheimer dementia, 11 got better (they suffered from emotional disorders) and 10 remained as MCI. In this study we describe an additional follow up period of two years of the ten patients who persisted with MCI. Five developed dementia (Alzheimer type with or without a vascular component). One got better, one developed a progressive supranuclear palsy, and only 3 remained as MCI. This clinical experience leads us to conclude that it is difficult to differentiate between MCI and emotional disorders in the elderly The second point is that MCI usually represents the prodromal phase of Alzheimer disease. There are two final comments. The first is that the diagnosis of Alzheimer disease could be considered in patients without dementia; the second one, that early diagnosis of MCI may allow the use of drugs

Colchicine alters apamin receptors, electrical activity, and skeletal muscle relaxation

A low conductance calcium‐activated K+ channel is thought to regulate the rate of firing of several excitable cells. In skeletal muscle the expression of this channel is under nerve control. Previously, we reported that axonal flow blockade of rat nerves, induced by colchicine, caused atransient increase in muscle apamin receptors, determined by 125I‐apamin binding to membrane fractions. The increase in apamin receptors was correlated with repetitive discharges resembling myotonic potentials in the electromyogram, that were blockable by apamin. Here we show that the increase in muscle apamin receptors and the alteration of the electromyogram are followed closely by a slowing of the twitch relaxation, that in turn, is decreased by apamin. Furthermore, the presence of myotonic‐like alterations in the electromyogram and a slowing of muscle relaxation when muscle apaminreceptors are increased suggests that these channels may participate, amongother factors, in the generation of some kind

Dementia Validation of the Spanish-language version of the Montreal Cognitive Assessment testin adults older than 60 year

Introducción: Existen pocas validaciones de la versión en español de la prueba Montreal Cognitive Assessment (MoCA-S) en Latinoamérica. Objetivo: Evaluar las propiedades psicométricas y la validez discriminativa del MoCA-S en adultos mayores de Santiago de Chile. Métodos: Ciento setenta y dos individuos agrupados según diagnóstico clínico basado en Clinical Dementia Rating (CDR) en: deterioro cognitivo leve tipo amnésico (DCL-a, n = 24), DCL noamnésico (DCL-na, n = 24), demencia leve (n = 20) y 104 cognitivamente sanos fueron evaluados con el MoCA-S y Mini-Mental test de Folstein (MMSE) como prueba de contraste, para determinar la validez discriminativa del MoCA-S. Resultados: Los promedios ± desviación estándar de edad y escolaridad fueron 73 ± 6 y 11 ± 4, respectivamente, sin diferencias significativas entre los grupos. La consistencia interna fue buena ( de Cronbach 0,772), la fiabilidad interevaluador muy buena (coeficiente de correlación de Spearman 0,846 [p < 0,01]) y la fiabilidad intraevaluador (test-retest) fue 0,922 bilateral (p < 0,001). La prueba fue eficaz y válida para la detección del DCL-a (ABC = 0,903) y demencia leve (ABC = 0,957); menos eficaz en DCL no-a (ABC = 0,629). El punto de corte de mejor rendimiento para DCL-a fue < 21 y para demencia leve < 20; sensibilidad/especificidad de 75/82% y 90/86%, respectivamente. La escolaridad mostró una importante influencia en el puntaje, por ello se adicionaron 2 puntos para escolaridad < 8 años y un punto para escolaridad entre 8 y 12 años (MoCA-S1-2). El MoCA-S1-2 fue significativamente más discriminativo que el MMSE para diferenciar DCL-a y demencia. Introducción: Existen pocas validaciones de la versión en español de la prueba Montreal Cognitive Assessment (MoCA-S) en Latinoamérica. Objetivo: Evaluar las propiedades psicométricas y la validez discriminativa del MoCA-S en adultos mayores de Santiago de Chile. Métodos: Ciento setenta y dos individuos agrupados según diagnóstico clínico basado en Clinical Dementia Rating (CDR) en: deterioro cognitivo leve tipo amnésico (DCL-a, n = 24), DCL noamnésico (DCL-na, n = 24), demencia leve (n = 20) y 104 cognitivamente sanos fueron evaluados con el MoCA-S y Mini-Mental test de Folstein (MMSE) como prueba de contraste, para determinar la validez discriminativa del MoCA-S. Resultados: Los promedios ± desviación estándar de edad y escolaridad fueron 73 ± 6 y 11 ± 4, respectivamente, sin diferencias significativas entre los grupos. La consistencia interna fue buena ( de Cronbach 0,772), la fiabilidad interevaluador muy buena (coeficiente de correlación de Spearman 0,846 [p < 0,01]) y la fiabilidad intraevaluador (test-retest) fue 0,922 bilateral (p < 0,001). La prueba fue eficaz y válida para la detección del DCL-a (ABC = 0,903) y demencia leve (ABC = 0,957); menos eficaz en DCL no-a (ABC = 0,629). El punto de corte de mejor rendimiento para DCL-a fue < 21 y para demencia leve < 20; sensibilidad/especificidad de 75/82% y 90/86%, respectivamente. La escolaridad mostró una importante influencia en el puntaje, por ello se adicionaron 2 puntos para escolaridad < 8 años y un punto para escolaridad entre 8 y 12 años (MoCA-S1-2). El MoCA-S1-2 fue significativamente más discriminativo que el MMSE para diferenciar DCL-a y demencia. Conclusiones: El MoCA-S1-2 es una prueba breve, de fácil administración y útil para el diag-nóstico de DCL-a y demencia leve.Introduction: Few studies have validated the Spanish-language version of the Montreal Cogni-tive Assessment (MoCA-S) test in Latin American populations.Objetive: To evaluate the psychometric properties and discriminant validity of the MoCA-S inelderly patients in Santiago de Chile.Methods: 172 individuals were grouped according to their clinical diagnosis based on the Clini-cal Dementia Rating (CDR) scale as follows: amnestic mild cognitive impairment (aMCI; n ± 24),non-amnestic MCI (naMCI; n ± 24), mild dementia (n ± 20), and cognitively normal (n ± 104). Par-ticipants were evaluated with both the MoCA-S and the Mini—Mental State Examination (MMSE)to determine the discriminant validity of the MoCA-S.Results: Mean age and years of schooling were 73 ± 6 and 11 ± 4 years, respectively, withno significant intergroup differences. The MoCA-S displayed good internal consistency (Cron-bach’s : 0.772), high inter-rater reliability (Spearman correlation coefficient: 0.846; P<.01),and high intra-rater reliability (test-retest reliability coefficient: 0.922; P<.001). The MoCA-Swas found to be an effective and valid test for detecting aMCI (AUC ± 0.903) and mild demen-tia (AUC ± 0.957); its effectiveness for detecting naMCI was lower (AUC ± 0.629). The optimalcut-off points for aMCI and mild dementia were < 21 and < 20, respectively, with sensitivity andspecificity rates of 75% and 82% for aMCI and 90% and 86% for mild dementia. The level of edu-cation had a great impact on scores: as a result, 2 points were added for patients with less than8 years of schooling and one point for patients with 8-12 years of schooling (MoCA-S1-2). TheMoCA-S1-2 showed significantly greater discriminant validity than the MMSE for differentiatingaMCI from dementia.Conclusions: The MoCA-S1-2 is a short, easy-to-use, and useful test for diagnosing aMCI andmild dementia

Neural control of the expression of a Ca2+-activated K+ channel involved in the induction of myotonic-like characteristics

1. Expression of the apamin-sensitive K+ channel (SK+) in rat skeletal muscle is neurally regulated. The regulatory effect of the nerve over the expression of some muscle ion channels has been attributed to the electrical activity triggered by the nerve and/or to a trophic effect of some molecules transported from the soma to the axonal endings. 2. SK+ channels apparently are involved in myotonic dystrophy (MD), therefore understanding the factors that regulate their expression may ultimately have important clinical relevance. 3. To establish if axoplasmic transport is involved in this process, we used two experimental approaches in adult rats: (a) Both sciatic nerves were severed, leaving a short or a long nerve stump attached to the anterior tibialis (AT), (b) Colchicine or vinblastine (VBL), two axonal transport blockers of different potencies, was applied on one leg to the sciatic nerve. To determine whether electrical activity affects the expression of SK+ channels, denervated A

Neural control of the expression of a Ca2+-activated K+ channel involved in the induction of myotonic-like characteristics

1. Expression of the apamin-sensitive K+ channel (SK+) in rat skeletal muscle is neurally regulated. The regulatory effect of the nerve over the expression of some muscle ion channels has been attributed to the electrical activity triggered by the nerve and/or to a trophic effect of some molecules transported from the soma to the axonal endings. 2. SK+ channels apparently are involved in myotonic dystrophy (MD), therefore understanding the factors that regulate their expression may ultimately have important clinical relevance. 3. To establish if axoplasmic transport is involved in this process, we used two experimental approaches in adult rats: (a) Both sciatic nerves were severed, leaving a short or a long nerve stump attached to the anterior tibialis (AT), (b) Colchicine or vinblastine (VBL), two axonal transport blockers of different potencies, was applied on one leg to the sciatic nerve. To determine whether electrical activity affects the expression of SK+ channels, denervated A

Batrachotoxin-modified sodium channels from squid optic nerve in planar bilayers: Ion conduction and gating properties

Squid optic nerve sodium channels were characterized in planar bilayers in the presence of batrachotoxin (BTX). The channel exhibits a conductance of 20 pS in symmetrical 200 mM NaCI and behaves as a sodium electrode. The single-channel conductance saturates with increasing the concentration of sodium and the channel conductance vs. sodium concentration relation is well described by a simple rectangular hyperbola. The apparent dissociation constant of the channel for sodium is 11 mM and the maximal conductance is 23 pS. The selectivity determined from reversal potentials obtained in mixed ionic conditions is Na+ -Li+ &gt; K+ &gt; Rb+ &gt; Cs+ Calcium blocks the channel in a voltage-dependent manner. Analysis of single-channel membranes showed that the probability of being open (P0) vs. voltage relation is sigmoidal with a value of 0.5 between -90 and -100 mV. The fitting of P0 requires at least two closed and one open state. The apparent gating charge required to move through the whole transme

Olfactory deficits and cognitive dysfunction in Parkinson's disease

Background: Olfactory deficits and executive dysfunction have been reported in Parkinson's disease (PD). However, the association between these deficits has not been thoroughly examined. Methods: We studied 44 PD subjects and 17 age-matched controls. In PD subjects, symptoms were assessed with the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr scale. Cognition in both groups was assessed by a neuropsychological battery. Olfactory identification and sensitivity was evaluated with the Sniffin' Sticks® test and olfactory detection threshold, respectively. Results: PD subjects showed significant deficits in olfactory function and working memory, executive function, speed of information processing, visuospatial skills and phonological verbal fluency tests when compared with the control group. Moreover, there was a significant correlation between olfactory sensory deficits and executive dysfunction. In PD patients with up to 12 months of motor symptoms, results were equival

Mitochondrial permeability transition pore contributes to mitochondrial dysfunction in fibroblasts of patients with sporadic Alzheimer's disease

© 2018 The Authors In the last few decades, many reports have suggested that mitochondrial function impairment is a hallmark of Alzheimer's disease (AD). Although AD is a neurodegenerative disorder, mitochondrial damage is also present in patients’ peripheral tissues, suggesting a target to develop new biomarkers. Our previous findings indicate that AD fibroblasts show specific defects in mitochondrial dynamics and bioenergetics, which affects the generation of adenosine triphosphate (ATP). Therefore, we explored the possible mechanisms involved in this mitochondrial failure. We found that compared with normal fibroblasts, AD fibroblasts had mitochondrial calcium dysregulation. Further, AD fibroblasts showed a persistent activation of the non-specific mitochondrial calcium channel, the mitochondrial permeability transition pore (mPTP). Moreover, the pharmacological blockage of mPTP with Cyclosporine A (CsA) prevented the increase of mitochondrial superoxide levels, and significantly i

Possible role of apamin‐sensitive K+ channels in myotonic dystrophy

Myotonic muscular dystrophy is a genetic disease characterized mainly by muscle atrophy and myotonia, a repetitive electrical activity of muscle. In the present study, the possible role of apamin‐sensitive K+ channels in the genesis of myotonia was investigated. Apamin is a peptide from bee venom that specifically blocks small conductance Ca2+‐activated K+ channels. The injection of a small amount of apamin (20–30 μl, 10 μmol/L) into the thenar muscle of myotonic dystrophy patients decreased the basal electrical activity during the electromyogram in the 6 patients studied. Myotonic discharges after muscle percussion were more difficult to trigger and of smaller intensity and duration. In 2 controls and in 2 patients with generalized myotonia, as well as in 1 patient with myotonia congenita (where the defect is in chloride channels), apamin had no effect. These results suggest that apamin‐sensitive K+ channels participate in the mechanism that generates myotonia in myotonic dystrophy.

On the role of mining exposure in epigenetic effects in parkinson’s disease

To explore the possible influence of heavy metal mining on incidence of Parkinson’s disease (PD), global DNA methylation was assessed in blood samples from a population of PD patients (n = 45) and control subjects (n = 52) in Antofagasta neighborhood, a Chilean city built for exclusive use of mining companies. Comparisons were made with PD subjects (n = 52) and control subjects (n = 59) from Santiago Chile, a city having little association with mining. All subjects were assessed by two neurologists and PD diagnosis was based on UK Parkinson’s Disease Society Brain Bank Clinical Diagnostic Criteria. From blood samples obtained from each individual, a decrease in global DNA methylation was observed in PD patients either exposed (49% of control, P < 0.001) or not exposed (47% of control, P < 0.001) to mining activity. Although there was no difference in levels of DNA methylation between PD patients from the two cities, there was a lower level of DNA methylation in control subjects from Santiago versus Antofagasta.FONDECYT no. 110016