Gene Expression of Disease-related Genes in Alzheimer's Disease is Impaired by Tau Aggregation.

Neuronal hyperexcitability linked to an increase in glutamate signalling is a peculiar trait of the early stages of Alzheimer's disease (AD) and tauopathies, however, a progressive reduction in glutamate release follows in advanced stages. We recently reported that in the early phases of the neurodegenerative process, soluble, non-aggregated Tau accumulates in the nucleus and modulates the expression of disease-relevant genes directly involved in glutamatergic transmission, thus establishing a link between Tau instability and altered neurotransmission. Here we report that while the nuclear translocation of Tau in cultured cells is not impaired by its own aggregation, the nuclear amyloid inclusions of aggregated Tau abolish Tau-dependent increased expression of the glutamate transporter. Remarkably, we observed that in the prefrontal cortex (PFC) of AD patient brain, the glutamate transporter is upregulated at early stages and is downregulated at late stages. The Gene Set Enrichment Analysis indicates that the modulation of Tau-dependent gene expression along the disease progression can be extended to all protein pathways of the glutamatergic synapse. Together, this evidence links the altered glutamatergic function in the PFC during AD progression to the newly discovered function of nuclear Tau.

[Management of glycemia: an audit in 66 ICUs]. / Gestion de la glycémie : un audit dans 66 réanimations.

INTRODUCTION: The interest of tight glucose control in ICU is still debated. In France, no data are available regarding this therapy and the implementation of its guidelines. STUDY DESIGN: Sub-study of a one-day audit performed between January and May 2009. PATIENTS AND METHODS: During a one-day audit performed in 66 ICUs, trained residents collected data regarding the presence of a formal glucose control protocol and its practical application. RESULTS: A formalized glucose control protocol was found in 88% of patients. During the day before the audit, 3645 glycemia measurements were performed accounting for six measurements [4-9] per patient with a median higher value of 1.6 [1.4-2.1]. Hypoglycemia (<0.8 g/L) and hyperglycemia (>1.4 g/L in non-diabetic and >1.8 g/L in diabetic patients) were found in 81 (15%) and 326 (58%) patients respectively. Two episodes (0.36%) of severe hypoglycemia (<0.4 g/L) were reported. Factors associated with glucose control protocol application were: a high SOFA score, cardioversion, mechanical ventilation, intracranial pressure monitoring, steroid use and nurse to patient ratio less than 1/2.5. Hepatic failure was the only factor associated with hypoglycemia. DISCUSSION: Glucose control protocols are available in more than 80% ICUs but their implementation is still imperfect. However, the median glycemia meets international current recommendations. Severe hypoglycemia is a very rare event in ICU.

[Neuropsychologic evaluation in Parkinson disease]. / Evaluación neuropsicológica en la enfermedad de Parkinson.

For decades Parkinson's disease has been considered to be limited to disturbed motor functions and its association with a cognitive deterioration is very recent. The frequency of cognitive decline varies according to the authors between 3% and 93% depending on the different criteria of evaluation. Owing to the discrepancy among the previous studies our object has been to determine the existence of cognitive changes of statistical significance, since even nowadays the relation between neuropsychology and physiopathology has been misunderstood. A total of 50 patients between 52 and 85 years old with Parkinson's disease have been neurological and neuropsychologically evaluated and the results correlated with 50 healthy controls. Patients, who presented clinical signs of demence according to the criteria of DSM III or any other neurological or general disease were excluded because of possible side effects on the motor cognitive phase. For the neuropsychological study Signoret's Battery of Cognitive Efficiency test (BEC 96) was used, it evaluates: the attention, orientation, thinking, memory, recognition, serial learning, fluency, naming and constructional functions. It was observed that all the patients with Parkinson's disease performed these tests worse than the controls, except for attention. From the statistical point of view the differences are highly significant (p < 0.001) for serial learning and constructional tests and significant (p < 0.05) for orientation, thinking fluency and naming. In the area of mnesic functions the patients with Parkinson's disease show an alteration that predominates significantly on serial learning, however, it is less important for logical memory. All the alterations correspond to the long term memory.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluacion neuropsicologica en la enfermedad de Parkinson / Neurological evaluation in Parkinson disease

La enfermedad de Parkinson fue considerada clásicamente un trastorno motor y su asociación con un deterioro cognitivo es reciente. Aún en la actualidad permanecen mal comprendidas la relación entre la neuropsicología y su fisiopatología. Fueron evaluadas neurológica y neuropsicológicamente 50 pacientes con enfermedad de parkinson y sus resultados fueron correlacionados con 50 controles sanos. Para la evaluación neuropsicológica se utilizó la Batería de Eficiencia Cognitiva de Signoret (BEC 96) que estudia la atención, la orientación, el pensamiento, el recuerdo, el reconocimiento, el aprendizaje, la fluencia, la denominación y la visuoconstrucción. Así se encontró que los pacientes con enfermedad de Parkinson, realizaron peor que los sujetos controles todas las pruebas salvo la atención. En el área de las funciones mnésicas los pacientes parkinsonianos mostraron una alteración que predomina significativamente en el aprendizaje serial siendo menos importante en la memoria lógica. Todos los trastornos correspondieron a la memoria a largo plazo. A nivel del lenguje encontramos alterada la denominación y la fluencia semática. El 56% de los pacientes con Parkinson tenían fallas en la prueba de denominación, de ellas el 40% fueron anomias de evocación y el 60% defectos visuo-perceptivos. Estos últimos fueron confirmados por la alteración significativa de la visuoconstrucción. El objetivo de este trabajo es presentar nuestras primeras conclusiones de la presencia de deterioro cognitivo en los pacientes parkinsonianos

Evaluación neuropsicológica en la enfermedad de Parkinson. / [Neuropsychologic evaluation in Parkinson disease]

For decades Parkinsons disease has been considered to be limited to disturbed motor functions and its association with a cognitive deterioration is very recent. The frequency of cognitive decline varies according to the authors between 3

and 93

depending on the different criteria of evaluation. Owing to the discrepancy among the previous studies our object has been to determine the existence of cognitive changes of statistical significance, since even nowadays the relation between neuropsychology and physiopathology has been misunderstood. A total of 50 patients between 52 and 85 years old with Parkinsons disease have been neurological and neuropsychologically evaluated and the results correlated with 50 healthy controls. Patients, who presented clinical signs of demence according to the criteria of DSM III or any other neurological or general disease were excluded because of possible side effects on the motor cognitive phase. For the neuropsychological study Signorets Battery of Cognitive Efficiency test (BEC 96) was used, it evaluates: the attention, orientation, thinking, memory, recognition, serial learning, fluency, naming and constructional functions. It was observed that all the patients with Parkinsons disease performed these tests worse than the controls, except for attention. From the statistical point of view the differences are highly significant (p < 0.001) for serial learning and constructional tests and significant (p < 0.05) for orientation, thinking fluency and naming. In the area of mnesic functions the patients with Parkinsons disease show an alteration that predominates significantly on serial learning, however, it is less important for logical memory. All the alterations correspond to the long term memory.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluación neuropsicológica en la enfermedad de Parkinson. / [Neuropsychologic evaluation in Parkinson disease]

For decades Parkinsons disease has been considered to be limited to disturbed motor functions and its association with a cognitive deterioration is very recent. The frequency of cognitive decline varies according to the authors between 3

and 93

depending on the different criteria of evaluation. Owing to the discrepancy among the previous studies our object has been to determine the existence of cognitive changes of statistical significance, since even nowadays the relation between neuropsychology and physiopathology has been misunderstood. A total of 50 patients between 52 and 85 years old with Parkinsons disease have been neurological and neuropsychologically evaluated and the results correlated with 50 healthy controls. Patients, who presented clinical signs of demence according to the criteria of DSM III or any other neurological or general disease were excluded because of possible side effects on the motor cognitive phase. For the neuropsychological study Signorets Battery of Cognitive Efficiency test (BEC 96) was used, it evaluates: the attention, orientation, thinking, memory, recognition, serial learning, fluency, naming and constructional functions. It was observed that all the patients with Parkinsons disease performed these tests worse than the controls, except for attention. From the statistical point of view the differences are highly significant (p < 0.001) for serial learning and constructional tests and significant (p < 0.05) for orientation, thinking fluency and naming. In the area of mnesic functions the patients with Parkinsons disease show an alteration that predominates significantly on serial learning, however, it is less important for logical memory. All the alterations correspond to the long term memory.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluacion neuropsicologica en la enfermedad de Parkinson / Neurological evaluation in Parkinson disease

La enfermedad de Parkinson fue considerada clásicamente un trastorno motor y su asociación con un deterioro cognitivo es reciente. Aún en la actualidad permanecen mal comprendidas la relación entre la neuropsicología y su fisiopatología. Fueron evaluadas neurológica y neuropsicológicamente 50 pacientes con enfermedad de parkinson y sus resultados fueron correlacionados con 50 controles sanos. Para la evaluación neuropsicológica se utilizó la Batería de Eficiencia Cognitiva de Signoret (BEC 96) que estudia la atención, la orientación, el pensamiento, el recuerdo, el reconocimiento, el aprendizaje, la fluencia, la denominación y la visuoconstrucción. Así se encontró que los pacientes con enfermedad de Parkinson, realizaron peor que los sujetos controles todas las pruebas salvo la atención. En el área de las funciones mnésicas los pacientes parkinsonianos mostraron una alteración que predomina significativamente en el aprendizaje serial siendo menos importante en la memoria lógica. Todos los trastornos correspondieron a la memoria a largo plazo. A nivel del lenguje encontramos alterada la denominación y la fluencia semática. El 56% de los pacientes con Parkinson tenían fallas en la prueba de denominación, de ellas el 40% fueron anomias de evocación y el 60% defectos visuo-perceptivos. Estos últimos fueron confirmados por la alteración significativa de la visuoconstrucción. El objetivo de este trabajo es presentar nuestras primeras conclusiones de la presencia de deterioro cognitivo en los pacientes parkinsonianos (AU)

Development of parkinsonism after transient ischemic attacks.

In order to correlate the influence of cerebrovascular disorders with the appearance of parkinsonism, 115 patients aged between 32 and 84 years (mean = 65) with transient ischemic attacks were followed up for one year. They were treated with platelet antiaggregant drugs. None of them received neuroleptics, calcium antagonists or other drugs known to induce parkinsonism. During the study, 8 patients (mean = 75 years) developed parkinsonism, bilateral in all but one, who remarkably enough was the only case responding to L-dopa treatment. On comparing recorded with expected incidence, our series showed significantly greater values. Our findings suggest that cerebrovascular disorders are factors contributing to parkinsonism in the elderly.

Creutzfeldt-Jakob disease. Report of 10 neuropathologically-verified cases in Argentina.

We describe 10 neuropathologically verified patients with Creutzfeldt-Jakob disease who died in Argentina between 1980 and 1987. Two of the ten cases were Chilean by birth. Another case visited Chile several times. Two cases (one Argentinian and one Chilean) regularly consumed sheep brain. Ages ranged from 42 to 63 years and the male to female ratio was 7:3. Disease duration ranged from 3.5 to 24 months. Prodromal symptoms presented as behavioral changes in 5 patients, lasting from one year to several weeks, and as neurological impairment in the other 5. Patients developed pyramidal, extrapyramidal and cerebellar disturbances, as well as movement disorders and progressive dementia. Visual alterations were found in 5 cases and periodic EEG activity in 7. Unequivocal cortical spongiform changes, together with varying degrees of neuronal depletion and astroglial hyperplasia were constant findings. No white matter involvement was apparent either from CT brain scans or on histopathological study of biopsied and autopsied material. Increasing awareness of this disease as well as possibilities of transmission is necessary in order to provide better information on its true incidence in Argentina.

Development of parkinsonism after transient ischemic attacks

Para tratar de correlacionar la influencia de los trastornos cerebrovasculares en el desarrollo de cuadros parkinsonianos, 115 pacientes con ataques isquémicos transitorios cuyas edades oscilan entre 32 y 84 años fueron evaluados durante un año. Los pacientes recibieron tratamiento con antiagregantes plaquetarios. En ningún caso fueron tratados con neurolépticos, antagonistas del calcio y otras drogas que pudieran causar parkinsonismo. Durante el estudio, 8 pacientes desarrollaron un cuadro parkinsoniano que fue bilateral en 7 de ellos. El único caso asimétrico fue también el único que respondió al tratamiento con L dopa. Al comparar la incidencia registrada con la esperada observamos un valor significativamente mayor en nuestra serie. Estos hallazgos sugieren que los trastornos cerebrovasculares son factores que contribuyen en el desarrollo del parkinsonismo en el anciano

Development of parkinsonism after transient ischemic attacks.

In order to correlate the influence of cerebrovascular disorders with the appearance of parkinsonism, 115 patients aged between 32 and 84 years (mean = 65) with transient ischemic attacks were followed up for one year. They were treated with platelet antiaggregant drugs. None of them received neuroleptics, calcium antagonists or other drugs known to induce parkinsonism. During the study, 8 patients (mean = 75 years) developed parkinsonism, bilateral in all but one, who remarkably enough was the only case responding to L-dopa treatment. On comparing recorded with expected incidence, our series showed significantly greater values. Our findings suggest that cerebrovascular disorders are factors contributing to parkinsonism in the elderly.

Creutzfeldt-Jakob disease. Report of 10 neuropathologically-verified cases in Argentina.

We describe 10 neuropathologically verified patients with Creutzfeldt-Jakob disease who died in Argentina between 1980 and 1987. Two of the ten cases were Chilean by birth. Another case visited Chile several times. Two cases (one Argentinian and one Chilean) regularly consumed sheep brain. Ages ranged from 42 to 63 years and the male to female ratio was 7:3. Disease duration ranged from 3.5 to 24 months. Prodromal symptoms presented as behavioral changes in 5 patients, lasting from one year to several weeks, and as neurological impairment in the other 5. Patients developed pyramidal, extrapyramidal and cerebellar disturbances, as well as movement disorders and progressive dementia. Visual alterations were found in 5 cases and periodic EEG activity in 7. Unequivocal cortical spongiform changes, together with varying degrees of neuronal depletion and astroglial hyperplasia were constant findings. No white matter involvement was apparent either from CT brain scans or on histopathological study of biopsied and autopsied material. Increasing awareness of this disease as well as possibilities of transmission is necessary in order to provide better information on its true incidence in Argentina.

Development of parkinsonism after transient ischemic attacks

Para tratar de correlacionar la influencia de los trastornos cerebrovasculares en el desarrollo de cuadros parkinsonianos, 115 pacientes con ataques isquémicos transitorios cuyas edades oscilan entre 32 y 84 años fueron evaluados durante un año. Los pacientes recibieron tratamiento con antiagregantes plaquetarios. En ningún caso fueron tratados con neurolépticos, antagonistas del calcio y otras drogas que pudieran causar parkinsonismo. Durante el estudio, 8 pacientes desarrollaron un cuadro parkinsoniano que fue bilateral en 7 de ellos. El único caso asimétrico fue también el único que respondió al tratamiento con L dopa. Al comparar la incidencia registrada con la esperada observamos un valor significativamente mayor en nuestra serie. Estos hallazgos sugieren que los trastornos cerebrovasculares son factores que contribuyen en el desarrollo del parkinsonismo en el anciano (AU)