Clinical applicability of diagnostic biomarkers in early-onset cognitive impairment.

BACKGROUND AND PURPOSE: Several diagnostic biomarkers are currently available for clinical use in early-onset cognitive impairment. The decision on which biomarker is used in each patient depends on several factors such as its predictive value or tolerability. METHODS: There were a total of 40 subjects with early-onset cognitive complaints (<65 years of age): 26 with Alzheimer's disease (AD), five with frontotemporal dementia and nine with diagnostic suspicion of non-neurodegenerative disorder. Clinical and neuropsychological evaluation, lumbar puncture for cerebrospinal fluid (CSF) AD core biochemical marker determination, medial temporal atrophy evaluation on magnetic resonance imaging, amyloid-positron emission tomography (PET) and 18 F-fluorodeoxyglucose-PET were performed. Neurologists provided pre- and post-biomarker diagnosis, together with diagnostic confidence and clinical/therapeutic management. Patients scored the tolerability of each procedure. RESULTS: Cerebrospinal fluid biomarkers and amyloid-PET increased diagnostic confidence in AD (77.4%-86.2% after CSF, 92.4% after amyloid-PET, P < 0.01) and non-neurodegenerative conditions (53.6%-75% after CSF, 95% after amyloid-PET, P < 0.05). Biomarker results led to diagnostic (32.5%) and treatment (32.5%) changes. All tests were well tolerated. CONCLUSIONS: Biomarker procedures are well tolerated and have an important diagnostic/therapeutic impact on early-onset cognitive impairment.

Decreased striatal dopamine transporter uptake in the non-fluent/agrammatic variant of primary progressive aphasia.

BACKGROUND AND PURPOSE: Patients with the non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) may develop atypical parkinsonian syndromes. However, there is no current biomarker to assess which patients are at high risk of developing parkinsonism. 123I-2ß-carbomethoxy-3ß-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane (123I-FP-CIT)-SPECT detects striatal dopamine dysfunction in vivo. The objective of the present study was to study whether non-fluent/agrammatic patients without parkinsonism at baseline present decreased striatal 123I-FP-CIT uptake. METHODS: Visual and semi-quantitative assessments of the striatal 123I-FP-CIT uptake ratio were carried out in 15 patients with nfvPPA, eight patients with the logopenic variant of PPA (lvPPA) and 18 controls. To rule out progranulin mutations or underlying Alzheimer's disease (AD), serum progranulin levels and cerebrospinal fluid (CSF) biomarkers of AD (Aß42 , total-tau, phosphorylated-tau181 ) were determined. A second 123I-FP-CIT-SPECT analysis in the biomarker-enriched groups was also carried out. RESULTS: Patients with nfvPPA presented reduced striatal 123I-FP-CIT binding, especially in the left hemisphere (P = 0.002), compared with controls. All lvPPA patients had normal striatal 123I-FP-CIT uptake. 123I-FP-CIT striatal binding in nfvPPA patients with normal progranulin and CSF biomarker levels (nfvPPA/bio-) was also significantly reduced (P < 0.05) compared with lvPPA patients with positive AD biomarkers. Sixty-four per cent (9/14) of nfvPPA patients and 80% of nfvPPA/bio- patients (8/10) showed a diminished individual left striatal 123I-FP-CIT uptake ratio. On follow-up, seven nfvPPA/bio- patients developed parkinsonism (median 1.9 years; range 1.2-2.9), six of them with baseline reduced 123I-FP-CIT uptake. CONCLUSIONS: Reduced striatal tracer uptake in nfvPPA patients prior to clinical parkinsonism can be detected by 123I-FP-CIT-SPECT, especially in those with nfvPPA/bio-, suggesting subclinical nigrostriatal degeneration. Decreased striatal 123I-FP-CIT binding might identify PPA patients at increased risk of developing atypical parkinsonian syndromes, probably related to tau-pathology.

Neuroimaging and biochemical markers in the three variants of primary progressive aphasia.

BACKGROUND/AIM: To investigate in variants of primary progressive aphasia (PPA) the association between current clinical and neuroimaging criteria and biochemical/genetic markers at the individual level. METHODS: Thirty-two PPA patients were classified as non-fluent/agrammatic (nfvPPA), semantic (svPPA), or logopenic variant (lvPPA) or as unclassifiable (uPPA). In all patients, we evaluated the neuroimaging criteria (magnetic resonance imaging and/or single photon emission computed tomography/positron emission tomography) of each variant and studied serum progranulin levels, APOE genotype and Alzheimer's disease (AD)-cerebrospinal fluid (CSF) biomarkers. Cases with a first-degree family history of early-onset dementia were genetically tested. RESULTS: Ten of 15 (66%) nfvPPA, 5/5 (100%) svPPA and 7/7 (100%) lvPPA patients showed at least one positive neuroimaging-supported diagnostic criterion. All lvPPA and 3/5 (60%) uPPA patients presented AD-CSF biomarkers, which were absent in nfvPPA and svPPA cases. Four (27%) nfvPPA patients had dementia-causing mutations: 2 carried a GRN mutation and 2 the C9ORF72 hexanucleotide expansion. CONCLUSIONS: There was an excellent association between clinical criteria and neuroimaging-supported biomarkers in svPPA and lvPPA, as well as with AD-CSF biochemical markers in the lvPPA. Neuroimaging, biochemical and genetic findings in nfvPPA were heterogeneous. Incorporating biochemical/genetic markers into the PPA clinical diagnosis would allow clinicians to improve their predictions of PPA neuropathology, especially in nfvPPA and uPPA cases.

Fuentes de información de los padres respecto a la salud de sus hijos / Sources of information for parents regarding their children's health

Objetivo: Evaluar la información que los padres buscan sobre la salud de sus hijos. Material y métodos: Estudio descriptivo de la población urbana atendida en un centro de atención primaria por el servicio de pediatría. Durante un periodo de 5 meses, un total de 201 padres que acudían a nuestras consultas rellenaron un cuestionario sobre las fuentes de información que utilizan respecto a la salud de sus hijos. Resultados: El 66% de los padres consulta algún medio de comunicación sobre problemas de salud. Los medios más utilizados son Internet (85%), las revistas especializadas (36%) y la televisión (18%). El 96% de respondedores tiene acceso a la red, y de éstos el 85% tiene conexión en casa. El 67% consultó algún problema médico en Internet durante el último año, y de éstos a un 93% le resultó útil. El 84% de los padres que habían consultado Internet en el último año se informaron por este medio de algún problema de salud antes y/o después de visitar a su pediatra/enfermera. Un 45% de los padres se alarmó después de leer alguna información médica en algún medio de comunicación, y un 65% de éstos consultó a su pediatra o enfermera por este motivo. Un 98% confía más en su pediatra que en Internet. Conclusión: Una elevada proporción de padres tiene acceso a Internet y lo utiliza para obtener información sobre temas de salud de sus hijos. Frecuentemente, esta búsqueda está relacionada con las visitas realizadas al personal sanitario. Los profesionales de la salud deberíamos estar preparados para orientar a los padres en la búsqueda de información en la Red(AU)

Objective: To evaluate the information that parents are looking for about their children’s health. Material and methods: Descriptive study of the urban population attended at a primary care center by the pediatric services. During a 5-month period, a total of 201 parents came to our consultations and filled out a questionnaire about the information sources that they use regarding their children’s health. Results: 66% of the parents consulted some kind of mass media about health issues. The most widely used are Internet (85%), specialized magazines (36%) and television (18%). 96%of respondents have access to the internet; of these 85% have access at their home. 67% consulted for a medical problem on the Internet during the last year, 93% of these found it helpful. 84% of the parents who had accessed Internet got information through this source about any kind of health problem before and or after visiting the pediatrician or nurse. 45% of the parents were alarmed after reading some medical information in mass media and 65% of these, consulted their doctor or nurse about it. A 98% have more confidence in their pediatrician tha non the Internet. Conclusion: A high percentage of parents have Internet access and uses it to obtain information on health issues about their children. This search is often related to visits by health professionals. Health professionals should be prepared on guiding parents to find information on the Internet(AU)

Alteración selectiva de los sistemas declarativos de memoriaen los pacientes tratados con un elevado número de sesionesde terapia electroconvulsiva / Selective alteration of the declarative memory systems in patients treated with a high number of electroconvulsive therapy sessions

Introducción. Los efectos electroquímicos reversibles de la terapia electroconvulsiva (TEC) sobre zonas cerebrales específicas permiten el estudio de las bases neuroanatómicas de algunas funciones cognitivas. Los estudios sobre los sistemas de memoria observan una alteración selectiva de los declarativos después de un tratamiento con TEC. Pocos trabajos han estudiado la alteración diferencial de los subsistemas de memoria en pacientes con un elevado número de sesiones de TEC. Objetivo. Estudiar el sistema declarativo y no declarativo de memoria en pacientes psiquiátricos sometidos a un tratamiento de TEC de mantenimiento, con un elevado número de sesiones de TEC previas. Pacientes y métodos. 20 pacientes sometidos a tratamiento con TEC (10 diagnosticados de depresión y 10 de esquizofrenia) y 20 pacientes controles apareados por edad, sexo y diagnóstico psicopatológico. Para la evaluación del sistema declarativo de memoria se utilizó la prueba de memoria lógica Wechsler Memory Scale (WMS). La prueba procedimental de la Torre de Hanoi se utilizó para valorar el sistema no declarativo. Resultados. Se observa un peor rendimiento de la prueba de memoria lógica de la WMS en pacientes tratados con TEC, que sólo es significativo en los pacientes diagnosticados de depresión. No se observan diferencias significativas en la Torre de Hanoi. Conclusiones. Se detecta una alteración selectiva de los sistemas declarativos en pacientes tratados con un número elevado de sesiones de TEC, mientras que los sistemas no declarativos de memoria se preservan (AU)

Asymmetric myoclonic parietal syndrome in a patient with Alzheimer's disease mimicking corticobasal degeneration.

We describe a patient who presented a progressive asymmetrical parietal syndrome including ideomotor apraxia, hemiinattention, unilateral limb dystonia and myoclonus. The clinical picture of this patient supported the clinical diagnosis of corticobasal degeneration (CBD). However, the neuropathologic examination revealed abundant cortical betaA4-amyloid deposits, and phosphorylated tau accumulation in neuritic plaques, neurofibrillary tangles and neuropil threads corresponding to Alzheimer's disease (AD) stage V of Braak and Braak. This case supports the clinical heterogeneity in AD and the existence of a clinical overlap between AD and CBD.

Síndrome parietal asimétrico en un paciente con enfermedad de Alzheimer simulando una degeneración corticobasal / Asymmetric myoclonic parietal syndrome in a patient with Alzheimer's disease mimicking corticobasal degeneration

Presentamos un paciente con un síndrome parietal asimétrico progresivo con apraxia ideomotriz, hemiinatención, distonía de miembro unilateral y mioclonías. El cuadro clínico de este paciente sugirió el diagnóstico clínico de degeneración corticobasal (DCB). Sin embargo, el examen neuropatológico reveló abundantes depósitos de amiloide A4 y acumulaciones de tau fosforilada en forma de placas neuríticas, ovillos neurofibrilares e hilos en el neuropilo correspondientes a una enfermedad de Alzheimer en estadio V de Braak y Braak. Este caso apoya la heterogeneidad clínica en la enfermedad de Alzheimer y la existencia de un solapamiento clínico entre ésta y la DCB. (AU)

A novel mutation (V89L) in the presenilin 1 gene in a family with early onset Alzheimer's disease and marked behavioural disturbances.

A novel mutation (V89L) in the presenilin 1 (PSEN1) gene is described in a family with pathologically confirmed Alzheimer's disease. The mutation was identified in two affected members with early onset Alzheimer's disease characterised by early and marked behavioural disturbances. The mutation is located on the same side of the helix as other described mutations in the first transmembrane domain and its relation to other mutations in this helix suggests that they share a common pathogenic mechanism.

A novel presenilin 2 gene mutation (D439A) in a patient with early-onset Alzheimer's disease.

The authors describe a novel missense mutation in the presenilin 2 (PSEN2) gene at residue 439 that predicts an aspartate-to-alanine substitution (D439A). This mutation was found in a 58-year old patient who displayed a progressive dementia at the age of 52. The mutation was absent in his cognitively normal relatives. Haplotype analysis indicated that his affected mother was the most probable mutation carrier. The D439A mutation is located near the C-terminal end of the PS2 protein, a region critical for endoproteolytic processing.

Detection of the presenilin 1 gene mutation (M139T) in early-onset familial Alzheimer disease in Spain.

In a family with early-onset Alzheimer disease (EOAD) from Spain we found a mutation in the presenilin 1 (PS1) gene that predicts a methionine-to-threonine change at the PS1 residue 139 (M139T). This mutation was previously reported in a independent French family. The age of onset of the disease was similar in the affected members from both families, suggesting a specific age of expression (range 47-50 years). The detection of the M139T mutation in an independent EOAD family strongly supports the pathogenicity of this mutation in familial Alzheimer disease (AD).

Effect of L-ethionine on the expression of the SOS system in Escherichia coli.

The effect of L-ethionine, the ethyl analog of the essential amino acid methionine, on the SOS system of Escherichia coli was studied. This compound does not induce either inhibition of cell division nor cessation of cell respiration in a RecA+ Met+ RelA+ strain, nor in RecA+ Met- RelA+ or RecA+ Met- RelA- mutants. Nevertheless, L-ethionine blocks the expression of both cited SOS functions in a recA441 mutant when it is growing at the restrictive temperature of 42 degrees C. Furthermore, the inhibitory effect of the L-ethionine on the induction of the SOS system in this mutant is increased when the cells are preincubated for several hours in the presence of the analog, before the temperature shift. Moreover, cultures of the recA441 mutant incubated at 42 degrees C in the presence of both L-ethionine and L-methionine present the same behaviour as the cultures of this mutant growing at the same temperature but without either amino acid. On the other hand, L-ethionine does not have any effect on the expression of the two mentioned SOS functions when these are induced by UV-irradiation in a RecA+ strain even if this compound is added to the cells several hours before irradiation.