RESUMEN
BACKGROUND AND PURPOSE: Transient global amnesia (TGA) is characterized by a sudden onset of anterograde amnesia lasting up to 24 h. One major differential for TGA is transient epileptic amnesia, which typically lasts < 1 h. However, TGA can also be short in duration and little is known about the time trends, characteristics and prognosis of TGA cases lasting < 1 h. METHODS: We compared the clinical features of TGA ascertained in two independent cohort studies in Oxfordshire, UK [Oxford cohort 1977-1987 versus Oxford Vascular Study (OXVASC) 2002-2018] to determine the time trends of clinical features of TGA. Results were validated in another independent contemporary TGA cohort in Italy [Northern Umbria TGA registry (NU) 2002-2018]. We compared the risk factors, clinical features and long-term prognosis (major cardiovascular events, recurrent TGA and seizure/epilepsy) of patients presenting with episodes lasting < 1 h versus those lasting ≥ 1 h. RESULTS: Overall, 639 patients with TGA were included (114 Oxford cohort, 100 OXVASC, 425 NU). Compared with the original Oxford cohort, there were more cases with TGA lasting < 1 h in OXVASC [32 (32.0%) vs. 9 (8.8%)] and NU (11.8% vs. 8.8% in Oxford cohort). In both OXVASC and NU, patient age, vascular risk factors and clinical features were largely similar between those with TGA lasting < 1 h versus those lasting ≥ 1 h. Moreover, there was no difference in the long-term risk of seizure/epilepsy or major cardiovascular events between TGA lasting < 1 h versus TGA lasting ≥ 1 h. CONCLUSIONS: Short-duration TGA episodes (<1 h) were not uncommon and were more frequent than in earlier studies. The clinical features and long-term prognosis of short-duration TGA did not differ from more typical episodes lasting ≥ 1 h.
Asunto(s)
Amnesia Global Transitoria , Amnesia , Amnesia Global Transitoria/diagnóstico , Amnesia Global Transitoria/epidemiología , Epilepsia/epidemiología , Humanos , Italia/epidemiología , PronósticoRESUMEN
BACKGROUND AND PURPOSE: Biomarkers support the aetiological diagnosis of neurocognitive disorders in vivo. Incomplete evidence is available to drive clinical decisions; available diagnostic algorithms are generic and not very helpful in clinical practice. The aim was to develop a biomarker-based diagnostic algorithm for mild cognitive impairment patients, leveraging on knowledge from recognized national experts. METHODS: With a Delphi procedure, experienced clinicians making variable use of biomarkers in clinical practice and representing five Italian scientific societies (neurology - Società Italiana di Neurologia per le Demenze; neuroradiology - Associazione Italiana di Neuroradiologia; biochemistry - Società Italiana di Biochimica Clinica; psychogeriatrics - Associazione Italiana di Psicogeriatria; nuclear medicine - Associazione Italiana di Medicina Nucleare) defined the theoretical framework, relevant literature, the diagnostic issues to be addressed and the diagnostic algorithm. An N-1 majority defined consensus achievement. RESULTS: The panellists chose the 2011 National Institute on Aging and Alzheimer's Association diagnostic criteria as the reference theoretical framework and defined the algorithm in seven Delphi rounds. The algorithm includes baseline clinical and cognitive assessment, blood examination, and magnetic resonance imaging with exclusionary and inclusionary roles; dopamine transporter single-photon emission computed tomography (if no/unclear parkinsonism) or metaiodobenzylguanidine cardiac scintigraphy for suspected dementia with Lewy bodies with clear parkinsonism (round VII, votes (yes-no-abstained): 3-1-1); 18 F-fluorodeoxyglucose positron emission tomography for suspected frontotemporal lobar degeneration and low diagnostic confidence of Alzheimer's disease (round VII, 4-0-1); cerebrospinal fluid for suspected Alzheimer's disease (round IV, 4-1-0); and amyloid positron emission tomography if cerebrospinal fluid was not possible/accepted (round V, 4-1-0) or inconclusive (round VI, 5-0-0). CONCLUSIONS: These consensus recommendations can guide clinicians in the biomarker-based aetiological diagnosis of mild cognitive impairment, whilst guidelines cannot be defined with evidence-to-decision procedures due to incomplete evidence.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico , Encéfalo/diagnóstico por imagen , Disfunción Cognitiva/diagnóstico , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/diagnóstico por imagen , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Disfunción Cognitiva/sangre , Disfunción Cognitiva/líquido cefalorraquídeo , Disfunción Cognitiva/diagnóstico por imagen , Consenso , Humanos , Italia , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones/métodosRESUMEN
Dementia with Lewy bodies (DLB) causes elevated outlays for the National Health Systems due to high institutionalization rate and patients' reduced quality of life and high mortality. Furthermore, DLB is often misdiagnosed as Alzheimer's disease. These data motivate harmonized multicenter longitudinal cohort studies to improve clinical management and therapy monitoring. The Italian DLB study group of the Italian Neurological Society for dementia (SINdem) developed and emailed a semi-structured questionnaire to 572 national dementia centers (from primary to tertiary) to prepare an Italian large longitudinal cohort. The questionnaire surveyed: (1) prevalence and incidence of DLB; (2) clinical assessment; (3) relevance and availability of diagnostic tools; (4) pharmacological management of cognitive, motor, and behavioural disturbances; (5) causes of hospitalization, with specific focus on delirium and its treatment. Overall, 135 centers (23.6 %) contributed to the survey. Overall, 5624 patients with DLB are currently followed by the 135 centers in a year (2042 of them are new patients). The percentage of DLB patients was lower (27 ± 8 %) than that of Alzheimer's disease and frontotemporal dementia (56 ± 27 %) patients. The majority of the centers (91 %) considered the clinical and neuropsychological assessments as the most relevant procedure for a DLB diagnosis. Nonetheless, most of the centers has availability of magnetic resonance imaging (MRI; 95 %), electroencephalography (EEG; 93 %), and FP-CIT single photon emission-computerized tomography (SPECT; 75 %) scan for clinical applications. It will be, therefore, possible to recruit a large harmonized Italian cohort of DLB patients for future cross-sectional and longitudinal multicenter studies.
Asunto(s)
Enfermedad por Cuerpos de Lewy/diagnóstico , Enfermedad por Cuerpos de Lewy/terapia , Enfermedad de Alzheimer/diagnóstico , Estudios de Cohortes , Diagnóstico Diferencial , Manejo de la Enfermedad , Humanos , Italia , Proyectos de Investigación , Encuestas y CuestionariosRESUMEN
BACKGROUND: In the field of Alzheimer's disease (AD), the validation of biomarkers for early AD diagnosis and for use as a surrogate outcome in AD clinical trials is of considerable research interest. OBJECTIVE: To characterize the clinical profile and genetic, neuroimaging and neurophysiological biomarkers of prodromal AD in amnestic mild cognitive impairment (aMCI) patients enrolled in the IMI WP5 PharmaCog (also referred to as the European ADNI study). METHODS: A total of 147 aMCI patients were enrolled in 13 European memory clinics. Patients underwent clinical and neuropsychological evaluation, magnetic resonance imaging (MRI), electroencephalography (EEG) and lumbar puncture to assess the levels of amyloid ß peptide 1-42 (Aß42), tau and p-tau, and blood samples were collected. Genetic (APOE), neuroimaging (3T morphometry and diffusion MRI) and EEG (with resting-state and auditory oddball event-related potential (AO-ERP) paradigm) biomarkers were evaluated. RESULTS: Prodromal AD was found in 55 aMCI patients defined by low Aß42 in the cerebrospinal fluid (Aß positive). Compared to the aMCI group with high Aß42 levels (Aß negative), Aß positive patients showed poorer visual (P = 0.001), spatial recognition (P < 0.0005) and working (P = 0.024) memory, as well as a higher frequency of APOE4 (P < 0.0005), lower hippocampal volume (P = 0.04), reduced thickness of the parietal cortex (P < 0.009) and structural connectivity of the corpus callosum (P < 0.05), higher amplitude of delta rhythms at rest (P = 0.03) and lower amplitude of posterior cingulate sources of AO-ERP (P = 0.03). CONCLUSION: These results suggest that, in aMCI patients, prodromal AD is characterized by a distinctive cognitive profile and genetic, neuroimaging and neurophysiological biomarkers. Longitudinal assessment will help to identify the role of these biomarkers in AD progression.
Asunto(s)
Enfermedad de Alzheimer/diagnóstico , Anciano , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Péptidos beta-Amiloides/líquido cefalorraquídeo , Apolipoproteínas E/genética , Biomarcadores/líquido cefalorraquídeo , Encéfalo/diagnóstico por imagen , Electroencefalografía , Femenino , Genotipo , Humanos , Imagen por Resonancia Magnética , Masculino , Pruebas Neuropsicológicas , Fragmentos de Péptidos/líquido cefalorraquídeo , Punción Espinal , Proteínas tau/líquido cefalorraquídeoRESUMEN
BACKGROUND: In the perspective of novel treatments with disease-modifying drugs, a timely diagnosis of Alzheimer's' disease (AD) at preclinical phase represents a major issue. To this purpose, in clinical setting, there is the need to detect the earliest cognitive symptoms not yet fulfilling Mild Cognitive Impairment criteria, in order to proceed to biomarker assessment for diagnostic definition. In terms of cognitive performance, Subjective Cognitive Decline (SCD) is still a controversial entity, due to the difficulty of reliably measuring subtle deficits. OBJECTIVE: To evaluate the possibility to predict the presence of AD-like CSF pattern in SCD individuals, according to their neuropsychological performance assessed by means of both traditional and computerized measures. DESIGN: Retrospective study. SETTING: Clinical setting (Centre for Memory Disturbances, Section of Neurology, University Hospital of Perugia, Italy). PARTICIPANTS: 74 consecutive SCD subjects who underwent an in-depth (paper-pencil and computerized) neuropsychological assessment and CSF analysis for AD biomarkers (Aß42/Aß40 ratio, phospho-tau, total tau). MEASUREMENTS: Neuropsychological assessment was composed of traditional tests assessing five cognitive domains (verbal memory, attention, executive functions, language, visuo-spatial abilities) and computerized tasks from CAmbridge Neuropsychological Test Automated Battery (CANTAB) (Pattern Recognition Memory, Paired Associates Learning and Spatial Working Memory). According to their performance at traditional tests, SCD individuals were categorized into cognitively normal (CN) and subtle impaired (SI); with respect to CANTAB, they were defined as CANTAB- in presence of normal performance, and CANTAB+ in presence of at least one pathological score. The subgroup with completely normal performance was defined as CN/CANTAB-, and the subgroup with impairment in both measures as SI/CANTAB+. Differences in prevalence of A/T/N profile according to cognitive profiles were assessed by Fisher's exact text for count data. RESULTS: None of CN/CANTAB- subjects showed A+/T+ status. SI/CANTAB+ subjects showed a significantly high prevalence of A+/T+ profile (14/35, 40%, p=0.03 vs CN/CANTAB-). CONCLUSION: The neuropsychological profile may be of help in identifying SCD subjects requiring biomarker assessment. If confirmed in larger cohorts, the combination of traditional and computerized tests (namely, CANTAB) might represent a feasible strategy in clinical setting for carrying out biomarker assessment in individuals before the MCI stage. Detection of AD in these subjects would give them the highest chances to halt disease progression by means of disease modifying treatments.
Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Humanos , Enfermedad de Alzheimer/psicología , Estudios Retrospectivos , Disfunción Cognitiva/psicología , Memoria a Corto Plazo , BiomarcadoresRESUMEN
BACKGROUND AND PURPOSE: SCA15 is a recently identified spinocerebellar ataxia with pure cerebellar involvement. Here, we report a novel SCA15 Italian family with atypical clinical features. METHODS: Three affected members from a three-generation family segregating an autosomal dominant cerebellar ataxia underwent clinical examination and genetic tests for hereditary ataxia. RESULTS: All affected members present with cognitive impairment and two of them with mild intermittent involuntary movements in association with the clinical hallmarks of SCA15 (gait ataxia, balance impairment, and dysarthria). Genetic tests detected a large deletion spanning ITPR1 and SUMF1 genes in affected members. CONCLUSION: Our findings help enlarging the clinical spectrum of SCA15.
Asunto(s)
Trastornos del Conocimiento/genética , Receptores de Inositol 1,4,5-Trifosfato/genética , Trastornos del Movimiento/genética , Ataxias Espinocerebelosas/genética , Anciano , Trastornos del Conocimiento/diagnóstico , Disartria/diagnóstico , Disartria/genética , Femenino , Ataxia de la Marcha/diagnóstico , Ataxia de la Marcha/genética , Genes Dominantes/genética , Predisposición Genética a la Enfermedad/genética , Humanos , Masculino , Trastornos del Movimiento/diagnóstico , Oxidorreductasas actuantes sobre Donantes de Grupos Sulfuro , Linaje , Ataxias Espinocerebelosas/diagnóstico , Sulfatasas/genéticaRESUMEN
BACKGROUND AND PURPOSE: Magnetization transfer ratio (MTR) technique has identified brain changes in grey and white matter in Parkinson's disease (PD), even in the early phase. However, how these tissue changes differ along the course of the illness is still unclear. This study was aimed at investigating how MTR values change from mild PD (PD1) to patients with advanced PD (PD2). METHODS: We measured MTR values by region of interest, in 11 PD1, 11 PD2 and 10 healthy age-matched subjects. RESULTS: Compared with controls, patients with PD1 exhibited a significant MTR reduction in substantia nigra pars compacta, substantia nigra pars reticulata, putamen, periventricular white matter and parietal white matter. In addition to the changes observed in PD1, the PD2 group exhibited a significant MTR reduction in caudate, pons, frontal white matter and lateral thalamus. CONCLUSION: These results suggest that MTR might reflect morphological changes induced by the disease in distinct brain areas at different stages.
Asunto(s)
Encéfalo/patología , Enfermedad de Parkinson/patología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: To measure cerebrospinal fluid (CSF) activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) in patients with Alzheimer's disease (AD) participating in randomized clinical trials from three European centers, before and after long-term treatment with different AChE inhibitors (AChEIs). MATERIALS AND METHODS: Of the 144 patients included in the study, 104 were treated with donepezil, 15 with galantamine, 16 with rivastigmine, and nine with placebo. CSF AChE and BChE activities were measured at baseline and after 1- year treatment. RESULTS: Donepezil and galantamine groups showed a significant increase in CSF AChE activity at follow-up, while no changes for BChE activity were observed; in donepezil group, a positive correlation between plasma concentration and AChE activity was documented. Conversely, in rivastigmine group, a decrease in CSF activity of both enzymes was observed. CSF AChE and BChE activities were not correlated with the clinical outcome in any group considered. CSF biomarkers did not show any change after treatment. CONCLUSIONS: AChEIs differently influence the activity of target enzymes in CSF independent of their pharmacodynamic effects.
Asunto(s)
Acetilcolinesterasa/líquido cefalorraquídeo , Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/tratamiento farmacológico , Butirilcolinesterasa/líquido cefalorraquídeo , Inhibidores de la Colinesterasa/uso terapéutico , Acetilcolinesterasa/sangre , Anciano , Anciano de 80 o más Años , Enfermedad de Alzheimer/sangre , Péptidos beta-Amiloides/líquido cefalorraquídeo , Butirilcolinesterasa/sangre , Método Doble Ciego , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Fragmentos de Péptidos/líquido cefalorraquídeo , Estadísticas no Paramétricas , Proteínas tau/líquido cefalorraquídeoRESUMEN
Mini-Mental State Examination (MMSE) lacks of sensitivity in detecting cognitive deficits associated with subcortical damage. The HIV-Dementia Scale (HDS), a screening tool originally created for detecting cognitive impairment due to subcortical damage in HIV + patients, has proved to be useful in other neurological diseases. Until now, an Italian version of the HDS is not available. We aimed at: (1) validating the HDS Italian version (HDS-IT) in a cohort of cognitively healthy subjects (CN); (2) exploring the suitability of HDS-IT in detecting cognitive impairment due to subcortical damage (scCI). The psychometric properties of the HDS-IT were assessed in 180 CN (mean age 67.6 ± 8.3, range 41-84) with regard to item-total correlation, test-retest reliability and convergent validity with MMSE. Item-total correlations ranged 0.44-0.72. Test-retest reliability was 0.70 (p < 0.001). The HDS-IT scores were positively associated with MMSE score (rS = 0.49, p < 0.001). Then, both the HDS-IT and the MMSE were administered to 44 scCI subjects (mean age 64.9 ± 10.6, range 41-84). Mean HDS-IT total score was close to the original version and significantly lower in the scCI group compared to CN (8.6 ± 3.6 vs. 12.6 ± 2.5, p < 0.001). ROC analysis yielded an optimal cutoff value of 11, with sensitivity of 0.70 and specificity of 0.82. Patients showed poorer scores on HDS-IT compared to CN (12.6 ± 2.5 vs. 8.6 ± 3.6, p < 0.001). Our results support the use of HDS-IT as a screening tool suitable for detecting cognitive deficits with prevalent subcortical pattern, being complementary to MMSE in clinical practice.
Asunto(s)
Complejo SIDA Demencia , Disfunción Cognitiva , Complejo SIDA Demencia/diagnóstico , Anciano , Cognición , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Humanos , Italia , Persona de Mediana Edad , Pruebas Neuropsicológicas , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
The autophagy-lysosomal degradation pathway plays a role in the onset and progression of neurodegenerative diseases. Clinical and genetic studies indicate that mutations of beta-glucocerebrosidase represent genetic risk factors for synucleinopathies, including Parkinson's Disease (PD) and Dementia with Lewy Bodies (DLB). We recently found a decreased activity of lysosomal hydrolases, namely beta-glucocerebrosidase, in cerebrospinal fluid of PD patients. We have thus measured the activity of these enzymes - alpha-mannosidase (EC 3.2.1.24), beta-mannosidase (EC 3.2.1.25), beta-glucocerebrosidase (EC 3.2.1.45), beta-galactosidase (EC 3.2.1.23) and beta-hexosaminidase (EC 3.2.1.52) - in cerebrospinal fluid of patients suffering from DLB, Alzheimer's Disease (AD), Fronto-Temporal Dementia (FTD) and controls. Alpha-mannosidase activity showed a marked decrease across all the pathological groups as compared to controls. Conversely, beta-glucocerebrosidase activity was selectively reduced in DLB, further suggesting that this enzyme might specifically be impaired in synucleinopathies.
Asunto(s)
Glucosilceramidasa/líquido cefalorraquídeo , Enfermedad por Cuerpos de Lewy/líquido cefalorraquídeo , Enfermedad por Cuerpos de Lewy/enzimología , Anciano , Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/enzimología , Demencia/líquido cefalorraquídeo , Demencia/enzimología , Femenino , Humanos , Masculino , Persona de Mediana Edad , alfa-Manosidasa/líquido cefalorraquídeo , beta-Galactosidasa/líquido cefalorraquídeo , beta-Manosidasa/líquido cefalorraquídeo , beta-N-Acetilhexosaminidasas/líquido cefalorraquídeoRESUMEN
BACKGROUND: Different cerebrospinal fluid (CSF) amyloid-beta 1-42 (Abeta(1-42)), total Tau (Tau) and Tau phosphorylated at threonine 181 (P-Tau) levels are reported, but currently there is a lack of quality control programmes. The aim of this study was to compare the measurements of these CSF biomarkers, between and within centres. METHODS: Three CSF-pool samples were distributed to 13 laboratories in 2004 and the same samples were again distributed to 18 laboratories in 2008. In 2004 six laboratories measured Abeta(1-42), Tau and P-Tau and seven laboratories measured one or two of these marker(s) by enzyme-linked immunosorbent assays (ELISAs). In 2008, 12 laboratories measured all three markers, three laboratories measured one or two marker(s) by ELISAs and three laboratories measured the markers by Luminex. RESULTS: In 2004, the ELISA intercentre coefficients of variance (interCV) were 31%, 21% and 13% for Abeta(1-42), Tau and P-Tau, respectively. These were 37%, 16% and 15%, respectively, in 2008. When we restricted the analysis to the Innotest (N = 13) for Abeta(1-42), lower interCV were calculated (22%). The centres that participated in both years (N = 9) showed interCVs of 21%, 15% and 9% and intra-centre coefficients (intraCV) of variance of 25%,18% and 7% in 2008. CONCLUSIONS: The highest variability was found for Abeta(1-42). The variabilities for Tau and P-Tau were lower in both years. The centres that participated in both years showed a high intraCV comparable to their interCV, indicating that there is not only a high variation between but also within centres. Besides a uniform standardization of (pre)analytical procedures, the same assay should be used to decrease the inter/intracentre variation.
Asunto(s)
Enfermedad de Alzheimer/líquido cefalorraquídeo , Bioensayo/métodos , Péptidos beta-Amiloides/líquido cefalorraquídeo , Ensayo de Inmunoadsorción Enzimática/métodos , Humanos , Reproducibilidad de los Resultados , Proteínas tau/líquido cefalorraquídeoRESUMEN
BACKGROUND AND PURPOSE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) can be considered a useful model of pure subcortical vascular dementia (SVD) because it occurs in young adults, unlikely to have concomitant age- and Alzheimer's disease (AD)-related pathology. In patients with CADASIL we evaluated the cerebrospinal fluid (CSF) levels of beta-amyloid 1-42 (Abeta42), total tau protein (t-tau) and phosphorylated tau protein (p-tau), which are well-accepted biomarkers of AD. METHODS: The CSF Abeta42, t-tau and p-tau levels were determined with Innotest beta-amyloid 1-42, Innotest hTAU-Ag and Innotest Phospho-tau 181p sandwich enzyme-linked immunoassay, in 10 CADASIL patients and 17 healthy age-matched subjects. A case-control statistical analysis was carried out. RESULTS: CSF Abeta42 levels were significantly lower in CADASIL patients than in controls, whereas CSF t-tau and p-tau levels did not differ between the two groups. CONCLUSIONS: The pattern found in CADASIL patients is similar to that reported in those with sporadic SVD, suggesting that decreased CSF Abeta42 might be related to the subcortical vascular lesions in the white matter.
Asunto(s)
Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/complicaciones , Péptidos beta-Amiloides/líquido cefalorraquídeo , CADASIL/líquido cefalorraquídeo , CADASIL/complicaciones , Fragmentos de Péptidos/líquido cefalorraquídeo , Proteínas tau/líquido cefalorraquídeo , Anciano , Enfermedad de Alzheimer/fisiopatología , Péptidos beta-Amiloides/análisis , Biomarcadores/análisis , Biomarcadores/líquido cefalorraquídeo , Encéfalo/metabolismo , Encéfalo/patología , Encéfalo/fisiopatología , CADASIL/fisiopatología , Comorbilidad , Humanos , Persona de Mediana Edad , Ovillos Neurofibrilares/metabolismo , Ovillos Neurofibrilares/patología , Fragmentos de Péptidos/análisis , Fosforilación , Placa Amiloide/metabolismo , Placa Amiloide/patología , Valor Predictivo de las Pruebas , Proteínas tau/análisisRESUMEN
High plasma homocysteine levels have been observed in Parkinson's disease (PD) patients treated with levodopa. In this study, we investigated the effects of C677T and A1298C MTHFR polymorphisms, in association with L-DOPA daily dose and vitamin status, on hyperhomocysteinemia development in PD patients. Plasma homocysteine and folate/vitamin B12 levels were assayed in 49 L-DOPA-treated PD patients, and compared with those of 86 healthy subjects. Genotyping for MTHFR polymorphisms was carried out by DG-DGGE. Homocysteine levels were significantly higher in patients than in controls (16.3 +/- 5.7 vs. 11.7 +/- 2.7 micromol/l, P < 0.01). No significant differences were found between patients and controls with regard to folate/vitamin B12 levels, and MTHFR allele distribution. The TT+AA genotype was significantly more frequent in PD patients than in controls (32.5% vs. 17.4%, P < 0.05), but not associated with an increased risk for PD (OR = 2.3, CI = 1.0-5.2). Further, patients carrier of this genotype exhibited a mild hyperhomocysteinemia (22.1 +/- 4.9 micromol/l), while a protective effect was observed in patients having the CC+AA genotype (11.2 +/- 1.6 micromol/l; OR = 0.19, CI = 0.06-0.59). Interestingly, homocysteine levels were also moderately increased in patients with CT heterozygous genotype, in the context of either AA or AC (14.5 +/- 3.6 micromol/l), in comparison to subjects with the CC + AA genotype. Finally, we did not find any significant association of combined C677T and A1298C MTHFR polymorphisms with an increased risk for hyperhomocysteinemia in PD patients. A better understanding of the role of homocysteine and MTHFR genotypes in PD is needed to reveal novel approaches for disease management.
Asunto(s)
Antiparkinsonianos/uso terapéutico , Homocisteína/sangre , Hiperhomocisteinemia/enzimología , Levodopa/uso terapéutico , Metilenotetrahidrofolato Reductasa (NADPH2)/fisiología , Enfermedad de Parkinson/tratamiento farmacológico , Polimorfismo Genético , Anciano , Femenino , Ácido Fólico/sangre , Humanos , Hiperhomocisteinemia/genética , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Persona de Mediana Edad , Enfermedad de Parkinson/enzimología , Enfermedad de Parkinson/genética , Vitamina B 12/sangreRESUMEN
Levetiracetam (LEV) monotherapy was investigated in 25 patients with advanced Alzheimer's disease (AD) and new-onset epileptic seizures in a prospective open-label study. At a daily dose of 1000-1500 mg, 72% were seizure-free for at least one year; 16% discontinued for untolerability; 8% were unresponsive; 4% were lost to follow-up. These results suggest the need for controlled studies to confirm if LEV can be a first-choice drug in AD.
Asunto(s)
Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/tratamiento farmacológico , Piracetam/análogos & derivados , Convulsiones/complicaciones , Convulsiones/tratamiento farmacológico , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Levetiracetam , Masculino , Piracetam/administración & dosificación , Estudios ProspectivosRESUMEN
Early identification of dementia and possible risk factors is a critical issue. The Basic Italian Cognitive Questionnaire (BICQ) is designed as a routine instrument for screening patients with initial cognitive impairment in daily practice. It is devoted to the general physician who needs a tool for deciding whether a subject deserves further diagnostic investigation in specialised centres. The administration of BICQ is easy, fast and does not require any training, since it is composed of 12 simple and ecologic questions referring to daily life. The discriminant analysis, a predictive model that generates a function based on linear combinations of the predictor variables, provided the best discrimination between controls with respect to the group of deteriorated patients. According to the classification function coefficients, the questionnaire score predicted correctly 100% of normal subjects and 85% of patients with cognitive impairment. Moreover, the receiving operating characteristics (ROC) analysis showed that the highest sensitivity and specificity were obtained at the cut-off value of 10. Thus, a Asunto(s)
Trastornos del Conocimiento/diagnóstico
, Demencia/diagnóstico
, Encuestas y Cuestionarios
, Anciano
, Anciano de 80 o más Años
, Femenino
, Humanos
, Masculino
, Persona de Mediana Edad
, Curva ROC
RESUMEN
BACKGROUND AND PURPOSES: Atrial fibrillation (AF) is an independent risk factor for stroke. The aims of this study were to assess: (i) the frequency of known or unknown AF in patients admitted to the hospital for a first-ever ischemic stroke and whether AF is associated with an adverse outcome at discharge (death or disability); (ii) the rates and determinants for the use of antithrombotic agents before stroke in patients with known AF and the adherence to the current treatment guidelines; and (iii) whether the lack of adherence to the current guidelines is associated with adverse outcome at discharge. METHODS: Consecutive patients with acute first-ever stroke admitted to an individual Stroke Unit between January 2000 to December 2003, were included in the study. Twelve-lead electrocardiogram (ECG) was performed in all patients on admission. Functional outcome was measured at discharge according to modified Rankin Score. RESULTS: A total of 1549 patients were included in the study: 238 patients (15.4%) were known to have AF and 76 (4.9%) were diagnosed with AF (unknown) on ECG performed on admission. At discharge 91 patients (5.9%) had died and 605 patients (39.0%) had died or were functionally dependent. Multivariate analysis showed that AF on admission was correlated with mortality or disability (OR = 1.58, 95% CI 1.09-2.30, P = 0.015). Before stroke, 124 out of 238 patients with known AF (52.1%) were not on antithrombotic therapy, 83 (34.9%) were receiving antiplatelet and 31 (13.0%) anticoagulant treatment. Previous transient ischemic attack, history of ischemic heart disease and hyperlipidemia were associated with the use of antithrombotic therapy. Only 24 out of 114 patients on antithrombotic treatment on admission were adequately treated according to the current guidelines. Of the adequately treated patients, 41.7% died or were disabled at discharge respect to 52.3% of the patients non-adequately treated (RR = 0.80, 95% CI 0.48-1.30). CONCLUSIONS: AF (on history or new diagnosis) was present in 20.3% of the patients with first-ever stroke admitted to a Stroke Unit and it was associated with increased mortality or disability. Only 10% of patients with known AF were previously receiving an adequate antithrombotic treatment according to current guidelines.
Asunto(s)
Fibrilación Atrial/complicaciones , Fibrilación Atrial/tratamiento farmacológico , Fibrinolíticos/uso terapéutico , Accidente Cerebrovascular/prevención & control , Anciano , Anciano de 80 o más Años , Fibrilación Atrial/epidemiología , Estudios de Casos y Controles , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Premedicación , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND AND PURPOSE: Prestroke dementia is frequent but usually not identified. Non-valvular atrial fibrillation (NVAF) is independently associated with an increased risk for dementia. However, the frequency and determinants of prestroke dementia in patients with NVAF have never been evaluated. OBJECTIVE: The aim of this study was to determine the frequency of prestroke dementia and associated factors in patients with a previously known NVAF. METHODS: This is an ancillary study of Stroke in Atrial Fibrillation Ensemble II (SAFE II), an observational study conducted in patients with a previously known NVAF, consecutively admitted for an acute stroke in French and Italian centers. Prestroke dementia was evaluated by the IQCODE in patients with a reliable informant. Patients were considered as demented before stroke when their IQCODE score was > or = 104. RESULTS: of 204 patients, 39 (19.1%; 95% confidence interval [CI]: 13.7%-24.5%) patients met criteria for prestroke dementia. The only variable independently associated with prestroke dementia was increasing age (adjusted odds ratio for 1 year increase in age: 1.10; 95 % CI: 1.04-1.17), and there was a nonsignificant tendency for previous ischemic stroke or TIA and arterial hypertension. CONCLUSION: One fifth of stroke patients with a previously known NVAF were already demented before stroke. The main determinant of prestroke dementia is increasing age. A large cohort is necessary to identify other determinants.
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Fibrilación Atrial/complicaciones , Fibrilación Atrial/epidemiología , Demencia Vascular/complicaciones , Demencia Vascular/epidemiología , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Factores de Edad , Anciano , Anciano de 80 o más Años , Intervalos de Confianza , Femenino , Humanos , Masculino , Persona de Mediana Edad , Observación , Factores de RiesgoAsunto(s)
Biomarcadores/líquido cefalorraquídeo , Encefalopatías/líquido cefalorraquídeo , Encefalopatías/patología , Fibras Nerviosas Mielínicas/patología , Enfermedad de Alzheimer/líquido cefalorraquídeo , Enfermedad de Alzheimer/patología , Péptidos beta-Amiloides/líquido cefalorraquídeo , Trastornos del Conocimiento/líquido cefalorraquídeo , Trastornos del Conocimiento/patología , Humanos , Degeneración Nerviosa/líquido cefalorraquídeo , Degeneración Nerviosa/patologíaRESUMEN
BACKGROUND AND PURPOSE: The pathogenesis of cervical artery dissection (CAD) remains unknown in most cases. Hyperhomocyst(e)inemia [hyperH(e)], an independent risk factor for cerebrovascular disease, induces damage in endothelial cells in animal cell culture. Consecutive patients with CAD and age-matched control subjects have been studied by serum levels of homocyst(e)ine and the genotype of 5,10-methylenetetrahydrofolate reductase (MTHFR). METHODS: Twenty-six patients with CAD, admitted to our Stroke Unit (15 men and 11 women; 16 vertebral arteries, 10 internal carotid arteries), were compared with age-matched control subjects. All patients underwent duplex ultrasound, MR angiography, and/or conventional angiography. RESULTS: Mean plasma homocyst(e)ine level was 17.88 micromol/L (range 5.95 to 40.0 micromol/L) for patients with CAD and 6.0+/-0.99 micromol/L for controls (P:<0.001). The genetic analysis for the thermolabile form of MTHFR in CAD patients showed heterozygosity in 54% and homozygosity in 27%; comparable figures for controls were 40% (P:=0.4) and 10% (P:=0.1), respectively. CONCLUSIONS: Mild hyperH(e) might represent a risk factor for cervical artery dissection. The MTHFR mutation is not significantly associated with CAD. An interaction between different genetic and environmental factors probably takes place in the cascade of pathogenetic events leading to arterial wall damage.
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Disección de la Arteria Carótida Interna/diagnóstico , Hiperhomocisteinemia/diagnóstico , Disección de la Arteria Vertebral/diagnóstico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Angiografía , Disección de la Arteria Carótida Interna/sangre , Disección de la Arteria Carótida Interna/epidemiología , Comorbilidad , Susceptibilidad a Enfermedades , Femenino , Ácido Fólico/sangre , Genotipo , Homocisteína/sangre , Homocistina/sangre , Humanos , Hiperhomocisteinemia/sangre , Hiperhomocisteinemia/epidemiología , Hiperhomocisteinemia/genética , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2) , Persona de Mediana Edad , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/genética , Factores de Riesgo , Disección de la Arteria Vertebral/sangre , Disección de la Arteria Vertebral/epidemiología , Vitamina B 12/sangreRESUMEN
In order to evaluate their prevalence in senile dementias, serum titer of antibodies against histones and double stranded deoxyribonucleic acid (dsDNA) were measured by means of the ELISA test in patients suffering from vascular dementia (VD), presenile Alzheimer's disease (AD), and senile dementia of the Alzheimer's type (SDAT). Only three subjects out of 87 had dsDNA autoantibodies. On the contrary, VD and SDAT showed high titers of antibodies against histones when compared to healthy controls. A significant relationship was also found between antihistone serum titer and degree of dementia in AD. Results were not influenced by gender, age, or duration of illness. Presence of antihistone antibodies in dementias might reflect an alteration of membrane fluidity and integrity with leakage of nuclear immunogens or disturbances of immune functions, as frequently observed in dementia disorders.