RESUMO
The spectrum of neurodegenerative diseases that primarily affect cognition and behaviorspreads from asymptomatic preclinical disease to very mild cognitive impairment to frank dementia. Alzheimer's disease (AD) is the most common cause of a decline in cognitive ability. Also, it is a devastating condition that affects patients and their entirefamilies of caregivers, exacting tremendous financial hardships. Diagnosis may be complicated by other forms of dementia that have symptoms and pathologies similar to AD. Knowing the key features and pathology of each type of dementia can help in the accurate diagnosis of patients, so they will receive the treatment and support services appropriate for their condition and maintain the highest possible functioning in daily life and quality of life. Differentiate, based on clinical criteria, neuropathology, and biomarkers, AD and its atypical variants from other common dementias including Dementia with Lewy Bodies, Vascular Cognitive Impairment, Frontotemporal Degeneration, and less frequent cognitive disorders. The importance of getting an accurate and early diagnosis of dementiais now increasingly significant to make important decisions about treatment, support, and care. Nonpharmacological as well as pharmacological interventions should be initiated once the diagnosis is obtained. Biochemical markers to identify Alzheimer's disease play a central role in the new diagnostic criteria for the disease and in the recent biological definition of AD. This review article presents up-to-date data regarding the recent diagnostic criteria of Alzheimer´s disease and related disorders, emphasizing its usefulness in routine clinical practice.
El espectro de enfermedades neurodegenerativas que afectan principalmente a la cognición y el comportamiento abarca desde la enfermedad preclínica asintomática hasta el deterioro cognitivo muy leve y la demencia franca. La enfermedad de Alzheimer (EA) es la causa más común de deterioro de la capacidad cognitiva. Es una enfermedad devastadora que afecta a los pacientes y a toda su familia de cuidadores, lo que supone enormes dificultades socioeconómicas y psicoemocionales. El diagnóstico puede complicarse debido a otras formas de demencia que presentan síntomas y patologías similares a la EA. Los marcadores bioquímicos para identificar la enfermedad de Alzheimer desempeñan un papel central en los nuevos criterios diagnósticos de la enfermedad y en la reciente definición biológica de la EA. Conocer las características claves y la patología de cada tipo de demencia puede ayudar en el diagnóstico preciso de los pacientes, a fin de que reciban el tratamiento y los servicios de apoyo adecuados a su condición y mantengan el mayor funcionamiento posible en la vida diaria y la calidad de vida. Por lo tanto es prioritario diferenciar, basándose en criterios clínicos, neuropatología y biomarcadores, la EA y sus variantes atípicas de otras demencias comunes como el Deterioro Cognitivo Vascular, la Degeneración Fronto- temporal entre otras, y los trastornos cognitivos menos frecuentes. Este artículo de revisión presenta datos actualizados relativos a los recientes criterios diagnósticos de algunas formas de demencia haciendo hincapié en su utilidad en la práctica clínica habitual. Se exponen los criterios de EA, de Demencia Vascular (DV), de la demencia Fronto-temporal (DFT) y de una forma rara de demencia, descripta en los últimos años, que se evidencia en pacientes muy añosos con un perfil similar a la EA. Se trata de la encefalopatía predominantemente límbica por tdp- 43 relacionada a la edad (LATE).
Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/diagnóstico , Estudos RetrospectivosRESUMO
Se estudiaron 241 personas, 119 controles y 122 pacientes con enfermedad de Alzheimer (EA) subagrupados en tres categorías de acuerdo con el estadio clínico de la dolencia, con el objetivo de investigar la influencia de niveles elevados de cobre libre y colesterol plasmático como factores de riesgo para la EA. Las conclusiones obtenidas de los resultados indicaron que los pacientes expuestos a una combinación de alto colesterol y de cobre no unido a ceruloplasmina tuvieron mayor proporción de marcadores de estrés oxidativo (carbonilos proteicos, sustancias reactivas al tiobarbiturato, glutatión oxidado y descenso de antioxidantes totales en sangre), conjuntamente con un incremento de HDL-colesterol peroxidado y lipoproteína "a" que correlacionó con la gravedad de su cuadro. Lo mismo sucedió con la relación entre péptidos amiloides (1-40) y (1-42) en plasma y los valores del mini-test de estado cognitivo (MMSE). Se halló que una función de adición de efectos que cuantificó el daño por cobre libre y colesterol oxidado resultó directamente proporcional a la pérdida de desempeño cognitivo estimada por medio del MMSE. Esta función es de fácil determinación y puede considerarse un nuevo biomarcador para estudiar riesgo en poblaciones expuestas, apoyar el diagnóstico clínico, o evaluar la eficacia de estrategias terapéuticas en pacientes con EA.
Alzheimer disease (AD) patients (122) compared to control subjects (119) were studied to determine the role of chronic exposure of hypercholesterolemic plasma levels and free copper (not bound to ceruloplasmin) as biomarkers of progression for AD. Oxidative stress parameters, lipid profile, amyloid levels, and cognitive status were studied in all participants. Conclusions obtained indicated that patients exposed simultaneously to free copper and increased cholesterol levels present higher indicators of oxidative stress (protein carbonyls, thiobarbituric acid-reactive substances, decreased total antioxidant activity in plasma and elevated oxidized HDL-cholesterol). Lipoprotein "a" concentrations also correlated with the clinical progression of the disease. The ratio amyloid ß(1-40)/ß(1-42) in plasma inversely correlated with the cognitive performance estimated by the Mini-Mental State Examination Test (MMSE). A defined function that weighs the contribution of the deleterious effect produced by combined free copper and Ox-HDL-cholesterol exposure directly correlated with the loss of cognitive performance. Thus, this biomarker could be a new tool for the screening of large populations under risk, or may be a useful way to estimate the efficacy of therapeuti approaches in patients suffering AD.
Foram estudadas 241 pessoas, 119 controles e 122 pacientes com doença de Alzheimer (DA), agrupados em três categorias de acordo com o estágio clínico da doença, com o objetivo de investigar a influência de níveis elevados de cobre livre e colesterol plasmático como fatores de risco para a DA. As conclusões obtidas a partir dos resultados indicaram que os pacientes expostos a uma combinação de colesterol alto e de cobre não ligados à ceruloplasmina apresentaram maior proporção de marcadores de estresse oxidativo (carbonilos proteicos, substâncias reativas ao tiobarbiturato, glutationa oxidada e diminuição dos antioxidantes totais no sangue ), juntamente com um aumento da HDL-colesterol peroxidado e lipoproteína "a" que correlacionou com a gravidade de sua condição. O mesmo aconteceu com a relação entre os peptídeos amilóides (1-40) e (1-42) em plasma e os valores do mini-teste do estado cognitivo (MMSE). Verificou-se que uma função de adição de efeitos que quantificou o dano por cobre livre e colesterol oxidado resultou diretamente proporcional à perda de desempenho cognitivo estimada através do MMSE. Esta função é fácil de determinar e pode ser considerada um novo biomarcador para estudar o risco em populações expostas, apoiar o diagnóstico clínico ou avaliar a eficácia de estratégias terapêuticas em pacientes com DA.
RESUMO
OBJECTIVE: Brain stroke is the third most important cause of death in developed countries. We studied the effect of different dietary lipids on the outcome of a permanent ischemic stroke rat model. METHODS: Wistar rats were fed diets containing 7% commercial oils (S, soybean; O, olive; C, coconut; G, grape seed) for 35 d. Stroke was induced by permanent middle cerebral artery occlusion. Coronal slices from ischemic brains and sham-operated animals were supravitally stained. Penumbra and core volumes were calculated by image digitalization after 24, 48, and 72 h poststroke. Homogenates and mitochondrial fractions were prepared from different zones and analyzed by redox status, inflammatory markers, ceramide, and arachidonate content, phospholipase A2, NOS, and proteases. RESULTS: Soybean (S) and G diets were mainly prooxidative and proinflammatory by increasing the liberation of arachidonate and its transformation into prostaglandins. O was protective in terms of redox homeostatic balance, minor increases in lipid and protein damage, conservation of reduced glutathione, protective activation of NOS in penumbra, and net ratio of anti-to proinflammatory cytokines. Apoptosis (caspase-3, milli- and microcalpains) was less activated by O than by any other diet. CONCLUSION: Dietary lipids modulate NOS and PLA2 activities, ceramide production, and glutathione import into the mitochondrial matrix, finally determining the activation of the two main protease systems involved in programmed cell death. Olive oil appears to be a biological source for the isolation of protective agents that block the expansion of brain core at the expense of penumbral neurons.
Assuntos
Antioxidantes/uso terapêutico , Encéfalo/efeitos dos fármacos , Gorduras na Dieta , Inflamação/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Óleos de Plantas/uso terapêutico , Acidente Vascular Cerebral , Animais , Antioxidantes/farmacologia , Apoptose , Biomarcadores/metabolismo , Encéfalo/citologia , Encéfalo/metabolismo , Isquemia Encefálica/dietoterapia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Cocos , Dieta , Gorduras na Dieta/efeitos adversos , Gorduras na Dieta/metabolismo , Gorduras na Dieta/farmacologia , Gorduras na Dieta/uso terapêutico , Inflamação/etiologia , Inflamação/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Neurônios , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Óxido Nítrico Sintase/metabolismo , Olea , Oxirredução , Óleos de Plantas/efeitos adversos , Óleos de Plantas/farmacologia , Ratos Wistar , Espécies Reativas de Oxigênio/efeitos adversos , Glycine max , Acidente Vascular Cerebral/dietoterapia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologia , VitisRESUMO
We have determined various biomarkers in the peripheral blood of Alzheimer, Parkinson and vascular dementia patients by comparing the samples with those of first-degree relatives and control subjects. Our results, together with correlation studies using data from the Mini-Mental State Examination (MMSE), suggest that the clinical evaluation of the nitrite (NOx) concentration in Alzheimer patients should be complemented by assays of protein carbonyls (PCs) levels, the ratio of reduced to oxidized glutathione (GSH/GSSG) in plasma, PCs in erythrocytes and PCs and calcium content in leukocytes. For Parkinson patients it would be useful to determine NOx, thiobarbituric-acid reactive substances (TBARS) and PCs in erythrocytes, and NOx and TBARS en leukocytes. For vascular-demented (VD) patients, determination of NOx, Cu, and GSH/GSSG in plasma and TBARS, and PCs in erythrocytes together with PCs in leukocytes should be assayed. Relatives of Alzheimer patients showed alterations in plasma Se and Zn concentrations, catalase (CAT) activity in erythrocytes and calcium content in leukocytes as possible predictive markers of the disease. Relatives of Parkinson patients showed elevated levels of NOx in leukocytes. In the case of vascular-demented patients we suggest NOx, GSH/GSSG and α-tocopherol in plasma, the CAT/superoxide dismutase ratio in erythrocytes and TBARS, GSSG and glutathione reductase in leukocytes as predictive markers. Large-scale longitudinal population-based studies using these suggested biomarkers are necessary in order to assess their level of reliability and specificity in clinical practice.
Assuntos
Doenças Neurodegenerativas/sangue , Doenças Neurodegenerativas/genética , Fatores Etários , Idoso , Doença de Alzheimer/sangue , Doença de Alzheimer/genética , Doença de Alzheimer/psicologia , Biomarcadores/sangue , Cognição/fisiologia , Demência Vascular/sangue , Demência Vascular/genética , Demência Vascular/psicologia , Eletrocardiografia , Enzimas/sangue , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Doenças Neurodegenerativas/psicologia , Testes Neuropsicológicos , Oxirredução , Doença de Parkinson/sangue , Doença de Parkinson/genética , Doença de Parkinson/psicologia , Reprodutibilidade dos Testes , Medição de Risco , Ultrassonografia Doppler DuplaRESUMO
The concentration of plasma copper, ceruloplasmin (CRP), non-ceruloplasmin-bound Cu (NCBC), and metallothioneins (MTs) were studied as putative biomarkers for neurodegenerative diseases in patients and in their first-degree relatives. We found increased levels of Cu in the plasma of Alzheimer's disease (AD), Parkinson's disease (PD), and vascular dementia (VD) patients, and the increase observed in VD group was linked to the evolution of the disease. CRP was also elevated in response to the inflammatory component of the diseases, however, a correlation with illness progression was only observed in VD patients. The level of MTs is proportional to the evolution of VD. The Cu/CRP and Cu/MTs ratios are both indicative of disease progression for AD patients but not for those with PD or VD. Moreover, there is a correlation between the NCBC levels and the cognitive impairment estimated through the Mini-mental State Examination (MMSE) scale. This dependence is linear for AD and PD patients and non-linear for the VD ones. The relative values of NCBC showed dependence on the disease duration, especially for AD. Copper measurement and the Cu/CRP ratio may be predictive markers of risk for the first-degree relatives of AD patients. We believe that these results are valuable as a reliable clinical tool.
Assuntos
Doença de Alzheimer/sangue , Ceruloplasmina/metabolismo , Cobre/sangue , Demência Vascular/sangue , Metalotioneína/sangue , Doença de Parkinson/sangue , Adulto , Idoso , Doença de Alzheimer/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Demência Vascular/metabolismo , Progressão da Doença , Família , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/metabolismo , Fatores de Risco , Fatores de TempoRESUMO
In the present chapter, that is part of a more comprehensive work performed by the Argentine Consortium for Dementia Study - Consortium Argentino para el Estudio de la Demencia (CAED), we describe the most frequent forms of beginning for the four more prevalent types of dementia: Alzheimer's disease, dementia with Lewy bodies, vascular dementia and frontotemporal dementia). Despite this, it must be kept in mind, that frequently the clinical presentation is not typical and the diagnostic impression at the disease's beginning is controversial comparing it with the etiological diagnosis reached when the dementia is definitively installed. This issue must be considered when the initial impression is given to the patient and/or relatives. It must be clarified, in this instance, that this impression is based in statistical data of ways of presentation, but the definitive diagnosis could be different according to the dementia evolution.