RESUMO
BACKGROUND: Benzodiazepines are frequently prescribed in patients with Alzheimer's disease. Unfortunately, studies evaluating their benefits and risks in these patients are limited. METHODS: Clinical trials focusing on the effect of benzodiazepines on cognitive functions, disease progression, behavioral symptoms, sleep disturbances, and the general frequency of benzodiazepine use were included in this review. Published articles from January 1983 to January 2015 were identified using specific search terms in MEDLINE and PubMed Library according to the recommendations of The Strengthening the Reporting of Observational Studies in Epidemiology initiative. RESULTS: Of the 657 articles found, 18 articles met predefined selection criteria and were included in this review (8 on frequency, 5 on cognitive functions, 5 on behavioral and sleep disturbances). The frequency of benzodiazepine use ranged from 8.5% to 20%. Five studies reported accelerated cognitive deterioration in association with benzodiazepine use. Two studies reported clinical efficacy for lorazepam and alprazolam to reduce agitation in Alzheimer's disease patients. No evidence was found for an improvement of sleep quality using benzodiazepines. CONCLUSION: This systematic review shows a relatively high prevalence of benzodiazepine use but limited evidence for clinical efficacy in Alzheimer's disease patients. However, there is a paucity of methodologically high quality controlled clinical trials. Our results underscore a need for randomized controlled trials in this area.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Benzodiazepinas/uso terapêutico , Psicotrópicos/uso terapêutico , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/fisiopatologia , Doença de Alzheimer/psicologia , Ensaios Clínicos como Assunto , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/fisiopatologia , Humanos , Prevalência , Transtornos do Sono-Vigília/tratamento farmacológico , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/fisiopatologiaRESUMO
An association between plasma Amyloid beta peptides (Aß) with blood lipids was reported in cross-sectional studies. The present study examined the 5-year prospective association of atherosclerotic risk factors with plasma Aß42 in 440 elderly persons without both Alzheimer's disease (AD) or mild cognitive impairment (MCI) at baseline. Persons in the highest tertile of total cholesterol (TC) or LDL-C at baseline showed low plasma Aß42 at 5 years. Regression analysis confirmed TC and LDL-C as negative predictors of Aß42 (p = 0.001). An increase over 5 years of HDL-C was a negative predictor and the presence of an APOE ε4 allele was a positive predictor for decrease of Aß42 in converters to MCI. In converters to AD, increase of both TC and of HbA1c were positive predictors of Aß42 levels at 5 years. Analysis of covariance showed a positive association between Δ-TC, Δ-LDL-C, Δ-HbA1c, and levels of Aß42 at 5 years (p = 0.006; 0.013 and 0.027 resp.) in converters to AD independently on lipid-lowering treatment. The association of vascular risk factors TC, LDL-C, and HbA1c with higher Aß42 levels might, after confirmation in other cohorts, influence the development of lifestyle interventions concerning plasma Aß42 and AD.
Assuntos
Doença de Alzheimer/sangue , Peptídeos beta-Amiloides/sangue , Aterosclerose/etiologia , Transtornos Cognitivos/sangue , Fragmentos de Peptídeos/sangue , Idoso , Índice de Massa Corporal , Colesterol/sangue , Feminino , Humanos , Lipoproteínas HDL/sangue , Estudos Longitudinais , Masculino , Escalas de Graduação Psiquiátrica , Psicometria , Fatores de Risco , Estatísticas não Paramétricas , Fatores de Tempo , Triglicerídeos/sangueRESUMO
OBJECTIVES: In clinical practice it is important to identify patients suffering from mild cognitive impairment (MCI) who will progress to Alzheimer's disease (AD). The purpose of this study is to investigate whether lipid metabolites and vitamin B12 and folate levels are effective biomarker for an accurate prediction of MCI-to-AD conversion. METHODS: During the standard diagnostic assessment at our memory clinic 48 cognitively healthy subjects and MCI patients were recruited. These participants were followed up after 7-9 years. Blood was collected, various biochemical markers (including vitamin B12 and folate) analysed and plasma lipids were measured using the AbsoluteIDQ p150 Kit. RESULTS: There was no significant change in lipid levels in controls converting to MCI. However, we found significant changes in five lipids in converters from controls to AD. Interestingly, also two lipids were altered when MCI re-converted to controls. Vitamin B12 levels were not affected by conversion but folate levels significantly decreased in MCI-AD conversion. CONCLUSIONS: Taken together, our study provides evidence that some plasma lipids are significantly altered in subjects converting to AD. Future studies will investigate whether the peripheral lipid changes correspond with changes in the brain during the course of the disease. Although this is a small study, there are indications that lipids may be suitable as prognostic markers.
Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/diagnóstico , Biomarcadores , Disfunção Cognitiva/diagnóstico , Progressão da Doença , Ácido Fólico , Humanos , Fosfatidilcolinas , Prognóstico , Vitamina B 12 , VitaminasRESUMO
OBJECTIVES: Depression in the elderly might represent a prodromal phase of Alzheimer disease (AD). High levels of plasma amyloid beta-42 (Aß42) were found in prestages of AD and also in depressed patients in cross-sectional studies. This study examined the association of emerging late-onset depression (LOD) and AD with plasma Aß42 in a sample of never depressed and not demented persons at baseline. DESIGN: Prospective 5-year longitudinal study. PARTICIPANTS: A community dwelling of older adults (N = 331) from the Vienna Transdanube Aging study. MEASUREMENTS: Laboratory measurements, cognitive functioning, and depressive symptoms were assessed at baseline, 2.5, and 5 years follow-ups. RESULTS: After exclusion of converters to AD, regression analysis revealed that higher plasma Aß42 at baseline was a positive predictor for conversion to first episode of LOD. Independent of whether persons with mild cognitive impairment (MCI) at 2.5 years were included or excluded into regressions, higher plasma Aß42 at baseline was a significant predictor for the development of probable or possible AD at 5 years. Higher conversion to AD was also associated with male gender but not with either higher scores on the Geriatric Depression Scale (GDS), with stroke or cerebral infarction nor apolipoprotein E ε4 allele. No association was found for an interaction between plasma Aß42 levels and GDS. CONCLUSIONS: Higher plasma Aß42 at baseline predicted the development of first episode of LOD and conversion to probable or possible AD. Emerging depression as measured by scores on GDS at the 2.5-year follow-up, either alone or as an interaction factor with plasma Aß42, failed to predict the conversion to AD at 5 years.
Assuntos
Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/sangue , Transtornos Cognitivos/diagnóstico , Transtorno Depressivo/diagnóstico , Fragmentos de Peptídeos/sangue , Idoso , Doença de Alzheimer/sangue , Doença de Alzheimer/genética , Apolipoproteína E4/genética , Transtornos Cognitivos/sangue , Transtornos Cognitivos/genética , Transtorno Depressivo/sangue , Transtorno Depressivo/genética , Progressão da Doença , Feminino , Avaliação Geriátrica/métodos , Humanos , Estudos Longitudinais , Masculino , Valor Preditivo dos Testes , Fatores de Risco , Caracteres SexuaisRESUMO
In the course of cognitive deterioration leading to Alzheimer's disease (AD) the increase of amyloid beta (Abeta42) in cerebrospinal fluid or plasma might be an initial event. We previously reported about the associations between concomitant medication and plasma Abeta42 levels in the non-demented population cohort of the Vienna transdanube aging study at baseline. In the present study, the longitudinal influence of insulin, gingko biloba, non-steroidal anti-inflammatory drugs (NSAIDs), oral anti-diabetics (sulfonylurea and biguanides), estrogens, fibrates, and statins on plasma Abeta42 are presented. Associated with medial temporal lobe atrophy (MTA), users of insulin showed significantly increased levels of Abeta42. Long-term users of gingko biloba, independent of their MTA, had significantly decreased plasma Abeta42 and the age-dependent increase of plasma Abeta42 was significantly smaller in long-term gingko biloba treated subjects. The use of fibrates also decreased plasma Abeta42 levels. In multiple testing considering interactions between medications, gender, APOE-epsilon4 presence and creatinine, insulin long-term users again showed significantly increased levels; fibrate and gingko biloba users showed a trend to rather decreased plasma Abeta42 levels compared to the non-users (p=0.05-0.08). Neither statins nor NSAIDs showed a significant effect on plasma Abeta42 in this model. Measuring the effect on cognition, no single medication studied was a significant predictor of conversion to AD or mild cognitive impairment (MCI). Whether the use of gingko biloba might prevent the conversion to MCI or AD needs to be proven in prospective, clinical trials.
Assuntos
Peptídeos beta-Amiloides/sangue , Fragmentos de Peptídeos/sangue , Medicamentos sob Prescrição/uso terapêutico , Fatores Etários , Idoso , Doença de Alzheimer/sangue , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Apolipoproteína E4/genética , Atrofia , Áustria , Transtornos Cognitivos/sangue , Feminino , Genótipo , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Medicamentos sob Prescrição/efeitos adversos , Estudos Prospectivos , Fatores de Risco , Lobo Temporal/patologiaRESUMO
Alzheimer's disease (AD) is a severe, progressive and chronic disorder with strong cognitive deficits. Diagnosis of probable AD can be performed by measuring biomarkers in cerebrospinal fluid (CSF). The aim of the present study was to measure CSF levels of nerve growth factor (NGF), the anti-NGF auto-antibody, and the cholinesterases AChE and BChE, and to correlate them with beta-amyloid, tau and phospho-tau-181. We could show that NGF-like immunoreactivity, but not anti-NGF auto-antibody, was significantly enhanced in AD patients compared to healthy subjects, while both cholinesterases were not changed. beta-Amyloid(1-42) was decreased, while tau and phospho-tau-181 were increased. The commercial Promega NGF ELISA detected mature NGF but not wild-type-human-pro-NGF. Using a bioassay of brain slices, we showed that recombinant mature NGF enhanced survival of cholinergic neurons, while wild-type human pro-NGF displayed a less pronounced effect. The addition of CSF to brain slices exhibited strong toxic effects on the survival of cholinergic neurons. We conclude that in CSF of AD patients (at least partly) mature NGF-like immunoreactivity is enhanced, and is masked in a bioassay by the toxic properties of CSF.
Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Autoanticorpos/líquido cefalorraquidiano , Encéfalo/fisiopatologia , Fator de Crescimento Neural/líquido cefalorraquidiano , Acetilcolinesterase/líquido cefalorraquidiano , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Bioensaio/métodos , Biomarcadores/líquido cefalorraquidiano , Butirilcolinesterase/líquido cefalorraquidiano , Sobrevivência Celular/fisiologia , Ensaio de Imunoadsorção Enzimática/métodos , Humanos , Neurônios/metabolismo , Fragmentos de Peptídeos/líquido cefalorraquidiano , Proteínas tau/líquido cefalorraquidianoRESUMO
INTRODUCTION: There is still a clear need for a widely available, inexpensive and reliable method to diagnose Alzheimer's disease (AD) and monitor disease progression. Liquid chromatography-mass spectrometry (LC-MS) is a powerful analytic technique with a very high sensitivity and specificity. OBJECTIVES: The aim of the present study is to measure concentrations of 20 bile acids using the novel Kit from Biocrates Life Sciences based on LC-MS technique. METHODS: Twenty bile acid metabolites were quantitatively measured in plasma of 30 cognitively healthy subjects, 20 patients with mild cognitive impairment (MCI) and 30 patients suffering from AD. RESULTS: Levels of lithocholic acid were significantly enhanced in plasma of AD patients (50 ± 6 nM, p = 0.004) compared to healthy controls (32 ± 3 nM). Lithocholic acid plasma levels of MCI patients (41 ± 4 nM) were not significantly different from healthy subjects or AD patients. Levels of glycochenodeoxycholic acid, glycodeoxycholic acid and glycolithocholic acid were significantly higher in AD patients compared to MCI patients (p < 0.05). All other cholic acid metabolites were not significantly different between healthy subjects, MCI patients and AD patients. ROC analysis shows an overall accuracy of about 66%. Discriminant analysis was used to classify patients and we found that 15/23 were correctly diagnosed. We further showed that LCA levels increased by about 3.2 fold when healthy subjects converted to AD patients within a 8-9 year follow up period. Pathway analysis linked these changes to a putative toxic cholesterol pathway. CONCLUSION: In conclusion, 4 bile acids may be useful to diagnose AD in plasma samples despite limitations in diagnostic accuracy.
RESUMO
The pro-inflammatory reaction of the immune system is a feature of healthy aging and might influence the progression of Alzheimer's disease (AD). Neopterin is a pteridine derivative, released from macrophages upon stimulation with pro-inflammatory cytokine interferon-gamma. Forty-three probable AD patients were investigated at baseline and follow up (14.5+/-0.5 months; mean+/-s.e.m.). We assessed the clinical progression by the Consortium to Establish a Registry for Alzheimer's disease (CERAD) battery and compared cognitive changes to serum concentrations of neopterin, C-reactive protein (CRP) and antibody to cytomegalovirus (CMV). The mean neopterin concentrations increased significantly from 9.8+/-1.0 to 13.6+/-2.1 nM (p=0.04). In contrast, mean CRP concentrations at baseline was 0.46+/-0.1 and non-significantly decreased to 0.28+/-0.04 mg/dl. Of AD patients 70% were CMV IgG-seropositive at baseline and CMV-antibody concentrations correlated with levels of neopterin (Spearman r=0.386, p=0.016). CERAD scores did not correlate with any of immune parameters at baseline. At follow up, the increase of neopterin correlated significantly with the decrease in the total CERAD and MMSE scores, according to the clinical progression (r=-0.353, p<0.05 and r=-0.401, p<0.01, respectively). Subdividing the sample with respect to baseline MMSE scores, neopterin concentrations significantly increased only in the group of MMSE<20. In the multiple testing covariated for age, gender, Apolipoprotein E-epsilon4 allele, time difference between both measurements, neopterin remained significantly associated with cognitive decline. In summary, neopterin concentrations correlated with cognitive decline in AD patients, which might be due to high CMV seropositivity in that population.
Assuntos
Doença de Alzheimer/diagnóstico , Transtornos Cognitivos/diagnóstico , Neopterina/sangue , Idoso , Doença de Alzheimer/imunologia , Anticorpos Antivirais/sangue , Proteína C-Reativa/metabolismo , Transtornos Cognitivos/imunologia , Citomegalovirus/imunologia , Progressão da Doença , Feminino , Seguimentos , Humanos , Imunoglobulina G/sangue , Masculino , Entrevista Psiquiátrica Padronizada , Sistema de RegistrosRESUMO
BACKGROUND: Mild cognitive impairment (MCI) has been suggested to represent a prodromal stage of dementia and to confer a high risk for conversion to dementia Alzheimer's type (DAT). OBJECTIVES: In this study, we examined the predictive value of depressive symptoms and neuropsychological variables on conversion of MCI to DAT. METHODS: Neuropsychological and clinical follow-up data of 260 MCI patients seen at the Psychiatric Memory Clinic of the Medical University of Innsbruck between 2005 and 2015 were analyzed retrospectively. Depression was assessed using the Geriatric Depression Scale (GDS). Potential predictors of conversion from MCI to DAT were analyzed by logistic regression analyses and additional survival-analytic methods. RESULTS: Of the 260 patients (mean age 71.5±7.7 years), 83 (32%) converted to DAT within a mean follow-up time of 3.2±2.2 years and estimated one-year conversion rate of 10.1%. The univariate analysis showed with few exceptions (gender, use of antidepressants, low GDS score) group differences at baseline in patients converted to DAT compared to stable MCI patients. Logistic regression analysis as well as survival analysis revealed moderate to severe depression together with higher age and specific cognitive deficits as predictors of conversion from MCI to DAT. CONCLUSION: Our results support the predictive value of different neuropsychological measures on the progression of DAT. In addition, we found a strong negative influence of depression on conversion to DAT in MCI patients. These results emphasize the importance of assessing depressive symptoms in the early stages of DAT when evaluating the conversion from MCI to DAT.
Assuntos
Doença de Alzheimer/complicações , Disfunção Cognitiva/complicações , Depressão/diagnóstico , Depressão/etiologia , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Testes Neuropsicológicos , Valor Preditivo dos Testes , Escalas de Graduação Psiquiátrica , Estudos Retrospectivos , Análise de SobrevidaRESUMO
Plasma amyloid beta (Abeta42) levels increase with age and are elevated in some patients during the early stages of Alzheimer's disease (AD). Although plasma Abeta42 is not useful for diagnosis of AD, it might be a biological risk factor. In the elderly population a considerable variety of concomitant medication is used for the treatment of various disorders. How this co-medication might influence Abeta42 levels is still to be investigated. Through the Vienna Transdanube Aging study (VITA), the authors measured cross-sectional Abeta42 plasma levels during the initial examination of 526 individuals aged 75 years without dementia. The medication considered included: treatment with calcium channel blockers, digitalis, anticoagulants, antihistamines, ergotamine, histamine H(2) receptor antagonists, bronchodilators, pentoxyfilline, neuroleptics, insulin, oral antidiabetics, l-dopa, benzodiazepines, oestrogen, Gingko biloba, vitamins, piracetam, non-steroidal anti-inflammatory drugs (NSAIDs), and statins. Of the study population aged 75 years, 90% were users of some of the above-mentioned medication. Depending on their medial temporal lobe atrophy (MTA), users of insulin showed significantly increased levels of Abeta42, while users of gingko biloba for at least 2 years of drug intake had significantly decreased Abeta42 plasma levels, independent of their MTA. Users of NSAIDs showed a non-significant trend to reduced Abeta42 plasma levels, while users of biguanides showed an increase in Abeta42 plasma levels. In the multiple regression analysis considering possible interactions between various medications statin users showed a significant decrease of Abeta42; insulin users had again significantly higher and long-term gingko biloba users lower plasma Abeta42 levels. Persons with a low degree of MTA had significantly increased Abeta42 plasma levels. Considering the increase of Abeta42 plasma levels as a risk factor for AD, any changes induced by medication by long-term use in the peripheral and possibly also in the central compartment, could be of clinical relevance.
Assuntos
Envelhecimento/metabolismo , Peptídeos beta-Amiloides/sangue , Atrofia/sangue , Encefalopatias/sangue , Fragmentos de Peptídeos/sangue , Lobo Temporal/metabolismo , Idoso , Envelhecimento/patologia , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Atrofia/epidemiologia , Atrofia/prevenção & controle , Áustria/epidemiologia , Encefalopatias/epidemiologia , Encefalopatias/prevenção & controle , Estudos de Coortes , Comorbidade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Ginkgo biloba/química , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/uso terapêutico , Imageamento por Ressonância Magnética , Masculino , Estudos Prospectivos , Fatores de Risco , Lobo Temporal/efeitos dos fármacos , Lobo Temporal/patologiaRESUMO
A huge amount of evidence has implicated amyloid beta (A beta) peptides and other derivatives of the amyloid precursor protein (beta APP) as central to the pathogenesis of Alzheimer's disease (AD). It is also widely recognized that age is the most important risk factor for AD and that the innate immune system plays a role in the development of neurodegeneration. Little is known, however, about the molecular mechanisms that underlie age-related changes of innate immunity and how they affect brain pathology. Aging is characteristically accompanied by a shift within innate immunity towards a pro-inflammatory status. Pro-inflammatory mediators such as tumour necrosis factor-alpha or interleukin-1 beta can then in combination with interferon-gamma be toxic on neurons and affect the metabolism of beta APP such that increased concentrations of amyloidogenic peptides are produced by neuronal cells as well as by astrocytes. A disturbed balance between the production and the degradation of A beta can trigger chronic inflammatory processes in microglial cells and astrocytes and thus initiate a vicious circle. This leads to a perpetuation of the disease.
Assuntos
Envelhecimento/imunologia , Doença de Alzheimer/etiologia , Encéfalo/fisiopatologia , Inflamação/complicações , Envelhecimento/patologia , Envelhecimento/fisiologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/fisiologia , Precursor de Proteína beta-Amiloide/metabolismo , Precursor de Proteína beta-Amiloide/fisiologia , Anti-Inflamatórios/uso terapêutico , Astrócitos/metabolismo , Astrócitos/patologia , Astrócitos/fisiologia , Encéfalo/efeitos dos fármacos , Encéfalo/patologia , Doença Crônica , Humanos , Imunidade Inata/fisiologia , Inflamação/tratamento farmacológico , Inflamação/fisiopatologia , Microglia/metabolismo , Microglia/patologia , Microglia/fisiologiaRESUMO
The dysregulation in the metabolism of beta-amyloid precursor protein and consequent deposition of amyloid-beta (Abeta) has been envisaged as crucial for the development of neurodegeneration in Alzheimer's disease (AD). Amyloid deposition begins 10-20 years before the appearance of clinical dementia. During this time, the brain is confronted with increasing amounts of toxic Abeta peptides and data from the last decade intriguingly suggest that both the innate and the adaptive immune systems may play an important role in the disorder. Innate immunity in the brain is mainly represented by microglial cells, which phagocytose and degrade Abeta. As the catabolism of Abeta decreases, glial cells become overstimulated and start to produce substances that are toxic to neurons, such as nitric oxide and inflammatory proteins. Pro-inflammatory cytokines can be directly toxic or stimulate Abeta production and increase its cytotoxicity. A therapeutic possibility arises from clinical studies, which demonstrate that nonsteroidal anti-inflammatory drugs (NSAIDs) may delay the onset and slow the progression of AD. Recent data show that in addition to the suppression of inflammatory processes in the brain NSAIDs may decrease the production of Abeta peptides. The role of adaptive immunity lies mainly in the fact that Abeta can be recognised as an antigen. Immunisation with Abeta peptides and peripheral administration of Abeta-specific antibodies both decrease senile plaques and cognitive dysfunction in murine models of AD. A recent trial in humans seems still to be hampered by adverse effects. As adaptive immunity decreases with aging while innate immunity remains intact, immunotherapy for AD will have to be adapted to this situation. Strategies that combine vaccination and inflammatory drug treatment could be considered.
Assuntos
Doença de Alzheimer/imunologia , Doença de Alzheimer/terapia , Doença de Alzheimer/prevenção & controle , Peptídeos beta-Amiloides/imunologia , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Anticorpos/uso terapêutico , Encéfalo/enzimologia , Encéfalo/patologia , Inibidores de Ciclo-Oxigenase/uso terapêutico , Modelos Animais de Doenças , Humanos , Imunidade Inata , Imunoterapia , Fragmentos de Peptídeos/uso terapêuticoRESUMO
The increasing number of pharmacological treatment options for bipolar disorder seems to be paralleled by the number of evidence-based guidelines published previously. The aim of this study was to systematically examine the adherence to published guidelines and any change in prescription habits over time in a psychiatric hospital setting. This is a retrospective study of 531 bipolar in patients who were consecutively admitted to the Department for Psychiatry and Psychotherapy in Innsbruck. Their complete medical histories were evaluated for psychotropic medications, with a special focus on mood stabilizers (MSs). To compare the use of individual MSs or combinations with other psychotropic medications in two preselected observation periods (1999-2003 and 2004-2007), we used Fisher's exact test. Overall, the proportion of patients receiving at least one MS increased significantly from 1999-2003 to 2004-2007 (74.1 vs. 83.1%, P=0.011). Among the individual MSs, valproate was used most frequently in both time periods, showing a significant increase (P<0.001). Prescriptions of quetiapine (P<0.001) and lamotrigine (P=0.033) increased significantly, carbamazepine showed a significant decrease (P<0.001). Prescriptions of lithium and olanzapine decreased without reaching significance. The significant increase in the prescription of MS reflects the increasing awareness and implementation of recent evidence-based medicine guidelines into clinical practice. Clinical decision making, usually made on the basis of individual clinical experience, should always be reevaluated using periodically updated evidence-based medicine guidelines.
Assuntos
Transtorno Bipolar/tratamento farmacológico , Padrões de Prática Médica , Psicotrópicos/uso terapêutico , Adulto , Antimaníacos/uso terapêutico , Antipsicóticos/uso terapêutico , Áustria , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/terapia , Estudos de Coortes , Terapia Combinada , Manual Diagnóstico e Estatístico de Transtornos Mentais , Quimioterapia Combinada , Medicina Baseada em Evidências , Feminino , Hospitais Universitários , Humanos , Classificação Internacional de Doenças , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/tendências , Estudos RetrospectivosAssuntos
Doença de Alzheimer/prevenção & controle , Peptídeos beta-Amiloides/administração & dosagem , Angiopatia Amiloide Cerebral/prevenção & controle , Vacinação/métodos , Doença de Alzheimer/imunologia , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/imunologia , Animais , Formação de Anticorpos/imunologia , Angiopatia Amiloide Cerebral/imunologia , Angiopatia Amiloide Cerebral/patologia , Humanos , Ativação Linfocitária/imunologia , Meningoencefalite/imunologia , Meningoencefalite/patologia , Camundongos , Camundongos Transgênicos , Fatores de Risco , Linfócitos T/imunologia , Linfócitos T/patologia , Resultado do Tratamento , Vacinação/efeitos adversosRESUMO
The changes of plasma amyloid beta (Abeta42) protein, homocysteine and medial temporal lobe atrophy (MTA) were studied by the transition from cognitive health to mild cognitive impairment (MCI) and to Alzheimer's disease (AD) in a prospective cohort of individuals aged 75 years. MTA but not plasma Abeta42 measured at baseline predicted which persons remained cognitively healthy (CH) and who developed AD 2.5 years later. The increase of plasma Abeta42 over time significantly distinguished between persons who remained CH on the one hand and MCI converters and AD converters out of cognitive health on the other (CH-to-MCI and CH-to-AD converters). Although both groups showed similar increase of Abeta42 levels, CH-to-AD converters had a higher increase of homocysteine compared to CH-to-MCI converters or to persons remaining CH. In comparison to all cognitive subgroups, the AD converters from MCI at baseline showed the smallest increase of Abeta42 levels and rather no increase of homocysteine. In logistic regression analysis, the increase of plasma Abeta42 but not change of MTA significantly predicted the conversion from CH to MCI, and changes of MTA and homocysteine but not of plasma Abeta42 predicted the conversion from CH to AD. The increase of plasma Abeta42 correctly allocated CH-to-MCI and CH-to-AD converters with low (63%) specificity (for both) and low (60%) sensitivity (54% for AD group). These results indicate that (1) plasma Abeta42 alone is not suitable as a biomarker for AD, (2) in the course of cognitive deterioration of the AD-type the increase of plasma Abeta42 seems to be an initial event, (3) similar to cerebrospinal fluid, changes of plasma Abeta42 may reflect the transition from cognitive health to AD, and (4) whether persons with MCI develop AD may depend on an accumulation of further toxic metabolites such as homocysteine.
Assuntos
Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/sangue , Transtornos Cognitivos/sangue , Transtornos Cognitivos/patologia , Homocistina/metabolismo , Fragmentos de Peptídeos/sangue , Lobo Temporal/patologia , Idoso , Doença de Alzheimer/sangue , Apolipoproteínas E/genética , Atrofia , Estudos de Coortes , Progressão da Doença , Feminino , Ácido Fólico/sangue , Humanos , Modelos Logísticos , Imageamento por Ressonância Magnética/métodos , Masculino , Testes Neuropsicológicos/estatística & dados numéricos , Valor Preditivo dos Testes , Psicometria/métodos , Estudos Retrospectivos , Vitamina B 12/sangueRESUMO
Cerebrospinal fluid (CSF) biological markers may be of valuable help in the diagnosis of dementia. The aim of the present study was to evaluate CSF levels of 13 potential biomarkers in patients with Alzheimer's disease (AD), frontotemporal lobe dementia, alcohol dementia, major depression and control patients without any neuropsychiatric disease. The study was performed using beta-amyloid 1-42 (Abeta42), total tau and phosphorylated tau-181 (P-tau181) as core markers. The ratio P-tau181/Abeta42 could significantly distinguish AD patients from all other diagnostic subgroups. CSF levels of 5 growth factors (HGF, GDNF, VEGF, BDNF, FGF-2) and 3 cytokines/chemokines (TNF-alpha, TGF-beta1, MIP-1alpha) did not significantly differentiate between the studied groups. However, depending on the degree of neurodegeneration (as expressed by the ratio P-tau181/Abeta42), patients with AD displayed significantly increased CSF levels of nerve growth factor (NGF) as compared to healthy controls. CSF levels of monocyte chemoattractant protein 1 (MCP-1) were found to be significantly increased with age in all groups but did not distinguish AD patients from healthy controls. The results confirmed the suitability of the ratio P-tau181/Abeta42 for the diagnosis of AD, while CSF levels of NGF and MCP-1 are less specific and reliable for AD. It is suggested that the increase in NGF depends on the extent of neurodegeneration of the AD type and the increase in MCP-1 on age.
Assuntos
Doença de Alzheimer/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Demência/líquido cefalorraquidiano , Transtorno Depressivo Maior/líquido cefalorraquidiano , Idoso , Transtorno Amnésico Alcoólico/líquido cefalorraquidiano , Transtorno Amnésico Alcoólico/diagnóstico , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Quimiocinas/líquido cefalorraquidiano , Citocinas/líquido cefalorraquidiano , Demência/diagnóstico , Transtorno Depressivo Maior/diagnóstico , Substâncias de Crescimento/líquido cefalorraquidiano , Humanos , Fragmentos de Peptídeos/líquido cefalorraquidiano , Fosforilação , Valor Preditivo dos Testes , Valores de Referência , Proteínas tau/líquido cefalorraquidianoRESUMO
In a pilot study designed as a case control study the efficacy of donepezil treatment was investigated in patients with Alzheimer's disease (AD). Patients were stratified according to radiological criteria into patients without (AD group) and with subcortical vascular lesions (AD+SVD group). Changes in cognition were assessed as the primary outcome measurement after 6 and 18 months of treatment by the Mini-Mental Status Examination (MMSE) and the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) test battery. After 6 months, patients had improved from baseline by 0.7 points in MMSE score in the AD group and by 1.8 in the AD+SVD group. After 18 months of treatment, the AD+SVD group performed significantly worse in one CERAD subscore, whereas a deterioration in two subscores was observed in the AD group. A comparison between the 2 groups revealed that treatment did not lead to statistically significant differences between the AD and AD+SVD groups in any of CERAD parameters following 6 or 18 months of treatment. These data support previous observations that donepezil therapy is effective in AD patients with and without subcortical vascular lesions.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Demência Vascular/complicações , Indanos/uso terapêutico , Nootrópicos/uso terapêutico , Piperidinas/uso terapêutico , Idoso , Doença de Alzheimer/complicações , Doença de Alzheimer/patologia , Estudos de Casos e Controles , Comorbidade , Donepezila , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Resultado do TratamentoRESUMO
Although it is generally recognized that the function of the immune system declines with age, the nature of the underlying defects is still poorly understood. We now demonstrate the predominance of CD8(+)CD28(-) T cell clonal expansions in elderly persons who fail to produce specific Abs following influenza vaccination. These clones express effector cell markers and are mostly CD45RA(+). When isolated and put into culture, they are unable to proliferate, but produce IFN-gamma (but no IL-5) upon stimulation with anti-CD3 or autoantigen. These autoreactive CD8(+) type 1 effector cells seem to trigger a Th1 polarization, as CD4(+) T cells from elderly persons without in vivo Ab production produce Th1, but only low amounts of Th2 cytokines upon in vitro stimulation with PHA. Therefore, the increased occurrence of CD8(+)CD28(-) clonal expansions may be decisive for the development of immune deficiency in the elderly.