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With increasing age, associations between traditional risk factors (TRFs) and cardiovascular disease (CVD) shift. It is unknown which mid-life risk factors remain relevant predictors for CVD in older people. We systematically searched PubMed and EMBASE on August 16th 2019 for studies assessing predictive ability of >1 of fourteen TRFs for fatal and non-fatal CVD, in the general population aged 60+. We included 12 studies, comprising 11 unique cohorts. TRF were evaluated in 2 to 11 cohorts, and retained in 0-70% of the cohorts: age (70%), diabetes (64%), male sex (57%), systolic blood pressure (SBP) (50%), smoking (36%), high-density lipoprotein cholesterol (HDL) (33%), left ventricular hypertrophy (LVH) (33%), total cholesterol (22%), diastolic blood pressure (20%), antihypertensive medication use (AHM) (20%), body mass index (BMI) (0%), hypertension (0%), low-density lipoprotein cholesterol (0%). In studies with low to moderate risk of bias, systolic blood pressure (SBP) (80%), smoking (80%) and HDL cholesterol (60%) were more often retained. Model performance was moderate with C-statistics ranging from 0.61 to 0.77. Compared to middle-aged adults, in people aged 60+ different risk factors predict CVD and current prediction models perform only moderate at best. According to most studies, age, sex and diabetes seem valuable predictors of CVD in old-age. SBP, HDL cholesterol and smoking may also have predictive value. Other blood pressure and cholesterol related variables, BMI, and LVH seem of very limited or no additional value. Without competing risk analysis, predictors are overestimated.
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Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus/epidemiologia , Fatores de Risco de Doenças Cardíacas , Fatores Etários , Idoso , Índice de Massa Corporal , Colesterol/sangue , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Humanos , Hipertensão , Pessoa de Meia-Idade , Países BaixosRESUMO
BACKGROUND: Systemic infection is associated with long-term cognitive deficits and functional decline. In this study we hypothesized that severe systemic inflammation leads to a neuroinflammatory response that is characterized by microglial activation, and that these effects might be more pronounced in patients using medication with anticholinergic side-effects. METHODS: Based on the results of a pilot study in 8 patients, we assessed the number of MHC-II and CD-68 positive cells by immunohistochemistry and compared the number of microglia in specific brain regions of 16 well-characterized patients with septic shock and 15 controls. RESULTS: In the pilot study, patients with sepsis tended to have higher density of MHC-II and CD-68 positive microglia in the basal ganglia (putamen, caudate nucleus and globus pallidus) and of MHC-II positive microglia in the hippocampus. In the validation study, patients with sepsis had a significantly higher number of CD-68 positive cells in hippocampus (1.5 fold; p = 0.012), putamen (2.2 fold; p = 0.008) and cerebellum (2.5 fold; p = 0.011) than control patients. The density of MHC-II positive microglia was similar between sepsis and control groups. There was no consistent correlation between microglia counts and anti-cholinergic activity drugs score. CONCLUSION: In patients who die during septic shock, severe systemic inflammation is accompanied by localized and strong upregulation of CD-68 positive microglia, but not of MHC-II positive microglia. We identified regional differences in the brain with increased microglial activation in putamen, hippocampus and cerebellum.
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Recognizing delirium superimposed on pre-existing cognitive impairment or dementia, 'delirium superimposed on dementia' (DSD), is challenging because signs of delirium might be interpreted as symptoms of pre-existing cognitive dysfunction.In this paper, we review the literature on the role of electrencephalography (EEG) in the differential diagnosis of delirium, dementia and DSD.Conventional EEG, applying twenty to thirty electrodes, taking thirty minutes registration, is not feasible in psychogeriatric patients. Recent studies suggest that it is possible to reliably detect delirium using only a limited number of EEG electrodes for a short period of time.With this, use of EEG in the detection of delirium in patients with cognitive impairment or clinically manifest dementia could be possible.
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Delírio/diagnóstico , Demência/diagnóstico , Eletroencefalografia/métodos , Diagnóstico Diferencial , HumanosRESUMO
Apathy is common after stroke and has been associated with cognitive impairment. However, causality between post-stroke apathy and cognitive impairment remains unclear. We assessed the course of apathy in relation to changes in cognitive functioning in stroke survivors. Using the Apathy Scale (AS) and cognitive tests on memory, processing speed and executive functioning at six- and 15 months post-stroke we tested for associations between (1) AS-scores and (change in) cognitive scores; (2) apathy course (persistent/incident/resolved) and cognitive change scores. Of 117 included participants, 29% had persistent apathy, 13% apathy resolving over time and 10% apathy emerging between 6-15 months post-stroke. Higher AS-scores were cross-sectionally and longitudinally associated with lower cognitive scores. Relations between apathy and cognitive change scores were ambiguous. These inconsistent relations between apathy and changes in cognition over time suggest that post-stroke apathy does not directly impact cognitive performance. Both these sequelae of stroke require separate attention.
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Apatia , Disfunção Cognitiva , Acidente Vascular Cerebral , Humanos , Estudos Prospectivos , Estudos Longitudinais , Cognição , Acidente Vascular Cerebral/complicações , Disfunção Cognitiva/psicologiaRESUMO
BACKGROUND: Apathy is a common symptom in various neuropsychiatric diseases including mild cognitive impairment (MCI) and dementia. Apathy may be associated with an increased risk of cognitive decline. The objective of this study was to investigate if apathy predicts the progression from MCI to Alzheimer's disease (AD). METHODS: The Alzheimer's Disease Neuroimaging Initiative is a prospective multicentre cohort study. At baseline, 397 patients with MCI without major depression were included. Clinical data and the Geriatric Depression Scale at baseline were used. Apathy was defined based on the 3 apathy items of the 15-item Geriatric Depression Scale. The main outcome measure was the association of apathy with progression from MCI to AD. RESULTS: During an average follow-up of 2.7 years (SD 1.0), 166 (41.8%) patients progressed to AD. The presence of symptoms of apathy without symptoms of depressive affect increased the risk of progression from MCI to AD (hazard ratio = 1.85, 95% CI = 1.09-3.15). Apathy in the context of symptoms of depressive affect or symptoms of depressive affect alone, without apathy, did not increase the risk of progression to AD. CONCLUSIONS: Symptoms of apathy, but not symptoms of depressive affect, increase the risk of progression from MCI to AD. Apathy in the context of symptoms of depressive affect does not increase this risk. Symptoms of apathy and depression have differential effects on cognitive decline.
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Doença de Alzheimer , Apatia , Transtornos Cognitivos , Depressão , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/psicologia , Estudos de Coortes , Depressão/diagnóstico , Depressão/etiologia , Progressão da Doença , Feminino , Avaliação Geriátrica/métodos , Nível de Saúde , Humanos , Masculino , Neuroimagem , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Fatores de RiscoRESUMO
Background: The arterial spin labeling-spatial coefficient of variation (sCoV) is a new vascular magnetic resonance imaging (MRI) parameter that could be a more sensitive marker for dementia-associated cerebral microvascular disease than the commonly used MRI markers cerebral blood flow (CBF) and white matter hyperintensity volume (WMHV). Methods: 195 community-dwelling older people with hypertension were invited to undergo MRI twice, with a three-year interval. Cognition was evaluated every two years for 6-8 years using the mini-mental state examination (MMSE). We assessed relations of sCoV, CBF and WMHV with cognitive decline during follow-up. We also registered dementia diagnoses, up to 9 years after the first scan. In an additional analysis, we compared these MRI parameters between participants that did and did not develop dementia. Results: 136/195 completed the second scan. sCoV and CBF were not associated with MMSE changes during 6-8 years of follow-up. Higher WMHV was associated with declining MMSE scores (-0.02 points/year/ml, 95%CI=-0.03 to -0.00). ScOv and CBF did not differ between participants who did (n=15) and did not (n=180) develop dementia, whereas higher WMHV was reported in participants who developed dementia after the first MRI (13.3 vs 6.1mL, p<0.001). There were no associations between longitudinal change in any of the MRI parameters and cognitive decline or subsequent dementia. Conclusion: Global sCoV and CBF were less sensitive longitudinal markers of cognitive decline and dementia compared to WMHV in community-dwelling older people with hypertension. Larger longitudinal MRI perfusion studies are needed to identify possible (regional) patterns of cerebral perfusion preceding cognitive decline and dementia diagnosis.
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BACKGROUND: Cardiovascular risk factors and lifestyle factors are associated with an increased risk of cognitive decline and dementia in observational studies, and have been targeted by multidomain interventions. OBJECTIVES: We pooled individual participant data from two multi-domain intervention trials on cognitive function and symptoms of depression to increase power and facilitate subgroup analyses. DESIGN: Pooled analysis of individual participant data. SETTING: Prevention of Dementia by Intensive Vascular Care trial (preDIVA) and Multidomain Alzheimer Preventive Trial (MAPT). PARTICIPANTS: Community-dwelling individuals, free from dementia at baseline. INTERVENTION: Multidomain interventions focused on cardiovascular and lifestyle related risk factors. MEASUREMENTS: Data on cognitive functioning, depressive symptoms and apathy were collected at baseline, 2 years and 3-4 years of follow-up as available per study. We analyzed crude scores with linear mixed models for overall cognitive function (Mini Mental State Examination [MMSE]), and symptoms of depression and apathy (15-item Geriatric Depression Scale). Prespecified subgroup analyses were performed for sex, educational level, baseline MMSE <26, history of hypertension, and history of stroke, myocardial infarction and/or diabetes mellitus. RESULTS: We included 4162 individuals (median age 74 years, IQR 72, 76) with a median follow-up duration of 3.7 years (IQR 3.0 to 4.1 years). No differences between intervention and control groups were observed on change in cognitive functioning scores and symptoms of depression and apathy scores in the pooled study population. The MMSE declined less in the intervention groups in those with MMSE <26 at baseline (N=250; MD: 0.84; 95%CI: 0.15 to 1.54; p<0.001). CONCLUSIONS: We found no conclusive evidence that multidomain interventions reduce the risk of global cognitive decline, symptoms of depression or apathy in a mixed older population. Our results suggest that these interventions may be more effective in those with lower baseline cognitive functioning. Extended follow-up for dementia occurrence is important to inform on the potential long-term effects of multidomain interventions.
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Doença de Alzheimer , Apatia , Idoso , Cognição , Depressão/epidemiologia , Depressão/prevenção & controle , Humanos , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVE: To determine variation in diagnostic strategies for diagnosing dementia between Dutch hospitals. DESIGN: Descriptive, retrospective research based on claim data of Dutch health insurers. METHOD: Information on the use of diagnostic ancillary services carried out from 2015 to 2018 was collected via national-level insurance claims for patients who received a (new) diagnose-coding for dementia in 2018. Hospitals were included in the analysis if they diagnosed >50 patients with dementia. We distinguished academic medical centres (AMC), non-academic training hospitals (TH) and general hospitals (GH). RESULTS: In 2018, 20.073 new cases of dementia were diagnosed in 71 hospitals. The percentages of patients undergoing MRI/CT-imaging ranged from 37 to 99% (median 76.7%), neuropsychological-assessment from 0-89% (median 31.8%), cerebrospinal fluid examination from 0-14% (median 2.4%), PET/SPECT-imaging from 0-16% (median 6.2%) and electroencephalography from 1-20% (median 5.8%). Practice variation was comparable in AMCs, THs and GHs and was evidently skewed for PET/SPECT-imaging, electroencephalography and cerebrospinal fluid examination. There were no distinct differences according to case-mix characteristics or hospital volume. The percentage of patients subjected to ancillary diagnostic investigations decreased sharply with increasing age. CONCLUSION: In the Netherlands, diagnostic ancillary methods used vary widely between hospitals both in frequency and modality. This variation may be driven by limited evidence of diagnostic accuracy and added value of different diagnostic tests, variations in doctor and patient preferences and differences in available diagnostic techniques per hospital. Further exploration of this heterogeneity may help to identify a strategy that combines the most benefit with the least burden.
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Demência/diagnóstico , Testes Diagnósticos de Rotina/métodos , Hospitais , Programas de Rastreamento/métodos , Padrões de Prática Médica , Líquido Cefalorraquidiano , Eletroencefalografia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Países Baixos , Testes Neuropsicológicos , Tomografia por Emissão de Pósitrons , Estudos Retrospectivos , Tomografia Computadorizada de Emissão de Fóton ÚnicoRESUMO
An atypical case of prion disease is described in a 54-year-old Dutch man, homozygous for valine at codon 129 of the prion protein gene (PRNP). The clinical phenotype was characterised by progressive dementia, spastic paraplegia and sensorimotor polyneuropathy. The disease duration was 20 months. Genetic analysis of PRNP did not reveal any abnormalities. Neuropathologically, only mild spongiform change and a coarse granular immunohistochemical staining for the abnormal prion protein, PrP(Sc), was observed, with poorly formed plaques in the molecular layer of the cerebellar cortex. However, Western blotting showed low but detectable levels of proteinase K(PK)-resistant PrP(Sc) occurring in an unusual ladder-like profile. These features define a phenotype that corresponds to the recently described protease-sensitive prionopathy (PSPr). Our report on the first Dutch patient with PSPr further expands the spectrum of prionopathies and exemplifies the need to re-evaluate cases of atypical prion disease.
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Doença de Gerstmann-Straussler-Scheinker/diagnóstico , Doença de Gerstmann-Straussler-Scheinker/genética , Proteínas PrPSc/metabolismo , Príons/genética , Encéfalo/metabolismo , Encéfalo/patologia , Endopeptidase K/metabolismo , Doença de Gerstmann-Straussler-Scheinker/enzimologia , Doença de Gerstmann-Straussler-Scheinker/patologia , Homozigoto , Humanos , Masculino , Países Baixos , Fenótipo , Polimorfismo Genético , Proteínas PriônicasRESUMO
BACKGROUND: Abnormal levels of biomarkers in cerebrospinal fluid (CSF) and atrophy of medial temporal lobe (MTL) structures on magnetic resonance imaging (MRI) are being used increasingly to diagnose early Alzheimer's disease (AD). We evaluated the claim that these biomarkers can detect preclinical AD before behavioural (i.e. memory) symptoms arise. METHOD: We included all relevant longitudinal studies of CSF and MRI biomarkers published between January 2003 and November 2008. Subjects were not demented at baseline but some declined to mild cognitive impairment (MCI) or to AD during follow-up. Measures of tau and beta-amyloid in CSF, MTL atrophy on MRI, and performance on delayed memory tasks were extracted from the papers or obtained from the investigators. RESULTS: Twenty-one MRI studies and 14 CSF studies were retrieved. The effect sizes of total tau (t-tau), phosphorylated tau (p-tau) and amyloid beta 42 (a beta 42) ranged from 0.91 to 1.11. The effect size of MTL atrophy was 0.75. Memory performance had an effect size of 1.06. MTL atrophy and memory impairment tended to increase when assessed closer to the moment of diagnosis, whereas effect sizes of CSF biomarkers tended to increase when assessed longer before the diagnosis. CONCLUSIONS: Memory impairment is a more accurate predictor of early AD than atrophy of MTL on MRI, whereas CSF abnormalities and memory impairment are about equally predictive. Consequently, the CSF and MRI biomarkers are not very sensitive to preclinical AD. CSF markers remain promising, but studies with long follow-up periods in elderly subjects who are normal at baseline are needed to evaluate this promise.
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Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/líquido cefalorraquidiano , Encéfalo/patologia , Transtornos Cognitivos/diagnóstico , Imageamento por Ressonância Magnética , Proteínas tau/líquido cefalorraquidiano , Doença de Alzheimer/líquido cefalorraquidiano , Atrofia , Biomarcadores/líquido cefalorraquidiano , Transtornos Cognitivos/líquido cefalorraquidiano , Diagnóstico Precoce , Hipocampo/patologia , Humanos , Testes Neuropsicológicos , Lobo Temporal/patologiaRESUMO
Extrapontine myelinolysis (EPM) is a rare cause of Parkinsonism. In this case report, we describe a 63-year-old woman with Parkinsonism due to EPM after correction of hyponatremia. During a 4-year follow-up, both the clinical features of Parkinsonism and the changes on magnetic resonance imaging resolved. Parkinsonism due to EPM should be recognized as it has a good prognosis.
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Mielinólise Central da Ponte/complicações , Doença de Parkinson/etiologia , Disartria/etiologia , Feminino , Humanos , Hipocinesia/etiologia , Hiponatremia/complicações , Imageamento por Ressonância Magnética , Masculino , Debilidade Muscular/etiologia , Exame Neurológico , Testes NeuropsicológicosRESUMO
OBJECTIVE: To assess whether intensive vascular care in GP practices can prevent dementia in a population of community-dwelling older people. METHOD: This pragmatic cluster-randomised open-label study (ISRCTN29711771) was conducted in persons aged 70-78 years who were registered with Dutch GP practices. The only exclusion criteria were a diagnosis of dementia and limited life expectancy. Practices were randomly assigned to an intervention arm or a control arm. Participants in the interventional arm underwent a cardiovascular check-up every 4 months for six years by a practice nurse. Primary outcomes were cumulative incidence of dementia and functional limitations. Main secondary outcomes were the incidence of cardiovascular disease and mortality. RESULTS: Between June 2006 and March 2009, 116 GP practices (3526 participants) were recruited and randomly assigned: 63 (1890 participants) to the intervention group and 53 (1636 participants) to the control group. Primary outcome data were obtained for 3454 (98%) participants; median follow-up was 6.7 years. In this period, dementia was diagnosed in 121/1853 (6.5%) participants in the intervention group and in 112/1601 (7.0%) participants in the control group. This difference was not significant (hazard ratio 0.92, 95% CI 0.71-1.19). No differences were found with regard to functional decline, incident cardiovascular disease and mortality. CONCLUSION: Long-term intensive vascular care for community-dwelling elderly patients, provided in a primary care setting, does not result in a reduced incidence of dementia, functional limitations or mortality. There is, however, possibly an effect in elderly patients with untreated or sub-optimally treated hypertension; this warrants further research.
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Cholinesterase inhibitors are widely prescribed in patients with Alzheimer's disease. Recently it has become clear that using these medications increases the risk of serious adverse events like cardiac arrhythmias, and some studies report a much-increased mortality in the treatment group on comparison with the placebo group. In the light of the at best, modest, treatment effects, we advocate that the safety of cholinesterase inhibitors should be the subject of continuing, intense scrutiny. Efforts should be made to delineate the profile of a true 'cholinergic deficiency syndrome', in order to be able to prescribe these medications to a group of patients in whom the benefits outweigh the risks.
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Doença de Alzheimer/tratamento farmacológico , Arritmias Cardíacas/induzido quimicamente , Inibidores da Colinesterase/efeitos adversos , Inibidores da Colinesterase/uso terapêutico , Humanos , Medição de Risco , Fatores de Risco , Segurança , Resultado do TratamentoRESUMO
The practice guideline 'Diagnosis and pharmaceutical treatment of dementia' emphasizes that a nosological diagnosis should be made and that it is important to assess the extent of need for care. The guideline recommends the use of diagnostic criteria for the various conditions that can cause dementia. With respect to ancillary investigations, the burden to the patient should be weighed against the benefits of increasing diagnostic confidence. Observation of the course of the disease, laboratory and cerebrospinal-fluid investigations, neuropsychological and EEG examinations, and neuroimaging all increase diagnostic confidence. Treatment with a cholinesterase inhibitor or memantine should always be embedded in a comprehensive-treatment protocol that includes explicit discussion of treatment goals and expectations at baseline, in combination with criteria for starting and stopping treatment. Guidelines for evaluating the effects of treatment with cholinesterase inhibitors or memantine are specified. If psychosis, depression or behavioural disturbances occur in patients with dementia, antidepressants, antipsychotics or anticonvulsants may be indicated.
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Antipsicóticos/uso terapêutico , Demência/diagnóstico , Demência/tratamento farmacológico , Guias de Prática Clínica como Assunto , Padrões de Prática Médica , Inibidores da Colinesterase/uso terapêutico , Efeitos Psicossociais da Doença , Humanos , Memantina/uso terapêutico , Países Baixos , Testes Neuropsicológicos , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate whether web-based interventions for cardiovascular risk factor management reduce the risk of cardiovascular disease in older people. DESIGN: Systematic review and meta-analysis. METHOD: Embase, Medline, Cochrane Library and CINAHL were systematically searched from January 1995 to 3 November 2014. We included all randomised controlled trials for web-based interventions targeting cardiovascular risk factors in populations with a mean age of 50 and older. The outcome measures were cardiovascular risk factors (blood pressure, HbA1c, LDL cholesterol, weight, smoking status and physical activity) and the incidence of cardiovascular disease. We used random-effects models to pool the results of the studies. RESULTS: A total of 57 studies (19,862 participants) fulfilled eligibility criteria, and 47 of these were suitable for meta-analysis. We found a significant reduction in systolic blood pressure (-2.66 mmHg, 95% CI -3.81 to -1.52), diastolic blood pressure (-1.26 mmHg, 95% CI -1.92 to -0.60), HbA1c level (-0.13%, 95% CI -0.22 to -0.05), LDL cholesterol level (-0.06 mmol/l, 95% CI -0.10 to -0.01), weight (-1.34 kg, 95% CI -1.91 to -0.77), and an increase in physical activity (standardized mean difference 0.25, 95% CI 0.10-0.39) in the intervention group when compared with the control group. Treatment effects were more pronounced in studies of short duration (< 12 months) and when combining the web-based intervention with human support by a health care professional. No difference in the incidence of cardiovascular disease was found between groups. CONCLUSION: Web-based interventions have a beneficial effect on the cardiovascular risk profile, but this effect is modest and declines with time. Currently, there is insufficient evidence that this can prevent cardiovascular disease. A focus on long-term effects, effect-sustainability and clinical endpoints is recommended for future studies.
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Doenças Cardiovasculares/prevenção & controle , Promoção da Saúde/métodos , Internet , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Humanos , Incidência , Pessoa de Meia-Idade , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: White matter hyperintensities of presumed vascular origin in elderly patients with hypertension may be part of a general cerebral perfusion deficit, involving not only the white matter hyperintensities but also the surrounding normal-appearing white matter and gray matter. We aimed to study the relation between white matter hyperintensity volume and CBF and assess whether white matter hyperintensities are related to a general perfusion deficit. MATERIALS AND METHODS: In 185 participants of the Prevention of Dementia by Intensive Vascular Care trial between 72 and 80 years of age with systolic hypertension, white matter hyperintensity volume and CBF were derived from 3D FLAIR and arterial spin-labeling MR imaging, respectively. We compared white matter hyperintensity CBF, normal-appearing white matter CBF, and GM CBF across quartiles of white matter hyperintensity volume and assessed the continuous relation between these CBF estimates and white matter hyperintensity volume by using linear regression. RESULTS: Mean white matter hyperintensity CBF was markedly lower in higher quartiles of white matter hyperintensity volume, and white matter hyperintensity volume and white matter hyperintensity CBF were negatively related (standardized ß = -0.248, P = .001) in linear regression. We found no difference in normal-appearing white matter or GM CBF across quartiles of white matter hyperintensity volume or any relation between white matter hyperintensity volume and normal-appearing white matter CBF (standardized ß = -0.065, P = .643) or GM CBF (standardized ß = -0.035, P = .382) in linear regression. CONCLUSIONS: Higher white matter hyperintensity volume in elderly individuals with hypertension was associated with lower perfusion within white matter hyperintensities, but not with lower perfusion in the surrounding normal-appearing white matter or GM. These findings suggest that white matter hyperintensities in elderly individuals with hypertension relate to local microvascular alterations rather than a general cerebral perfusion deficit.
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Alzheimer's disease is aetiologically heterogeneous, but the pathogenesis is often considered to be initiated by the deposition of amyloid fibrils, followed by neuritic tau pathology and neuronal death. A variety of inflammatory proteins has been identified in the brains of patients with Alzheimer's disease post mortem. In this article, Piet Eikelenboom and colleagues review evidence to suggest that the inflammatory processes are intimately involved in several crucial events in the pathological cascade. This suggests possibilities for the treatment of Alzheimer's disease with anti-inflammatory drugs.
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Doença de Alzheimer/patologia , Inflamação/patologia , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Animais , Humanos , Inflamação/tratamento farmacológicoRESUMO
OBJECTIVE: To determine whether measures of quantitative spectral electroencephalography (EEG) can predict survival in patients with early Alzheimer disease. DESIGN: Prospective cohort study; median duration of follow-up was 4.4 years in survivors and 2.6 years in nonsurvivors. Cox proportional hazards models, with adjustment for age and sex were used to estimate relationships between EEG measures and survival. Log relative percentage values of EEG bands were used as predictors. SETTING: Outpatient university memory clinic. PARTICIPANTS: One hundred one consecutively referred patients with early probable Alzheimer disease according to National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria were studied with EEG at the time of diagnosis. The mean age of the patients was 79.2 years, which was higher than in previous EEG studies. MAIN OUTCOME MEASURE: Mortality. RESULTS: Fifty-one patients (50.5%) died during follow-up, with a median survival time in all patients of 4.1 years. The following EEG variables were significantly associated with increased risk of mortality: from parieto-occipital leads, higher theta (hazard ratio, 2.05; 95% confidence interval, 1.15-3.66; P<.05), lower alpha (hazard ratio, 0.43; 95% confidence interval, 0.25-0.76; P<.01), and lower beta (hazard ratio, 0.38; 95% confidence interval, 0.22-0.68; P<.001) activity; and from frontocentral leads, higher theta activity (hazard ratio, 2.07; 95% confidence interval, 1.17-3.66; P<.05). Stepwise Cox regression analysis showed that loss of parieto-occipital beta (P<.01) and alpha (P<.05) power were independent and significant predictors of mortality. Both beta (12.6-35.4 Hz) and alpha (7.5-12.5 Hz) activity remained significantly associated with mortality after adjustment for education, dementia severity, symptom duration, level of cognitive function, presence of extrapyramidal symptoms or hallucinations, presence of vascular risk factors, and presence of leukoaraiosis or local cortical atrophy. CONCLUSIONS: Decreases of beta and alpha activity on quantitative spectral EEG are independent predictors of mortality in patients with early Alzheimer disease. In the clinical context, the use of EEG technology for prediction of survival in individual patients remains to be determined.
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Doença de Alzheimer/mortalidade , Doença de Alzheimer/fisiopatologia , Eletroencefalografia , Idoso , Eletroencefalografia/métodos , Feminino , Seguimentos , Humanos , Masculino , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Estudos Prospectivos , Risco , Análise de SobrevidaRESUMO
OBJECTIVE: To study the sensitivity and specificity of 14-3-3 testing in a prospective series of patients suspected of having Creutzfeldt-Jakob disease (CJD). BACKGROUND: The 14-3-3 protein immunoassay on CSF has favorable test characteristics as a premortem diagnostic tool in CJD. However, the 14-3-3 protein is a normal cellular protein expressed in various tissues, and its presence in CSF reflects extensive destruction of brain tissue as in CJD, but also in ischemic stroke and meningoencephalitis. METHODS: 14-3-3 was tested in the CSF of a prospective series of 110 consecutive patients suspected of having CJD. RESULTS: The sensitivity was 97% and the specificity was 87% in this series. False-positive results were mainly caused by stroke and meningoencephalitis. CONCLUSION: The 14-3-3 protein is a highly sensitive and specific marker for CJD when used in the appropriate clinical context.
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Astrocitoma/diagnóstico , Neoplasias Encefálicas/diagnóstico , Síndrome de Creutzfeldt-Jakob/diagnóstico , Linfoma/diagnóstico , Proteínas/análise , Tirosina 3-Mono-Oxigenase , Proteínas 14-3-3 , Adulto , Idoso , Astrocitoma/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Encefalopatias/líquido cefalorraquidiano , Encefalopatias/diagnóstico , Neoplasias Encefálicas/líquido cefalorraquidiano , Líquido Cefalorraquidiano/química , Síndrome de Creutzfeldt-Jakob/líquido cefalorraquidiano , Diagnóstico Diferencial , Reações Falso-Positivas , Feminino , Humanos , Linfoma/líquido cefalorraquidiano , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e EspecificidadeRESUMO
The authors describe the clinical characteristics, MRI abnormalities, and molecular findings in a patient with a novel variant of a two-octarepeat insertion mutation in the prion protein gene. This patient presented with moderately progressive dementia of presenile onset and gait ataxia. MRI showed extensive cortical atrophy and white matter abnormalities. The mutation consists of a two-octarepeat insertion mutation and irregularities in the nucleotide sequence of the octarepeat region.