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BACKGROUND: Patients and their loved ones often report symptoms or complaints of cognitive decline that clinicians note in free clinical text, but no structured screening or diagnostic data are recorded. These symptoms/complaints may be signals that predict who will go on to be diagnosed with mild cognitive impairment (MCI) and ultimately develop Alzheimer's Disease or related dementias. Our objective was to develop a natural language processing system and prediction model for identification of MCI from clinical text in the absence of screening or other structured diagnostic information. METHODS: There were two populations of patients: 1794 participants in the Adult Changes in Thought (ACT) study and 2391 patients in the general population of Kaiser Permanente Washington. All individuals had standardized cognitive assessment scores. We excluded patients with a diagnosis of Alzheimer's Disease, Dementia or use of donepezil. We manually annotated 10,391 clinic notes to train the NLP model. Standard Python code was used to extract phrases from notes and map each phrase to a cognitive functioning concept. Concepts derived from the NLP system were used to predict future MCI. The prediction model was trained on the ACT cohort and 60% of the general population cohort with 40% withheld for validation. We used a least absolute shrinkage and selection operator logistic regression approach (LASSO) to fit a prediction model with MCI as the prediction target. Using the predicted case status from the LASSO model and known MCI from standardized scores, we constructed receiver operating curves to measure model performance. RESULTS: Chart abstraction identified 42 MCI concepts. Prediction model performance in the validation data set was modest with an area under the curve of 0.67. Setting the cutoff for correct classification at 0.60, the classifier yielded sensitivity of 1.7%, specificity of 99.7%, PPV of 70% and NPV of 70.5% in the validation cohort. DISCUSSION AND CONCLUSION: Although the sensitivity of the machine learning model was poor, negative predictive value was high, an important characteristic of models used for population-based screening. While an AUC of 0.67 is generally considered moderate performance, it is also comparable to several tests that are widely used in clinical practice.
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Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/diagnóstico , Disfunção Cognitiva/diagnóstico , Humanos , Aprendizado de Máquina , Programas de Rastreamento , Processamento de Linguagem NaturalRESUMO
INTRODUCTION: The European Medical Information Framework consortium has assembled electronic health record (EHR) databases for dementia research. We calculated dementia prevalence and incidence in 25 million persons from 2004 to 2012. METHODS: Six EHR databases (three primary care and three secondary care) from five countries were interrogated. Dementia was ascertained by consensus harmonization of clinical/diagnostic codes. Annual period prevalences and incidences by age and gender were calculated and meta-analyzed. RESULTS: The six databases contained 138,625 dementia cases. Age-specific prevalences were around 30% of published estimates from community samples and incidences were around 50%. Pooled prevalences had increased from 2004 to 2012 in all age groups but pooled incidences only after age 75 years. Associations with age and gender were stable over time. DISCUSSION: The European Medical Information Framework initiative supports EHR data on unprecedented number of people with dementia. Age-specific prevalences and incidences mirror estimates from community samples in pattern at levels that are lower but increasing over time.
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Área Programática de Saúde/estatística & dados numéricos , Demência/epidemiologia , Registros Eletrônicos de Saúde/estatística & dados numéricos , Informática Médica/estatística & dados numéricos , Distribuição por Idade , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Demência/diagnóstico , Europa (Continente)/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Valores de Referência , Estudos Retrospectivos , Fatores de TempoRESUMO
BACKGROUND: Amyloid-related imaging abnormalities due to haemosiderin deposition (ARIA-H) occur in patients with mild to moderate dementia due to Alzheimer's disease (AD) and have been reported with increased incidence in clinical trials of amyloid-lowering therapies under development for AD. OBJECTIVE: Our objective was to explore the relationship between the incidences of ARIA-H during treatment with placebo and different doses of bapineuzumab, a humanised monoclonal antibody directed against amyloid ß. METHODS: Two neuroradiologists independently reviewed 2572 GRE/T2* MRI sequences from 262 participants in two phase two clinical trials of bapineuzumab and an open-label extension study. Readers were blinded to the participant's therapy, APOE ε4 genotype and medical history. RESULTS: Several risk factors for small ARIA-H <10â mm (microhaemorrhages) were identified: APOE ε4, bapineuzumab treatment, pre-existing small ARIA-H and use of antithrombotics. The HR (95%CI) for incident ARIA-H <10â mm associated with the number of APOE ε4 alleles was 11.9 (3.3 to 42.5) for 2 versus no alleles and 3.5 (1.0 to 12.0) for 1 versus no allele. The HR for bapineuzumab therapy was 3.5 (1.0 to 12.0); for the presence of baseline ARIA-H <10â mm, it was 3.5 (1.6 to 7.8), and for the use of antithrombotic agents it was 2.2 (1.0 to 4.8). The incidence rate for ARIA-H <10â mm was elevated only in the initial 6â months of active treatment and declined after this interval to a rate similar to that observed in the group treated with placebo. CONCLUSIONS: ARIA-H represents a spectrum of MRI findings due to haemosiderin deposition that appears to be related to impaired vascular integrity. The increased risk for ARIA-H associated with APOE ε4 allele frequency, pre-existing ARIA-H, treatment with bapineuzumab and use of antithrombotic agents provides additional support for this hypothesis of loss of integrity of cerebral vessels due to amyloid burden. TRIAL REGISTRATION: NCT00112073 and NCT00606476.
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Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides , Anticorpos Monoclonais Humanizados/uso terapêutico , Hemossiderina/análise , Nootrópicos/uso terapêutico , Placa Amiloide/patologia , Idoso , Idoso de 80 Anos ou mais , Peptídeos beta-Amiloides/antagonistas & inibidores , Anticorpos Monoclonais Humanizados/administração & dosagem , Apolipoproteína E4/sangue , Ensaios Clínicos Fase II como Assunto , Estudos de Coortes , Relação Dose-Resposta a Droga , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Neuroimagem , Nootrópicos/administração & dosagem , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia , Substância Branca/patologiaRESUMO
BACKGROUND: the objective of the study was to estimate and compare the incidence rates of ischaemic and haemorrhagic stroke and seizure among cohorts with and without Alzheimer's disease (AD) dementia. METHODS: we conducted a retrospective cohort study using electronic medical records (EMRs) from primary care practices that participated in The Health Improvement Network (THIN) in the United Kingdom from 1 January 1990 to 31 July 2009. For each AD-dementia patient, we selected one general population control patient without AD-dementia matched to one AD-dementia patient on year of birth, sex and physician practice. FINDINGS: the AD-dementia cohorts were 68% female and averaged 80 years of age at the start of follow-up. Populations for analysis included 19,902 AD-dementia and matched non-AD-dementia patients with no history of stroke at baseline in which 790 incident cases of stroke occurred, and similarly, 22,084 AD-dementia and matched patients with no history of seizure at baseline in which 286 cases of seizure occurred. After adjusting for risk factors for each outcome, hazard ratios comparing AD-dementia with non-AD-dementia patients indicated higher rates among AD-dementia patients for stroke (HR = 1.29, 95% CI 1.11, 1.50) and seizure (HR = 5.31, 95% CI 3.97, 7.10). For stroke and seizure, the incidence rate ratios comparing AD-dementia patients with non-AD-dementia controls were greatest for the younger age groups. AD-dementia was observed to be a risk factor for both haemorrhagic stroke and seizures. Increasing age was associated with a decrease in relative risk and an increase in absolute risk.
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Doença de Alzheimer/complicações , Avaliação Geriátrica/métodos , Vigilância da População/métodos , Convulsões/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Registros Eletrônicos de Saúde , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Convulsões/etiologia , Acidente Vascular Cerebral/etiologia , Reino Unido/epidemiologiaRESUMO
PURPOSE: To estimate the relative importance that Alzheimer's disease (AD) caregivers in the United States and Germany place on preserving patients' ability to perform activities of daily living. METHODS: US and German residents providing care for a person with AD completed an online preference survey. Each respondent completed five best-worst scaling questions. Each question related to five of 10 activities from the Disability Assessment for Dementia scale. Preference weights, indicating the relative importance of preserving the ability to perform these 10 activities for 36 months, were estimated using maximum-difference scaling. A separate model was estimated for each country. RESULTS: Four hundred and three US and 400 German caregivers completed the survey. In both countries, preserving a patients' ability to use the toilet without accidents was the most important activity and handling money was the least important activity. There were few differences between US and German caregivers in the relative importance across activities. CONCLUSIONS: Caregivers generally placed greater importance on preserving basic activities of daily living than on preserving instrumental activities of daily living. Understanding differences in the relative importance of functional items in the DAD may contribute to a better understanding of the benefits of different AD treatment and support measures.
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Atividades Cotidianas/psicologia , Doença de Alzheimer/terapia , Cuidadores/psicologia , Qualidade de Vida , Inquéritos e Questionários , Cuidadores/estatística & dados numéricos , Estudos Transversais , Avaliação da Deficiência , Escolaridade , Feminino , Alemanha , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Classe Social , Estados UnidosRESUMO
BACKGROUND: Functional impairment is a core symptom of Alzheimer's disease (AD) often measured by loss of ability to perform activities of daily living (ADL). The objective is to describe the progressive loss of specific ADL functional capabilities expressed by AD patients' cognitive ability. METHODS: Data are from ELN-AIP-901, an observational study of cognitive progression in participants aged 50-85 with AD (n = 196), mild cognitive impairment (n = 70), or cognitively normal (n = 75). Participants were evaluated using the Mini-Mental Status Exam (MMSE) and the Disability Assessment for Dementia (DAD) every six months for ≤2 years. Hierarchical regression was used to estimate annual change in DAD and MMSE; first, by individuals' rate of change using linear regression, then controlling for baseline diagnosis. RESULTS: Over a two-year period, in AD participants, a 1-point change in MMSE was associated with a 3-point change in DAD (2.79, 95% CI: 1.97-3.63); DAD items within the finance, medication, and outings subdomains were impacted earlier than other subdomains; a hierarchy of functional impairment was observed, with instrumental ADL generally impaired prior to basic ADL. CONCLUSIONS: ADL are impacted in a progressive and hierarchical manner associated with cognitive decline, but substantial variability remains among individuals, as well as in the relative order of items affected.
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Atividades Cotidianas , Doença de Alzheimer/fisiopatologia , Transtornos Cognitivos/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/psicologia , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/psicologia , Avaliação da Deficiência , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Análise de RegressãoRESUMO
BACKGROUND: Population allele frequencies of apolipoprotein E (APOE) vary by geographic region. The purpose of this study is to summarize and evaluate published estimates for the prevalence of APOE e4 carrier status among the population diagnosed with Alzheimer's disease (AD) by geographic region and country. METHODS: A systematic review of English-language publications from January 1, 1985, through May 31, 2010, was conducted. Studies reporting APOE e4 status for patients diagnosed with AD were included in the analysis; trials and autopsies were excluded. APOE e4 data were pooled, and prevalence and 95% confidence intervals (CIs) were calculated. RESULTS: Pooled estimates for APOE e4 carrier prevalence data were derived from 142 independent samples: 48.7% (95% CI: 46.5-51.0), and from 73 samples for e4/4 (homozygotes): 9.6% (95% CI: 8.4-10.8). The highest estimates were in Northern Europe: 61.3% (95% CI: 55.9-66.7), e4/4 prevalence: 14.1% (95% CI: 12.2-16.0). The lowest estimates were in Asia and Southern Europe. Substantial heterogeneity of these prevalence estimates was observed. CONCLUSIONS: APOE e4 genotype prevalence varies among AD patients by region and within each country. Further exploration is warranted to better understand the substantial heterogeneity of these prevalence estimates.
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Doença de Alzheimer/genética , Apolipoproteínas E/genética , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Ásia/epidemiologia , Europa (Continente)/epidemiologia , Feminino , Frequência do Gene , Heterogeneidade Genética , Genética Populacional , Genótipo , Heterozigoto , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , América do Norte/epidemiologia , Prevalência , Análise de Regressão , América do Sul/epidemiologiaRESUMO
BACKGROUND: The purpose of conducting this study was to identify areas of concordance and sources of variation for the published rates of prevalence and incidence associated with various definitions for mild cognitive impairment (MCI). METHODS: The study used systematic review of studies published in English since 1984. Studies were identified by searching MEDLINE and EMBASE databases. Population-based observational studies of incidence or prevalence of MCI and related terms were eligible for inclusion. RESULTS: A total of 3,705 citations were identified, and 42 were accepted for inclusion; 35 included data on prevalence and 13 on incidence. The following four terms predominated: age-associated memory impairment (AAMI); cognitive impairment no dementia (CIND); MCI; and amnestic MCI (aMCI). Within each term, the operational definition varied. Substantial variation was observed for both incidence (MCI: 21.5-71.3; aMCI: 8.5-25.9 per 1,000 person-years) and prevalence of each definition of cognitive impairment (AAMI 3.6%-38.4%; CIND 5.1%-35.9%; MCI 3%-42%; aMCI 0.5%-31.9%). CIND and MCI showed increasing prevalence among older age groups, whereas age-specific rates of aMCI were lower and without any apparent age relationship. CONCLUSIONS: Prevalence and incidence estimates associated with MCI vary greatly both between definitions and within a definition across the 42 publications. These wide differences pose a significant challenge to our understanding of the social burden of this disease. Enhancement and standardization of operational definitions of the subtypes of cognitive impairment could improve estimates of disease burden and provide a mechanism to assist in the identification of individuals at risk for future Alzheimer's disease and other dementias.
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Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/psicologia , Bases de Dados Bibliográficas/estatística & dados numéricos , Humanos , Incidência , PrevalênciaRESUMO
BACKGROUND: The ε4 allele of apolipoprotein E (APOE) is associated with Alzheimer's disease (AD). However, attributable risk due to APOE4 varies by region and by race/ethnicity. METHODS: A literature review and meta-analysis were conducted to estimate the prevalence of APOE4 by geographic area among AD patients. RESULTS: Although estimates varied significantly by study design and case definition, AD patients recruited in Asian and southern European/Mediterranean communities seemed to have significantly lower E4 carrier status estimates (37 and 43%) than those recruited in North America (58%) or northern Europe (64%; all: p < 0.05). CONCLUSIONS: APOE4 genotype frequency varies among AD patients in regional patterns similar to that of the general population. Study level differences may also contribute to the heterogeneity of published estimates of APOE4 in AD cases.
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Doença de Alzheimer/epidemiologia , Doença de Alzheimer/genética , Apolipoproteína E4/genética , Alelos , Autopsia , Interpretação Estatística de Dados , Meio Ambiente , Frequência do Gene , Predisposição Genética para Doença , Geografia , Heterozigoto , Humanos , Análise de Regressão , Bancos de TecidosRESUMO
BACKGROUND: hip fractures result in a significant burden to the patient, their caregivers and the health care system. Patients with Alzheimer's disease (AD) have a higher incidence of hip fracture compared with other older people without AD, although it is not clear if AD is an independent risk factor for hip fracture. METHODS: a retrospective cohort study was conducted using anonymised electronic medical records from primary care practices in the United Kingdom. Proportional hazards regression modelling with adjustment for potential confounders was used to evaluate AD as an independent risk factor for predicting hip fractures. RESULTS: the incidence of hip fracture among patients with and without AD was 17.4 (95% CI, 15.7-19.2) and 6.6 (95% CI, 5.8-7.6) per 1,000 person years, respectively. Patients with AD had a hazard that was 3.2 (95% CI, 2.4-4.2) times that of non-AD patients after controlling for potential confounders. AD patients who experienced a hip fracture also had an increased mortality rate compared with non-AD patients who experienced a hip fracture (hazard ratio = 1.5; 95% CI, 1.1-1.9). CONCLUSION: patients with AD and their caregivers should be advised on how to prevent hip fractures and more attention should be given to AD patients who are undergoing rehabilitation following a hip fracture.
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Doença de Alzheimer/mortalidade , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/mortalidade , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/epidemiologia , Estudos de Coortes , Feminino , Fraturas do Quadril/reabilitação , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Health care planning and research would benefit from tools that enable researchers to project the future burden of Alzheimer's disease (AD) and evaluate the effect of potential interventions. METHODS: We created a web-based application of the AD prevalence model developed by Brookmeyer et al (Am J Public Health 1998;88:1337-42; Alzheimers Dement 2007;3:186-91). The user defines the disease parameters and any interventions that may either reduce risk or slow disease progression. We expanded the parameters to include the cost and weights for disability-adjusted life years. APPLICATION: The secure, web-based application generates detailed AD projections for each calendar year to 2050, and allows users to create personal accounts for them to save, retrieve, and modify the input parameters. The flexibility of the application is illustrated with a forecast for the state of Maryland, USA. CONCLUSIONS: The application generates AD burden projections, costs, and disability-adjusted life years, along with changes associated with potential interventions.
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Doença de Alzheimer/economia , Doença de Alzheimer/epidemiologia , Internet/economia , Doença de Alzheimer/prevenção & controle , Humanos , Maryland/epidemiologia , Serviços Preventivos de SaúdeRESUMO
OBJECTIVES: We sought to determine whether treatment with steroids, immunosuppressives (ISs), and anti-tumor necrosis factor (TNF) agents is associated with an increased risk of adverse events in patients with Crohn's disease (CD). METHODS: This study analyzed claims from patients with CD and controls without CD from the United States with private insurance (2002-2005). Patients were classified by treatment with steroids, ISs, anti-TNF agents, combinations of two or three, and none of these medications. Follow-up adverse events in patients with CD and controls were compared across different treatment categories and are presented as hazard ratios (HRs) and 95% confidence intervals (CIs). Within the CD patients, a subset analysis examined the relationship between therapies and outcomes. RESULTS: A total of 22,310 patients with CD (8,581 longitudinal cohort cases) and 111,550 controls were identified. Compared with the controls, CD patients had higher rate ratios for all pre-specified events. Within the CD patient population subgroup, monotherapy with steroids, ISs, or anti-TNF agents was associated with an increased risk of tuberculosis (TB) (HR 2.7; 95% CI, 1.0-7.3), candidiasis (HR 2.7; 95% CI, 1.8-4.0), herpes zoster (HR 1.7; 95% CI, 1.0-2.7), sepsis (HR 1.3; 95% CI, 1.1-1.5), demyelinating conditions (HR 3.2; 95% CI, 1.5-6.9), and cervical dysplasia (HR 1.5; 95% CI, 1.2-2.0) as compared with patients not receiving these medications. The use of two or three of these medications further increased these risks: TB (HR 7.4; 95% CI, 2.1-26.3), candidiasis (HR 3.8; 95% CI, 2.0-7.6), herpes zoster (HR 3.7; 95% CI, 1.8-7.5), sepsis (HR 1.6; 95% CI, 1.2-2.1), and cervical dysplasia (HR 1.8; 95% CI, 1.1-3.0). CONCLUSIONS: Treatment with steroids, ISs, or anti-TNF agents singly and in combination in patients with CD is associated with increased risks of infection, demyelinating disorders, and cervical dysplasia.
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Anticorpos Monoclonais/efeitos adversos , Doença de Crohn/tratamento farmacológico , Imunossupressores/efeitos adversos , Esteroides/efeitos adversos , Adalimumab , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Humanizados , Azatioprina/efeitos adversos , Azatioprina/uso terapêutico , Budesonida/efeitos adversos , Budesonida/uso terapêutico , Estudos de Casos e Controles , Comorbidade , Doença de Crohn/epidemiologia , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/uso terapêutico , Infliximab , Estudos Longitudinais , Masculino , Mercaptopurina/efeitos adversos , Mercaptopurina/uso terapêutico , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Prednisona/efeitos adversos , Prednisona/uso terapêutico , Prevalência , Modelos de Riscos Proporcionais , Esteroides/uso terapêutico , Estados Unidos/epidemiologiaRESUMO
Alzheimer disease (AD) is a progressive, ultimately fatal neurodegenerative illness affecting millions of patients, families, and caregivers. Effective disease-modifying therapies for AD are desperately needed, but none currently exist on the market. Thus, accelerating the discovery, development, and approval of new disease-modifying drugs for AD is a high priority for individuals, physicians, and medical decision makers. Potentially disease-modifying drugs likely will have significant therapeutic benefits but also may have treatment-related risks. We quantified older Americans' treatment-related risk tolerance by eliciting their willingness to accept the risk of treatment-related death or permanent severe disability in exchange for modifying the course of AD. A stated-choice survey instrument was administered to 2146 American residents 60 years of age and older. On average, subjects were willing to accept a 1-year risk of treatment-related death or permanent severe disability from stroke of over 30% for a treatment that prevents AD from progressing beyond the mild stage. Thus, most people in this age cohort are willing to accept considerable risks in return for disease-modifying benefits of new AD drugs. These results are consistent with other studies indicating that individuals view AD as a serious, life threatening illness that imposes heavy burdens on both patients and caregivers.
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Doença de Alzheimer/tratamento farmacológico , Fármacos Neuroprotetores/efeitos adversos , Assunção de Riscos , Idoso , Coleta de Dados , Humanos , Pessoa de Meia-Idade , Medição de Risco , Estados UnidosRESUMO
BACKGROUND: The doubling time is the number of chronological years for the age-specific incidence rate to double in magnitude. Doubling times describe the rate of increase of the risk of Alzheimer's disease (AD) with advancing age. Estimates of doubling times of AD assist in understanding disease etiology and forecasting future disease prevalence. The objective of this study was to investigate regional and gender differences in the doubling of AD age-specific incidence rates. METHODS: We identified all studies in the peer review literature that reported age-specific incidence rates for AD. We modeled the logarithm of the incidence rate as a linear function of age. We used both fixed effects models and random effects models to account for interstudy variation. RESULTS: AD incidence rates exponentially increase with increasing age. The overall estimate of the doubling time was 5.5 years. The doubling times from studies performed in North America and Europe were 6.0 and 5.8, respectively; whereas the doubling times in all other parts of the world were 5.0. There was no significant geographic differences in doubling times (P = .3). Although the doubling times were slightly longer for men (6.5 years) than for women (5.4 years), the difference was not significant (P = .3). CONCLUSIONS: Doubling times of AD incidence rates are not statistically significantly different among populations throughout the world. The risk of AD grows exponentially with age, doubling approximately every 5 to 6 years. Although the shapes of the incidence curves are similar, there is considerable variation in absolute incidence rates throughout the world. Currently, there are limited epidemiologic data at the oldest ages, and further study is needed to accurately define the incidence curve above age 90.
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Doença de Alzheimer/epidemiologia , Distribuição por Idade , Fatores Etários , Algoritmos , Feminino , Humanos , Incidência , MasculinoRESUMO
BACKGROUND: Our goal was to forecast the global burden of Alzheimer's disease and evaluate the potential impact of interventions that delay disease onset or progression. METHODS: A stochastic, multistate model was used in conjunction with United Nations worldwide population forecasts and data from epidemiological studies of the risks of Alzheimer's disease. RESULTS: In 2006, the worldwide prevalence of Alzheimer's disease was 26.6 million. By 2050, the prevalence will quadruple, by which time 1 in 85 persons worldwide will be living with the disease. We estimate about 43% of prevalent cases need a high level of care, equivalent to that of a nursing home. If interventions could delay both disease onset and progression by a modest 1 year, there would be nearly 9.2 million fewer cases of the disease in 2050, with nearly the entire decline attributable to decreases in persons needing a high level of care. CONCLUSIONS: We face a looming global epidemic of Alzheimer's disease as the world's population ages. Modest advances in therapeutic and preventive strategies that lead to even small delays in the onset and progression of Alzheimer's disease can significantly reduce the global burden of this disease.
RESUMO
BACKGROUND: Amyloid-related imaging abnormalities (ARIA) consist of ARIA-E (with effusion or edema) and ARIA-H (hemosiderin deposits [HDs]). OBJECTIVES: To address accurate ascertainment of ARIA identification, a final magnetic resonance imaging (MRI) reading was performed on patients with mild-to-moderate Alzheimer's disease randomized to bapineuzumab IV or placebo during two Phase III trials (APOE É4 allele carriers or noncarriers). METHODS: Final MRI central review consisted of a systematic sequential locked, adjudicated read in 1,331 APOE É4 noncarriers and 1,121 carriers by independent neuroradiologists. Assessment of ARIA-E, ARIA-H, intracerebral hemorrhages, and age-related white matter changes is described. RESULTS: In the Final Read, treatment-emergent ARIA-E were identified in 242 patients including 76 additional cases not noted previously in real time. Overall, incidence proportion of ARIA-E was higher in carriers (active 21.2%; placebo 1.1%) than in noncarriers (pooled active 11.3%; placebo 0.6%), and was more often identified in homozygote APOE É4 carriers than heterozygotes (34.5% versus 16.9%). Incidence rate of ARIA-E increased with increased dose in noncarriers. Frequency of ARIA-E first episodes was highest after the first and second bapineuzumab infusion and declined after repeated infusions. Incidence of total HDs <10âmm (cerebral microhemorrhages) was higher in active groups versus placebo. CONCLUSION: ARIA was detected more often on MRI scans when every scan was reviewed by trained neuroradiologists and results adjudicated. There was increased incidence of ARIA-E in bapineuzumab-treated carriers who had a microhemorrhage at baseline. ARIA-E was a risk factor for incident ARIA-H and late onset ARIA-E was milder radiologically. Age-related white matter changes did not progress during the study.
Assuntos
Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/tratamento farmacológico , Anticorpos Monoclonais Humanizados/uso terapêutico , Encéfalo/efeitos dos fármacos , Encéfalo/diagnóstico por imagem , Fatores Imunológicos/uso terapêutico , Doença de Alzheimer/epidemiologia , Doença de Alzheimer/genética , Amiloide/efeitos dos fármacos , Anticorpos Monoclonais Humanizados/efeitos adversos , Apolipoproteína E4/genética , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/genética , Progressão da Doença , Relação Dose-Resposta a Droga , Heterozigoto , Humanos , Fatores Imunológicos/efeitos adversos , Incidência , Estimativa de Kaplan-Meier , Imageamento por Ressonância Magnética , Prevalência , Fatores de Risco , Índice de Gravidade de Doença , Substância Branca/diagnóstico por imagem , Substância Branca/efeitos dos fármacosRESUMO
INTRODUCTION: Immunotherapeutic agents against amyloid beta (Aß) are associated with adverse events, including amyloid-related imaging abnormalities with edema and effusion (ARIA-E). Recently, a magnetic resonance imaging (MRI) rating scale was developed for ARIA-E detection and classification. The aim of this study was to validate the use of this rating scale in a larger patient group with multiple raters. METHODS: MRI scans of 75 patients (29 with known ARIA-E and 46 control subjects) were analyzed by five neuroradiologists with different degrees of expertise, according to the ARIA-E rating scale. For each patient, we included a baseline and a follow-up fluid-attenuated inversion recovery image. Interrater agreement was calculated using intraclass correlation coefficient (ICC). RESULTS: On average, 4.1% of the ARIA-E cases were missed. We observed a high interrater agreement for scores of sulcal hyperintensity (SH; ICC = .915; 95% CI 85-95) and for the combined scores of the 2 ARIA-E findings, parenchymal hyperintensity (PH) and SH (ICC = .878; 95% CI 79-93). A slightly lower agreement for PH (ICC = .678; 95% CI 51-81) was noted. CONCLUSION: The ARIA-E rating scale is a simple tool to evaluate the extent of ARIA-E in patients recruited into Aß-lowering therapeutic trials. It shows high interrater agreement among raters with different degrees of expertise.
Assuntos
Doença de Alzheimer/diagnóstico por imagem , Imageamento por Ressonância Magnética , Placa Amiloide/diagnóstico por imagem , Idoso , Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Recent increases in life expectancy may greatly expand future Alzheimer's Disease (AD) burdens. China's demographic profile, aging workforce and predicted increasing burden of AD-related care make its economy vulnerable to AD impacts. Previous economic estimates of AD predominantly focus on health system burdens and omit wider whole-economy effects, potentially underestimating the full economic benefit of effective treatment. METHODS: AD-related prevalence, morbidity and mortality for 2011-2050 were simulated and were, together with associated caregiver time and costs, imposed on a dynamic Computable General Equilibrium model of the Chinese economy. Both economic and non-economic outcomes were analyzed. FINDINGS: Simulated Chinese AD prevalence quadrupled during 2011-50 from 6-28 million. The cumulative discounted value of eliminating AD equates to China's 2012 GDP (US$8 trillion), and the annual predicted real value approaches US AD cost-of-illness (COI) estimates, exceeding US$1 trillion by 2050 (2011-prices). Lost labor contributes 62% of macroeconomic impacts. Only 10% derives from informal care, challenging previous COI-estimates of 56%. INTERPRETATION: Health and macroeconomic models predict an unfolding 2011-2050 Chinese AD epidemic with serious macroeconomic consequences. Significant investment in research and development (medical and non-medical) is warranted and international researchers and national authorities should therefore target development of effective AD treatment and prevention strategies.
Assuntos
Doença de Alzheimer/economia , Custos de Cuidados de Saúde , Modelos Econômicos , Doença de Alzheimer/epidemiologia , China , Efeitos Psicossociais da Doença , Produto Interno Bruto , HumanosRESUMO
The prevalence of mild cognitive impairment (MCI) and dementia according to age remain uncertain. We systematically extracted age-stratified estimates of MCI and dementia prevalence reported in European studies published since 1995, and performed meta-analyses for dementia. We identified 10 relevant studies on MCI and 26 studies on dementia. Studies on MCI presented substantial heterogeneity preventing a meta-analysis, with a majority reporting an increase in prevalence at ≥75 years old. Pooled prevalence of dementia rose continuously from 55 years of age, reaching 44.7% (39.8; 49.6) in those ≥95 years of age. Homogenization of MCI criteria, and additional studies in Northern European population would be warranted.
Assuntos
Disfunção Cognitiva/epidemiologia , Demência/epidemiologia , Fatores Etários , Europa (Continente)/epidemiologia , Humanos , PrevalênciaRESUMO
BACKGROUND: The purpose of this study was to summarize published estimates for conversion from mild cognitive impairment or amnestic mild cognitive impairment to Alzheimer's dementia. We carried out a systematic review of English language publications to identify cohort studies published since January 2006 that reported the risk or rate of conversion. SUMMARY: Thirty-two cohort studies were identified, of which 14 reported annualized conversion rates (ACRs). Conversions over 1 year ranged from 10.2 to 33.6% (5 studies, median: 19.0%), and over 2 years from 9.8 to 36.3% (7 studies, median: 18.6%). ACRs ranged from 7.5 to 16.5% (7 studies, median: 11.0%) per person-year for studies recruiting from clinics, and from 5.4 to 11.5% (7 studies, median: 7.1%) for community samples. KEY MESSAGE: Extensive variation was observed in conversion rates due to the population sampled, diagnostic criteria, and duration, and because many studies did not account for loss to follow-up.