Novel Diagnostic Approaches for the Diagnosis of Alzheimer's Disease: Technology Assessment and Clinical Effectiveness
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 304
- 试验地点
- 4
- 主要终点
- Change in quality of life at 2 years
研究概览
简要总结
Background: New research criteria for the diagnosis of Alzheimer's disease (AD) have recently been developed to enable an early diagnosis of AD pathophysiology by relying on emerging biomarkers. To enable efficient allocation of health care resources, evidence is needed to support decision makers on the adoption of emerging biomarkers in clinical practice. The research goals are to 1) assess the diagnostic test accuracy (of current clinical diagnostic work-up and emerging biomarkers in Magnetic Resonance Imaging (MRI), Positron Emission Tomography (PET) and Cerebrospinal Fluid (CSF), 2) perform a cost-consequence analysis and 3) assess long-term cost-effectiveness by an economic model.
Methods/design: In a cohort design 304 consecutive patients suspected of having a primary neurodegenerative disease are approached in four academic memory clinics and followed for two years. Clinical data and data on quality of life data, costs and emerging biomarkers are gathered.
Diagnostic test accuracy is determined by relating the clinical practice and new research criteria diagnoses to the reference diagnosis. The clinical practice diagnosis at baseline is reflected by a consensus procedure among experts using clinical information only (no biomarkers). The diagnosis based on the new research criteria is reflected by decision rules that combine clinical and biomarker information. The reference diagnosis is determined by a consensus procedure among experts based on clinical information on the course of symptoms over a two-year time period.
A decision analytic model is build combining available evidence from different resources among which (accuracy) results from the study, literature and expert opinion to assess long-term cost-effectiveness of the emerging biomarkers.
Discussion: Several other multi-centre trials study the relative value of new biomarkers for early evaluation of AD and related disorders. The uniqueness of this study is the assessment of resource utilization and quality of life to enable an economic evaluation. The study results are generalizable to a population of patients who are referred to a memory clinic due to their memory problems.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All new consecutive patients of the participating memory clinics who are suspected of having a primary neurodegenerative disease. This means all patients with subjective and/or objective memory complaints.
- •CDR 0, 0.5 or 1
- •MMSE score must be 20 or higher.
- •Availability of a reliable informer or proxy (who visits or contacts the patient at least once a week).
排除标准
- •Normal Pressure Hydrocephalus (NPH)
- •Huntington's disease
- •Recent Transient Ischaemic Attack (TIA) (<2 years) or Cerebral Vascular Accident (CVA) or TIA/CVA followed by cognitive impairment (within 3 months)
- •History of Schizophrenia, other psychotic disorders (< 12 months)
- •Major depression (< 12 months)
- •Alcohol abuse
- •Brain-tumor, epilepsy, encephalitis
- •Absence of a reliable informant
- •Probably not available for follow-up
结局指标
主要结局
Change in quality of life at 2 years
时间窗: baseline, 3 months follow up, 1 year follow up, 2 year follow up
Measured by the Euro-Qol-5D both by the patient and caregiver and measured by the Quality of life Alzheimer's disease state (QoL-AD) both by the patient and caregiver.
Change in cognition at 2 years
时间窗: baseline, 1 year follow up, 2 year follow up
Measured by the Mini-mental state examination (MMSE).
Change in dementia severity at 2 years
时间窗: baseline, 1 year follow up, 2 year follow up
Measured by the clinical dementia rating (CDR) scale.
Diagnostic accuracy of Magnetic Resonance Imaging (MRI)
时间窗: baseline
Diagnostic test accuracy (in terms of sensitivity and specificity) of three MRI markers (Whole brain and hippocampal volume, white matter integrity, and functional connectivity) is determined by relating the particular marker to a reference diagnosis. The reference diagnosis is determined by a consensus procedure among experts based on clinical information on the course of symptoms over a two-year time period.
Health care resource use during 2 years
时间窗: baseline, 3 months follow up, 1 year follow up, 2 year follow up
By means of questionnaires the health care resource usage is measured by the Resource Utilization in Dementia-questionnaire (RUD-lite) over a period of 2 years using 4 measurement moments to interpolate the data.
Change in productivity at 2 years
时间窗: baseline, 3 months follow up, 1 year follow up, 2 year follow up
Work status, income, and productivity losses of both the patient and caregiver are assessed by the adjusted PRODISQ (PROductivity and DISease Questionnaire). The consequences of informal caregiving on paid or unpaid work are assessed by the Health and Labour Questionnaire.
Diagnostic accuracy of cerebrospinal fluid (CSF)
时间窗: baseline
Diagnostic test accuracy (in terms of sensitivity and specificity) of three CSF markers (CSF total tau, CSF phosphorylated tau, and CSF Aβ1-42) is determined by relating the particular marker to a reference diagnosis. The reference diagnosis is determined by a consensus procedure among experts based on clinical information on the course of symptoms over a two-year time period.
次要结局
- Change in sense of competence at 2 years(baseline, 1 year follow up, 2 year follow up)
- Demographic changes at 2 years(baseline, 1 year follow up, 2 year follow up)
- General clinical changes at 2 years(baseline, 1 year follow up, 2 year follow up)
- Change in behavioural and psychological problems at 2 years(baseline, 1 year follow up, 2 year follow up)
- Change in cognitive functioning at 2 years(baseline, 1 year follow up, 2 year follow up)
- Change in basic and instrumental activities in daily activities at 2 years(baseline, 1 year follow up, 2 year follow up)
- Change in depression at 2 years(baseline, 1 year follow up, 2 year follow up)
- Change in Care-related quality of life(baseline, 3 months follow up, 1 year follow up, 2 year follow up)