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.
Study Type
OBSERVATIONAL
Enrollment
304
VU University Medical Center
Amsterdam, Netherlands
Leiden University Medical Center
Leiden, Netherlands
Maastricht University Medical Center
Maastricht, Netherlands
Radboud University Nijmegen Medical Centre
Nijmegen, Netherlands
Diagnostic accuracy of Magnetic Resonance Imaging (MRI)
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.
Time frame: baseline
Change in cognition at 2 years
Measured by the Mini-mental state examination (MMSE).
Time frame: baseline, 1 year follow up, 2 year follow up
Change in dementia severity at 2 years
Measured by the clinical dementia rating (CDR) scale.
Time frame: baseline, 1 year follow up, 2 year follow up
Change in quality of life at 2 years
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.
Time frame: baseline, 3 months follow up, 1 year follow up, 2 year follow up
Health care resource use during 2 years
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.
Time frame: baseline, 3 months follow up, 1 year follow up, 2 year follow up
Change in productivity at 2 years
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.
Time frame: baseline, 3 months follow up, 1 year follow up, 2 year follow up
Diagnostic accuracy of cerebrospinal fluid (CSF)
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.
Time frame: baseline
Demographic changes at 2 years
Course of cognitive symptoms, Civil status, and Living situation are assessed.
Time frame: baseline, 1 year follow up, 2 year follow up
General clinical changes at 2 years
Smoking behaviour, alcohol intake, length, weight, blood pressure, neuropsychological problems, and co-morbidities are assessed.
Time frame: baseline, 1 year follow up, 2 year follow up
Change in behavioural and psychological problems at 2 years
Measured by the Neuropsychiatric Inventory (NPI).
Time frame: baseline, 1 year follow up, 2 year follow up
Change in basic and instrumental activities in daily activities at 2 years
Measured by the Disability assessment for Dementia (DAD).
Time frame: baseline, 1 year follow up, 2 year follow up
Change in depression at 2 years
Measured by the geriatric depression scale 15 (GDS-15).
Time frame: baseline, 1 year follow up, 2 year follow up
Change in cognitive functioning at 2 years
A neuropsychological examination is performed using the: * Rey's Verbal Learning Test, Visual Association Test, and Digit-Span to assess memory; * Letter Digit Substitution Test to assess mental processing rate; and * Stroop Color-Word Test and Trail Making Test to assess attention, concentration and interference.
Time frame: baseline, 1 year follow up, 2 year follow up
Change in sense of competence at 2 years
Measured by the Sense of Competence Questionnaire (SoCQ).
Time frame: baseline, 1 year follow up, 2 year follow up
Change in Care-related quality of life
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Assessed by the CarerQol by the informal caregiver.
Time frame: baseline, 3 months follow up, 1 year follow up, 2 year follow up