Health Technology Assessment of Diagnostic Approaches in Alzheimer's Disease

Sponsor

Maastricht University Medical Center (Other)

Overall Status

Completed

CT.gov ID

NCT01450891

Collaborator

Center for Translational Molecular Medicine (Other), Leiden University Medical Center (Other), Radboud University Medical Center (Other), Amsterdam UMC, location VUmc (Other)

304

Enrollment

Locations

Duration (Months)

Patients Per Site

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Neurodegenerative Diseases Memory Disturbances

Study Design

Study Type:

Observational

Actual Enrollment :

304 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Novel Diagnostic Approaches for the Diagnosis of Alzheimer's Disease: Technology Assessment and Clinical Effectiveness

Study Start Date :

Sep 1, 2009

Actual Primary Completion Date :

Jul 1, 2013

Actual Study Completion Date :

Jul 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
total patient group all new consecutive patients of the participating memory clinics who are suspected of having a primary neurodegenerative disease, meaning that all patients with subjective as well as objective memory complaints are included

Outcome Measures

Primary Outcome Measures

Diagnostic accuracy of Magnetic Resonance Imaging (MRI) [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.
Change in cognition at 2 years [baseline, 1 year follow up, 2 year follow up]
Measured by the Mini-mental state examination (MMSE).
Change in dementia severity at 2 years [baseline, 1 year follow up, 2 year follow up]
Measured by the clinical dementia rating (CDR) scale.
Change in quality of life at 2 years [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.
Health care resource use during 2 years [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 [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) [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.

Secondary Outcome Measures

Demographic changes at 2 years [baseline, 1 year follow up, 2 year follow up]
Course of cognitive symptoms, Civil status, and Living situation are assessed.
General clinical changes at 2 years [baseline, 1 year follow up, 2 year follow up]
Smoking behaviour, alcohol intake, length, weight, blood pressure, neuropsychological problems, and co-morbidities are assessed.
Change in behavioural and psychological problems at 2 years [baseline, 1 year follow up, 2 year follow up]
Measured by the Neuropsychiatric Inventory (NPI).
Change in basic and instrumental activities in daily activities at 2 years [baseline, 1 year follow up, 2 year follow up]
Measured by the Disability assessment for Dementia (DAD).
Change in depression at 2 years [baseline, 1 year follow up, 2 year follow up]
Measured by the geriatric depression scale 15 (GDS-15).
Change in cognitive functioning at 2 years [baseline, 1 year follow up, 2 year follow up]
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.
Change in sense of competence at 2 years [baseline, 1 year follow up, 2 year follow up]
Measured by the Sense of Competence Questionnaire (SoCQ).
Change in Care-related quality of life [baseline, 3 months follow up, 1 year follow up, 2 year follow up]
Assessed by the CarerQol by the informal caregiver.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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).

Exclusion Criteria:

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

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	VU University Medical Center	Amsterdam	Netherlands	1100 DD
2	Leiden University Medical Center	Leiden	Netherlands	2333 ZA
3	Maastricht University Medical Center	Maastricht	Netherlands	6200 MD
4	Radboud University Nijmegen Medical Centre	Nijmegen	Netherlands	6500 HC