Health Technology Assessment of Diagnostic Approaches in Alzheimer's Disease

NCT01450891 | Completed

• 2 other identifiers: 09-3-03802N-101
• Study Type: observational
• Target: 304
• Locations: 1 country
• Sites: 4

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.

Conditions

Neurodegenerative Diseases; Memory Disturbances

Keywords

Alzheimer's disease; Diagnosis; Costs; Benefits; subjective and/or objective memory complaints

Outcome Measures

Primary Outcomes (7)

• 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.

  baseline

• Change in cognition at 2 years

  Measured by the Mini-mental state examination (MMSE).

  baseline, 1 year follow up, 2 year follow up

• Change in dementia severity at 2 years

  Measured by the clinical dementia rating (CDR) scale.

  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.

  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.

  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.

  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.

  baseline

Secondary Outcomes (8)

• 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 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

Study Arms (1)

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

304 consecutive patients, of four academic memory clinics specialized in the diagnosis and treatment of memory disorders, who were suspected of having a primary neurodegenerative disease were approached for participating in the study. This included all patients with subjective and/or objective memory complaints. Eligibility criteria were chosen to represent current clinical situation and enable generalisability to clinical practice.

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Maastricht University Medical Center: lead
• Center for Translational Molecular Medicine: collaborator
• Leiden University Medical Center: collaborator
• Radboud University Medical Center: collaborator
• Amsterdam UMC, location VUmc: collaborator

Study Sites (4)

VU University Medical Center

Amsterdam, 1100 DD, Netherlands

Location

Leiden University Medical Center

Leiden, 2333 ZA, Netherlands

Location

Maastricht University Medical Center

Maastricht, 6200 MD, Netherlands

Location

Radboud University Nijmegen Medical Centre

Nijmegen, 6500 HC, Netherlands

Location

Related Publications (1)

• Handels RL, Aalten P, Wolfs CA, OldeRikkert M, Scheltens P, Visser PJ, Joore MA, Severens JL, Verhey FR. Diagnostic and economic evaluation of new biomarkers for Alzheimer's disease: the research protocol of a prospective cohort study. BMC Neurol. 2012 Aug 10;12:72. doi: 10.1186/1471-2377-12-72.

  PMID: 22883691 BACKGROUND

Related Links

• organizational framework for the study

Biospecimen

Retention: SAMPLES WITHOUT DNA

Cerebrospinal fluid

MeSH Terms

Conditions

Neurodegenerative Diseases; Alzheimer Disease; Disease

Condition Hierarchy (Ancestors)

Nervous System Diseases; Dementia; Brain Diseases; Central Nervous System Diseases; Tauopathies; Neurocognitive Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2011
• First Posted: October 12, 2011
• Study Start: September 1, 2009
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: May 28, 2015

Record last verified: 2015-05

Locations

NL (4)