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Completed

NCT Number: NCT01450891

Health Technology Assessment of Diagnostic Approaches in Alzheimer's Disease

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.

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Key information

Conditions

Neurodegenerative Diseases Alzheimer Disease Brain Diseases Central Nervous System Diseases Dementia Disease Memory Disturbances Mental Disorders Nervous System Diseases Neurocognitive Disorders Pathologic Processes Pathological Conditions, Signs and Symptoms Tauopathies

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

VU University Medical Center, Amsterdam, Netherlands

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Primary outcomes

  1. Diagnostic accuracy of Magnetic Resonance Imaging (MRI)

    Time frame: 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.

  2. Change in cognition at 2 years

    Time frame: baseline, 1 year follow up, 2 year follow up

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

  3. Change in dementia severity at 2 years

    Time frame: baseline, 1 year follow up, 2 year follow up

    Measured by the clinical dementia rating (CDR) scale.

  4. Change in quality of life at 2 years

    Time frame: 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.

  5. Health care resource use during 2 years

    Time frame: 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.

  6. Change in productivity at 2 years

    Time frame: 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.

  7. Diagnostic accuracy of cerebrospinal fluid (CSF)

    Time frame: 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 outcomes

  1. Demographic changes at 2 years

    Time frame: baseline, 1 year follow up, 2 year follow up

    Course of cognitive symptoms, Civil status, and Living situation are assessed.

  2. General clinical changes at 2 years

    Time frame: baseline, 1 year follow up, 2 year follow up

    Smoking behaviour, alcohol intake, length, weight, blood pressure, neuropsychological problems, and co-morbidities are assessed.

  3. Change in behavioural and psychological problems at 2 years

    Time frame: baseline, 1 year follow up, 2 year follow up

    Measured by the Neuropsychiatric Inventory (NPI).

  4. Change in basic and instrumental activities in daily activities at 2 years

    Time frame: baseline, 1 year follow up, 2 year follow up

    Measured by the Disability assessment for Dementia (DAD).

  5. Change in depression at 2 years

    Time frame: baseline, 1 year follow up, 2 year follow up

    Measured by the geriatric depression scale 15 (GDS-15).

  6. Change in cognitive functioning at 2 years

    Time frame: 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.

  7. Change in sense of competence at 2 years

    Time frame: baseline, 1 year follow up, 2 year follow up

    Measured by the Sense of Competence Questionnaire (SoCQ).

  8. Change in Care-related quality of life

    Time frame: baseline, 3 months follow up, 1 year follow up, 2 year follow up

    Assessed by the CarerQol by the informal caregiver.

Sponsors and collaborators

Lead sponsor

Maastricht University Medical Center

Other

Collaborators

  • Amsterdam UMC, location VUmc
  • Center for Translational Molecular Medicine
  • Leiden University Medical Center
  • Radboud University Medical Center

Registry information

Official study title

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

Important dates

Study start
2009
Primary completion
2013
Study completion
2013
First posted
Oct 12, 2011
Registry last updated
May 28, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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