Early Diagnosis of Alzheimer's Disease - a Multidisciplinary Approach

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by Skåne University Hospital
Sponsor:
Collaborator:
Lund University
Information provided by (Responsible Party):
Oskar Hansson, Skåne University Hospital
ClinicalTrials.gov Identifier:
NCT01208675
First received: September 23, 2010
Last updated: April 17, 2013
Last verified: April 2013
  Purpose

The present study aims at combining biochemical methods with various types of imaging techniques to identify the pathophysiology of Alzheimer's disease (AD). The main interest is to find markers associated with the very early steps in the pathology of this disease. The investigators shall thus screen for i) molecules in cerebrospinal fluid (CSF) and plasma specific for AD, and ii) brain imaging markers (e.g. MRI and PET) that correlate to detailed clinical assessments.

Biomarkers of interest would then be useful to:

  1. Enable accurate detection of the disease early on. Such biomarkers need to specifically reflect the very early pathophysiology of AD and distinguish it from disorders with similar symptomatology, such as other types of dementia and major depression. The sensitivity and specificity of these biomarkers in combination with clinical assessment should be of at least 90%.
  2. Enable prediction of the course of events of the disease, such as the disease rate in individual patients. Biomarkers that can predict the pattern of future symptoms will be extremely valuable.
  3. Allow monitoring of early effects of new disease-modifying therapies (so-called surrogate biomarkers). Currently clinical therapeutic trials for AD require large patient groups together with long-term treatment. Both size of the groups and treatment time will be reduced with the help of surrogate biomarkers.
  4. Study the pathogenesis of the disease. Biomarkers can be used to investigate in detail early alterations in AD patients. For instance, changes in the levels of certain molecules in CSF together with genetic predisposition could then be correlated to clinical signs and changes detectable by brain imaging. This can lead to identification of new therapeutic targets that could easily be monitored in future trials.

Condition
Mild Cognitive Impairment
Alzheimer's Disease
Dementia With Lewy Bodies
Vascular Dementia

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Early Diagnosis of Alzheimer's Disease - a Multidisciplinary Approach

Resource links provided by NLM:


Further study details as provided by Skåne University Hospital:

Primary Outcome Measures:
  • To compare the time to conversion to clinically probable AD in MCI subjects or healthy elderly subjects with normal and abnormal biomarkers (CSF, blood, MRI, PET) [ Time Frame: Time zero equals the baseline visit. All subjects will subsequently attend follow-up visits every year for approximately 4-6 years after baseline. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Rate of cognitive decline as measured by various cognitive tests, Activities of Daily Living (FAQ) and Global Deterioration Scale. [ Time Frame: Time zero equals the baseline visit. All subjects will subsequently attend follow-up visits every year for approximately 4-6 years after baseline. ] [ Designated as safety issue: No ]
  • Group differences for imaging and wet biomarker measurements. [ Time Frame: At baseline, 1 years, 2 years, 3 years and 4 years. ] [ Designated as safety issue: No ]
  • Rate of volume change of structural MRI measures and amyloid PET [ Time Frame: At baseline, 2 years, 4 years. ] [ Designated as safety issue: No ]
  • Rates of change on each specified biochemical biomarker [ Time Frame: At baseline, 2 years, 4 years. ] [ Designated as safety issue: No ]
  • Correlations between biomarkers and biomarker change [ Time Frame: At baseline, 2 years, 4 years. ] [ Designated as safety issue: No ]
  • Subgroups analyses: Abnormal CSF biomarkers, positive amyloid imaging, APOE genotype. [ Time Frame: At baseline, 2 years, 4 years. ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Cerebrospinal fluid, plasma, DNA, mRNA


Estimated Enrollment: 600
Study Start Date: September 2010
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts
Mild cognitive impairment
400 patients with mild cognitive impairment or subjective cognitive symptoms at baseline.
Healthy elderly subjects
300 elderly subjects, who are cognitively healthy at baseline.

Detailed Description:
  1. Baseline investigations of patients with mild cognitive deficits

    We are conducting a prospective, longitudinal study in which we consecutively include patients with mild cognitive deficits (MCI), who seek medical care at the Neuropsychiatric Clinic (Malmö, Sweden) or Unit for Cognitive Medicine (Lund, Sweden). At baseline the MCI patients undergo detailed neurological and psychiatric examination, including assessment of depressive symptoms and ADL-capacity as well as cognitive and motor tests. Patients are also genotyped for APOE. Samples of plasma, blood (for DNA and mRNA) and CSF are also collected. All patients undergo an advanced MRI scan of the brain. A subset will undergo 18F-Flutemetamol PET. We will include patients over a period of three years.

    1.2 Follow-up of MCI patients

    Thereafter, we follow patients for at least 4 and for a maximum of 6 years with repeated testing and clinical evaluation. During clinical follow-up we estimate how many of the patients develop any type of dementia, for instance AD. Moreover we also estimate how aggressive the progression of the disease is in those patients that develop AD with the help of repeated cognitive testing.

  2. Baseline investigations of healthy elderly volunteers

    To answer the question if new biomarkers could detect early signs of AD in healthy people, we have included 200 elderly volunteer subjects. These people are recruited from a population-based study in Malmö ("Malmö Kost Cancer") where people without memory problems or cognitive difficulties, and who performs well on cognitive tests, are offered to participate. These individuals will undergo the same baseline studies that MCI patients (see above), including cognitive tests, psychiatric assessment, lumbar puncture, blood tests and MRI scan. A subset is also examined with 18F-Flutemetamol PET.

    2.1 Follow-up of elderly volunteers

    This population will also be followed-up for 4-6 years with repeated cognitive tests to determine which subjects develop cognitive impairment (e.g. memory problems) over this period of time.

  3. Analyses of CSF and plasma/blood

    CSF and plasma/blood sampling is done at baseline, 2 and 4 years of follow-up. To find novel and better biomarkers to predict AD in both healthy and MCI patients, the CSF, plasma and blood will be analyzed by various biomedical techniques. We will also screen for biomarkers that can help us to predict how fast the disease will progress. We will use two different approaches, namely: a) analysis of various candidate biomarkers and b) unbiased screening using proteomics.

  4. Magnetic resonance imaging (MRI) MRI is done at baseline, 2 and 4 years of follow-up, using the same MRI scanner. We will evaluate the potential benefits of new MRI protocols for prediction of future AD. MRI will also be used to study the pathogenesis of AD. These new approaches include: 3D-MP RAGE, T2* GRE, DTI/DTT, ASL and MRS.
  Eligibility

Ages Eligible for Study:   60 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Probability Sample
Study Population

Community sample

Criteria

Inclusion Criteria:

Healthy elderly subjects

  • No cognitive symptoms reported by patient and/or informant
  • Normal performance on cognitive tests
  • General cognition and functional performance preserved such that a diagnosis of MCI or dementia cannot be made by physician at the time of the baseline visit
  • Between 60 and 90 years of age
  • Fluent in Swedish
  • Agrees to at least one lumbar puncture, and neuropsychological testing.

Mild cognitive impairment

  • Cognitive symptoms reported by patient and/or informant
  • Between 60 and 80 years of age
  • Mini-Mental State Exam score between 24 and 30
  • General cognition and functional performance sufficiently preserved such that a diagnosis of dementia cannot be made by physician at the time of the baseline visit
  • Fluent in Swedish
  • Agrees to at least one lumbar puncture, and neuropsychological testing.

Exclusion Criteria (for both MCI and healthy elderly):

  • Any significant neurologic disease other than dementia disorders, such as Huntington's disease, normal pressure hydrocephalus, brain tumor, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities.
  • Major depression as described in DSM-IV.
  • History of schizophrenia or other recurrent psychotic disorder
  • History of alcohol or substance abuse or dependence within the past 5 years
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01208675

Contacts
Contact: Oskar Hansson, MD, PhD Oskar.Hansson@med.lu.se

Locations
Sweden
Memory Clinic, Skåne University Hospital Completed
Lund, Sweden, 20502
Memory Clinic; Skåne University Hospital Recruiting
Malmö, Sweden, 20502
Contact: Lennart Minthon, MD, PhD       Lennart.Minthon@skane.se   
Memory Clinic, Hospital of Ängelholm Recruiting
Ängelholm, Sweden
Contact: Per Johansson, MD, PhD       Per.M.Johansson@skane.se   
Sponsors and Collaborators
Skåne University Hospital
Lund University
Investigators
Principal Investigator: Oskar Hansson, MD, PhD Lund University
  More Information

No publications provided

Responsible Party: Oskar Hansson, Associate Professor, Skåne University Hospital
ClinicalTrials.gov Identifier: NCT01208675     History of Changes
Other Study ID Numbers: TiDiS-2010
Study First Received: September 23, 2010
Last Updated: April 17, 2013
Health Authority: Sweden: Regional Ethical Review Board

Additional relevant MeSH terms:
Dementia
Dementia, Vascular
Lewy Body Disease
Delirium, Dementia, Amnestic, Cognitive Disorders
Alzheimer Disease
Cognition Disorders
Mild Cognitive Impairment
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Mental Disorders
Cerebrovascular Disorders
Intracranial Arteriosclerosis
Intracranial Arterial Diseases
Leukoencephalopathies
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Cardiovascular Diseases
Parkinsonian Disorders
Basal Ganglia Diseases
Movement Disorders

ClinicalTrials.gov processed this record on August 26, 2014