Dominantly Inherited Alzheimer Network (DIAN) (DIAN)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT00869817
Recruitment Status : Recruiting
First Posted : March 26, 2009
Last Update Posted : September 28, 2017
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Washington University School of Medicine

March 25, 2009
March 26, 2009
September 28, 2017
January 2009
June 2019   (Final data collection date for primary outcome measure)
  • Positive predictive power of a biomarker or group of biomarkers [ Time Frame: Variable follow-up assessment based on age in relation to age at onset of affected parent. ]
  • Biomarkers obtained by blood draw, lumbar puncture, MRI, FDG PET, PET amyloid imaging [ Time Frame: Variable follow-up assessment based on age in relation to age at onset of affected parent ]
  • Clinical markers also examined from clinical interview and cognitive testing [ Time Frame: Variable follow-up assessment based on age in relation to age at onset of affected parent ]
Same as current
Complete list of historical versions of study NCT00869817 on Archive Site
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Dominantly Inherited Alzheimer Network (DIAN)
Dominantly Inherited Alzheimer Network (DIAN)
The purpose of this study is to identify potential biomarkers that may predict the development of Alzheimer's disease in people who carry an Alzheimer's mutation.

Dominantly inherited Alzheimer's disease (AD) represents less than 1% of all cases of AD and is an important model for study because the responsible mutations have known biochemical consequences that are believed to underlie the pathological basis of the disorder. Three major hypotheses will be tested:

  • First, that there is a period of preclinical (presymptomatic) AD in individuals who are destined to develop early-onset dementia (gene carriers) that can be detected by changes in biological fluids and in neuroimaging correlates in comparison with individuals who will not develop early-onset dementia (non-carriers).
  • Second, because all identified causative mutations for AD affect the normal processing of amyloid precursor protein (APP) and increase brain levels of amyloid-beta 42 (Aβ42), the sequence of preclinical changes initially will involve Aβ42 (production and clearance; reduced levels in cerebrospinal fluid [CSF]), followed by evidence for cerebral deposition of Aβ42 (amyloid imaging), followed by cerebral metabolic activity (functional imaging), and finally by regional atrophy (structural imaging).
  • Finally, that the phenotype of symptomatic early-onset familial AD, including its clinical course, is similar to that of late-onset "sporadic" AD.

The following specific aims will be used to test these hypotheses:

  1. Maintain the established international DIAN registry of individuals (mutation carriers and non-carriers; pre-symptomatic and symptomatic) who are biological adult children of a parent with a known causative mutation for AD in the APP, PSEN1, or PSEN2 genes and assess participants every 2 years with the uniform DIAN protocol.
  2. Maintain the integrated DIAN database and biospecimen repository to disseminate data and tissue to qualified investigators (within and outside of DIAN) in a user-friendly manner and to permit analyses within, between, and among the various data domains that will include:

    1. In asymptomatic mutation carriers (using non-carriers as controls), determine the temporal ordering and rate of intraindividual change in clinical, cognitive, behavioral, imaging, and fluid biomarkers of AD prior to estimated age of symptom onset.
    2. In symptomatic mutation carriers, compare the clinical and neuropathological phenotypes of ADAD to those of LOAD, using datasets such as ADNI.
  3. Utilize the DIAN cohort and its database and biospecimen repository to support new scientific studies, including use of exome chip technology to examine potential modifiers of age at symptomatic onset, exploratory investigation of new biomarker analytes, imaging modalities and techniques, perform exploratory genetic analysis to test whether novel AD genes identified through GWAS and sequencing of late onset AD cases also influence variation in age at onset of changes in biomarker endophenotypes in FAD kindred, and generate genome-wide DNA methylation data for pilot study and perform exploratory analyses to look for changes in DNA methylation in longitudinal samples from DIAN participants.
  4. Provide genetic counseling to any and all DIAN participants who wish to learn their mutation status and, for those who decide to learn their status after counseling, provide genetic testing by Clinical Laboratory Improvement Amendments (CLIA) - approved laboratories (i.e., outside of DIAN).
Observational Model: Cohort
Time Perspective: Prospective
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Retention:   Samples With DNA
buffy coat, plasma, cerebral spinal fluid
Non-Probability Sample
Mutation carriers and non-carriers from families with a mutation (which is different from the genetic risk factor Apo-E4) known to cause Alzheimer's disease.
Alzheimer's Disease
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  • 1
    Mutation Positive
  • 2
    Mutation Negative

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
June 2019
June 2019   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  • Written informed consent obtained from participant and collateral source prior to any study-related procedures.
  • Aged 18 (inclusive) or older and the child of an affected individual (clinically or by testing) in a pedigree with a known mutation for ADAD.
  • Cognitively normal. Primary enrollment will focus on recruitment of asymptomatic adult children who are more than 15 years younger than the estimated age of symptom onset. Enrollment of new participants with very mild, mild, or moderate cognitive impairment is allowed with the prior approval of the DIAN Coordinating Center.
  • Has two persons who are not their full-blooded siblings who can serve as collateral sources for the study.
  • Fluent in a language approved by the DIAN Coordinating Center at about the 6th grade level (international equivalent) or above.

Exclusion Criteria:

  • Under age 18
  • Medical or psychiatric illness that would interfere in completing initial and follow-up visits
  • Requires nursing home level care
  • Has no one who can serve as a study informant
Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
Contact: DIAN Global Coordinator 314-747-1940
Contact: Laura Swisher, MS 314-747-1940
Argentina,   Australia,   Germany,   Japan,   United Kingdom,   United States
U19AG032438 ( U.S. NIH Grant/Contract )
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Washington University School of Medicine
Washington University School of Medicine
National Institute on Aging (NIA)
Principal Investigator: Randall J. Bateman, MD Washington University School of Medicine
Washington University School of Medicine
September 2017