Dominantly Inherited Alzheimer Network (DIAN)

NCT ID: NCT00869817

Last Updated: 2025-10-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

700 participants

Study Classification

OBSERVATIONAL

Study Start Date

2009-01-31

Study Completion Date

2026-07-31

Brief Summary

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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.

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Detailed Description

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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 (MCs and non-carriers (NC), symptomatic and asymptomatic) who are biological adult children of an affected parent with an APP, PSEN1, or PSEN2 mutation causing AD and assess participants every 2 years with the uniform DIAN protocol.
2. Recruit to the registry 50 new asymptomatic participants, both MCs and NCs, in Year 1 of the next budget period to maintain the total DIAN cohort at \~250 individuals. These new participants will include those who are more than 15 years younger than the estimated age of symptomatic onset (EAO) to explore the earliest observable biomarker changes of preclinical AD.
3. 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 MCs (using NCs as controls), determine the temporal ordering and rate of intraindividual change in clinical, cognitive, imaging, and fluid biomarkers of AD prior to EAO
2. In symptomatic MCs, compare the clinical and neuropathological phenotypes of ADAD to those of LOAD, using datasets such as ADNI.
4. 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. Pursue other new scientific initiatives that are funded independently of the DIAN grant but are conducted within the DIAN infrastructure at no cost to DIAN including: Dermal fibroblasts and induced pluripotent stem cells (iPSCs), examine biomarker surrogates for neurogeneration in CSF including Visinin-like protein-1 (VILIP-1), Tau seeding assay, Stable Isotope Leucine Kinetics (SILK) in DIAN participants, determine the exact Abeta species that underlie AD pathology using Mass spectrometry, exome sequencing on all DIAN participants to search for both positive and negative modifiers of EYO, and amyloid imaging crossover to \[18F\]florbetapir.
5. 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).

Conditions

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Alzheimer's Disease

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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1

Mutation Positive

No interventions assigned to this group

2

Mutation Negative

No interventions assigned to this group

Eligibility Criteria

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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 to very mild or mild cognitive impairment (CDR score range 0-1.0). Primary enrollment will focus on the recruitment of asymptomatic adult children who are more than 15 years younger than the estimated age of symptom onset. Enrollment of new participants with 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute on Aging (NIA)

NIH

Sponsor Role collaborator

Washington University School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Eric McDade, DO

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Alisha Daniels, MD,MHA

Role: STUDY_DIRECTOR

(314) 273-9057

Locations

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Mayo Clinic Jacksonville

Jacksonville, Florida, United States

Site Status RECRUITING

Indiana University-Indiana Alzheimer Disease Center

Indianapolis, Indiana, United States

Site Status RECRUITING

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Washington University in St. Louis School of Medicine

St Louis, Missouri, United States

Site Status RECRUITING

Columbia University

New York, New York, United States

Site Status SUSPENDED

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Butler Hospital

Providence, Rhode Island, United States

Site Status RECRUITING

University of Washington

Seattle, Washington, United States

Site Status RECRUITING

Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia" (FLENI) Instituto de Investigaciones Neurológicas Raúl Correa

Buenos Aires, , Argentina

Site Status RECRUITING

Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (FLENI)

Salta, , Argentina

Site Status RECRUITING

Neuroscience Research Australia

Sydney, New South Wales, Australia

Site Status RECRUITING

Mental Health Research Institute, University of Melbourne

Melbourne, Victoria, Australia

Site Status SUSPENDED

Sir James McCusker Alzheimer's Disease Research Unit, Edith Cowan University

Perth, Western Australia, Australia

Site Status RECRUITING

Hospital das Clinicas da Faculdade de Medicina da Universidade de São Paulo

São Paulo, , Brazil

Site Status RECRUITING

McGill University Research Centre for Studies in Aging

Verdun, Quebec, Canada

Site Status NOT_YET_RECRUITING

Grupo Neurociencias de Antioquia

Medellín, , Colombia

Site Status RECRUITING

German Center for Neurodegenerative Diseases (DZNE) Munich, and University Hospital Ludwig-Maximilians-Universitat (LMU) Munich

Munich, , Germany

Site Status RECRUITING

German Center for Neurodegenerative Diseases (DZNE) Tübingen and Hertie-Institute for Clinical Brain Research, University of Tübingen

Tübingen, , Germany

Site Status RECRUITING

Niigata University

Niigata, , Japan

Site Status RECRUITING

Osaka City University

Osaka, , Japan

Site Status SUSPENDED

Tokyo University

Tokyo, , Japan

Site Status RECRUITING

Instituto Nacional de Neurología y Neurocirugía "Manuel Velasco Suarez"

Mexico City, , Mexico

Site Status RECRUITING

Amsterdam UMC

Amsterdam, , Netherlands

Site Status RECRUITING

Asan Medical Center

Seoul, Songpa-Gu, South Korea

Site Status RECRUITING

Hospital Clinic Barcelona

Barcelona, Catalonia, Spain

Site Status SUSPENDED

Institute of Neurology, Queen Square

London, , United Kingdom

Site Status RECRUITING

Countries

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United States Argentina Australia Brazil Canada Colombia Germany Japan Mexico Netherlands South Korea Spain United Kingdom

Central Contacts

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Alisha Daniels, MD,MHA

Role: CONTACT

(314) 273-9057

DIAN Obs Admin Core

Role: CONTACT

Facility Contacts

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Ercilia Moncayo

Role: primary

Kandise Chrestensen, BS

Role: backup

Jill Buck, RN

Role: primary

317-963-1847

Courtney Maa

Role: primary

Valentina Pinilla

Role: backup

McCrae Johnson, RN, MSN

Role: primary

Georgia Stobbs-Cucchi, RN

Role: backup

Zana Ikonomovic, MD

Role: primary

412-692-2740

Courtney Bodge, PhD

Role: primary

401-455-6403

Emmaline Seth

Role: primary

Patricio Chrem, MD

Role: primary

Patricio Chrem

Role: primary

Jacob Bechara

Role: primary

William Brooks, MBBS, MPH

Role: backup

Kevin Taddei

Role: primary

+61-(0)8-6304-5107

Samantha Gardener

Role: backup

Aline Nishizawa

Role: primary

Carreira Luzia Lima

Role: backup

Tamar Tatigian

Role: primary

Yudy Milena León Varela

Role: primary

Ilona Ruge

Role: primary

Beatrice Spring

Role: primary

Sumie Tsuruki

Role: primary

Ayana Oga

Role: backup

Haruko Kuzuyamah

Role: primary

Gabriela Rojas de la Torre, MS, MA

Role: primary

Bram Bongers

Role: primary

Jee Hoon Roh, MD, PhD

Role: primary

82-2-3010-3443

Helen Rice, RN

Role: primary

07741 671 840

References

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Mintun MA, Larossa GN, Sheline YI, Dence CS, Lee SY, Mach RH, Klunk WE, Mathis CA, DeKosky ST, Morris JC. [11C]PIB in a nondemented population: potential antecedent marker of Alzheimer disease. Neurology. 2006 Aug 8;67(3):446-52. doi: 10.1212/01.wnl.0000228230.26044.a4.

Reference Type BACKGROUND
PMID: 16894106 (View on PubMed)

Fagan AM, Roe CM, Xiong C, Mintun MA, Morris JC, Holtzman DM. Cerebrospinal fluid tau/beta-amyloid(42) ratio as a prediction of cognitive decline in nondemented older adults. Arch Neurol. 2007 Mar;64(3):343-9. doi: 10.1001/archneur.64.3.noc60123. Epub 2007 Jan 8.

Reference Type BACKGROUND
PMID: 17210801 (View on PubMed)

Godbolt AK, Cipolotti L, Anderson VM, Archer H, Janssen JC, Price S, Rossor MN, Fox NC. A decade of pre-diagnostic assessment in a case of familial Alzheimer's disease: tracking progression from asymptomatic to MCI and dementia. Neurocase. 2005 Feb;11(1):56-64. doi: 10.1080/13554790490896866.

Reference Type BACKGROUND
PMID: 15804925 (View on PubMed)

Morris JC, McKeel DW Jr, Storandt M, Rubin EH, Price JL, Grant EA, Ball MJ, Berg L. Very mild Alzheimer's disease: informant-based clinical, psychometric, and pathologic distinction from normal aging. Neurology. 1991 Apr;41(4):469-78. doi: 10.1212/wnl.41.4.469.

Reference Type BACKGROUND
PMID: 2011242 (View on PubMed)

Galvin JE, Powlishta KK, Wilkins K, McKeel DW Jr, Xiong C, Grant E, Storandt M, Morris JC. Predictors of preclinical Alzheimer disease and dementia: a clinicopathologic study. Arch Neurol. 2005 May;62(5):758-65. doi: 10.1001/archneur.62.5.758.

Reference Type BACKGROUND
PMID: 15883263 (View on PubMed)

Wagemann O, Li Y, Hassenstab J, Aschenbrenner AJ, McKay NS, Gordon BA, Benzinger TLS, Xiong C, Cruchaga C, Renton AE, Perrin RJ, Berman SB, Chhatwal JP, Farlow MR, Day GS, Ikeuchi T, Jucker M, Lopera F, Mori H, Noble JM, Sanchez-Valle R, Schofield PR, Morris JC, Daniels A, Levin J, Bateman RJ, McDade E, Llibre-Guerra JJ; Dominantly Inherited Alzheimer Network. Investigation of sex differences in mutation carriers of the Dominantly Inherited Alzheimer Network. Alzheimers Dement. 2024 Jan;20(1):47-62. doi: 10.1002/alz.13460. Epub 2023 Sep 23.

Reference Type DERIVED
PMID: 37740921 (View on PubMed)

Prescott JW, Doraiswamy PM, Gamberger D, Benzinger T, Petrella JR; Dominantly Inherited Alzheimer Network. Diffusion Tensor MRI Structural Connectivity and PET Amyloid Burden in Preclinical Autosomal Dominant Alzheimer Disease: The DIAN Cohort. Radiology. 2022 Jan;302(1):143-150. doi: 10.1148/radiol.2021210383. Epub 2021 Oct 12.

Reference Type DERIVED
PMID: 34636637 (View on PubMed)

Gordon BA, Blazey TM, Su Y, Hari-Raj A, Dincer A, Flores S, Christensen J, McDade E, Wang G, Xiong C, Cairns NJ, Hassenstab J, Marcus DS, Fagan AM, Jack CR Jr, Hornbeck RC, Paumier KL, Ances BM, Berman SB, Brickman AM, Cash DM, Chhatwal JP, Correia S, Forster S, Fox NC, Graff-Radford NR, la Fougere C, Levin J, Masters CL, Rossor MN, Salloway S, Saykin AJ, Schofield PR, Thompson PM, Weiner MM, Holtzman DM, Raichle ME, Morris JC, Bateman RJ, Benzinger TLS. Spatial patterns of neuroimaging biomarker change in individuals from families with autosomal dominant Alzheimer's disease: a longitudinal study. Lancet Neurol. 2018 Mar;17(3):241-250. doi: 10.1016/S1474-4422(18)30028-0. Epub 2018 Feb 1.

Reference Type DERIVED
PMID: 29397305 (View on PubMed)

Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, Marcus DS, Cairns NJ, Xie X, Blazey TM, Holtzman DM, Santacruz A, Buckles V, Oliver A, Moulder K, Aisen PS, Ghetti B, Klunk WE, McDade E, Martins RN, Masters CL, Mayeux R, Ringman JM, Rossor MN, Schofield PR, Sperling RA, Salloway S, Morris JC; Dominantly Inherited Alzheimer Network. Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med. 2012 Aug 30;367(9):795-804. doi: 10.1056/NEJMoa1202753. Epub 2012 Jul 11.

Reference Type DERIVED
PMID: 22784036 (View on PubMed)

Related Links

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http://knightadrc.wustl.edu/

Washington University St. Louis Knight Alzheimer's Disease Research Center

Other Identifiers

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U19AG032438

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IA0147

Identifier Type: -

Identifier Source: org_study_id

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