Clinical Trials

Dominantly Inherited Alzheimer Network (DIAN)

Study Overview
Record IDs:	ADEAR: IA0147, NLM: NCT00869817
Current Status:	Recruiting
Purpose:	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.
Sponsor(s):	National Institute on Aging (NIA) An anonymous Foundation
Official Title:	Dominantly Inherited Alzheimer Network (DIAN)
Principal Investigator(s):	John Morris MD, Washington University School of Medicine
Start Date:	January 2009	Anticipated End Date:	June 2014
Expected Enrollment:	400

Qualifications for this Study

Minimum Age	Maximum Age	Gender	Accepts Healthy Volunteers?	Disease Stage	Inpatient/Outpatient
18	None	Both	Yes

Inclusion Criteria:

Age 18 or older
Child of an individual with a known mutation in a pedigree with autosomal dominant Alzheimer's disease
Cognitively normal, or if demented, does not require nursing home level care
Fluent in English or Spanish at the 6th grade level
Has someone who is not a child of the affected parent who can serve as an informant for the study

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

Prohibited Medications:

Study Description

N/A, , Defined Population, Prospective Study

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. Establish an international, multicenter 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 in which the individuals are evaluated in a uniform manner at entry and longitudinally thereafter with standardized instruments.
2. In pre-symptomatic individuals, compare mutation carriers and non-carriers to determine the order in which changes in clinical, cognitive, neuroimaging, and biomarker indicators of AD occur prior to the occurrence of dementia.
3. In symptomatic individuals, compare the clinical and neuropathological phenotypes of autosomal dominant AD to those of late-onset "sporadic" AD (using the data sets established by ADNI and by NACC).
4. Maintain the DIAN Central Archive, an integrated database incorporating all information obtained from individuals in the registry to permit analyses within, between, and among the various data domains and also to disseminate the data to qualified investigators in a user-friendly manner.
5. All DIAN participants who wish to know their mutation status will have the costs of genetic counseling and clinical mutation testing paid for by the grant. The clinical genetic counseling and testing is provided as an optional participant benefit and is not part of the DIAN research design.

Study Contact
Name:	DIAN Global Coordinator
Telephone:	314-286-2683
Email:

All U.S. Trial Sites:

State	City	Zip Code	Location	Contact
California	Los Angeles	90095	University of California, Los Angeles	Ana Isabel Alvarez-Retuerto, PhD 310-794-0355 aialvarez@mednet.ucla.edu
Indiana	Indianapolis	46202	Indiana University-Indiana Alzheimer Disease Center	Francine Epperson, AGS 317-274-1590 freppers@iupui.edu
Massachusetts	Boston	02115	Brigham and Women's Hospital	Meghan Frey, MA 617-732-8085 mfrey1@partners.org
Missouri	St. Louis	63108	Washington University School of Medicine	Wendy Sigurdson, RN, MHS 314-362-2256 sigurdsonw@neuro.wustl.edu
New York	New York	10032	Columbia University	Jennifer Williamson, MS,CGC,MPH 212-305-4655 jlw61@columbia.edu
Rhode Island	Providence	02906	Butler Hospital	Michelle Gardner 401-455-6403 MLGardner@butler.org

Trial Sites Outside U.S.:

Country	State	City	Zip Code	Location	Contact
Australia	New South Wales	Sydney	2031	Prince of Wales Medical Research Institute	Clement Loy , MBBS, FRACP +61 2 9399 1003 c.loy@powmri.edu.au
Australia	Victoria	Melbourne	3130	Mental Health Research Institute, University of Melbourne	Alicia Rooney a.rooney@mhri.edu.au
Australia	Western Australia	Perth	6009	Sir James McCusker Alzheimer's Disease Research Unit, Edith Cowan University	Kevin Taddei +61-(0)8-6304-5107 k.taddei@ecu.edu.au
United Kingdom		London	WC1N 3BG	Institute of Neurology, Queen Square	Jane Douglas , RN MPhil. 0044 (0)845 155 5000 ext.723560 jdouglas@drc.ion.ac.uk

References:

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. PubMed Link
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. Epub 2007 Jan 8. PubMed Link
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. PubMed Link
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. PubMed Link
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. PubMed Link

Dominantly Inherited Alzheimer Network (DIAN)

Record IDs:

Current Status:

Purpose:

Sponsor(s):

Official Title:

Principal Investigator(s):

Start Date:

Anticipated End Date:

Expected Enrollment:

Qualifications for this Study

Inclusion Criteria:

Exclusion Criteria:

Prohibited Medications:

Study Description

Name:

Telephone:

Email:

References:

Links: