Promoting Interactions With Basic Scientists and Clinicians: The NIA Alzheimer's Disease Data Coordinating Center

STATISTICS IN MEDICINE
Statist. Med. 2000; 19:1453–1461
Promoting interactions with basic scientists and clinicians:

the NIA Alzheimer’s Disease Data Coordinating Center
Diane Cronin-Stubbs1; ∗; † , Steven T. DeKosky2 , John C. Morris3 and Denis A. Evans1

1Rush Institute for Healthy Aging; 1645 West Jackson Blvd:; Chicago; IL 60612; U.S.A.
2 Alzheimer’s Disease Research Center; University of Pittsburgh; 4-West Monteÿore Hospital; 200 Lothrop Street;
Pittsburgh; PA 15213; U.S.A.
3 Washington University School of Medicine; Alzheimer’s Disease Research Center; Campus Box 8111-ADRC; 660
South Euclid Avenue; St. Louis; MO 63110; U.S.A.
SUMMARY
To beneÿt Alzheimer’s disease research, a central data co-ordinating centre (CDCC) is planned that will
systematically collect data from 27 Alzheimer’s disease centres (ADCs) located nationwide. This CDCC
will combine, analyse and disseminate epidemiologic, demographic, clinical and neuropathological data to
researchers from the ADCs and the broader scientiÿc community. New and larger scale collaborative studies
on Alzheimer’s disease will be possible through this centre. Since 1 July 1997, an interim data co-ordinating
centre (IDCC) has been serving as the agent of the ADCs to begin the data sharing process until a permanent
CDCC is established. The data collected by the IDCC are limited to administrative information and to indexing
of specimens and clinical material, with future plans for the transfer of the data collected to the CDCC once
it is established. Copyright ? 2000 John Wiley & Sons, Ltd.
BACKGROUND AND RATIONALE OF THE DATA SHARING PROJECT
Background of the data sharing project
The Alzheimer’s Disease Centers (ADC) Program, funded since 1984 by the National Institute
on Aging (NIA), National Institutes on Health, consists of 27 ADCs nationwide. The ADCs
support a multi-faceted approach to Alzheimer’s disease, including research on basic mechanisms,
diagnoses, clinical course, treatment, and professional and public education. In the 15 years since
the beginning of the programme, the centres have evolved from having multiple, often informally
organized data sets to having relatively well-operated databases with input for their design and
management from professional data managers and biostatisticians. While it is characteristic for a
program that is implemented in diverse locations to be marked by considerable heterogeneity, it
∗ Correspondence to: Diane Cronin-Stubbs, Rush Institute for Healthy Aging, 1645 West Jackson Blvd., Chicago, IL 60612,
U.S.A.
† E-mail: stubbs@crha.rpslmc.edu
Copyright ? 2000 John Wiley & Sons, Ltd.

1454 D. CRONIN-STUBBS ET AL.
became apparent that certain common elements existed among the 27 ADCs and could be used in
an initial common database.
Rationale for the data sharing project

The main reasons for initiating the data sharing project are to: (a) promote comparability among the
ADCs; (b) index resources that are available at each ADC; (c) promote the conduct of Alzheimer’s
disease research, and (d) provide administrative information for management of the overall NIA
programme. Outcomes of the data sharing project may be the eventual standardization of the
approach to the diagnosis of Alzheimer’s disease, follow-up of those persons who have the disease
as well as those who are disease free, and to collect the common data elements about these
subjects from the ADCs. While variation among the individual ADCs will be preserved, a core of
common elements will promote data sharing among the ADCs, with researchers outside the ADC
programme, and with the public.
The project currently provides administrative information that will help the NIA monitor the
programme. A list of available resources that is included in the database will provide ADCs with
information about participants and specimens that exist at each ADC and other resources that might
be available for wider use under appropriate circumstances. This information will also promote co-
operative studies that use data from many ADCs, will allow identication of subsets of participants
that meet dierent criteria, and will promote sharing of scarce resources.
A nal aim of the project is to promote the conduct of collaborative analyses among the ADCs.
The shared database provides access to information about larger numbers of participants than is
possible from any one ADC. These data can promote multi-site collaborative studies on Alzheimer’s
disease. Further, by collating data, a larger number of rare dementing disorders can be identied
more eectively, thereby increasing the power for symptom characterization, genetic analyses,
neuroimaging proles, and other studies across ADCs. Moreover, with autopsy conrmation in
many cases, in a disease that has no specic diagnostic test, these aggregate data are especially
valuable. Ultimately, this collation will allow for larger scale, more rapid determination of clinical
criteria for diagnosis of specic, especially uncommon dementias.
Discussions of data sharing have progressed since 1992 and have included experts to discuss
substantive questions of common interest and to determine the content of the minimum database.
Because resources were limited and database content at dierent ADCs varied widely, it was
decided that the list of items representing the initial minimum database would be brief. After
about a year-and-a-half of deliberations about the substantive issues of the database, the Interim
Data Coordinating Center was established to begin the process of developing data transmission
procedures.
ACTIVITIES OF THE ADCs INTERIM DATA COORDINATING CENTER
Since 1 July 1997, the IDCC has been serving as the agent of the ADCs, under the direction
of the Executive Committee of the ADC Directors, to begin the process of data sharing until a
permanent CDCC is established. The main activities of the IDCC have included preparing the
minimum database (MDB) form for transmission of data from all ADCs to the Interim Data
Center, and assuring quality in the aggregate data. Specically, this involved: (a) encouraging all
ADCs to participate in planning and decision-making; (b) identifying data to be included in the
Copyright ? 2000 John Wiley & Sons, Ltd. Statist. Med. 2000; 19:1453–1461
ALZHEIMER’S DISEASE DATA CO-ORDINATING CENTRES 1455
initial database; (c) developing data checking procedures for application early in the data collating
process, and (d) pretesting the data checking and data transmission procedures. The latter was
done with a subset of 10 ADCs prior to formally requesting data from the 27 ADCs.
These activities have been occurring in the context of modest resources for both the IDCC and
the 27 ADCs. Also, in the 15 years of the ADC programme’s history, diverse data collection
and management methods had evolved among the ADCs. In the near future, substantial resources
will be available to the Central Data Coordinating Center and for each of the individual ADCs
to participate in the data sharing project. In the interim, ADCs are contributing to the database
without additional funding, re ecting altruism and maturation of the programme and recognition
of the value of sharing data. This level of co-operation and altruism re ects a signicant evolution
in the ADCs, as well as ADCs collective faith in the research potential of the CDCC.
STRATEGIES OF THE INTERIM DATA CENTER FOR PROMOTING INTERACTIONS

WITH BASIC SCIENTISTS AND CLINICIANS
Activity: Prepare MDB for transmission of data from all ADCs to IDCC
The main strategy used to prepare the MDB for data transmission was to obtain agreement among
the ADCs on a common set of items. This included: (a) focused meetings with Directors, Admin-
istrators, and persons who would represent each ADC’s data management group for the project;
(b) development of a database by the data management representatives; (c) obtaining consultation
from experts in selected content areas, and (d) eliciting and using feedback from all the ADCs.
Promoting interaction among key persons involved in the data sharing process resulted in the
achievement of consensus by the 27 ADCs on the content of the MDB at the Spring 1997 Director’s
meeting. Agreement on the procedures for transmitting data from the ADCs to the IDCC was
accomplished at the Fall 1997 Director’s meeting. A copy of the minimum database form is
included in Appendix A.
Activity: Assure quality in the aggregate data

Strategies for assuring the quality of the data include developing standardized protocols for mapping
ADCs’ data to the MDB, such as the reference manual and codebook for the MDB. This codebook
includes the variable name, label, column position, eld length, and allowable codes for each
variable. During its development it was distributed to all ADCs and their feedback resulted in
minor revisions.
To promote uniformity of the data sets we developed a data checking program to assure that
the protocols for mapping the data were followed. We developed the documentation manual for
the data checking program that species the methods for applying the program to the data. This
program generates an output report that identies possible errors and ags potential incongruities
in the data. In some cases it provides prescriptions for correcting the errors.
This method promotes monitoring of errors in the data in a decentralized manner that is the
responsibility of the individual ADCs. Those who are accountable for the accuracy of the data
identify and correct the possible errors.
Uniformity in collecting data was then fostered by pretesting the data mapping, data transmis-
sion, and error correction methods with 10 volunteer ADCs. With the results of the pretest, the
data collection and data checking mechanisms were revised. The rst request for data from all
ADCs was then issued by the IDCC. Currently, the Interim Center is processing and collating the
aggregate data. Preliminary results show that entries were received from the 27 ADCs and two
former programs for approximately 38000 persons: approximately 61 per cent were women and
39 per cent were men; 67 per cent were white, 11 per cent were black, and a small number were
from other races. Approximately 22 per cent have died, and brain tissue specimens are available
for over 3000 of the sample.
FUTURE PLANS FOR THE DATA CENTER
After the establishment of the fully funded CDCC, the data collected by the IDCC will be trans-
ferred to the newly established CDCC. With the resources allocated for the CDCC, the data sharing
project will expand the minimum data set to facilitate the conduct of science. The primary aims of
the CDCC will be to (a) systematically collect data from the 27 ADCs, and (b) combine, analyse
and disseminate epidemiologic, demographic, clinical and neuropathological data to researchers
from the ADCs and the broader research community.
Questions about the status of the NIA Alzheimer’s Disease Data Coordinating Center, and the
data set managed by the Interim Data Center can be directed to Creighton H. Phelps, PhD, Director,
Alzheimer’s Disease Research Centers Program, National Institute on Aging – National Institutes
of Health.
ACKNOWLEDGEMENTS
We would like to thank: Creighton H. Phelps, PhD, Dementias of Aging Branch, National Institute on Aging;
Daniel J. Tancredi, MS, Biostatistics, Rush Institute for Healthy Aging; George J. Dombrowski, Jr., BS,
Data Management, Rush Institute for Healthy Aging; and Directors, Administrators, and Data Management
representatives of the Alzheimer’s disease centres who are contributing to the data sharing initiative.
APPENDIX A: ALZHEIMER’S DISEASE CENTERS MINIMUM DATABASE FORM,

VERSION 1.10
Version 1.10 ALZHEIMER’S DISEASE CENTERS MINIMUM DATABASE
1. FORM IDENTIFIER: |M|D|B|0|0|1| (1–6)

2. Center ID (8–9)
3. Patient ID (11–20)
4. Date record was abstracted from center data:
4a. Month (22–23)
4b. Day (25–26)
4c. Year (28–31)
5. Patient date of birth:
5a. Month (33–34)
5b. Day (36–37)
5c. Year (39–42)
6. Patient sex (44)

1 Male
2 Female
7. Patient race (46–47)
1 White
2 Black
3 American Indian or Alaskan Native
4 Asian or Pacic Islander
8. Is the patient Spanish=Hispanic=Latino? (49)
1 Yes
2 No
9. Patient preferred language (51)
1 English
2 Spanish
3 Other
10. Patient education: Highest grade or number of years of regular school completed
(53–54)
11. Marital status at most recent evaluation (56)
1 Married
2 Widowed
3 Divorced
4 Separated
5 Never married
12. Type of residence at most recent evaluation (58)
1 Private residence
2 Retirement community
3 Assisted living
4 Skilled nursing facility
5 Other
13. Date of initial Alzheimer’s Disease Center evaluation:
13a. Month (60–61)
13b. Day (63–64)
13c. Year (66–69)
14. Mini-Mental State Exam score (0 to 30) at initial evaluation
(if done)
(71–72)
15. Date of most recent Alzheimer’s Disease Center evaluation:
15a. Month (74–75)
15b. Day (77–78)
15c. Year (80–83)
16. Mini-Mental State Exam score (0 to 30) at most recent evaluation (if done) (85–86)
17. Did the patient meet clinical criteria for dementia at the most recent evaluation? (88)
1 Yes
2 No
IF 1, GO TO ITEM 18
IF 2 OR 9, GO TO ITEM 17A
17a. Was the diagnosis “Not demented=control” or “Questionable dementia or cognitive

impairment?” (90)
1 Not demented=control
2 Questionable dementia or cognitive impairment
3 Other
IF 1, 2, 3, OR 9, GO TO ITEM 22
18. At what age did the patient develop dementia? (92–94)
19. What was the primary clinical dementia diagnosis at the most recent evaluation? (96)
1 Probable Alzheimer’s disease
2 Possible Alzheimer’s disease
3 Non-Alzheimer’s dementia
IF 1 OR 2, GO TO ITEM 20
20. If the primary clinical dementia diagnosis is possible or probable Alzheimer’s disease,
does the patient also meet clinical criteria for dementia with Lewy bodies? (98)
1 Yes
2 No
IF 1, 2, OR 9, GO TO ITEM 22
21. If the primary clinical dementia diagnosis is non-Alzheimer’s dementia, what is the
suspected etiology? (100–101)
1 Frontal lobe dementia
2 Parkinson’s disease
3 Huntington’s disease
4 Progressive supranuclear palsy
5 Alcoholic dementia
6 Corticobasal degeneration
7 Communicating hydrocephalus
8 Vascular dementia
9 Dementia with Lewy bodies
10 Prion-associated dementia
11 Human immunodeciency virus (HIV) encephalopathy
12 Primary progressive aphasia
13 Posterior cortical dysfunction
14 Down syndrome
15 Other
22. Does the person have any of the following conditions which may result in cognitive
impairment?
YES NO
22a. Stroke 1 2 (103)
22b. Parkinson’s disease without dementia 1 2 (105)
22c. Depression 1 2 (107)
22d. Delirium 1 2 (109)
23. Were rst degree relatives aected by dementia? (111)

1 Yes
2 No
IF 1, GO TO ITEM 23a
23a. How many rst degree relatives were aected by dementia? (113–114)
24. Is the patient from a multiple birth (twin, triplet, etc.)? (116)
1 Yes
2 No
25. The person’s last known vital status is: (118)
1 Alive
2 Dead
IF 2, GO TO ITEM 26
26. Patient date of death:
26a. Month (120–121)
26b. Day (123–124)
26c. Year (126–129)
27. Has autopsy been performed? (131)
1 Yes
2 No
IF 1, GO TO ITEM 29
28. Has brain biopsy been performed? (133)
1 Yes
2 No
IF 1, GO TO ITEM 29
29. What is the primary neuropathological diagnostic classication? (135–136)
1 Normal brain
2 Alzheimer’s disease – Denite [using CERAD or other neuropathological criteria]
3 Alzheimer’s disease – Probable [using CERAD or other neuropathological criteria]
4 Alzheimer’s disease – Possible [using CERAD or other neuropathological criteria]
5 Idiopathic Parkinson’s disease with cortical and=or subcortical Lewy bodies
6 Dementia with Lewy bodies with Alzheimer’s disease (Lewy body variant of
Alzheimer’s disease)
7 Dementia with Lewy bodies without signicant Alzheimer’s disease changes (pure
diuse Lewy body disease)
8 Vascular dementia
9 Pick’s disease
10 Lobar atrophy without Pick’s bodies
11 Hippocampal sclerosis
14 Prion-associated disease
15 Down syndrome
16 Other
30. What is the secondary neuropathological diagnostic classication? (138–139)
1 No secondary neuropathological diagnostic classication
5 Idiopathic Parkinson’s disease with cortical and=or subcortical Lewy bodies
6 Dementia with Lewy bodies with Alzheimer’s disease (Lewy body variant of
Alzheimer’s disease)
7 Dementia with Lewy bodies without signicant Alzheimer’s disease changes (pure
diuse Lewy body disease)
8 Vascular dementia
9 Pick’s disease
10 Lobar atrophy without Pick’s bodies
11 Hippocampal sclerosis
14 Prion-associated disease
15 Down syndrome
16 Other
31. Is banked frozen brain accessible? (141)
1 Yes
2 No
32. Is formalin-xed brain tissue accessible? (143)
1 Yes
2 No
33. Are paran-embedded blocks of brain tissue accessible? (145)
1 Yes
2 No
34. Is banked postmortem cerebrospinal uid (CSF) accessible? (147)
1 Yes
2 No
35. Is banked antemortem cerebrospinal uid (CSF) accessible? (149)
1 Yes
2 No
36. Is banked DNA accessible? (151)
1 Yes
2 No
37. Is banked serum accessible? (153)
1 Yes
2 No
38. Has apolipoprotein-E (APOE) genotyping been performed? (155)
1 Yes
2 No
39. Are neuropsychological test results available? (157)
1 Yes
2 No
40. Are neuroimaging studies (e.g., CT, PET, SPECT, MRI) available? (159)
1 Yes
2 No
IF 1, GO TO ITEM 41
41. Did the patient have any of the following neuroimaging studies done?
YES NO
41a. Computed tomography (CT) 1 2 (161)
41b. Positron emission tomography (PET) 1 2 (163)
41c. Single photon emission computed tomography (SPECT) 1 2 (165)
41d. Magnetic resonance imaging (MRI) 1 2 (167)
42. Version of MDB001 Form k1|:|1|0| (169–173)
43. Record termination: Code X in Column 175 (175)
Questions about this form can be directed to: Creighton H. Phelps, PhD, Director, Alzheimer’s
Disease Research Centers Program, National Institute on Aging, National Institutes of Health,
7201 Wisconsin Avenue, Suite 3C307, Bethesda, MD 20892, U.S.A. Phone 301-496-9350, Fax
301-496-1494, e-mail phelpsc@exmur.nia.nih.gov.
The Central Data Coordinating Center described in this paper, the successor to the Interim Data
Center in Chicago, is located at the University of Washington with Dr Walter Kukull as the Di-
rector. Further information about the Data Center can be obtained at hhttp: ==www.alz.washington.
edui.

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STATISTICS IN MEDICINE

Statist. Med. 2000; 19:1453–1461