CERAD An Overview

The Consortium to Establish a Registry for Alzheimers Disease

The Consortium to Establish a Registry for Alzheimers Disease (CERAD) was
established in 1986 by a grant from the National Institute on Aging (NIA), to
standardize procedures for the evaluation and diagnosis of patients with Alzheimers
disease (AD). Patients and nondemented control subjects were recruited from 24 NIAsponsored Alzheimers Disease Research Centers and other university programs in the
US. Using standardized diagnostic criteria and assessment instruments, CERAD
subjects were examined at entry and annually thereafter, to observe the natural
progression of AD. Autopsy examination of the brain was included, to the extent
possible, to obtain neuropathologic confirmation of the clinical diagnosis.
The major standardized instruments developed by CERAD are now used by many AD
research centers in the US and abroad, by physicians in clinical practice, and in
population-based surveys. They have been translated into Bulgarian, Chinese, Dutch,
Finnish, French, German, Italian, Japanese, Korean, Portuguese, and Spanish.
Approximately 75 papers describing CERAD findings have been published in Englishspeaking scientific medical journals. While focusing on the standardization of
assessment instruments and methods, the CERAD study obtained information on the
natural history of AD, its clinical, neuropsychological, and neuropathological
correlations; its family history; and behavioral and associated personality changes.
Data were obtained on 1,094 carefully screened, nationally distributed White and
African-American patients with AD and on 463 nondemented controls, many of whom
were observed for periods as long as seven years. The clinical diagnosis of AD was
confirmed in 87% of autopsied cases.

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CERAD Contact
A complete listing of CERAD assessment instruments and related materials available
for purchase is listed on our Order Form. The assessment instruments and data are
available on request for use by non-CERAD investigators.
Written inquiries are welcome
Contact :
Albert Heyman, MD
e-mail: CERAD (stric007@mc.duke.edu)
Box 3203 DUMC
Durham, NC 27710
Phone: (919) 286-6406
FAX: (919) 286-9219

Gerda Fillenbaum, PhD

e-mail: Gerda.Fillenbaum@duke.edu
Dept. of Psychiatry & Behavioral Sciences
Box 3003 DUMC
Durham, NC 27710
Phone: (919) 660-7530
FAX: (919) 684-8569

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CERAD ASSESSMENT INSTRUMENTS

CERAD developed the following standardized instruments to assess the various
manifestations of Alzheimers disease:

Clinical/Neuropsychology
Neuropathology
Behavior Rating Scale for Dementia
Family History Interviews
Assessment of Service Needs

Members of the clinical staff at participating clinical sites were trained and certified in
the uniform administration of these assessments. Data were gathered from carefully
screened patients with Alzheimers disease and from control subjects, who were also
enrolled in the CERAD study. The CERAD database comprises 1094 patients and 463
non-demented elderly control subjects who were evaluated annually for as long as
seven years. This case material has been a valuable resource for information on
Alzheimers disease and is the basis for some 75 publications describing the CERAD
research findings. Autopsy examination of the brain was carried out, to the extent
possible, in an effort to obtain neuropathologic confirmation of clinical diagnoses.
A complete listing of CERAD assessment instruments and related materials available
for purchase is listed on our Order Form. The assessment instruments and data are
available on request for use by non-CERAD investigators. Written inquiries are
welcome.

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CERAD Clinical and Neuropsychology Assessment

This Clinical Assessment Packet consists of a battery of brief evaluations designed to
gather demographic, clinical, neurological and neuropsychological data on cognitively
impaired subjects, sufficient to establish a clinical diagnosis of dementia based on
CERAD criteria.
Table of contents of CERAD Protocol 5: Assessment Packet for Probable Alzheimers
Disease (AD):
A. DEMOGRAPHIC DATA
F. CLINICAL DIAGNOSIS
SUBJECT
F1 CDR Staging
B. DEMOGRAPHIC DATA
F2 Diagnostic Impression
INFORMANT
A) Cognitive Function Normal
C. CLINICAL HISTORY
B) Impaired Cognition
C1 Clinical History
F3 Diagnostic Impression
A) Cognitive Impairment/Dementia
A) Alzheimers Disease
B) Systemic Illnesses
B) AD with Other Illness
C) Cerebrovascular Disease
C) Other Disorders
D) Parkinsons Disease
J. NEUROPSYCHOLOGICAL FORMS
E) Depression
J0 Summary of J Tests
F) Drug Effects
J1 Verbal Fluency
C2 Blessed Dementia Scale (ADL)
J2 Boston Naming Test
C3 Behavior Rating Scale
J3 Mini-mental State Exam
C4 Short Blessed Test
J4 Word List Memory
C5 Calculation, Clock and Language
J5 Constructional Praxis
D. CLINICAL EXAMINATIONS
J6 Word List Recall
D1 Physical Examination
J7 Word List Recognition
D2 Neurologic Examination
J8 Recall of Constructional Praxis
E. LABORATORY AND IMAGING STUDIES
A) Clinical laboratory studies
B) Neuroimaging studies
See the CERAD list of publications on clinical and neuropsychological findings in AD.
For information regarding purchase of this assessment material, check the Order Form.

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CERAD Neuropathology Assessment

The CERAD neuropathology criteria are widely used in the US and abroad for studies
of Alzheimers disease and other dementias of the elderly. This assessment was
developed to fulfill the following aims and purposes:

To establish accurate, reliable, and standardized neuropathological criteria for the

diagnosis of Alzheimers disease (AD) and other dementias;

To develop a practical protocol for postmortem examination of the brain and provide
standard, reliable measures for determining the neuropathological spectrum and
heterogeneity of Alzheimers disease and other dementias;

To extend the CERAD assessments to include dementias associated with other

disorders such as vascular disease, Parkinsons disease, alcoholism, and
depression;

To establish a data base for pooling the neuropathological findings of Alzheimers

disease and other dementias with clinical information on demented and cognitively
normal subjects.

The Neuropathology assessment packet includes the following data forms:

A. Demographic Data
B. Clinical History
C. Gross Examination of the Brain
D. Cerebral Vascular Disease: Gross Findings
E. Microscopic Vascular Findings
F. Major Non-vascular Microscopic Findings
G. Microscopic Evaluation of Hippocampus and Neocortex
H. Assessment of Neurohistological Findings
I. Neuropathological Diagnosis
J. Final Assessment

This assessment packet includes a detailed manual, The CERAD Guide to the
Neuropathological Assessment of Alzheimers Disease and Other Dementias.
See the CERAD list of publications on neuropathological findings in AD. For
information regarding purchase of this assessment material, check the Order Form.

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CERAD Behavior Rating Scale for Dementia (BRSD)

The CERAD Behavior Rating Scale for Dementia (BRSD) is a standardized instrument
for rating behavioral abnormalities in demented or cognitively impaired subjects.
Descriptive items are scaled according to frequency of psychopathological behavior.
In a pilot test, the initial 51-item scale was administered by trained examiners to
informants for 303 subjects with probable AD who had undergone standardized clinical
evaluation by CERAD. Wide variability was found in the nature of the behavioral
disturbances; factor analysis indicated eight preliminary factors that mapped onto the
following clinically relevant domains:
depressive features
psychotic features
defective self-regulation
irritability/agitation
vegetative features
apathy
aggression
affective lability
This scale was found to be reliable with high interrater agreement. It has since been
modified slightly on the basis of this study. The questionnaire is now available for
purchase in either a 46-item version or a shorter 17-item version, together with an
instruction manual. A video training tape is also available.
See the CERAD list of publications on behavioral changes in AD.
For information regarding purchase of materials, check the Order Form.

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CERAD Family History Assessment

In response to the need for a uniform family history assessment in genetic and
epidemiological studies of AD, CERAD developed a standardized Family History
Assessment of AD. This assessment consists of interview instruments, coding forms,
and hierarchical rating systems designed to determine the presence of AD, Parkinsons
disease, and Down syndrome among relatives of cases of AD and their spouse
controls.
These instruments are relatively brief (taking about 45 minutes to complete) and easy
to administer.
This assessment was used in a multi-center family history study of AD to evaluate 118
cases with AD and their non-demented spouses, enrolled at 11 different CERAD sites
in the US. The study found that first-degree relatives of patients with AD had a
significantly greater cumulative risk of AD than did the relatives of spouse controls.
Furthermore, the cumulative risk of AD was significantly greater among female
relatives than among male relatives. The numbers of affected first-degree relatives with
Parkinsons disease or Down syndrome did not differ between the families of cases
and those of controls.
See the CERAD list of publications on Family History.
For information regarding purchase of this material, contact the main CERAD office.

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CERAD Assessment of Service Needs

Large sums of money are currently spent for health care and for other services needed
for persons with Alzheimers disease and other dementias of the elderly. Precise
information is lacking, however, as to the specific services needed and used in the
long-term care of these persons.
For this reason, CERAD developed a questionnaire for administration to caregivers of
CERAD subjects with AD. It assesses the need for and the extent of use of the most
common services for care of persons with dementia. This questionnaire usually takes
about 15 minutes to administer and includes questions on:

The caregivers current situation

Overnight care for the patient outside the home
Day care for the patient outside the home
Care required for the patient in the home
Help for the caregiver
Need for other services.

For information regarding purchase of this material, see the Order Form.

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CERAD Study Population (Database)

Basic Characteristics of cases with Alzheimer's Disease
(N=1094) and Control Subjects (N=463) at Entry into CERAD
CASES

CONTROLS

Year Entered
1987

148

122

1988

315

219

1989

181

78

1991

188

15

1992-95

146

No Dementia

460

Uncertain

37

Stage of Dementia (CDR Scale)

Mild

564

Moderate

425

68

Less than 65

187

139

Age at Entry (Years)

65 - 74

423

226

More than 74

484

98

White

890

429

Black

204

34

197

38

124

18

134

39

636

638

Male

448

160

Female

646

303

Race

Number of Return visits

Sex

Education (Years)
Not Known

0-8

234

36

9 11

117

39

12

324

136

Greater than 12

413

252

Yes

519

18

No

575

445

Yes

411

25

No

683

438

Yes

202

No

209

17

Entered Nursing Home

Death

Brain Autopsy

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CERAD PUBLICATIONS
1988 - 2003
Clinical
Reliable information on the rate of progression of cognitive impairment was obtained in
a well-characterized group of patients with AD who were followed using standardized
CERAD assessments. Rate of decline was slower for patients with less severe
dementia. Significant weight loss was found to be more frequent in patients than in
controls. CERAD studies also reported the impact of depression on AD, those with
early- vs. late-onset dementia, and comparisons of patients with AD and those with
schizophrenia.
Clark CM, Sheppard L, Fillenbaum GG, et al. Variability in annual Mini-Mental
State score in patients with probable Alzheimer's disease: a clinical perspective
of data from CERAD. Arch Neurol 1999;56:857-962.
Davidson MD, Harvey P, Welsh KA, et al. Cognitive functioning in late-life
schizophrenia: a comparison of elderly schizophrenic patients and patients with
Alzheimer's disease. Am J Psychiatry 1996;153:1274-1279.
Fillenbaum GG, Beekly D, Edland SD, et al. Consortium to Establish a Registry
for Alzheimer's Disease (CERAD): Development, data base structure, and
selected findings. Top Health Inform Management 1997;18:47-58.
Galasko D, Edland SD, Morris JC, et al. CERAD Part XI. Clinical milestones In
patients with Alzeimer's disease followed over three years. Neurology
1995;45:1451-1455.
Heyman A, Fillenbaum G, Mirra SS. CERAD: Clinical, neuropsychological, and
neuropathological components. Aging: Clin Exp Res 1991;2:416-424.
Heyman A, Fillenbaum G, Nash F, eds. Consortium to Establish a Registry for
Alzheimer's Disease: The CERAD experience. Neurology 1997;49 (suppl 3,
whole issue).
Koss E, Edland S, Fillenbaum G, et al. Clinical and neuropsychological
differences between patients with earlier and later onset of Alzheimer's disease:
a CERAD analysis, Part XII. Neurology 1996;46:136-141.
Koss E, Peterson B, Fillenbaum GG. Determinants of attrition in a natural history
study of Alzheimer disease. Alzheimer Dis Assoc Disord 1999;13:209-215.
McDaniel K, Edland S, Heyman A, et al. Relationship between level of insight
and severity of dementia in Alzheimer's disease. Alzheimer Dis Assoc Disord
1995;9:101-104.

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Morris JC, Mohs RC, Rogers H, et al. CERAD: clinical and neuropsychological
assessment of Alzheimer's disease. Psychopharmacol Bull 1988;4:641-652.
Morris JC, Heyman A, Mohs RC, et al. The Consortium to Establish a Registry
for Alzheimers Disease (CERAD) Part I. Clinical and neuropsychological
assessment of Alzheimer's disease. Neurology 1989;39:1159-1165.
Morris JC, Edland S, Clark CM, et al. Consortium to Establish a Registry for
Alzheimers Disease (CERAD) Part IV. Rates of cognitive change, a longitudinal
assessment of probable Alzheimer's disease. Neurology 1993;43:2457-2465.
Morris JC. Clinical and neuropathological findings from CERAD. In: Becker R,
Giacobini E, eds. Alzheimer disease: from molecular biology to therapy.
Birkhauser, Boston 1997:8-12.
Weiner M, Edland S, Luszczynska H. Prevalence and incidence of major
depression in Alzheimer's disease. Am J Psychiatry 494;151:1006-1009.
White H, Pieper C, Schmader K, et al. Weight change in Alzheimer's disease. J
Am Geriatr Soc 1996;44:265-272.
White H, Pieper C, Schmader K, et al. A longitudinal analysis of weight change
in Alzheimer's disease [letter]. J Am Geriatr Soc 1997;45:531-532.
Neuropsychology
The Neuropsychology Battery developed by CERAD includes tests of verbal fluency
(naming animals); a modified 15-item Boston Naming Test; Mini-Mental State
Examination; word list memory, recall, and recognition; constructional praxis; and recall
of constructional praxis. Word list recall was found to distinguish best between AD
patients and normal controls.
Fillenbaum G, Wilkinson W, Welsh K, et al. Discrimination between stages of
Alzheimer's disease with subsets of Mini-Mental State Examination items: an
analysis of CERAD data. Arch Neurol 1994;51:916-921.
Henderson VW, Buckwalter JG. Cognitive deficits of men and women with
Alzheimer's disease. Neurology 1994;44:90-96.
Welsh K, Butters N, Hughes JP, et al. Detection of abnormal memory decline in
mild cases of Alzheimer's disease using CERAD neuropsychological measures.
Arch Neurol 1991;48:278-281.
Welsh K, Butters N, Hughes JP, et al. Detection and staging of dementia in
Alzheimer's disease - use of the neuropsychological measures developed for
CERAD. Arch Neurol 1992;49:448-452.

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Welsh K, Butters N, Mohs RC, et al. CERAD Part V: a normative study of the
neuropsychological battery. Neurology 1994;44:609-614.
Fillenbaum GG, Unverzagt FW, Ganguli M, Welsh-Bohmer KA, Heyman A. The
CERAD neuropsychological battery: performance of representative community
and tertiary care samples of African American and European American elderly.
In Ferraro FR (ed.) Minority and cross cultural aspects of neuropsychological
assessment. Swets and Zeitlinger, Lisse, NL, 2002.
Neuroimaging
Although the CERAD attempt to standardize neuroimaging measures of AD suggests
that uniform reading of brain scans at any one clinical site was possible, uniform
reading across multiple sites proved difficult to achieve.
Davis PC, Gray L, Albert M, et al. CERAD Part III: reliability of a standardized
MRI evaluation of Alzheimer's disease. Neurology 1992;42:1676-1680.
Davis PC, Gearing M, Gray L, et al. The CERAD experience, Part VIII:
neuroimaging-neuropathology correlates of temporal lobe changes in
Alzheimer's disease. Neurology 1995;45:178-179.
Neuropathology
Findings obtained using the CERAD neuropathology protocol confirmed the clinical
diagnosis of AD in 87% of autopsied CERAD patients. This widely-used protocol has
since been modified for use by general pathologists for the diagnosis of dementia.
(See also section on Associated Dementias.)
Cochran EJ, Gostanian OM, Mirra SS. Autopsy practices at CERAD and
Alzheimer disease center sites: a survey of neuropathologists. Alzheimer Dis
Assoc Disord 1995;9:203-207.
Ellis RJ, Olichney JM, Thal LJ, et al. Cerebral amyloid angiopathy in the brains
of patients with Alzheimer's disease: the CERAD experience, Part XV.
Neurology 1996;46:1592-1596.
Fillenbaum GG, Huber MS, Beekly D, et al. CERAD Part XIII. Obtaining autopsy
in Alzheimer's disease. Neurology 1996;46:142-145.
Gearing M, Mirra SS, Hedreen J, et al. CERAD Part X. Neuropathology
confirmation of the clinical diagnosis of Alzheimer's disease. Neurology
1995;45:461-466.
Mirra SS, Heyman A, McKeel DW, et al. CERAD Part II. Standardization of the
neuropathological assessment of Alzheimer's disease. Neurology 1991;41:479486.

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Mirra SS, Hart MN, Terry RD. Making the diagnosis of Alzheimer's disease: a
primer for practicing pathologists. Arch Pathol Lab Med 1993;117:132-144.
Mirra SS. Neuropathological assessment of Alzheimer's disease: the
experiences of the Consortium to Establish a Registry for Alzheimer's Disease
(CERAD). Internat Psychogeriatrics 1997;9:263-268:Discussion 269-272.
Mirra SS, Gearing M, Sumi SM, et al. The neuropathology assessment of
Alzheimer's disease and related dementias: the CERAD experience. In Corain
B, et al., eds. Alzheimer's disease: advances in clinical and basic research. John
Wiley & Sons Ltd, 1993:207-211.
Mirra SS, Gearing M, McKeel DW, et al. Interlaboratory comparison of
neuropathology assessments in Alzheimer's disease: a CERAD study. J
Neuropath Exp Neurol 1994;53(3):303-315.
Mirra SS. The CERAD neuropathology protocol and consensus
recommendations for the postmortem diagnosis of Alzheimer's disease: a
commentary. Neurobiol Aging 1997;18(suppl):S91-S94.
Olichney JM, Ellis RJ, Katzman R, et al. Types of cerebrovascular lesions
associated with severe cerebral amyloid angiopathy in Alzheimer's disease. Ann
NY Acad Sci 1997;826:493-497.

Minority Studies
In CERAD, as in other longitudinal studies, recruitment and retention of African
American subjects often required special measures. When age, education, and
severity of disease at entry were controlled, race was found to have only a very mild
effect on progression of dementia.
Ballard E, Nash F, Raiford K, et al. Recruitment of black elderly for clinical
research studies of dementia: the CERAD experience. Gerontologist
1993;33:561-565.
Fillenbaum GG, Peterson B, Welsh-Bohmer KA, et al. Progression of
Alzheimer's disease in black and white patients: the CERAD experience, Part
XVI. Neurology 1998;51:154-158.
Fillenbaum GG, Heyman A, Huber MS, Ganguli M, Unverzagt FW. Performance
of elderly African American and White community residents on the CERAD
Neuropsychological Battery. JINS 2001;7:502-509.

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Welsh K, Ballard E, Nash F, et al. Issues affecting minority participation in

research studies of Alzheimer's disease. Alzheimer Dis Assoc Disord 1994;8
Suppl 4:38-48.
Welsh K, Fillenbaum GG, Wilkinson W, et al. Neuropsychological test
performance in African-American and white patients with Alzheimer's disease.
Neurology 1995;45:2207-2211.
Health Economics
AD is reported to be the third most expensive disease in the US, after heart disease
and cancer. There are few published studies on Medicare-reimbursed services for
patients with an accurate diagnosis of AD. CERAD studies indicated that the frequency
and duration of hospitalization were greater for AD subjects than for matched controls.
These studies further indicate that multiple years of Medicare-based data are needed
to identify persons with AD.
Fillenbaum G, Heyman A, Peterson B, Pieper C, Weiman AL. Frequency and
duration of hospitalization of patients with AD based on Medicare data: CERAD
XX. Neurology 2000;54:740-743.
Fillenbaum G, Heyman A, Peterson BL, Pieper CF, Weiman AL. Use and cost of
hospitalization of patients with AD by stage and living arrangement: CERAD XXI.
Neurology 2001;56:201-206.
Fillenbaum G, Heyman A, Peterson BL, Pieper CF, Weiman AL. Use and cost of
outpatient visits of AD patients: CERAD XXII. Neurology 2001;56:1706-1711.
Taylor DH, Fillenbaum GG, Ezell ME. The accuracy of Medicare claims data in
identifying Alzheimer's disease. J Clin Epidemiol 2002;55:929-937.
Family History
In our study comparing the families of 118 patients with AD and their nondemented
spouses, we found a significantly greater risk for AD among families of patients than
among those of controls. There was also a greater risk of AD among female relatives
than among males.
Edland SD, Silverman JM, Peskind ER, et al. Increased risk of dementia in
mothers of Alzheimer's disease cases: evidence for maternal inheritance.
Neurology 1996;47:254-256.
Silverman J, Raiford K, Edland S, et al. CERAD Part VI: family history
assessment: a multi-center study of relatives of AD probands and non-demented
spouse controls. Neurology 1994;44:1253-1259.
Outcomes
Age, sex, and severity of dementia were found to be the major predictors of survival of

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patients with AD, whereas race, education, and marital status were not important
predictors. The major predictors of time to nursing home admission were sex, age,
marital status (men only), and severity of dementia. Death certificates were found to be
poor sources of information regarding the presence of dementia, since dementia was
not mentioned in nearly a third of the death certificates of CERAD patients who had an
overt clinical diagnosis of AD.
Heyman A, Peterson B, Fillenbaum G, et al. CERAD Part XIV: demographic and
clinical predictors of survival in patients with Alzheimer's disease. Neurology
1996;46:656-660.
Heyman A, Peterson B, Fillenbaum G, et al. Predictors of time to
institutionalization of patients with Alzheimer's disease. The CERAD experience,
Part XVII. Neurology 1997;48:1304-1309.
Raiford K, Anton-Johnson S, Haycox Z, et al. CERAD Part VII: accuracy of
reporting dementia on death certificates of patients with Alzheimer's disease.
Neurology 1994;44:2208-2209.
Associated Dementias
Neuropathologic examination of the brains of CERAD cases with autopsy-confirmed
AD disclosed coexisting lesions of Parkinsons disease in 21% of them, and of
cerebrovascular disease in an additional 28%. Patients with cerebrovascular lesions
tended to be older, more severely demented, and performed more poorly on
neuropsychology testing.
Clark CM, Ewbank D, Lerner A, et al. The relationship between extrapyramidal
signs and cognitive performance in patients with Alzheimer's disease enrolled in
the CERAD study. Neurology 1997;49:70-75.
Heyman A, Fillenbaum GG, Welsh-Bohmer KA, et al. Cerebral infarcts in
patients with autopsy-proven Alzheimer's disease. CERAD. Part XVIII.
Neurology 1998;51:159-162.
Heyman A, Fillenbaum GG, Gearing M, et al. Comparison of Lewy body variant
of Alzheimer's disease with pure Alzheimer's disease: CERAD Part XIX.
Neurology, 1999;52:1839-1844.
Hulette C, Mirra SS, Wilkinson W, et al. CERAD Part IX: a prospective
cliniconeuropathologic study of Parkinson's features in Alzheimer's disease.
Neurology 1995;45:1991-1995.
Hulette C, Nochlin D, McKeel D, et al. Clinical-neuropathologic findings in multiinfarct dementia: a report of six autopsied cases. Neurology 1997;48:668-672.
Welsh-Bohmer KA, Gearing M, Saunders AM, et al. Apolipoprotein E genotypes

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in a neuropathological series from CERAD. Ann Neurol 1997;42:319-325.

Behavioral Studies
The CERAD Behavior Rating Scale for Dementia (BRSD) identified eight behavioral
domains that may be related to AD, including agitation, depression, and hallucinatory
phenomena. Both a full (46 item) and a short (17 item) version of this scale are
available.
Patterson MB, Mack JL, Mackell JA, et al. A longitudinal study of behavioral
pathology across five levels of dementia severity in Alzheimer's disease: the
CERAD Behavior Rating Scale for Dementia. Alzheimer Dis Assoc Disorder
1997;11:S40-S44.
Patterson MB, Mack JL. CERAD Behavioral Rating Scale for Dementia (BRSD).
Alzheimer Dis Assoc Disord 1997;11:S40-S44.
Tariot PN, Mack JL, Patterson MB, et al. The CERAD Behavior Rating Scale for
Dementia. Am J Psychiatry 1995;152:1349-1357.
Tariot PN. CERAD Behavior Rating Scale for Dementia. Int Psychogeriatr
1996;8(suppl 3):317-320.
Mack JL, Patterson MB, Tariot PN. Behavior Rating Scale for Dementia:
Development of test scales and presentation of data for 555 individuals with
disease. J Geriatr Psychiatry Neurol 1999;12:211-223.
Studies In Foreign Languages
Considerable attention has been given to equivalence in translating CERAD
assessment instruments into foreign languages. Such translations are currently being
used in German-speaking populations in Switzerland, Austria, and Germany, and in a
standardized national population study in Finland. The following studies showed the
French- and English-language versions to be comparable.
Demers P, Robillard A, Lafleche G, et al. Translation of clinical and
neuropsychological instruments into French: the CERAD experience. Age
Ageing 1994;23:449-451.
Panisset M, Simonetto I, Boller F, et al. Performance of normal elderly subjects
using the [English and French versions of the] CERAD neuropsychology battery.
In: Poncet M, Michel B, Nieoullon A, eds. Update on AD and related syndromes.
Marseille, Solal: 1994:357-359.
Statistics and Data Management
CERAD has developed improved methods for analyzing longitudinal data, which
maximize the amount of information provided by a sample with rolling enrollment and

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different lengths of time in the study. Less conventional approaches to examining data,
based on fuzzy set theory, have also been examined.
Edland SD, Grosser S, Barnhart R, et al. Improved efficiency in the relationship
between level and slope. American Statistical Association. 1995 Proceedings of
the Biometrics Section: 148-153.
Fillenbaum GG, Woodbury M. Typology of Alzheimer's Disease: findings from
CERAD data. Aging Mental Health 1998;2:105-127.
Unger J, van Belle G, Heyman A. Cross-sectional vs. longitudinal estimates of
cognitive change in the non-demented elderly. J Am Geriatr Soc 1999;47:559563.
Woodbury MA, Fillenbaum GG. Psychometric characteristics of the Mini-Mental
State Examination in patients with Alzheimer's disease: a grade of membership
analysis of CERAD data: Part II. Int J Geriatr Psychiat 1996;11:543-553.
Sampling Issues
Characteristics of the measures used and of the study population can influence
findings. We found that the widely-used Clinical Dementia Rating Scale is indeed valid.
While the most ill patients are more likely to drop out of longitudinal studies of
nondemented elderly, studies of persons with AD showed that the most ill are more
likely to stay. Continued participation of control subjects who are spouses of enrolled
patients is interdependent. Not surprisingly, the continued participation of one is related
to the continued participation of the other.
Fillenbaum GG, Peterson B, Morris JC. Estimating the validity of the Clinical
Dementia Rating scale: the CERAD experience. Aging: Clin Exp Res
1996;8:379-385.
Peterson B. Re: Association of education with reported age of onset and
severity of Alzheimer's disease at presentation: Implications for the use of
clinical samples [letter]. Am J Epidemiol 1996;143:1177.
Smith DS, Fillenbaum G. Comparison of spouse and community controls within
CERAD. Aging: Clin Exp Res 1994;6:151-157.
Theses and Dissertations
Barnett M. (1992) Standardization of Clinical Dementia Rating (CDR) among 23
Alzheimer's disease study centers. Master's thesis, Department of Biostatistics,
University of Washington.
Blazina LB. (1996) Investigation of possible behavioral profiles in Alzheimer's
disease. Doctoral dissertation, The Fielding Institute, Santa Barbara, California.

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Fisher NJ. (1997) External validation of distinct neuropsychological subgroups of

Alzheimer's disease patients: preliminary findings from the CERAD data.
Doctoral dissertation, University of Windsor.
Miller S. (1996) Time to nursing home admission for patients with Alzheimer's
disease: The effect of healthcare system characteristics. Doctoral dissertation,
University of Illinois.

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Unger J. (1993) A comparison of longitudinal and cross-sectional rates of

decline in MMSE scores in Alzheimer's controls. Master's thesis, Department of
Biostatistics, University of Washington.
Yang M. (1993) Cross-cultural comparison of the Mini-Mental State Examination
(MMSE) in patients with Alzheimer's disease. Master's thesis, Department of
Biostatistics, University of Washington.
Additional Publications
The authors of most of the following papers were not members of the original CERAD
group. They have, however, published important studies based on CERAD data and
concepts.
Behavioral Studies
Ferris SH, Mackell JA. Behavioral outcomes in clinical trials for Alzheimer
disease. Alzheimer Dis Assoc Disord 1997;11 Suppl 4:S10-15.
Perrault A, Oremus M, Demers L, et al. Review of outcome measurement
instruments in Alzheimers disease drug trials: psychometric properties of
behavior and mood scales. J Geriatr Psychiat and Neurology 2000;13:181-196.
Clinical
Henderson VW, Buckwalter JG. Cognitive deficits of men and women with
Alzheimer's disease. Neurology 1994; 44:90-96.
Neumann PJ, Araki SS, Arcelus A, et al. Measuring Alzheimer's disease
progression with transition probabilities: estimates from CERAD. Neurology
2001;57:951-964.
Olichney JM, Galasko D, Salmon DP. Cognitive decline is faster in Lewy body
variant than in Alzheimer's disease. Neurology 1998;51:351-357.
Miller SC, Prohaska TR, Furner SE, et al. Time to nursing home admission for
persons with Alzheimer's disease: the effect of health care system
characteristics. J Gerontol: Social Sciences 1998;53B:S341-S353.
Epidemiology
Ganguli M, Ratcliff G, Huff FJ. Effects of age, gender, and education on
cognitive tests in a rural elderly community sample. Neuroepidemiology
1991;10:42-52.
Guruje O, Unverzagt FW, Osuntokun BO. The CERAD Neuropsychological Test
Battery: norms from a Yoruba-speaking Nigerian sample. West African J Med
1995;14:29-33.
Lee DY, Lee JH, Ju YS, et al. The prevalence of dementia in older people in an

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urban population of Korea: the Seoul study. J Am Geriatr Soc 2002;50:12331239.

Liu CK, Lai CL, Tai CT, et al. Incidence and subtypes of dementia in southern
Taiwan: impact of socio-demographic factors. Neurology 1998;50:1572-1579.
Riley KP, Snowdon DA, Saunders AM, et al. Cognitive function and
apolipoprotein E in very old adults: findings from the Nun Study. J Gerontol
Series B-Psychological Sciences & Social Sciences 2000;55:S69-75.
Unverzagt FW, Hui SL, Farlow MR et al. Cognitive decline and education in mild
dementia. Neurology 1998;50:181-185.
Neuropathology
Neuropathology Group. Medical Research Council Cognitive Function and Aging
Study. Pathological correlates of late-onset dementia in a multicentre,
community based population. Lancet 2002; 359: 624-625.
Neuropsychology
Stewart R, Richards M, Brayne C. Cognitive function in UK community-dwelling
African Caribbean elders: normative data for a test battery. Int J Geriatr Psych
2001; 16:518-527.
Statistical Analyses
Gillen TE, Gregg KM, Yuan H, et al. Clinical trials in Alzheimers disease.
Calculating Alzheimer Disease Assessment Scale - cognitive subsection with the
data from the Consortium to Establish a Registry for Alzheimers Disease.
Psychopharm Bull 2001;35:83-96.
Mendiondo MS, Ashford JW, Kryscio RJ. Modeling mini-mental state
examination changes in Alzheimer's disease. Stat Med 2002;19:1607-16.
Translations
Lee JH, Lee KU, Lee DY, et al. Development of the Korean version of the
Consortium to Establish a Registry for Alzheimers disease. J Gerontol Series BPsychological Sciences & Social Sciences 2000;57:P47-53.
Berres M, Monsch AU, Bernasconi F, et al. Normal ranges of
neuropsychological tests for the diagnosis of Alzheimer's disease. Studies In
Health Technology and Informatics 2000;77:195-199.

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CERAD - Materials
Following its organization in 1986, the Consortium to Establish a Registry for
Alzheimers Disease enrolled 24 university medical centers in the U.S. engaged in
Alzheimers disease (AD) research. The purpose of this consortium at that time was to
develop brief, standardized and reliable procedures for the evaluation and diagnosis of
patients with AD and other dementias of the elderly. These procedures included data
forms, flipbooks, guidebooks, brochures, instruction manuals and demonstration tapes,
which are now available for purchase. The CERAD assessment material can be used
for research purposes as well as for patient care.
Purchase orders should be accompanied by a brief description of the proposed use of
the assessment instruments, the approximate number of subjects to be tested each
year as well as plans, if any, for publication. CERAD material purchased by the
approved applicant is restricted to his or her use only and must not be sold or
redistributed to others without authorization.
CERAD has developed several basic standardized instruments, each consisting of brief
forms designed to gather data on normal persons as well as on cognitively impaired or
behaviorally disturbed individuals. Such data permit the identification of dementia
based on clinical, neuropsychological, behavioral or neuropathological criteria.
Staff at participating CERAD sites were trained and certified to administer the
assessment instruments and to evaluate the subjects enrolled in the study. Cases and
controls were evaluated at entry and annually thereafter including (when possible)
autopsy examination of the brain to track the natural progression of AD and to obtain
neuropathological confirmation of the clinical diagnosis. The CERAD data base has
become a major resource for research in Alzheimers disease. It contains longitudinal
data for periods as long as seven years on the natural progression of the disorder as
well as information on clinical and neuropsychological changes and neuropathological
manifestations.

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CERAD - Materials
1. Clinical/Neuropsychological Assessment for Alzheimers Disease - $65
The clinical forms request information from the subject (and, where appropriate, from a
knowledgeable informant) regarding the patients clinical history, systemic disorders,
cerebrovascular disease, parkinsonism, depression, the Blessed Dementia Rating Scale,
Short Blessed Test, calculation, clock and language tests, physical examination, laboratory
studies, the Clinical Dementia Rating scale and finally, a diagnostic impression of either AD
alone, AD associated with other disorders or non-AD dementia.
The neuropsychological assessment includes measures of verbal fluency, confrontational
naming (15-item Boston Naming Test), the Mini-Mental State examination, measures of
verbal learning, recall and recognition, and constructional praxis performance and recall.

Spiral-Bound Flipbooks: For use with neuropsychological battery -$30 each

1A -Modified Boston Naming Test : 15 line drawings for identification
1B -Word List Memory, Recall and Recognition Test
2. CERAD Video Demonstration Tapes - $75 each
2A -Administration of the Neuropsychological Battery (J Forms and L Forms)
2B -Demonstration of Behavior Rating Scale for Dementia
2C -French Language Tape: Administration de la Batterie Neuropsychologique
3. CERAD Neuropathological Assessment for Alzheimers Disease - $85
This assessment is a highly respected instrument which is widely used in the U.S. and
abroad for clinical studies of AD and other progressive dementias of the elderly. Its purpose
is to establish more accurate and standardized neuropathological criteria for the diagnosis
of AD. It is a practical protocol for post-mortem examination of the brain and provides
measures for determining the neuropathological spectrum and heterogeneity of AD and
other dementias. This assessment packet includes forms for collecting information on
demographic data and gross and microscopic findings on cerebrovascular disease. It also
includes an assessment of the neurohistological findings and final neuropathological
diagnoses. It is accompanied by a detailed manual, the CERAD Guide to Neuropathological
Assessment of AD and Other Dementias.

4. The Behavior Rating Scale for Dementia (BRSD) - $85

This assessment is a standardized instrument for rating behavioral abnormalities in
demented or cognitively impaired individuals. Items are scaled according to their frequency
of occurrence. The scale is informant-based and consists of 46 items which can be
categorized into clinically relevant domains, i.e., depressive features, psychotic symptoms,
behavioral dysregulation, irritability/agitation, vegetative features, aggression and affective
lability. A shorter 17 item version is also available. The BRSD includes an additional packet
containing a comprehensive instruction manual including results of factor analysis, scoring
forms, scoring tables, instructions to informant and response cards.

5. Assessment of Service Needs of Patients with Dementia - $25

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A questionnaire is available for administration to caregivers of subjects with AD. It assesses

the need for and extent of use of the most common services required for care of persons
with dementia. The questionnaire includes questions on the caregivers current situation,
day and over-night care for the patient outside the home and care of the patient at home.

6. Autopsy Resource Packet - $20

This is a set of guidelines, sample correspondence, and forms available for medical centers
interested in obtaining brain autopsies. It includes educational pamphlets designed to
encourage autopsy examination.

7. CD-ROM: The CERAD Database and Assessment Instruments - $600

The CERAD study population includes 1094 patients with a clinical diagnosis of AD and 463
control subjects who were enrolled at 24 university medical centers in the U.S. These
patients and controls were evaluated annually between 1987 and 1996. The resulting
longitudinal data include clinical findings and neuropsychological test scores, behavioral
manifestations of dementia, time to death or admission to a nursing home and
neuropathological findings. Standardized neuropathological confirmation of the clinical
diagnosis was made at autopsy in approximately half of the decedents.

The CD-ROM contains:

The complete CERAD dataset;
CERAD assessment batteries: data-gathering forms and testing instructions;
Condensed versions of the data forms with variable names;
Selected ancillary and educational materials;
A Manual of Operations giving the history of the CERAD study and information on
the database.

Shipping and handling cost of $10 will be added to all orders.

Prices are current as of June, 2003 but are subject to change at any time.

Please contact CERAD for information regarding the availability of CERAD assessment
instruments in additional languages, e.g., Bulgarian, Chinese, Dutch, Finnish, French,
German, Italian, Japanese, Korean, Portuguese, Spanish.
CERAD
Box 3203
Duke University Medical Center
Durham, NC 27710
FAX #: (919) 286-9219
PHONE #: (919) 286-6406
e-mail address: stric007@mc.duke.edu

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