Design and implementation of a longitudinal multicenter database.
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Biomedical subjects
Publications and source records attributed to D Beekly.
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The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) was funded in 1986 by the National Institute on Aging to develop standardized assessments for patients with Alzheimer's disease (AD). Since that time, CERAD has developed and evaluated clinical and neuropsychological test batteries, a neuroimaging protocol, and an assessment of the neuropathological findings of the brains of these patients at autopsy. Approximately 1,200 carefully screened patients with AD and 450 control subjects were evaluated using these instruments at 24 major medical centers around the United States. Annual follow-up observations of these subjects were made for up to eight years. Autopsy examinations of the brain were done in over half of the deceased cases and the clinical diagnosis of AD was confirmed in 85 percent of them. This article outlines the procedures used for identifying the clinical sites, the entry and annual evaluations of patients and control subjects, the collection and analysis of data at a central Methodology and Data Management Center, and evaluation of the CERAD measures. We also present selected data from the 50 or so peer-reviewed papers published to date, with particular emphasis on findings from African-American patients with AD, and related policy implications.
Although autopsy rates in the United States have been decreasing steadily, the necessity for brain autopsy to confirm Alzheimer's disease (AD) remains. Of 308 consecutively deceased AD patients at 24 CERAD (Consortium to Establish a Registry for Alzheimer's Disease) sites, 167 (54%) were autopsied; 141 (46%) were not. The autopsied and nonautopsied groups were comparable in gender (men, 57.5% versus 49.7%), marital status (married, 69.3% versus 67.1%), age at entry (73 versus 74 years), age at death (76 versus 77 years), and stage of disease at entry (mild, 46% versus 43%). However, the autopsied patients were significantly more likely to be white (94.5% versus 82.1%), to be better educated (13.1 versus 11.3 years), to have been in the study longer (mean, 3.3 versus 2.6 years), and to have had longer total duration of AD (8.1 versus 6.7 years). Of the 24 CERAD sites, 13 stressed the importance of autopsy by dedicating a staff member to seek autopsy and by providing free autopsy and transportation; 11 did not. Logistic regression analysis showed that white race (odds ratio [OR] = 2.74; 95% confidence interval [CI] = 1.10-6.83), increased education (OR = 1.12; 95% CI = 1.04-1.21), and emphasis on autopsy (OR = 4.69; 95% CI = 2.67-8.25) were the only significant factors. Although race and education were important, autopsy was more likely to be obtained when sites dedicated resources to this endeavor.
We studied the frequency, severity, and clinical correlations of cerebral amyloid angiopathy (CAA) in 117 CERAD subjects with autopsy-confirmed AD. Eighty-three percent showed at least a mild degree of amyloid angiopathy. Thirty of 117 brains (25.6%) showed moderate to severe CAA affecting the cerebral vessels in one or more cortical regions. These brains also showed a significantly higher frequency of hemorrhages or ischemic lesions than those of subjects with little or no amyloid angiopathy (43.3% versus 23.0%; odds ratio = 2.6, 95% CI = 1.1 to 6.2) High CAA scores also correlated with the presence of cerebral arteriosclerosis and with older age at onset of dementia. Our findings suggest that factors contributing to non-AD-related vascular pathology (e.g., atherosclerosis) may play a role in amyloid deposition in cerebral vessels in AD.
Little information exists on the performance of black versus white patients with Alzheimer's disease on neuropsychological tests for dementia. In this study, we compared performance on the CERAD (Consortium to Establish a Registry for Alzheimer's Disease) neuropsychological battery between white (n = 830) and black (n = 158) patients with Alzheimer's disease enrolled in the CERAD study at 23 university medical centers in the United States. The black patients were older, had fewer years of formal education, and were more impaired in their activities of daily living than were the white patients. After controlling for these characteristics and for duration of the disease and severity of dementia, there were differences in the performance of black and white patients on several of the cognitive measures. Black patients scored lower than whites on tests of visual naming and constructional praxis and on the Mini-Mental State Examination. There were no statistical differences in performance on tests of fluency and word list memory. These findings suggest that cultural or experiential differences may modify performance on specific neuropsychological tests. These factors, in addition to age and educational background, should be considered when interpreting performance on neuropsychological tests in elderly black patients with dementia.
The neuropsychological tests developed for the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) are currently used to measure cognitive impairments of Alzheimer's disease (AD) in clinical investigations of this disorder. This report presents the normative information for the CERAD battery, obtained in a large sample (n = 413) of control subjects (ages 50 to 89) who were enrolled in 23 university medical centers in the United States participating in the CERAD study from 1987 to 1992. We compared separately the performance of subjects with high (> or = 12) and low (< 12) years of formal education. For many of the individual cognitive measures in the highly educated group, we observed significant age and gender effects. Only the praxis measure showed a significant age effect in the low-education group. Delayed recall, when adjusted for amount of material acquired (savings), was relatively unaffected by age, gender, and level of education. Our findings suggest that the savings scores, in particular, may be useful in distinguishing between AD and normal aging.