The Neuropathology Task Force of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) has developed a practical and standardized neuropathology protocol for the postmortem assessment of dementia and control subjects. The protocol provides neuropathologic definitions of such terms as "definite Alzheimer's disease" (AD), "probable AD," "possible AD," and "normal brain" to indicate levels of diagnostic certainty, reduce subjective interpretation, and assure common language. To pretest the protocol, neuropathologists from 15 participating centers entered information on autopsy brains from 142 demented patients clinically diagnosed as probable AD and on eight nondemented patients. Eighty-four percent of the dementia cases fulfilled CERAD neuropathologic criteria for definite AD. As increasingly large numbers of prospectively studied dementia and control subjects are autopsied, the CERAD neuropathology protocol will help to refine diagnostic criteria, assess overlapping pathology, and lead to a better understanding of early subclinical changes of AD and normal aging.

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) has developed brief, comprehensive, and reliable batteries of clinical and neuropsychological tests for assessment of patients with the clinical diagnosis of Alzheimer's disease (AD). We administered these batteries in a standardized manner to more than 350 subjects with a diagnosis of AD and 275 control subjects who were enrolled in a nationwide registry by a consortium of 16 university medical centers. The tests selected for this study measured the primary cognitive manifestations of AD across a range of severity of the disorder, and discriminated between normal subjects and those with mild and moderate dementia. The batteries also detected deterioration of language, memory, praxis, and general intellectual status in subjects returning for reassessment 1 year later. Interrater and test-retest reliabilities were substantial. Long-term observations of this cohort are in progress in an effort to validate the clinical and neuropsychological assessments and to confirm the diagnosis by postmortem examinations. Although information on validation is limited thus far, the CERAD batteries appear to fill a need for a standardized, easily administered, and reliable instrument for evaluating persons with AD in multicenter research studies as well as in clinical practice.

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.

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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.

Reliable information on rate of progression of cognitive impairment in probable Alzheimer's disease (AD) is important for evaluating possible beneficial effects of therapeutic agents and in planning long-term care for patients with this chronic illness. However, wide variability exists in published rates of change for psychometric measures of the dementing process, and there is need for an accurate analysis of large numbers of persons with the disorder studied over long periods. Utilizing the large, well-characterized sample of the Consortium to Establish a Registry for Alzheimer's Disease and employing a least squares regression method to adjust for different levels of impairment and periods of observation, we report rates of change on the Short Blessed Test, Mini-Mental State Examination, Blessed Dementia Scale, Clinical Dementia Rating, and other cognitive measures in 430 patients with probable AD (mean age at entry = 70.9 +/- 8.0 SD years) studied for up to 4 years. We found that rate-of-change determinations are less reliable when the observation period is 1 year or less, that dementia progression may be nonlinear when described by certain measures, and that simple change scores do not accurately characterize the rate of decline. We also found that rate of progression in AD is determined by the severity of cognitive impairment: the less severe the dementia, the slower the rate of decline.

A re-analysis of the data from 11 case-control studies was performed to investigate the association between head trauma and Alzheimer's disease (AD). To increase comparability of studies, exposures were limited to head trauma with loss of consciousness (hereafter referred to as 'head trauma') and comparisons were restricted to community (versus hospital) controls. Test for heterogeneity across studies was negative; consequently, data were pooled in subsequent analyses. The pooled relative risk for head trauma was 1.82 (95% confidence interval: 1.26-2.67). Stratified analyses showed stronger associations in cases without a positive family history of dementia and in males (versus females). Adjustment of the pooled relative risk for family history of dementia, education and alcohol consumption did not alter significantly the association between head trauma and AD. There was no interaction effect between head trauma and family history of dementia, suggesting that these risk factors operate independently. Mean age of onset was not significantly different in cases with a history of head trauma compared to cases without such a history. The findings of the pooled analysis support an association between reported head trauma and AD.

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) was funded by the National Institute on Aging in 1986 to develop standardized, validated measures for the assessment of Alzheimer's disease (AD). The present report describes the measures that CERAD developed during its first decade, and their continued use in their original and translated forms. These measures include clinical, neuropsychological, neuropathological and behavioral assessments of AD, and also assessment of family history and parkinsonism in AD. An approach to evaluating neuroimages did not meet the standards desired. Further evaluations which could not be completed because of lack of funding (but where some materials are available), include evaluation of very severe AD, and of service use and need by patient and caregiver. The information that was developed in the U.S. and abroad permits standardized assessment of AD in clinical practice, facilitates epidemiological studies, and provides information valuable for individual and public health planning. CERAD materials and data remain available for those wishing to use them. KeywordsConsortium to Establish a Registry for Alzheimer's Disease; CERAD; Alzheimer's disease; clinical assessment; neuropsychological assessment; neuropathological assessment; norms; prevalence; incidence BackgroundDementing disorders have long been recognized, 1 with the identification of Alzheimer's disease (AD) typically dated back to Alzheimer's century-old paper. 2 Although considerable attention has been paid to Alzheimer's disease and substantial progress has been made in identifying its characteristics, nevertheless much remains unclear. As diagnostic procedures improve, the complexities of this disease become more apparent, and the threat it imposes becomes increasingly evident. In the population 65 years of age and older, both the incidence and prevalence of this disorder double every succeeding five years, 3 with estimated prevalence as high as 40% among those over the age of 85. AD, not recognized as a leading cause of death in 1980, was recognized as the fifth leading cause of death in 2003 among persons 65 years of age and older. 4 There is presently no cure and inadequate amelioration for this condition. It can not only strip personality and capability, but is demanding on family members, seriously disrupting their lives and their work. It is expensive for the long term care system, where about half of the residents may suffer from dementia, a substantial proportion of whom can no longer afford their own care. Although people are now reaching their older years in better health, 5,6 it remains to be seen whether there will be a decrease in the incidence of AD. Currently the fastest growing element of the population is among those 85 years of age and older, the age group where the incidence of AD is greatest.A major step in the management of a disease lies in accurate diagnosis. Relevant to current work, clinical diagnostic criteria for dementia and AD were specified about 25 years ago, and the...