Albert Heyman

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease

The Neuropathology Task Force of the Consortium to Establish a Registry for Alzheimers 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 Alzheimers 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). Part I. Clinical and neuropsychological assesment of Alzheimer's disease

The Consortium to Establish a Registry for Alzheimers Disease (CERAD) has developed brief, comprehensive, and reliable batteries of clinical and neuropsychological tests for assessment of patients with the clinical diagnosis of Alzheimers 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 testretest 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 Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part V. A normative study of the neuropsychological battery

The neuropsychological tests developed for the Consortium to Establish a Registry for Alzheimers Disease (CERAD) are currently used to measure cognitive impairments of Alzheimers 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 (≥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.

Cerebral amyloid angiopathy in the brains of patients with Alzheimer's disease: The CERAD experience, part XV

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. NEUROLOGY 1996;46: 1592-1596

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) Part IV. Rates of cognitive change in the longitudinal assessment of probable Alzheimer's disease

Reliable information on rate of progression of cognitive impairment in probable Alzheimers 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 Alzheimers 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.

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part X. Neuropathology Confirmation of the Clinical Diagnosis of Alzheimer's Disease

Article abstract-This report summarizes the neuropathologic findings in the first 106 autopsies of CERAD (Consortium to Establish a Registry for Alzheimers Disease) dementia patients diagnosed clinically as having Alzheimers disease (AD). In 92 (87%) of the 106 cases, neuropathologists confirmed Alzheimers disease (AD) as the primary dementing illness. Coexistent Parkinsons disease (PD) changes were present in 19 (21%) and vascular lesions of varying nature and size in 26 (28%) of these 92 AD cases. The 14 cases in which AD was not interpreted as the primary dementing illness can be divided into four major subgroups based on their neuropathology findings: PD and related pathology (n = 5), hippocampal sclerosis (n = 3), miscellaneous neurodegenerative and other disorders (n = 3), and no significant changes (n = 3). Despite the relatively high level of clinical diagnostic accuracy, further refinement of assessment batteries may facilitate distinction of non-AD dementias from AD. NEUROLOGY 1995;45: 461-466

The pilot Stroke Data Bank: definition, design, and data.

Four university centers collaborated to contribute 1158 patients with acute episodes of cerebrovascular disease to the pilot Stroke Data Bank, initiated by NINCDS in 1978. During the pilot project a standard set of data collection forms were developed and used at each of the collaborating centers. Data on clinical course, laboratory findings, therapy and outcome were gathered prospectivcly throughout the patients hospitalization and at specified follow-up intervals. Using operational definitions of stroke sub-types, consecutive cases were systematically allocated to specific categories of brain and vascular pathology. The definitions were based on clinical criteria as well as on laboratory data, including computer- ized tomography (CT), and angiography findings. This paper describes the pilot Stroke Data Bank and presents the distribution of cases by diagnostic and demographic categories. It represents one of the largest series of prospectively collected stroke cases studied by CT (90% of the cases) and angiography (42%). Based upon the methods and processes of this pilot study, a main phase of the Stroke Data Bank has been established to address a number of questions pertaining to stroke classification, evolution, diagnosis, and prognosis. Stroke Vol 15, No 4, 1984

Risk of stroke in asymptomatic persons with cervical arterial bruits: a population study in Evans County, Georgia.

A survey of the rural community in Evans County, Georgia, revealed cervical arterial bruits in 72 (4.4 per cent) of 1620 persons 45 years of age of older without previous stroke, transient ischemic attacks, or overt ischemic heart disease. The prevalence of such asymptomatic bruits increased with age and was greater in women and persons with hypertension. We estimated the risk of stroke associated with cervical bruits during a six-year follow-up period, taking age and blood pressure into account. The presence of asymptomatic bruits was associated with a significantly higher risk of stroke in men but not in women, with odds ratios of 7.5 and 1.6, respectively. Despite the high risk of stroke among men with bruits, the correlation between the location of the bruits and the type of subsequent stroke was poor. Moreover, cervical bruits in men were a risk factor for death from ischemic heart disease. We suggest that asymptomatic cervical bruits are an indication of systemic vascular disease and do not themselves justify invasive diagnostic procedures or surgical correction of underlying extracranial arterial lesions.

Sensitivity and specificity of standardized screens of cognitive impairment and dementia among elderly black and white community residents

Six standardized published measures of cognitive function were evaluated as screens of dementia in a sample of 164 (83 black, 81 white) community residents aged 65 and over selected from the Duke University EPESE (Established Populations for Epidemiologic Studies of the Elderly), a biracial cohort of 4164 residents in a five county area of piedmont North Carolina. Of these 164 persons, 26 were subsequently diagnosed as demented. The weighted data from this sample represent the estimated performance of these measures among elderly blacks and whites in a five county area. The 6 measures evaluated in this study (specificity figures for blacks precede those for whites) were (1) Orientation-Memory-Concentration Test (38%, 79%), (2) Mental Status Questionnaire (71%, 96%), (3) Mini-Mental State (58%, 94%), (4) Storandt et al. Battery (42%, 69%), (5) Iowa Battery (26%, 69%) and (6) Kendrick Cognitive Tests (92%, 97%). All but the Kendrick Cognitive Tests showed substantial sensitivity (90-100%) in detecting the presence of dementia. The specificity of the tests was particularly poor for blacks. The briefer, simpler measures tended to have greater accuracy than the longer and more complex measures. With rare exceptions, the scores obtained on these screens correlated with race and education.

Relationship of health and demographic characteristics to Mini-Mental State Examination score among community residents

Mini-Mental State findings from an age 60+ random community sample (N = 1681) indicate that score is related to education, age and race (but not sex) and to functional status, but not to selected aspects of physical or mental health. Adjustment for demographic characteristics, particularly education, is recommended lest cognitive impairment be overestimated.