Neuropathological Assessment of Alzheimer's Disease: The Experience of the Consortium to Establish a Registry for Alzheimer's Disease

Abstract

The Consortium to Establish a Registry for Alzheimer's Disease (CERAD), a multicenter longitudinal study, has worked to establish standardized instruments for the evaluation of individuals clinically diagnosed as having Alzheimer's disease (AD). Since its formation in 1986, clinical neuropsychological, neuroimaging, and neuropathology assessment batteries have been developed. The neuropathology protocol not only establishes levels of certainty for the diagnosis of AD, but also facilitates correlations with clinical, genetic, and other data. We find a high rate of diagnostic accuracy: the clinical diagnosis of AD was confirmed in 176 of 201 (87.6%) CERAD dementia subjects. Coexistent vascular lesions, usually infarcts, were found in 32% of these confirmed AD cases, and 23% had coexisting Parkinson's disease (PD) changes (nigral degeneration and Lewy bodies at any site). In the remaining 25 cases (12.4%), neuropathologists attributed the primary cause of dementia to other conditions. In studies comparing neuropathology protocols for AD, several groups have found that the CERAD diagnosis most closely correlates with measures of dementia severity, such as the Mini-Mental State Examination (MMSE). Others have adopted the CERAD neuropathology protocol for multicenter brain banking, citing its relative simplicity and adaptability among laboratories, the experience of many AD centers with the protocol, and its application to other dementing conditions. The CERAD data set and batteries are increasingly used for a wide array of clinical, neuropathological, and genetic studies.