Typology of Alzheimer's disease: Findings from CERAD data

Abstract

To identify heterogeneity in Alzheimer's disease (AD) we analyzed clinical and neuropsychological data obtained from the first 718 AD patients submitted to the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). These patients, who met stringent exclusion criteria, were entered by 23 tertiary US medical centers and had the advantages of uniform evaluation, substantial size and reduction in selection biases reflecting investigator interests. A Grade of Membership (GoM) analysis was used. GoM, based in fuzzy set theory, identifies the underlying pure types in the data. GoM recognizes that individuals need not fall crisply into a particular type, but that their characteristics may fit different pure types to different extents. Clinical and neuropsychological data obtained at entry were analyzed. Six clinical pure types were identified: AD with parkinsonism; AD with depressive symptomatology; AD with mild language problems (parkinsonism and depressive symptoms absent); AD presenting with impaired cognitive status and problems performing instrumental activities of daily living; late onset, mild AD; late onset AD of long duration, severe at entry and with additional chronic disease present. Five neuropsychological pure types were identified. They differed primarily in level of performance of the measures examined. No notable relationships between the clinical and neuropsychological pure types were found. Additional pure types may be present (e.g. familial AD), but cannot be identified in the absence of information in the data base. It is clear, however, that in a group of AD patients meeting strict criteria, heterogeneity of disease is present.