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Brain Advance Access published online on July 22, 2003
Brain, doi:10.1093/brain/awg236
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© 2003 The Guarantors of Brain

Article

Homogeneity and heterogeneity in mild cognitive impairment and Alzheimer's disease: a cross-sectional and longitudinal study of 55 cases

Matthew A. Lambon Ralph 1*, Karalyn Patterson 1, Naida Graham 1, Kate Dawson 2, and John R. Hodges 3*

1 MRC Cognition and Brain Sciences Unit, Cambridge, UK
2 University Neurology Unit, Addenbrooke's Hospital, Cambridge, UK
3 MRC Cognition and Brain Sciences Unit, Cambridge, UK; University Neurology Unit, Addenbrooke's Hospital, Cambridge, UK

* Corresponding author. E-mail: john.hodges{at}mrc-cbu.cam.ac.uk.

Received 25 June 2002 ; revised 17 March 2003 ; accepted 19 May 2003

Abstract

This study investigated cross-sectional and longitudinal neuropsychological data from 55 patients: 38 with Alzheimer's disease and 18 with mild cognitive impairment (MCI). The analyses were designed to investigate two issues: the relationship of MCI to Alzheimer's disease, and that of atypical to typical Alzheimer's disease. When longitudinal data were averaged across individual patients, a consistent staging of neuropsychological deficits emerged: the selective amnesia characteristic of the MCI phase was joined next by semantic and other linguistic impairments plus emerging difficulties with demanding visuospatial tasks. A two-stage statistical procedure was used to extract underlying factors that corresponded to the severity-governed decline in neuropsychological test scores and then to the consistent deviations away from this typical longitudinal profile; i.e. identifying patterns of atypical Alzheimer's disease. The severity-based factor accounted for nearly 60% of the variance in this MCI-Alzheimer's disease longitudinal and cross-sectional database. This suggests that there is a fairly high degree of homogeneity within this group of patients, and that most of their longitudinal progression can be predicted by dementia severity alone. There were also two main patterns of atypical variation corresponding to patients with exaggerated semantic or visuospatial deficits. Although such cases may mimic more focal lobar degenerative conditions, patients with atypical Alzheimer's disease have pronounced episodic memory impairments, suggesting amnesia as a critical diagnostic feature.

Keywords: Alzheimer's disease; mild cognitive impairment; episodic memory; semantic memory
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