Distinct cognitive phenotypes in Alzheimer's disease in older people

Background: Alzheimer's disease (AD) is considered to be a disorder predominantly affecting memory. It is increasingly recognized that the cognitive profile may be heterogeneous. We hypothesized that it would be possible to define distinct "cognitive phenotypes" in older people with AD. Methods: Participants from three individual studies were included, consisting of 109 patients with a diagnosis of probable AD, and 91 age-and gender-matched control participants. All had demographic and cognitive assessment data available, including the Cambridge Cognitive Examination of the Elderly (CAMCOG). The CAMCOG scores and sub-scores were further analyzed using hierarchical cluster analysis and factor analysis. Results: Three clusters were identified. The scores loaded onto three factors representing the domains of attention, praxis, calculation, and perception; memory; and language comprehension and executive function. The main difference between the clusters related to degree of memory impairment. The composite score for memory between the clusters remained significantly different despite adjustment for illness duration and age of onset (p < 0.001). Conclusions: These data suggest clinical heterogeneity within an older group of people with AD. This may have implications for diagnosis, prognosis, response to currently available treatments, and the development of novel therapies.