Staging of the cognitive decline in Alzheimer's disease: insights from a detailed neuropsychological investigation of mild cognitive impairment and mild Alzheimer's disease.

OBJECTIVE The decline of episodic memory in Alzheimer's disease (AD) is well established, but the exact appearance and staging of deficits in other cognitive domains is sometimes contentious. The current investigation attempted to elucidate the appearance of additional cognitive deficits in the non-episodic domains and to understand these deficits with respect to the known pathological staging of AD. METHODS A cross-sectional investigation compared cognitively normal age-matched controls with patients with mild AD and mild cognitive impairment (MCI) using a detailed neuropsychological assessment. RESULTS The systematic investigation of cognitive performance across the major cognitive domains demonstrates that the appearance of additional cognitive deficits in MCI and AD can be predicted, with impaired semantic cognition performance pre-empting the appearance of attention/executive dysfunction and visuospatial deficits in the majority of patients with MCI. CONCLUSIONS This progressive pattern of cognitive deficits fits with the known pathological staging of AD, and the data further highlight the relative rarity of pure amnestic MCI. These results indicate that any neuropsychological test battery used to assess patients with MCI should include language and semantic memory tests in addition to typical episodic memory tests, as changes within this domain might be a sensitive indication of incipient AD.