Neuroimaging of hippocampal atrophy in early recognition of Alzheimer's disease--a critical appraisal after two decades of research.

As a characteristic feature of Alzheimer's disease (AD) hippocampal atrophy (HA) can be demonstrated in the majority of patients by using neuroimaging techniques in particular magnetic resonance imaging (MRI). Hippocampal atrophy is associated with declarative memory deficits and can also be associated with changes of adjacent medial temporal substructures such as the parahippocampal gyrus or the the entorhinal cortex. Similar findings are present in patients with mild cognitive impairment (MCI) albeit to a lesser extent. While these finding facilitate the diagnostic process in patients with clinical suspicious AD, the metric properties of hippocampal atrophy for delineating healthy aging from MCI and mild AD still appear to be rather limited; as such it is not sufficient to establish the diagnosis of AD (and even more so of MCI). This limitation partly refers to methodological issues and partly to the fact that hippocampal tissue integrity is subject to various pathogenetic influences other than AD. Moreover,the effects of hippocampal atrophy on the behavioral level (e.g. cognitive deficits) are modulated by the individual's cognitive reserve. From a clinical standpoint these observations are in line with the hypothesis that the onset and course of AD is influenced by a number of peristatic factors which are partly conceptualized in the concepts of brain and/or cognitive reserve. These complex interactions have to be considered when using the presence of hippocampal atrophy in the routine diagnostic procedure of AD.