Review articleEarly diagnosis of alzheimer’s disease: contribution of structural neuroimaging
Section snippets
Definition of terms
Dementia: deficits in two or more areas of cognition, sufficient to interefere significantly in social and occupational functioning (DSMIV; American Psychiatric Association, 1994).
AD: patients with clinically probable AD according NINCDS-ADRDA (McKhann et al., 1984) or DSMIV (American Psychiatric Association, 1994) criteria.
Mild AD: Patients with probable AD at a mild stage of global cognitive impairment as assessed by MMSE >20 and/or a CDR score <1.
Accuracy: Although when referring to
Methodological considerations
Three different types of studies involving structural imaging in early AD can be distinguished. First, if there exist structural magnetic resonance imaging (MRI) indices able to predict the development of AD in at-risk subjects, then in a first approximation such indices would be expected to remain prominently abnormal at later stages of the disease. Therefore, studies that compare healthy aged subjects (HAS) and AD patients should be considered a first but necessary step in the quest for early
Studies comparing mild AD to has
The first volumetric MRI study of AD was published in 1988 (Seab et al., 1988). It disclosed a decrease in Hcp volume averaging 40% in AD patients when compared to healthy aged subjects (HAS), which probably preceded overall brain atrophy. There was no overlap of individual values. Since then, studies have repeatedly found significant atrophy of the hippocampal and parahippocampal formation in AD, ranging from 20 to 52% (Mega et al., 2000, for review), and already present at the first stages of
Cross-sectional studies on at-risk subjects
Table 2 lists the percentage change in cerebral structure size in different categories of at risk subjects as compared to HAS and probable AD. The accuracy of atrophy measurements is not listed in this table for it was only assessed in Convit et al 1997, Xu et al 2000, Du et al 2001, and De Santi et al. (2001) (see below) and has but little interest, because of the heterogeneity of the at-risk population. Furthermore, in most of these studies, the AD patients were not exclusively at an early
Longitudinal studies on at-risk subjects
De Leon et al. (1989) were the first to publish a small-scale MRI study on MCI subjects with longitudinal follow-up. The results of this preliminary study were confirmed in 1993 on a larger sample and with longer follow-up; therefore, only the results from this second study are presented here. These authors visually assessed the dilatation of the perihippocampal fissure according to a 4-point scale and found that significant dilatation was much more frequent in those MCI subjects who eventually
Conclusions
Quite logically guided by histopathological data on the distribution of neurodegenerative changes at early stages of AD, structural imaging studies have targeted the hippocampal region. However, these histopathological studies have also shown that what differentiates AD from “normal” aging is the involvement of the association neocortex, and this corresponds to the operational criteria for AD which require impairment in memory and at least one other cognitive function. Quite appropriately, this
Suggestions for future research
Based on the above review, it is clear that further prospective studies on larger samples, with sufficient but also same follow-up for all subjects, a detailed analysis of both medial temporal and association neocortex substructures, and incorporating sensitive cognitive tests, are needed to complement these preliminary findings. It will also be of interest to consider in future studies the fraction of MCI patients that convert in a reasonably short interval (“rapid converters”), as being able
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