From Healthy Aging to Early Alzheimer's Disease: In Vivo Detection of Entorhinal Cortex Atrophy

Abstract

Using quantitative structural MRI protocols, we examined the effects of age on alterations in entorhinal cortex (EC) volume. The left EC was found to be smaller than the right in both young and healthy aged subjects. More importantly, the right EC, but not the left, was significantly smaller in elderly participants compared to young controls. In an attempt to determine the earliest sites of involvement in mild and incipient Alzheimer's disease (AD), we compared entorhinal and hippocampal volume in (1) healthy elderly controls, (2) patients with very mild AD, and (3) elderly patients who were evaluated for cognitive complaints, but did not meet criteria for dementia. Both patient groups differed from controls in EC volume, but not from each other. In contrast, the two patient groups differed in hippocampal volume from controls, as well as from each other, with the mild AD cases showing the greatest atrophy. These results suggest that degeneration of the EC and hippocampal formation occurs before the onset of overt dementia. In fact, follow-up clinical evaluations available on 23 of 28 nondemented patients indicated that 12 of 23 had converted to AD. Converters could be best differentiated from nonconverters on the basis of entorhinal volume.

Evidence of neurodegeneration in brains of older adults who do not yet fulfill MCI criteria

“…Consistent with previous studies, we found ERC, parahippocampal, and fusiform atrophy, and decreased posterior cingulate NAA/mI in MCI patients relative to controls (Visser et al, 1999;Kantarci et al, 2000;Xu et al, 2000;de Toledo-Morrell et al, 2000;Dickerson et al, 2001;Catani et al, 2001;Wolf et al, 2003;Chetelat et al, 2005). However, the lack of a significant main group effect for hippocampal volume was somewhat surprising given that hippocampal atrophy has been well documented in MCI Jack et al, 1999;Du et al, 2001).…”

“…Consistent with these findings, several imaging studies have noted atrophy in the parahippocampal gyrus (Visser et al, 1999;Wolf et al, 2003) and entorhinal cortex (ERC) (de Toledo-Morrell et al, 2000;Dickerson et al, 2001;Du et al, 2001) in MCI patients compared to normal elderly. ERC atrophy has also been reported to accurately predict future conversion of MCI to AD (de Toledo-Morrell et al, 2000;Killiany et al, 2000;Dickerson et al, 2001;de Leon et al, 2001). Therefore, the third objective of this study was to compare the volumes of the ERC and parahippocampal gyrus in preMCI, MCI, and control subjects.…”

“…Some authors have found that ERC measurements show better classification between controls than MCI than hippocampal volume (Pennanen et al, 2004). de Toledo-Morrell and colleagues reported that baseline ERC volume was a better predictor than hippocampal volume of conversion to AD among a group of non-demented subjects who had cognitive complaints (de Toledo-Morrell et al, 2000;Dickerson et al, 2001). It is interesting to note that not everyone in that group had demonstrable cognitive impairment, similar to the preMCI subjects in the present study and the CC subjects studied by Saykin and colleagues.…”

Differential effects of aging and Alzheimer's disease on medial temporal lobe cortical thickness and surface area

“…Previous work has shown a relationship between entorhinal volume and memory performance in older, MCI, and AD subjects (De Toledo-Morrell et al, 2000;Du et al, 2003;Rosen et al, 2003;Rodrigue and Raz, 2004;Stoub et al, 2006), but, to our knowledge, there have been no investigations of the thickness or surface area of ERC or of other MTL cortical regions in relation to memory performance. We found here that the ERC and PRC thinning in AD relates to poorer delayed verbal recall performance, but that surface area of MTL regions does not relate to memory performance.…”

Functional MRI in the early diagnosis of Alzheimer’s disease: is it time to refocus?

“…• An abnormal cerebrospinal fluid biomarker Measurement of the structural integrity and rate of atrophy in the MTL and its subregions, including the hippocampus [9][10][11] and entorhinal cortex [12,13], has proven useful as a clinical aid. However, measurement of atrophy in the MTL is currently not standardized (and therefore is susceptible to methodological differences) and MTL atrophy is not unique to AD [14].…”