Structure and function of medial temporal and posteromedial cortices in early Alzheimer’s disease

Abstract

Medial temporal lobe (MTL) atrophy and posteromedial cortical hypometabolism are consistent imaging findings in Alzheimer's disease (AD). As the MTL memory structures are affected early in the course of AD by neurofibrillary tangle pathology, the posteromedial metabolic abnormalities have been postulated to represent remote effects of MTL alterations. In this study, we investigated with functional MRI (fMRI) the structure-function relationship between the MTL and posteromedial regions, including the retrosplenial, posterior cingulate and precuneal cortices, in 21 older controls (OCs), 18 subjects with amnestic mild cognitive impairment (MCI) and 16 AD patients during a word list learning task. In the voxel-based morphometric and volumetric analyses, the MCI subjects showed smaller entorhinal volume than OCs (P = 0.0001), whereas there was no difference in the hippocampal or posteromedial volume. AD patients, as compared with MCI patients, showed pronounced loss of volume in the entorhinal (P = 0.0001), hippocampal (P = 0.01) and posteromedial (P = 0.001) regions. The normal pattern of posteromedial fMRI task-induced deactivation during active encoding of words was observed bilaterally in the OCs, but only in restricted unilateral left posteromedial areas in the MCI and AD patients. Across all subjects, more extensive impairment of the retrosplenial and posterior cingulate function was significantly related to smaller entorhinal (P = 0.001) and hippocampal (P = 0.0002) volume. These findings demonstrate that entorhinal atrophy and posteromedial cortical dysfunction are early characteristics of prodromal AD, and precede and/or overwhelm atrophy of the hippocampus and posteromedial cortices. Disturbances in posteromedial cortical function are associated with morphological changes in the MTL across the continuum from normal aging to clinical AD.

On the early diagnosis of Alzheimer's Disease from multimodal signals: A survey

“…It has been found that AD patients have reduced activity in the MTL [117], particularly in the hippocampus [117][118][119][120][121], but also in the entorhinal cortex [117], while an increased activation has been reported in the prefrontal cortex, probably, due to a compensation mechanism [122,123]. Deactivation in posteromedial cortical areas such as the posterior cingulate and the medial parietal cortex has also been found to be anomalous in AD patients [124,125]. Nevertheless, these anomalies are much less evident in MCI patients, which could complicate the use of fMRI as an early detection component.…”

Can multi-modal neuroimaging evidence from hippocampus provide biomarkers for the progression of amnestic mild cognitive impairment?

“…Most of the studies found that smaller hippocampal volumes, predominantly in the subicular and CA1 areas, are related to an increased risk for conversion from aMCI to AD [20][21][22][23][24] , despite some inconsistent findings [25,26] .…”

Parahippocampal corpora amylacea and neuronal lipofuscin in human aging

“…The presence of the two older groups (second and the third) in our study, in which age was not significantly different but the number of lipofuscin-bearing neurons and CA were, might be explained as the consequence of different brain aging patterns [49]. Finally, such a metabolic state of the parahippocampal gyrus neurons can indirectly support Keller's [4] hypothesis that such senescence-related changes, like CA and lipofuscin deposits, might represent predecessors for more serious changes, like the ones observed in the early phase of AD in the entorhinal area as part of the parahippocampal region [5][6][7][8][9][10][11][12][13][14][15]. Future research should include the development of in vivo methods of CA and lipofuscin deposit detection and quantification in the brain of the elderly individuals.…”

“…These findings, and the fact that in the early phases of AD the first pathological changes occur in the entorhinal cortex [5][6][7][8][9][10][11][12][13][14][15], stressed the importance of the histological findings, especially of MTL areas, that might improve the understanding of the cellular basis for the various degrees of cognitive decline within healthy elderly populations. Until recently it was generally believed that age-related impairments in cognitive performance are the result of age-related neuron loss, especially within the hippocampus and most neocortical areas.…”

“…Taking into the consideration the importance of the MTL in memory processing, a large number of cross-sectional volumetric neuroimaging studies were performed. They predominantly focused on the comparison of MTL structure volumes, or the degree of their atrophy, between healthy individuals, age-matched cases suffering from mild cognitive impairment (MCI) and cases at different stages of Alzheimer's disease (AD) [5][6][7][8][9][10][11][12][13][14][15]. Their results showed a significant reduction of MTL component volumes in cases with mild cognitive impairment and AD.…”