Relationships between Hippocampal Atrophy, White Matter Disruption, and Gray Matter Hypometabolism in Alzheimer's Disease

Abstract

In early Alzheimer's disease (AD), the hippocampal region is the area most severely affected by cellular and structural alterations, yet glucose hypometabolism predominates in the posterior association cortex and posterior cingulate gyrus. One prevalent hypothesis to account for this discrepancy is that posterior cingulate hypometabolism results from disconnection from the hippocampus through disruption of the cingulum bundle. However, only partial and indirect evidence currently supports this hypothesis. Thus, using structural magnetic resonance imaging and 2-[ 18 F]fluoro-2-deoxy-D-glucose positron emission tomography in 18 patients with early AD, we assessed the relationships between hippocampal atrophy, white matter integrity, and gray matter metabolism by means of a whole-brain voxel-based correlative approach. We found that hippocampal atrophy is specifically related to cingulum bundle disruption, which is in turn highly correlated to hypometabolism of the posterior cingulate cortex but also of the middle cingulate gyrus, thalamus, mammillary bodies, parahippocampal gyrus, and hippocampus (all part of Papez's circuit), as well as the right temporoparietal associative cortex. These results provide the first direct evidence supporting the disconnection hypothesis as a major factor contributing to the early posterior hypometabolism in AD. Disruption of the cingulum bundle also appears to relate to hypometabolism in a large connected network over and above the posterior cingulate cortex, encompassing the whole memory circuit of Papez (consistent with the key location of this white matter tract within this loop) and also, but indirectly, the right posterior association cortex.

Portraying the unique contribution of the default mode network to internally driven mnemonic processes

“…The joint recruitment of bilateral hippocampi and RSC during semantic fluency is consistent with the similar activity patterns seen in these structures in a different memory task (60). The involvement of hippocampi and RSC in semantic word fluency may further explain the degraded performance of individuals with Alzheimer's disease on semantic fluency tasks (61), because the earliest metabolic decline in Alzheimer's disease is centered on the RSC (62,63), whereas early structural changes are seen in the hippocampi (63).…”

Functional Disintegration of the Default Mode Network in Prodromal Alzheimer’s Disease

“…The role of these three parietal regions indicating a prodromal AD-related assembly of posterior parietal regions is well established in AD [23,88,89]. This suggests that these regions segregate from remaining DMN nodes in prodromal AD, potentially resulting from the high metabolic activity and accumulation of amyloid plaques [22,90,91]. The second cluster comprises the vmPFC and hippocampus.…”

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

“…This technique can help diagnosing AD in two ways: on one hand, it allows to measure MTL's atrophy, which is closely related to cognition and memory, with very high definition [103,104] and on the other hand, it enables changes on tissue characteristics due to vascular damage to be detected [87]. MTL's atrophy is earliest evidenced in the hippocampus and the entorhinal cortex [28,[105][106][107], followed closely by the parahippocampus and the amygdala [87].…”