While the loss of neurons in the MTL region represents an early structural change in AD, neuroimaging studies with PET have shown that another characteristic of the neuropathology in its early stages is glucose hypometabolism of the temporoparietal region, which at an early stage is grossly normal in structure (Meguro et al., 2001; Mosconi et al., 2004).
The entorhinal cortex has extensive reciprocal connections with other cortical and limbic regions (Meguro et al., 1999). Loss of structuro-functional integrity in this area results in a breakdown of its circuitry with other regions, and studies have shown a relationship between EC atrophy and temporoparietal hypometabolism, leading some researchers to suggest that the structural medial-temporal changes, present at the earliest, in fact, pre-clinical stages of the disease lead to functional abnormalities at a neocortical level in early AD (Meguro et al., 1999; Mosconi et al., 2004)
Temporoparietal structures (such as the inferior temporal gyrus, superior temporal gyrus & the inferior parietal lobe) have been implicated by activation and lesion studies in semantic memory function (Hirono, Mori, Ishii, & Imamura, 2001; Weintrob et al., 2002). Moreover, studies have shown that impairment of the semantic system develops with disease progression, and that levels of hypometabolism correlate with scores on different semantic tasks (Hirono et al., 2001; Lambon Ralph, Powell, Howard, & Whitworth, 2001; Salmon et al., 1999; Spaan et al., 2003). While some researchers have suggested that AD results in an impairment of retrieval from a relatively intact semantic store (Nebes & Brady, 1988; Nebes, Martin, & Horn, 1984), more recent studies have shown that it is the semantic store itself that gradually breaks down in DAT (Salmon et al., 1999).
Importantly, while loss of semantic ability can be a feature of some non-Alzheimer's type dementias, such as semantic dementia (Lambon Ralph et al., 2001; Rogers, Hodges, Ralph, & Patterson, 2003), in practical clinical terms decline in semantic ability is not easily detectable by simple semantic paradigms in early AD. Instead, semantic impairment becomes more evident in later stages of the disease, when the temporoparietal region begins to show significant atrophy, suggesting that a profound impairment of semantic functioning identifies progression to more advanced stages of the disease.