Brain profile of hypometabolism in early Alzheimer's disease:: relationships with cognitive deficits and atrophy.

While accurate and early prediction of patients that will develop Alzheimer's disease (AD) in the near future is urgently needed, the amnestic Mild Cognitive Impairment (MCI) state is of particular interest since it most conveniently represents the pre-dementia stage of AD. Consistently, the profile of brain functional alteration constantly evidenced in resting-state SPECT and PET studies is similar to that observed in mild AD, mainly involving the posterior cingulate and temporo-parietal regions. While the former is a characteristic feature of MCI, since it is present in each patient at this stage, the latter seems specifically associated with the future conversion to AD. Moreover right temporoparietal hypometabolism has been found to be the best predictor of subsequent global cognitive decline, over and above neuropsychological and MRI volumetric measurements. This review also presents a discussion on the relationships between the brain profile of hypometabolism on the one hand, and cognitive impairment as well as cerebral structural alterations on the other. Thus, firstly, while functional impairment in the posterior cingulate region seems to be associated with deficits in retrieval of episodic memories in MCI, the relationship between right temporo-parietal hypometabolism and cognitive impairment is still obscure. However, several arguments point to its relation with visuo-spatial deficits, which are often associated with future conversion to AD. Secondly, the discordance between brain areas of major functional changes, and those of highest structural alterations, leads to some relevant questions about the relations between both pathological manifestations and their underlying mechanisms. More specifically, additional hypometabolism-inducing factors could occur in areas of highest hypometabolism compared to atrophy, i.e. mainly in posterior associative cortical regions, leading to genuine functional perturbation in early AD before the development of real atrophy and perhaps of disease as well. By contrast, the hippocampus is the main site of atrophy while its functional alteration is still debated, suggesting that compensation/protective mechanisms probably specifically occur in this structure to maintain a high level of metabolism relative to its structural alteration.