Limbic hypometabolism in Alzheimer's disease and mild cognitive impairment

Abstract

The neural basis of the amnesia characterizing early Alzheimer's disease (AD) remains uncertain. Postmortem pathological studies have suggested early involvement of the mesial temporal lobe, whereas in vivo metabolic studies have shown hypometabolism of the posterior cingulate cortex. Using a technique that combined the anatomic precision of magnetic resonance imaging with positron emission tomography, we found severe reductions of metabolism throughout a network of limbic structures (the hippocampal complex, medial thalamus, mamillary bodies, and posterior cingulate) in patients with mild AD. We then studied a cohort with mild cognitive impairment in whom amnesia was the only cognitive abnormality and found comparable hypometabolism through the same network. The AD and mild cognitive impairment groups were differentiated, however, by changes outside this network, the former showing significant hypometabolism in amygdala and temporoparietal and frontal association cortex, whereas the latter did not. The amnesia of very early AD reflects severe but localized limbic dysfunction.

Basal forebrain atrophy is a presymptomatic marker for Alzheimer's disease

“…Individuals with MCI, an early manifestation of AD (60), have alterations in multiple cortical and subcortical areas, including the parietotemporal and prefrontal cortices, posterior cingulate gyrus (61-64), insula, mammillary bodies, and thalamus (43,65). Alteration of the temporoparietal cortex and posterior cingulate gyrus are strong predictors of incident AD in subjects with MCI (62,63,66).…”

Increased white matter connectivity in euthymic bipolar patients: diffusion tensor tractography between the subgenual cingulate and the amygdalo-hippocampal complex

“…The AH complex included the hippocampus, subiculum, parahippocampal gyrus/entorhinal zone and the medial bank of the collateral sulcus as well as the amygdala with adjacent parts of the gyrus ambiens and semilunar gyrus (the amygdala cortical nuclei). The AH seed mask was drawn on the coronal plane with the posterior limit at the level of the posterior commissure and closed laterally by a line that connected the pit of the collateral sulcus to the lateral hippocampus in accordance with Nestor et al 40 To define the anterior limit more easily, a tracing at the level of the widest slice in the transverse plane was done.…”

Detecting hippocampal hypometabolism in Mild Cognitive Impairment using automatic voxel-based approaches

“…In contrast to the growing evidence of early and marked structural alterations of the hippocampal region in AD (Nestor et al, 2004), findings regarding the metabolic status of this key area at the early stage of the disease have been somewhat divergent. Hippocampal hypometabolism has been reported in aMCI and mild AD in several PET studies using various methods (De Leon et al, 1997;Ouchi et al, 1998;De Santi et al, 2001;Nestor et al, 2003;Anchisi et al, 2005;Mosconi et al, 2005; but not in others using either similar or different methodological approaches (Minoshima et al, 1994;Desgranges et al, 1998;Ibanez et al, 1998;Ishii et al, 1998;De Leon et al, 2001;Alexander et al, 2002;Herholz et al, 2002;Nestor et al, 2003;Mosconi et al, 2005;Kawachi et al, 2006), even though the finding of significant correlation between relative hippocampal metabolism and severity of episodic memory impairment suggested sensitivity was not the issue. The question of hippocampal metabolic preservation or alteration in early AD is crucial to support clinical diagnosis, to better understand the pathological mechanisms underlying this neurodegenerative disease and to guide pharmacological research.…”