Posterior cingulate cortex atrophy and regional cingulum disruption in mild cognitive impairment and Alzheimer's disease
Introduction
Although structural neuroimaging studies have consistently shown the earliest volume losses in medial temporal lobe (MTL) structures such as entorhinal cortex (ERC) and hippocampus in Alzheimer's disease (AD) and mild cognitive impairment (MCI) (Bottino et al., 2002, Convit et al., 1997, Jack et al., 1999, Killiany et al., 2002, Mosconi et al., 2005, Pennanen et al., 2004, Xu et al., 2000), functional imaging studies have revealed that hypometabolism or hypoperfusion first occur in the posterior cingulate cortex (PCC) in AD or MCI (Chételat et al., 2003, Ishii et al., 2003, Minoshima et al., 1997, Nestor et al., 2003a, Nestor et al., 2003b, Nestor et al., 2006). This functional–structural discrepancy concerning the first brain regions involved in AD process has been hypothetically explained by PCC hypofunction due to the indirect effect of the degeneration of cingulum fibers secondary to MTL atrophy, because the cingulum connects the MTL with the PCC (Wakana et al., 2004, Catani et al., 2002). Alternatively, PCC hypofunction could be due to the direct effect of early PCC atrophy.
In terms of PCC atrophy, no study has been performed yet in MCI, although two studies found that PCC volume is significantly reduced in clinically evident AD patients (Callen et al., 2001, Jones et al., 2006). In terms of cingulum bundle degeneration, several diffusion tensor imaging (DTI) studies (Fellgiebel et al., 2005, Firbank et al., 2007, Rose et al., 2006, Takahashi et al., 2002, Xie et al., 2005, Zhang et al., 2007) have reported bundle disruption in MCI and AD. However, the majority of previous DTI studies has focused on the cingulum adjacent to the PCC or on the overall integrity of the cingulum, and thus, information concerning regional disruption patterns along the cingulum bundle in AD or MCI patients is very limited. Furthermore, the structural relationships between cingulum regional impairment and atrophy of the ERC, hippocampus, and PCC have not been clarified, although some have suggested that the hippocampus or global brain atrophy affect cingulum integrity in AD (Takahashi et al., 2002, Xie et al., 2005). In addition to MTL atrophy, PCC atrophy may also contribute to cingulum disruption in AD, because the cingulum contains efferent fibers from PCC, as well as from MTL structures.
The authors first aimed to investigate the volumetric changes of the PCC, ERC and hippocampus, and then to examine regional disruption of the cingulum bundle in patients with MCI and AD patients. In addition, we explored specific relationships between ERC, hippocampus or PCC volumetric changes and regional disruptions of the cingulum bundle, and association between brain structural changes and episodic memory performance was also evaluated.
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Subjects
19 individuals with MCI and 19 patients with AD were recruited from a cohort regularly followed at the Dementia & Age-Associated Cognitive Decline Clinic at Seoul National University Hospital. Individuals with MCI met Peterson's criteria for amnestic MCI (Petersen, 2004): (a) memory complaint corroborated by an informant, (b) objective memory impairment for age, education and gender, (c) essentially preserved general cognitive function, (d) largely intact functional activities, (e) not
Demographic characteristics
Subject characteristics are summarized in Table 1. The MCI, AD and NC groups were similar in terms of age (p = 0.906, by ANOVA), education (p = 0.125, by ANOVA) and gender (χ2 = 0.236, p = 0.889). AD patients had significantly lower MMSE scores than NC (p < 0.001) or MCI subjects (p < 0.001), but no significant difference was found between NC and MCI (p = 0.064). AD patients showed markedly lower WLR test scores than NC (p < 0.001) or MCI subjects (p = 0.008), and MCI patients also had lower WLR scores than NC
Discussion
Our findings of significantly reduced ERC and hippocampus volumes in AD patients versus normal controls are comparable, in general, to those of previous volumetric studies (Bottino et al., 2002, Convit et al., 1997, Du et al., 2001, Killiany et al., 2002, Pennanen et al., 2004, Xu et al., 2000). In addition, we also found a significant ERC volume reduction in MCI patients versus controls and a significant hippocampus volume reduction in AD patients versus MCI patients. These findings suggest
Disclosure
We have no conflicts of interest to disclose. We have no contracts relating to our research with any organization that could benefit financially from our research. There are no agreements that involve any financial interest in our work.
Acknowledgement
This study was supported by the Seoul National University Hospital Research Fund (Grant No. 04 - 2006 – 091).
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