Clinical significance of corpus callosum atrophy in a mixed elderly population
Introduction
The corpus callosum (CC) is the largest interconnecting white matter tract in the brain, containing some 200 million axons [47] traversing the subcortical white matter. Atrophy of the CC is characteristic for normal aging, as well as for a variety of neurodegenerative diseases [4], [8], [18], [32], [41], [44], [54], [55], [56], [59]. However, the pathological and clinical significance of CC atrophy is poorly understood.
Age-related white matter changes (ARWMC) are frequently seen on computed tomography (CT) and especially on magnetic resonance imaging (MRI) in elderly subjects. The descriptive term leukoaraiosis was coined in the late eighties, pointing to rarefaction of the white matter with the likely origin being cerebral ischemia [35]. Thus, ARWMC may mostly reflect ischemic damage such as gliosis, degeneration of myelin, and loss of fibers, according to histopathological findings [7], [12], [21], [38].
Since the CC is composed of interhemispheric fibers traversing the subcortical white matter, CC atrophy may result from axonal disruption due to ARWMC. ARWMC have been associated with cognitive, motor, and mood disturbances [25], [30], [34], [45] which all may contribute to disability in the elderly. Therefore, if cognitive, motor and mood disturbances are related to damage of the white matter in subjects with ARWMCs, callosal atrophy may be an important indicator for disability.
The clinical significance of CC atrophy in elderly with ARWMCs has been investigated in two smaller studies by Yamauchi et al. [57], [58] in relation with cognitive symptoms, and in one by Moretti et al. [29] in relation to gait. The largest study included 62 patients (age 49–86 years) [58]. In that study it was shown that the degree of cognitive impairment, was correlated with the severity of CC atrophy in patients with lacunar infactions and extensive white matter lesions. They concluded that only CC atrophy, and not white matter lesions, may be an important predictor for global cognitive impairment in patients with white matter lesions [57], [58]. Moretti et al. studied 30 patients, and they found that CC atrophy was associated with gait impairment [29].
The aim of this study was to investigate the clinical and functional correlates of CC atrophy in a cross-sectional design, based on a large prospective study in a mixed elderly population. We hypothesize that CC atrophy is related to impairments in cognitive and motor functions and to depressive symptoms. We further hypothesize that this association is independent of the degree of ARWMC, as other factors such as cortical atrophy and changes in normal-appearing white matter may also be related to CC atrophy.
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Patients
The study included 639 (M/F: 257/312) subjects from a mixed elderly population with ARWMC who participated in the longitudinal study Leukoaraiosis And DISability in the elderly (LADIS) described in details elsewhere [33]. The objective of the LADIS study was to assess the role of ARWMC as an independent predictor of the transition to disability in the initially non-disabled elderly and to describe health related consequences of ARWMC.
The LADIS subjects had different grades of ARWMC severity and
Clinical characteristics, ARWMC and corpus callosum area
Clinical characteristics for the 569 subjects (age: 64–85 years, M/F: 257/312) included in the study are given in Table 1. Of the 569 participants, 515 subjects were right-handed, 27 subjects were left-handed, 26 were ambidextrous, and 1 subject was not classified.
The mean volumes of ARWMC were 6573 ± 4666, 18844 ± 7650 and 51977 ± 26253 mm3 in the subgroup of patients with mild, moderate, and severe grade of ARWMC, respectively. For the total group the mean volumes was 21477 ± 22852 mm3. The mean total
Discussion
With data from 569 subjects this study is the largest study to date to have analysed the functional and clinical significance of CC morphology on cognition, motor and mood disturbance in the elderly. Atrophy of the CC areas correlated significantly with impairments of global cognitive as well as motor functions. The strongest correlation was found for motor function, where reductions in the total area of the CC, as well as of all subregions, correlated significantly with impaired walking speed.
Conclusion
In this large study of non-disabled elderly patients with age-related white matter changes, the area of the corpus callosum, as measured by normalised MR scans, correlated significantly with impaired cognitive, and motor functions and the correlation remained after correction for age-related white matter changes load. Furthermore, it was found that corpus callosum areas in subjects with subjective gait difficulty were significantly smaller than in those without gait problems. Our results
Acknowledgements
This study was supported by the European Union (grant QLRT-2000-00446, Impact of age-related brain white matter changes on transition to disability in the elderly “Leukoaraiosis And DISability”). We would also like to acknowledge the financial support from the Danish Velux Foundation, and the Danish Alzheimer Research Foundation.
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2015, Behavioural Brain ResearchCitation Excerpt :Significant atrophy of this brain region was found in elders with cognitive complaints, MCI, or AD, with atrophy being more important in patients with AD [45]. Moreover, smaller corpus callosum volumes were associated with lower general cognitive performance [46,47]. In sum, increased inter-hemispherical callosal integration post-MBI appears to be a suitable mechanism favoring strong frontal executive functions necessary for effective disengagement of the default mode network and for regulating emotions arising from limbic areas.
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A list of collaborators of the LADIS study is presented in Appendix A.