Elsevier

Neurobiology of Aging

Volume 28, Issue 6, June 2007, Pages 955-963
Neurobiology of Aging

Clinical significance of corpus callosum atrophy in a mixed elderly population

https://doi.org/10.1016/j.neurobiolaging.2006.04.008Get rights and content

Abstract

Corpus callosum (CC) is the main tract connecting the hemispheres, but the clinical significance of CC atrophy is poorly understood. The aim of this work was to investigate clinical and functional correlates of CC atrophy in subjects with age-related white matter changes (ARWMC). In 569 elderly subjects with ARWMC from the Leukoaraiosis And DISability (LADIS) study, the CC was segmented on the normalised mid-sagittal magnetic resonance imaging (MRI) slice and subdivided into five regions. Correlations between the CC areas and subjective memory complaints, mini mental state examination (MMSE) score, history of depression, geriatric depression scale (GDS) score, subjective gait difficulty, history of falls, walking speed, and total score on the short physical performance battery (SPPB) were analyzed.

Significant correlations between CC atrophy and MMSE, SPPB, and walking speed were identified, and the CC areas were smaller in subjects with subjective gait difficulty. The correlations remained significant after correction for ARWMC grade. In conclusion, CC atrophy was independently associated with impaired global cognitive and motor function in subjects with ARWMC.

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.

Section snippets

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.

References (61)

  • S.J. Teipel et al.

    Regional pattern of hippocampus and corpus callosum atrophy in Alzheimer's disease in relation to dementia severity: evidence for early neocortical degeneration

    Neurobiol Aging

    (2003)
  • J.C. Wu et al.

    Magnetic resonance and positron emission tomography imaging of the corpus callosum: size, shape and metabolic rate in unipolar depression

    J Affect Disord

    (1993)
  • J.A. Yesavage et al.

    Development and validation of a geriatric depression screening scale: a preliminary report

    J Psychiatr Res

    (1982)
  • F. Aboitiz et al.

    Age-related changes in fibre composition of the human corpus callosum: sex differences

    Neuroreport

    (1996)
  • S.E. Black et al.

    Callosal atrophy correlates with temporal lobe volume and mental status in Alzheimer's disease

    Can J Neurol Sci

    (2000)
  • A. Brun et al.

    Regional pattern of degeneration in Alzheimer's disease: neuronal loss and histopathological grading

    Histopathology

    (1981)
  • A. Brun et al.

    A white matter disorder in dementia of the Alzheimer type: a pathoanatomical study

    Ann Neurol

    (1986)
  • H.L. Burke et al.

    Systematic variations in callosal morphology: the effects of age, gender, hand preference, and anatomic assymetry

    Neuropsycology

    (1994)
  • T.F. Cootes et al.

    Active appearance models

    IEEE Trans Pattern Anal Mach Intell

    (2001)
  • R. Duara et al.

    Neuroanatomic differences between dyslexic and normal readers on magnetic resonance imaging scans

    Arch Neurol

    (1991)
  • F. Fazekas et al.

    MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging

    AJR Am J Roentgenol

    (1987)
  • F. Fazekas et al.

    The morphologic correlate of incidental punctate white matter hyperintensities on MR images

    AJNR Am J Neuroradiol

    (1991)
  • M. Fischer et al.

    Mechanisms of interhemispheric transfer and patterns of cognitive function in acallosal patients of normal intelligence

    Arch Neurol

    (1992)
  • J.M. Guralnik et al.

    A short physical performance battery assessing lower extremity function: association with self-reported disability and prediction of mortality and nursing home admission

    J Gerontol

    (1994)
  • C.R. Guttmann et al.

    White matter abnormalities in mobility-impaired older persons

    Neurology

    (2000)
  • H. Hampel et al.

    Corpus callosum atrophy is a possible indicator of region- and cell type-specific neuronal degeneration in Alzheimer disease: a magnetic resonance imaging analysis

    Arch Neurol

    (1998)
  • H. Hampel et al.

    In vivo imaging of region and cell type specific neocortical neurodegeneration in Alzheimer's disease. Perspectives of MRI derived corpus callosum measurement for mapping disease progression and effects of therapy. Evidence from studies with MRI, EEG and PET

    J Neural Transm

    (2002)
  • G.M. Innocenti

    General organization of callosal connections

    (1986)
  • I. Janota et al.

    Neuropathologic correlates of leuko-araiosis

    Arch Neurol

    (1989)
  • J.S. Janowsky et al.

    Atrophy of the corpus callosum in Alzheimer's disease versus healthy aging

    J Am Geriatr Soc

    (1996)
  • Cited by (58)

    • Potential benefits of mindfulness-based interventions in mild cognitive impairment and Alzheimer's disease: An interdisciplinary perspective

      2015, Behavioural Brain Research
      Citation 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.

    View all citing articles on Scopus
    1

    A list of collaborators of the LADIS study is presented in Appendix A.

    View full text