Corpus callosum atrophy as a predictor of age-related cognitive and motor impairment: A 3-year follow-up of the LADIS study cohort
Introduction
The corpus callosum (CC) is the most important structure involved in transmission of interhemispheric information. Organization within the commissure is roughly topographical and atrophy of the CC may lead to interhemispheric disconnection [1] resulting in functional disability because of reduced integration of the hemispheres. The CC contains subregions with different fiber topography resulting in structurally and functionally distinct connections. These subregions might be affected differentially in the development of disease.
Motor-specific CC subregions are fairly well established as the rostral body and anterior midbody subregions of the CC primarily having premotor, supplementary motor, and motor cortical fibers transversing through them [2], [3], [4].
The potential contribution of atrophy of the CC to the development of cognitive deficits is uncertain. Besides connecting the interhemispheres, it is thought that the CC mainly serves an excitatory role in interhemispheric communication, and at times transmits inhibitory impulses [5]. Altogether, the CC may therefore be an important brain structure that subserves a variety of cognitive processes.
In our previous cross-sectional study we found that atrophy of the CC was associated with cognitive as well as motor deficits in a mixed independent elderly population with various degrees of white matter changes [6]. However, little is known about the potential relation between CC atrophy and future clinical performance. The aim of the present longitudinal study was to investigate whether CC atrophy may predict future motor and cognitive impairment in a mixed elderly population. More specifically, we investigated the association between the size of CC and it's subregions in relation to decline in motor performance, global cognitive performance and the risk of developing dementia in a 3-year prospective follow-up study.
Section snippets
Subjects
The study included 639 (M/F: 288/351) subjects from a mixed elderly population with Age-Related White Matter Changes (ARWMC) who participated in the longitudinal multicenter study Leukoaraiosis And DISability in the elderly (LADIS), as described in detail elsewhere [7]. The main 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 [8].
The
Results
The clinical characteristics of the final cohort are shown in Table 1. Table 2 shows the relationship between the size of the CC with subregions at baseline and the clinical data obtained at the 3rd year follow-up (presence of “subjective memory complaints”, “subjective gait difficulty”, “history of falls”, along with “dementia”). Scores for all three post-baseline time points were available in 60% of the 563 patients for MMSE, 61% for SPPB, and 60% walking speed. In Table 3, the correlation
Discussion
To our knowledge, this is the first longitudinal study that has analyzed the relationship between CC morphology and subsequent development of cognitive and motor impairment in the elderly. This study, which was unique in including a very large cohort of elderly subjects in a 3-year longitudinal design, indicated that atrophy of CC may predict impairment of cognitive and motor functions. Importantly, the impact of CC atrophy on cognitive and motor performance was significant even after
Conclusion
In conclusion, this longitudinal study suggested that CC atrophy might predict progressive cognitive- and motor impairment in elderly subjects with ARWMC. CC atrophy, as an indicator of reduced functional connectivity between cortical areas, seems to contribute independently of the ARWMC load and general atrophy to cognitive and motor decline in the elderly. However, it cannot be excluded that regional cortical atrophy contributed to the association. Therefore, future structural and functional
Acknowledgments
We are grateful to Mikkel Stegmann, MSc, PhD, for development of software used for segmentation of the corpus callosum. The LADIS 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.
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A list of collaborators of the LADIS study is presented at the end of the paper.