Frontal white matter integrity in adults with Down syndrome with and without dementia

Abstract

Adults with Down syndrome (DS) are at high risk for developing Alzheimer's disease after the age of 40 years. To detect white matter (WM) changes in the brain linked to dementia, fractional anisotropy (FA) from diffusion tensor imaging was used. We hypothesized that adults with DS without dementia (DS n = 10), DS with dementia (DSAD n = 10) and age matched non-DS subjects (CTL n = 10) would show differential levels of FA and an association with scores from the Brief Praxis Test and the Severe Impairment Battery. WM integrity differences in DS compared with CTL were found predominantly in the frontal lobes. Across all DS adults, poorer Brief Praxis Test performance correlated with reduced FA in the corpus callosum as well as several association tracts, primarily within frontoparietal regions. Our results demonstrate significantly lower WM integrity in DS compared with controls, particularly in the frontal tracts. DS-related WM integrity reductions in a number of tracts were associated with poorer cognition. These preliminary results suggest that late myelinating frontal pathways may be vulnerable to aging in DS.

Keywords: Aging; BPT; Brief praxis test; DMR; Dementia questionnaire for persons with mental retardation; Diffusion tensor imaging; Fractional anisotropy; SIB; Severe impairment battery; Trisomy 21.

Fig. 1

FA is lower in DS compared with controls without DS, and further reduced with dementia in DS (DSAD). FA decreases in DS are associated with lower BPT scores. Images show axial slices in MNI space and illustrate representative sampling of FA analyses. Z is the voxel coordinate in MNI 1-mm template space. Yellow illustrates the underlying FA skeleton common to all participants. Blue shows areas that had reduced FA when comparing nondemented DS adults with non-DS controls (p < 0.01, corrected). Green shows areas where demented adults with DS have lower FA than nondemented adults with DS (p < 0.001, uncorrected). Red shows areas where lower FA is associated with lower BPT scores. Abbreviations: BPT, Brief Praxis Test; DS, Down syndrome; DSAD, Down syndrome with dementia; FA, fractional anisotropy; MNI, Montreal Neurologic Institute.

Fig. 2

A 3D transparent view illustrating regions where FA is associated with DS, dementia and BPT scores. Blue shows areas that had reduced FA when comparing nondemented DS adults with non-DS controls (p < 0.01 corrected). Green shows areas where demented adults with DS have lower FA than nondemented adults with DS (p < 0.001, uncorrected). Red shows areas where lower FA is associated with lower BPT scores in DS adults. Abbreviations: BPT, Brief Praxis Test; DS, Down syndrome; FA, fractional anisotropy.

Fig. 3

A graph illustrating the association between average brain FA from all the significant voxels from Analysis 3 (red in figures 1 and 2) and individual BPT scores in DS and DS with AD. FA is strongly correlated with BPT scores in demented individuals. Abbreviations: AD, Alzheimer’s disease; BPT, Brief Praxis Test; DS, Down syndrome; FA, fractional anisotropy.