Structural connectivity networks in Alzheimer's disease and Lewy body disease

Abstract

Objective: We evaluated disruption of the white matter (WM) network related with Alzheimer's disease (AD) and Lewy body disease (LBD), which includes Parkinson's disease and dementia with Lewy bodies.

Methods: We consecutively recruited 37 controls and 77 patients with AD-related cognitive impairment (ADCI) and/or LBD-related cognitive impairment (LBCI). Diagnoses of ADCI and LBCI were supported by amyloid PET and dopamine transporter PET, respectively. There were 22 patients with ADCI, 19 patients with LBCI, and 36 patients with mixed ADCI/LBCI. We investigated the relationship between ADCI, LBCI, graph theory-based network measures on diffusion tensor images, and cognitive dysfunction using general linear models after controlling for age, sex, education, deep WM hyperintensities (WMH), periventricular WMH, and intracranial volume.

Results: LBCI, especially mixed with ADCI, was associated with increased normalized path length and decreased normalized global efficiency. LBCI was related to the decreased nodal degree of left caudate, which was further associated with broad cognitive dysfunction. Decreased left caudate nodal degree was associated with decreased fractional anisotropy (FA) in the brain regions vulnerable to LBD. Compared with the control group, the LBCI group had an increased betweenness centrality in the occipital nodes, which was associated with decreased FA in the WM adjacent to the striatum and visuospatial dysfunction.

Conclusion: Concomitant ADCI and LBCI are associated with the accentuation of LBCI-related WM network disruption centered in the left caudate nucleus. The increase of occipital betweenness centrality could be a characteristic biologic change associated with visuospatial dysfunction in LBCI.

Keywords: alzheimer's disease; graph analysis; lewy body disease; structural connectivity.

FIGURE 1

Disease‐related changes in local network measures. Disease‐related local network changes in terms of nodal degree (a, b) and betweenness centrality (c). Group‐wise comparisons of local network measures showed several nodes where the mixed disease group had lower nodal degree than the control group (a) and those where the pure LBCI group had a higher betweenness centrality than the control group (c). The presence of LBCI was negatively associated with regional nodal degree being independent of ADCI (b). ADCI was not independently associated with local network measures being independent of LBCI. Red colored nodes indicate brain nodes where FDR‐corrected P values were significant, while blue colored nodes indicate brain nodes where uncorrected P values were significant. The size of nodes represents absolute t‐value. FDR‐corrected p <.05 was considered significant. Abbreviations: ADCI, Alzheimer's disease‐related cognitive impairment; AMYG, Amygdala; CAL, Calcarine fissure and surrounding cortex; CAU, Caudate nucleus; CUN, Cuneus; DCG, Middle cingulate and paracingulate gyri; FDR, false discovery rate; IOG, Inferior occipital gyrus; ITG, Inferior temporal gyrus; L, Left; LBCI, Lewy body‐related cognitive impairment; MFG, Middle frontal gyrus; MOG, Middle occipital gyrus; OLF, Olfactory cortex; ORBsup, Superior frontal gyrus, orbital part; PCG, Posterior cingulate gyrus; R, Right; REC, Gyrus rectus; SFGdor, Superior frontal gyrus, dorsolateral; TPOsup, Temporal pole, superior temporal gyrus; WMH, white matter hyperintensities

FIGURE 2

White matter disruptions correlating with the local network measures. Regional white matter disruption correlating with the left caudate nodal degree (a) and the betweenness centrality in the left inferior occipital gyrus (b). Voxel‐wise TBSS GLMs on FA skeleton using the left caudate nodal degree as a predictor were performed in overall study participants (a), while those using the betweenness centrality in the left occipital gyrus as a predictor were performed in the combined group of control and pure LBCI. Red colored voxels indicate positive correlation and blue colored voxels indicate negative correlation. Abbreviations: FA, Fractional anisotropy; GLM, general linear model; LBCI, Lewy body‐related cognitive impairment; TBSS, tract‐based spatial statistics