Independent and interaction effects of Alzheimer’s disease and Lewy body disease on the brain networks: a diffusion tensor imaging study

Abstract

Alzheimer’s disease (AD) and Lewy body disease (LBD), which includes Parkinson’s disease and dementia with Lewy bodies, are the first and second most common causes of degenerative dementia, respectively. White matter (WM) disruption has been observed in AD and LBD. Previous autopsy studies have shown that LBD and AD pathologies frequently co-occur. However, most of previous clinical studies overlooked mixed AD/LBD, and only considered each disease separately. In this study, we evaluated the independent and interaction effects of AD and LBD on the WM network disruption. 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 positron emission tomography (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. LBCI, especially mixed with ADCI, was associated with increased normalized characteristic 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. 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.