Associations between White Matter Hyperintensities and β Amyloid on Integrity of Projection, Association, and Limbic Fiber Tracts Measured with Diffusion Tensor MRI

Abstract

The goal of this study was to assess the relationship between Aβ deposition and white matter pathology (i.e., white matter hyperintensities, WMH) on microstructural integrity of the white matter. Fifty-seven participants (mean age: 78±7 years) from an ongoing multi-site research program who spanned the spectrum of normal to mild cognitive impairment (Clinical dementia rating 0–0.5) and low to high risk factors for arteriosclerosis and WMH pathology (defined as WMH volume >0.5% total intracranial volume) were assessed with positron emission tomography (PET) with Pittsburg compound B (PiB) and magnetic resonance and diffusion tensor imaging (DTI). Multivariate analysis of covariance were used to investigate the relationship between Aβ deposition and WMH pathology on fractional anisotropy (FA) from 9 tracts of interest (i.e., corona radiata, internal capsule, cingulum, parahippocampal white matter, corpus callosum, superior longitudinal, superior and inferior front-occipital fasciculi, and fornix). WMH pathology was associated with reduced FA in projection (i.e., internal capsule and corona radiate) and association (i.e., superior longitudinal, superior and inferior fronto-occipital fasciculi) fiber tracts. Aβ deposition (i.e., PiB positivity) was associated with reduced FA in the fornix and splenium of the corpus callosum. There were interactions between PiB and WMH pathology in the internal capsule and parahippocampal white matter, where Aβ deposition reduced FA more among subjects with WMH pathology than those without. However, accounting for apoE ε4 genotype rendered these interactions insignificant. Although this finding suggests that apoE4 may increase amyloid deposition, both in the parenchyma (resulting in PiB positivity) and in blood vessels (resulting in amyloid angiopathy and WMH pathology), and that these two factors together may be associated with compromised white matter microstructural integrity in multiple brain regions, additional studies with a longitudinal design will be necessary to resolve this issue.

Measuring Cortical Connectivity in Alzheimer’s Disease as a Brain Neural Network Pathology: Toward Clinical Applications

“…Other recent studies examined white matter changes in asymptomatic individuals showing biomarker evidence of amyloid or tau pathology (Bendlin et al, 2012;Chao et al, 2013;Gold et al, 2014;Kantarci et al, 2014;Molinuevo et al, 2014;Racine et al, 2014;Stenset et al, 2011). These cross-sectional studies of at-risk populations are now increasingly being complemented by longitudinal follow-up studies that allow relating the detected imaging abnormalities to future clinical outcomes Fletcher et al, 2013;Mielke et al, 2012;Zhuang et al, 2012).…”

Clinical effect of white matter network disruption related to amyloid and small vessel disease

“…Several studies have already shown relationships between SVD markers and WM injury. 29,30 However, to our knowledge, only a few studies have evaluated these relationships from a regional network perspective. 8 Nodal efficiency, one of the network parameters, quantifies the importance of each node for communication within a network.…”

The role of exercise in mitigating subcortical ischemic vascular cognitive impairment

“…This trial reported that high-intensity progressive resistance training resulted in a modest regression of WMH in periventricular and parietal zones while non-progressive resistance training groups displayed WMH progression; however, these results did not survive whole-brain correction (Suo et al 2016). White matter hyperintensities are also associated with reduced white matter integrity in both projection and association fiber tracts (Chao et al 2013). One study reported that light physical activity was associated with greater white matter integrity in parahippocampal regions in healthy older adults (Burzynska et al 2014).…”