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.
Highlights
IntroductionFocal and diffuse lesions in the white matter, seen as hyperintensities on T2-weighted magnetic resonance images (MRI) (i.e., white matter hyperintensities; WMH) are the most ubiquitous age-related alteration seen in the brain [1]
Focal and diffuse lesions in the white matter, seen as hyperintensities on T2-weighted magnetic resonance images (MRI) are the most ubiquitous age-related alteration seen in the brain [1]
In our examination of the effects of WMH pathology and Ab deposition on white matter microstructural integrity, we found that (1) WMH pathology was significantly associated with reduced fractional anisotropy (FA) in projection and association fibers
Summary
Focal and diffuse lesions in the white matter, seen as hyperintensities on T2-weighted magnetic resonance images (MRI) (i.e., white matter hyperintensities; WMH) are the most ubiquitous age-related alteration seen in the brain [1]. Heterogeneity exists with respect to the presence of WMH On one hand, they are related to cardiovascular risk factors, such as hypertension and atherosclerosis [2,3,4]. They are abundantly present in patients with an underlying amyloid pathology such as cerebral amyloid angiopathy (CAA) [5]. Another common pathological change in the aging brain is cerebral b-amyloid (Ab) deposition. We recently showed that aggregate coronary disease risk has a moderately strong association with cerebral amyloid deposition [9], consistent with the theory that vascular risk factors (e.g., low high density lipoportein) contribute to AD pathology [10]. The goal of this study was to assess the relationship between Ab deposition and WMH pathology, defined as greater than 0.5% of total intracranial volume (ICV) [11], on microstructural integrity of the white matter
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
