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

• Published in: PloS one Vol. 8; no. 6; p. e65175
• Main Authors: Chao, Linda L., DeCarli, Charles, Kriger, Stephen, Truran, Diana, Zhang, Yu, Laxamana, Joel, Villeneuve, Sylvia, Jagust, William J., Sanossian, Nerses, Mack, Wendy J., Chui, Helena C., Weiner, Michael W.
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 06.06.2013; Public Library of Science (PLoS)
• Subjects: Aged; Aged, 80 and over; Aging; Amyloid beta-Peptides - genetics; Amyloid beta-Peptides - metabolism; Anisotropy; Apolipoprotein E; Apolipoprotein E4; Apolipoprotein E4 - genetics; Apolipoprotein E4 - metabolism; Arteriosclerosis; Atherosclerosis; Biology; Blood vessels; Brain; Brain Mapping; Brain research; Cingulum; Cognitive ability; Cognitive Dysfunction - diagnosis; Cognitive Dysfunction - genetics; Cognitive Dysfunction - pathology; Cognitive Dysfunction - physiopathology; Corona; Corpus callosum; Covariance; Dementia; Dementia disorders; Deposition; Diffusion; Diffusion Tensor Imaging; Disease; Emission analysis; Female; Fornix; Gene Expression; Health care; Humans; Hypertension; Integrity; Limbic System - metabolism; Limbic System - pathology; Longitudinal Studies; Magnetic resonance; Magnetic resonance imaging; Male; Medical imaging; Medicine; Multivariate Analysis; Neuroimaging; Neurology; Neuropsychological Tests; Neurosciences; NMR; Nuclear magnetic resonance; Older people; Parahippocampal gyrus; Parenchyma; Pathology; Positron emission; Positron emission tomography; Risk analysis; Risk factors; Stroke; Substantia alba; Tomography; Traumatic brain injury; Veterans; Los Angeles California; San Francisco California; California; United States > US
• DOI: 10.1371/journal.pone.0065175
• ISSN: 1932-6203

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.