title: Cerebral Amyloid and Hypertension are Independently Associated with White Matter Lesions in Elderly.
abstract: In cognitively normal (CN) elderly individuals, white matter hyperintensities (WMH) are commonly viewed as a marker of cerebral small vessel disease (SVD). SVD is due to exposure to systemic vascular injury processes associated with highly prevalent vascular risk factors (VRFs) such as hypertension, high cholesterol, and diabetes. However, cerebral amyloid accumulation is also prevalent in this population and is associated with WMH accrual. Therefore, we examined the independent associations of amyloid burden and VRFs with WMH burden in CN elderly individuals with low to moderate vascular risk. Participants (n = 150) in the Alzheimer's Disease Neuroimaging Initiative (ADNI) received fluid attenuated inversion recovery (FLAIR) MRI at study entry. Total WMH volume was calculated from FLAIR images co-registered with structural MRI. Amyloid burden was determined by cerebrospinal fluid Aβ1-42 levels. Clinical histories of VRFs, as well as current measurements of vascular status, were recorded during a baseline clinical evaluation. We tested ridge regression models for independent associations and interactions of elevated blood pressure (BP) and amyloid to total WMH volume. We found that greater amyloid burden and a clinical history of hypertension were independently associated with greater WMH volume. In addition, elevated BP modified the association between amyloid and WMH, such that those with either current or past evidence of elevated BP had greater WMH volumes at a given burden of amyloid. These findings are consistent with the hypothesis that cerebral amyloid accumulation and VRFs are independently associated with clinically latent white matter damage represented by WMHs. The potential contribution of amyloid to WMHs should be further explored, even among elderly individuals without cognitive impairment and with limited VRF exposure.
authors.affiliation: IDeA Laboratory, Department of Neurology, University of California, Davis Davis, CA, USA.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Scott
authors.affiliation: Imaging Genetics Center, Keck School of Medicine, University of Southern California Marina del Rey, CA, USA.
authors.forename: Meredith N
authors.initials: MN
authors.lastname: Braskie
authors.affiliation: Center for Imaging Neurodegenerative Diseases, VA Medical Center, University of California, San Francisco San Francisco, CA, USA.
authors.forename: Duygu
authors.initials: D
authors.lastname: Tosun
authors.affiliation: Imaging Genetics Center, Keck School of Medicine, University of Southern California Marina del Rey, CA, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
authors.affiliation: Center for Imaging Neurodegenerative Diseases, VA Medical Center, University of California, San Francisco San Francisco, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Weiner
authors.affiliation: IDeA Laboratory, Department of Neurology, University of California, Davis Davis, CA, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: DeCarli
authors.affiliation: Brain and Metabolism Imaging in Chronic Disease Lab, Pennington Biomedical Research Center, Louisiana State University Baton Rouge, LA, USA.
authors.forename: Owen T
authors.initials: OT
authors.lastname: Carmichael
keywords: ADNI; FLAIR; MRI; amyloid; hypertension; normal aging