title: Cerebral amyloid is associated with greater white-matter hyperintensity accrual in cognitively normal older adults.
abstract: Cross-sectional studies show that elevated cerebral amyloid is associated with greater white-matter hyperintensity (WMH) burden in cognitively normal (CN) older adults. However, the relative time courses of amyloid and WMH accrual are unclear. To address this, we tested the associations between known WMH correlates-age, hypertension, and amyloid-with WMH accrual rate. We used brain magnetic resonance imaging to measure WMH change in 112 CN Alzheimer's Disease Neuroimaging Initiative (GO/2) participants over a 2-year period. A linear mixed effects model assessed baseline cerebrospinal fluid amyloid beta (Aβ) 1-42, hypertension, age, and their interactions, as predictors of greater WMH accrual. Greater amyloid burden was associated with greater WMH accrual over time. Those with hypertension showed a stronger association between greater amyloid burden and WMH accrual rate. Greater age was not significantly associated with greater WMH accrual in this model. Although the direction of the relationship cannot be tested in this model, CN individuals harboring cerebral amyloid had greater accrual of WMH over a 2-year period after accounting for hypertension and age. Impaired amyloid clearance and cerebral small vessel disease may both underlie the more rapid emergence of WM lesions. The role of cerebral amyloid burden in white-matter injury should thus be considered as a relevant factor when WMHs are detected clinically.
authors.affiliation: Department of Neurology, University of California Davis, Davis, CA, USA. Electronic address: jscott1@scu.edu.
authors.forename: Julia A
authors.initials: JA
authors.lastname: Scott
authors.affiliation: Department of Neurology, University of Southern California, Los Angeles, CA, USA.
authors.forename: Meredith N
authors.initials: MN
authors.lastname: Braskie
authors.affiliation: Department of Radiology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Duygu
authors.initials: D
authors.lastname: Tosun
authors.affiliation: Department of Neurology, University of California Davis, Davis, CA, USA.
authors.forename: Pauline
authors.initials: P
authors.lastname: Maillard
authors.affiliation: Department of Neurology, University of Southern California, Los Angeles, CA, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Thompson
authors.affiliation: Department of Radiology, University of California San Francisco, San Francisco, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Weiner
authors.affiliation: Department of Neurology, University of California Davis, Davis, CA, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: DeCarli
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, LA, USA.
authors.forename: Owen T
authors.initials: OT
authors.lastname: Carmichael
mesh_terms: D000368:Aged; D000375:Aging / Q000378:metabolism* / Q000473:pathology* / Q000523:psychology; D058227:Amyloidogenic Proteins / Q000378:metabolism*; D003071:Cognition / Q000502:physiology*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D006973:Hypertension; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging; D066127:White Matter / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
chemical_list: D058227:Amyloidogenic Proteins
keywords: ADNI; Amyloid; FLAIR; Hypertension; MRI; Normal aging