title: White matter hyperintensity microstructure in amyloid dysmetabolism.
abstract: Accumulating evidence suggests associations between cerebrovascular disease (CVD) and Alzheimer's disease (AD). White matter hyperintensities of presumed vascular origin (WMHs) are increased in subjects with mild cognitive impairment (MCI) and AD, but the exact pathomechanistic link is unknown. The current study investigated effects of amyloid dysmetabolism on the microstructure of WMHs in subjects with MCI or subjective cognitive decline (N = 51), dichotomized according to pathological or normal levels of amyloid-β peptide (Aβ42) in cerebrospinal fluid (CSF). Thirty-one subjects with low CSF Aβ42(Aβ+) and 20 subjects with normal CSF Aβ42(Aβ-) were assessed with magnetic resonance diffusion tensor imaging (DTI), and fractional anisotropy (FA), radial diffusivity (DR), axial diffusivity (DA), and mean diffusivity (MD) were determined. There were no significant differences in WMH volume or distribution between the groups, and neither age nor WMH volume had significant impact on the DTI indices. Nevertheless, there were significantly higher DA, DR, and MD in WMHs in Aβ+ relative to Aβ-; however, no differences in FA were found. The present results suggest that amyloid accumulation is associated with impaired structural integrity (e.g. relating to more extensive demyelination and loss of axons) in WMHs putatively adding to effects of ischemia.
authors.affiliation: Department of Neurology, Akershus University Hospital, Lørenskog, Norway Lisa.Flem.Kalheim@ahus.no.|Institute of Clinical Medicine, Campus Ahus, University of Oslo, Oslo, Norway.
authors.forename: Lisa F
authors.initials: LF
authors.lastname: Kalheim
authors.affiliation: The Intervention Centre, Oslo University Hospital, Oslo, Norway.
authors.forename: Atle
authors.initials: A
authors.lastname: Bjørnerud
authors.affiliation: Department of Neurology, Akershus University Hospital, Lørenskog, Norway.|Institute of Clinical Medicine, Campus Ahus, University of Oslo, Oslo, Norway.
authors.forename: Tormod
authors.initials: T
authors.lastname: Fladby
authors.affiliation: Department of Radiology, Akershus University Hospital, Lørenskog, Norway.
authors.forename: Kjetil
authors.initials: K
authors.lastname: Vegge
authors.affiliation: Department of Neurology, Akershus University Hospital, Lørenskog, Norway.
authors.forename: Per
authors.initials: P
authors.lastname: Selnes
mesh_terms: D000368:Aged; D000544:Alzheimer Disease; D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D058227:Amyloidogenic Proteins / Q000378:metabolism; D016880:Anisotropy; D016022:Case-Control Studies; D002561:Cerebrovascular Disorders; D003711:Demyelinating Diseases; D038524:Diffusion Magnetic Resonance Imaging; D056324:Diffusion Tensor Imaging; D006801:Humans; D008875:Middle Aged; D066127:White Matter / Q000473:pathology / Q000648:ultrastructure*
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D058227:Amyloidogenic Proteins
keywords: Alzheimer’s; cerebrospinal fluid; cognitive impairment; diffusion tensor imaging; white matter disease