title: White matter hyperintensities predict amyloid increase in Alzheimer's disease.
abstract: Impaired amyloid clearance probably contributes to increased amyloid deposition in sporadic Alzheimer's disease (AD). Diminished perivascular drainage due to cerebral small-vessel disease (CSVD) has been proposed as a cause of reduced amyloid clearance. White matter hyperintensities (WMHs) are considered to reflect CSVD and can be measured using fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI). Amyloid deposition can be determined in vivo using Pittsburgh compound B ([11C]PiB) positron emission tomography (PET). We aimed to elucidate the association between WMH and the progression of amyloid deposition in patients with AD. Twenty-two patients with probable AD underwent FLAIR-MRI and [11C]PiB-PET examinations at baseline (BL) and after a mean follow-up (FU) interval of 28 months. The relationship between BL-WMH and the progression of cerebral amyloid between BL and FU was examined using a regions-of-interest (ROI) approach. The region-specific variability of this relationship was analyzed using a voxel-based method. The longitudinal analysis revealed a statistically significant association between the amount of BL-WMH and the progression of amyloid load between BL and FU (p = 0.006, adjusted R2 = 0.375, standardized coefficient β = 0.384). The association was particularly observed in parieto-occipital regions and tended to be closer in regions adjacent to the brain surface. According to our knowledge, this is the first in vivo study in human being supporting the hypothesis that impaired amyloid clearance along perivascular drainage pathways may contribute to β-amyloid deposition in sporadic AD. The extent of WMH might be a relevant factor to be assessed in antiamyloid drug trials.
authors.affiliation: Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar der Technischen Universität München, Ismaninger Str. 22, 81675 Munich, Germany. t.grimmer@lrz.tum.de
authors.forename: Timo
authors.initials: T
authors.lastname: Grimmer
authors.forename: Maximilian
authors.initials: M
authors.lastname: Faust
authors.forename: Florian
authors.initials: F
authors.lastname: Auer
authors.forename: Panagiotis
authors.initials: P
authors.lastname: Alexopoulos
authors.forename: Hans
authors.initials: H
authors.lastname: Förstl
authors.forename: Gjermund
authors.initials: G
authors.lastname: Henriksen
authors.forename: Robert
authors.initials: R
authors.lastname: Perneczky
authors.forename: Christian
authors.initials: C
authors.lastname: Sorg
authors.forename: Behrooz H
authors.initials: BH
authors.lastname: Yousefi
authors.forename: Alexander
authors.initials: A
authors.lastname: Drzezga
authors.forename: Alexander
authors.initials: A
authors.lastname: Kurz
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000235:genetics / Q000473:pathology*; D000682:Amyloid / Q000378:metabolism*; D000814:Aniline Compounds; D053327:Apolipoprotein E4 / Q000235:genetics; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D001931:Brain Mapping; D003430:Cross-Sectional Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000000981:diagnostic imaging / Q000473:pathology*; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography; D011237:Predictive Value of Tests; D011569:Psychiatric Status Rating Scales; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D000682:Amyloid; D000814:Aniline Compounds; D053327:Apolipoprotein E4; D013844:Thiazoles