title: Reduced glucose uptake and Aβ in brain regions with hyperintensities in connected white matter.
abstract: Interstitial concentration of amyloid beta (Aß) is positively related to synaptic activity in animal experiments. In humans, Aß deposition in Alzheimer's disease overlaps with cortical regions highly active earlier in life. White matter lesions (WML) disrupt connections between gray matter (GM) regions which in turn changes their activation patterns. Here, we tested if WML are related to Aß accumulation (measured with PiB-PET) and glucose uptake (measured with FDG-PET) in connected GM. WML masks from 72 cognitively normal (age 61.7 ± 9.6 years, 71% women) individuals were obtained from T2-FLAIR. MRI and PET images were normalized into common space, segmented and parcellated into gray matter (GM) regions. The effects of WML on connected GM regions were assessed using the Change in Connectivity (ChaCo) score. Defined for each GM region, ChaCo is the percentage of WM tracts connecting to that region that pass through the WML mask. The regional relationship between ChaCo, glucose uptake and Aß was explored via linear regression. Subcortical regions of the bilateral caudate, putamen, calcarine, insula, thalamus and anterior cingulum had WM connections with the most lesions, followed by frontal, occipital, temporal, parietal and cerebellar regions. Regional analysis revealed that GM with more lesions in connecting WM and thus impaired connectivity had lower FDG-PET (r = 0.20, p<0.05 corrected) and lower PiB uptake (r = 0.28, p<0.05 corrected). Regional regression also revealed that both ChaCo (β = 0.045) and FDG-PET (β = 0.089) were significant predictors of PiB. In conclusion, brain regions with more lesions in connecting WM had lower glucose metabolism and lower Aß deposition.
authors.affiliation: Center for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, USA.|Department of Radiology, New York University School of Medicine, New York, USA.
authors.forename: L
authors.initials: L
authors.lastname: Glodzik
authors.affiliation: Department of Radiology and Brain and Mind Research Institute, Weill Cornell Medical College, New York, USA.
authors.forename: A
authors.initials: A
authors.lastname: Kuceyeski
authors.affiliation: Department of Radiology, New York University School of Medicine, New York, USA.
authors.forename: H
authors.initials: H
authors.lastname: Rusinek
authors.affiliation: Center for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, USA.
authors.forename: W
authors.initials: W
authors.lastname: Tsui
authors.affiliation: Center for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, USA.
authors.forename: L
authors.initials: L
authors.lastname: Mosconi
authors.affiliation: Center for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Center for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Osorio
authors.affiliation: Center for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, USA.
authors.forename: S
authors.initials: S
authors.lastname: Williams
authors.affiliation: Center for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, USA.
authors.forename: C
authors.initials: C
authors.lastname: Randall
authors.affiliation: Center for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, USA.
authors.forename: N
authors.initials: N
authors.lastname: Spector
authors.affiliation: Center for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, USA.
authors.forename: P
authors.initials: P
authors.lastname: McHugh
authors.affiliation: Center for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, USA.
authors.forename: J
authors.initials: J
authors.lastname: Murray
authors.affiliation: Center for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, USA.
authors.forename: E
authors.initials: E
authors.lastname: Pirraglia
authors.affiliation: Department of Radiology and Brain and Mind Research Institute, Weill Cornell Medical College, New York, USA.
authors.forename: S
authors.initials: S
authors.lastname: Vallabhajosula
authors.affiliation: Department of Radiology and Brain and Mind Research Institute, Weill Cornell Medical College, New York, USA.
authors.forename: A
authors.initials: A
authors.lastname: Raj
authors.affiliation: Center for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: de Leon
mesh_terms: D000368:Aged; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D001786:Blood Glucose / Q000378:metabolism*; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D013844:Thiazoles; D066127:White Matter / Q000378:metabolism* / Q000473:pathology
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D001786:Blood Glucose; D013844:Thiazoles; D019788:Fluorodeoxyglucose F18
keywords: Aging; Amyloid beta; Cerebrovascular disorders; Magnetic resonance imaging; Positron emission tomography