Amyloid Dysmetabolism Relates to Reduced Glucose Uptake in White Matter Hyperintensities

Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and cause of dementia, and is characterized by amyloid plaques and neurofibrillary tangles. AD has traditionally been considered to primarily affect grey matter, but multiple lines of evidence also indicate white matter (WM) p...

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Main Authors: Lisa Flem Kalheim, Per Selnes, Atle Bjørnerud, Christopher Coello, Kjetil Vegge, Tormod Fladby
Format: Article
Language:English
Published: Frontiers Media S.A. 2016-11-01
Series:Frontiers in Neurology
Subjects:
Online Access:http://journal.frontiersin.org/Journal/10.3389/fneur.2016.00209/full
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author Lisa Flem Kalheim
Per Selnes
Atle Bjørnerud
Christopher Coello
Kjetil Vegge
Tormod Fladby
author_facet Lisa Flem Kalheim
Per Selnes
Atle Bjørnerud
Christopher Coello
Kjetil Vegge
Tormod Fladby
author_sort Lisa Flem Kalheim
collection DOAJ
description Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and cause of dementia, and is characterized by amyloid plaques and neurofibrillary tangles. AD has traditionally been considered to primarily affect grey matter, but multiple lines of evidence also indicate white matter (WM) pathology and associated small-vessel cerebrovascular disease (CVD). WM glucose delivery and metabolism may have implications for local tissue integrity, and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) may be helpful to assess neuroglial and axonal function in WM. Hypothesizing that affection of oligodendroglia will be associated with loss of glucose uptake, we aimed to investigate glucose metabolism in MRI white matter hyperintensities (WMHs) and normal-appearing white matter in patients with and without evidence of amyloid plaques. Subjects with mild cognitive impairment or subjective cognitive decline were included and dichotomized according to pathological (Aβ+) or normal (Aβ-) concentrations of cerebrospinal fluid amyloid-β 1-42. A total of fifty subjects were included, of whom thirty subjects were classified as Aβ(+) and twenty subjects as Aβ(-). All subjects were assessed with MRI and FDG-PET. FDG-PET images were corrected for effects of partial voluming and normalized to cerebellar WM, before determining WMH FDG uptake. Although there were no significant differences between the groups in terms of age, WMH volume, number of individual WMHs or WMH distribution, we found significantly lower (p = 0.021) FDG uptake in WMHs in Aβ(+) subjects (mean = 0,662, SD = 0.113) compared to Aβ(-) subjects (mean = 0.596, SD = 0.073). There were no significant group differences in the FDG uptake in normal-appearing white matter. Similar results were obtained without correction for effects of partial voluming. Our findings add to the evidence for a link between Aβ dysmetabolism and white matter pathology in AD.
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spelling doaj.art-6ad5239a0ad34e4dadd36f6650df09ec2022-12-21T23:58:50ZengFrontiers Media S.A.Frontiers in Neurology1664-22952016-11-01710.3389/fneur.2016.00209229167Amyloid Dysmetabolism Relates to Reduced Glucose Uptake in White Matter HyperintensitiesLisa Flem Kalheim0Per Selnes1Atle Bjørnerud2Christopher Coello3Kjetil Vegge4Tormod Fladby5Akershus University HospitalAkershus University HospitalOslo University HospitalUniversity of OsloAkershus University HospitalAkershus University HospitalAlzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and cause of dementia, and is characterized by amyloid plaques and neurofibrillary tangles. AD has traditionally been considered to primarily affect grey matter, but multiple lines of evidence also indicate white matter (WM) pathology and associated small-vessel cerebrovascular disease (CVD). WM glucose delivery and metabolism may have implications for local tissue integrity, and 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) may be helpful to assess neuroglial and axonal function in WM. Hypothesizing that affection of oligodendroglia will be associated with loss of glucose uptake, we aimed to investigate glucose metabolism in MRI white matter hyperintensities (WMHs) and normal-appearing white matter in patients with and without evidence of amyloid plaques. Subjects with mild cognitive impairment or subjective cognitive decline were included and dichotomized according to pathological (Aβ+) or normal (Aβ-) concentrations of cerebrospinal fluid amyloid-β 1-42. A total of fifty subjects were included, of whom thirty subjects were classified as Aβ(+) and twenty subjects as Aβ(-). All subjects were assessed with MRI and FDG-PET. FDG-PET images were corrected for effects of partial voluming and normalized to cerebellar WM, before determining WMH FDG uptake. Although there were no significant differences between the groups in terms of age, WMH volume, number of individual WMHs or WMH distribution, we found significantly lower (p = 0.021) FDG uptake in WMHs in Aβ(+) subjects (mean = 0,662, SD = 0.113) compared to Aβ(-) subjects (mean = 0.596, SD = 0.073). There were no significant group differences in the FDG uptake in normal-appearing white matter. Similar results were obtained without correction for effects of partial voluming. Our findings add to the evidence for a link between Aβ dysmetabolism and white matter pathology in AD.http://journal.frontiersin.org/Journal/10.3389/fneur.2016.00209/fullCerebrospinal FluidPETAlzheimer’s diseasewhite mattercerebrovascular disease
spellingShingle Lisa Flem Kalheim
Per Selnes
Atle Bjørnerud
Christopher Coello
Kjetil Vegge
Tormod Fladby
Amyloid Dysmetabolism Relates to Reduced Glucose Uptake in White Matter Hyperintensities
Frontiers in Neurology
Cerebrospinal Fluid
PET
Alzheimer’s disease
white matter
cerebrovascular disease
title Amyloid Dysmetabolism Relates to Reduced Glucose Uptake in White Matter Hyperintensities
title_full Amyloid Dysmetabolism Relates to Reduced Glucose Uptake in White Matter Hyperintensities
title_fullStr Amyloid Dysmetabolism Relates to Reduced Glucose Uptake in White Matter Hyperintensities
title_full_unstemmed Amyloid Dysmetabolism Relates to Reduced Glucose Uptake in White Matter Hyperintensities
title_short Amyloid Dysmetabolism Relates to Reduced Glucose Uptake in White Matter Hyperintensities
title_sort amyloid dysmetabolism relates to reduced glucose uptake in white matter hyperintensities
topic Cerebrospinal Fluid
PET
Alzheimer’s disease
white matter
cerebrovascular disease
url http://journal.frontiersin.org/Journal/10.3389/fneur.2016.00209/full
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AT atlebjørnerud amyloiddysmetabolismrelatestoreducedglucoseuptakeinwhitematterhyperintensities
AT christophercoello amyloiddysmetabolismrelatestoreducedglucoseuptakeinwhitematterhyperintensities
AT kjetilvegge amyloiddysmetabolismrelatestoreducedglucoseuptakeinwhitematterhyperintensities
AT tormodfladby amyloiddysmetabolismrelatestoreducedglucoseuptakeinwhitematterhyperintensities