title: Amyloid Dysmetabolism Relates to Reduced Glucose Uptake in White Matter Hyperintensities.
abstract: 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 gray matter, but multiple lines of evidence also indicate white matter (WM) pathology and associated small-vessel cerebrovascular disease. 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 magnetic resonance imaging (MRI) white matter hyperintensities (WMHs) and normal-appearing WM 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 50 subjects were included, of whom 30 subjects were classified as Aβ(+) and 20 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 WM. Similar results were obtained without correction for effects of partial voluming. Our findings add to the evidence for a link between Aβ dysmetabolism and WM pathology in AD.
authors.affiliation: Department of Neurology, Akershus University Hospital, Lørenskog, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Lisa Flem
authors.initials: LF
authors.lastname: Kalheim
authors.affiliation: Department of Neurology, Akershus University Hospital , Lørenskog , Norway.
authors.forename: Per
authors.initials: P
authors.lastname: Selnes
authors.affiliation: The Intervention Centre, Oslo University Hospital , Oslo , Norway.
authors.forename: Atle
authors.initials: A
authors.lastname: Bjørnerud
authors.affiliation: Preclinical PET/CT, Institute of Basic Medical Sciences, University of Oslo , Oslo , Norway.
authors.forename: Christopher
authors.initials: C
authors.lastname: Coello
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; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Tormod
authors.initials: T
authors.lastname: Fladby
keywords: Alzheimer’s disease; PET; cerebrospinal fluid; cerebrovascular disease; white matter