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Fascicle- and Glucose-Specific Deterioration in White Matter Energy Supply in Alzheimer’s Disease
- Source :
- Journal of Alzheimer's Disease. 76:863-881
- Publication Year :
- 2020
- Publisher :
- IOS Press, 2020.
-
Abstract
- Background White matter energy supply to oligodendrocytes and the axonal compartment is crucial for normal axonal function. Although gray matter glucose hypometabolism is extensively reported in Alzheimer's disease (AD), glucose and ketones, the brain's two main fuels, are rarely quantified in white matter in AD. Objective Using a dual-tracer PET method combined with a fascicle-specific diffusion MRI approach, robust to white matter hyper intensities and crossing fibers, we aimed to quantify both glucose and ketone metabolism in specific white matter fascicles associated with mild cognitive impairment (MCI; n = 51) and AD (n = 13) compared to cognitively healthy age-matched controls (Controls; n = 14). Methods Eight white matter fascicles of the limbic lobe and corpus callosum were extracted and analyzed into fascicle profiles of five sections. Glucose (18F-fluorodeoxyglucose) and ketone (11C-acetoacetate) uptake rates, corrected for partial volume effect, were calculated along each fascicle. Results The only fascicle with significantly lower glucose uptake in AD compared to Controls was the left posterior cingulate segment of the cingulum (-22%; p = 0.016). Non-significantly lower glucose uptake in this fascicle was also observed in MCI. In contrast to glucose, ketone uptake was either unchanged or higher in sections of the fornix and parahippocampal segment of the cingulum in AD. Conclusion To our knowledge, this is the first report of brain fuel uptake calculated along white matter fascicles in humans. Energetic deterioration in white matter in AD appears to be specific to glucose and occurs first in the posterior cingulum.
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
Glucose uptake
Corpus callosum
Gyrus Cinguli
White matter
03 medical and health sciences
0302 clinical medicine
Alzheimer Disease
Fluorodeoxyglucose F18
Internal medicine
medicine
Humans
Cognitive Dysfunction
Gray Matter
Aged
Aged, 80 and over
business.industry
General Neuroscience
Fornix
General Medicine
Limbic lobe
Middle Aged
Fascicle
White Matter
Psychiatry and Mental health
Clinical Psychology
Diffusion Magnetic Resonance Imaging
Diffusion Tensor Imaging
Glucose
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Ketone bodies
Female
Geriatrics and Gerontology
business
030217 neurology & neurosurgery
Diffusion MRI
Subjects
Details
- ISSN :
- 18758908 and 13872877
- Volume :
- 76
- Database :
- OpenAIRE
- Journal :
- Journal of Alzheimer's Disease
- Accession number :
- edsair.doi.dedup.....cf0f92153b20ad1d0d6680fd11687cc0