Regional Amyloid-β Load and White Matter Abnormalities Contribute to Hypometabolism in Alzheimer’s Dementia

• Published in: Molecular neurobiology 2019-07, Vol.56 (7), p.4916-4924
• Main Authors: Schilling, Lucas Porcello, Pascoal, Tharick A., Zimmer, Eduardo R., Mathotaarachchi, Sulantha, Shin, Monica, de Mello Rieder, Carlos Roberto, Gauthier, Serge, Palmini, André, Rosa-Neto, Pedro
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - metabolism; Alzheimer's disease; Amyloid beta-Peptides - metabolism; Anisotropy; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cognitive ability; Cortex (parietal); Dementia; Dementia disorders; Energy Metabolism - physiology; Female; Fluorodeoxyglucose F18 - metabolism; Glucose; Humans; Magnetic resonance imaging; Male; Medical imaging; Neostriatum; Neurobiology; Neuroimaging; Neurology; Neurosciences; NMR; Nuclear magnetic resonance; Positron emission tomography; Positron-Emission Tomography - methods; Substantia alba; White Matter - diagnostic imaging; White Matter - metabolism
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-018-1405-1

We investigated the association between amyloid-β deposition and white matter (WM) integrity as a determinant of brain glucose hypometabolism across the Alzheimer’s disease (AD) spectrum. We assessed ninety-six subjects (27 cognitively normal, 49 mild cognitive impairment, and 20 AD dementia) who underwent [ 18 F]FDG and [ 18 F]Florbetapir positron emission tomography (PET) as well as magnetic resonance imaging (MRI) with diffusion tensor imaging. Among the regions with reduced fractional anisotropy (FA) in the AD group, we selected a voxel of interest in the angular bundle bilaterally for subsequent analyses. Using voxel-based interaction models at voxel level, we tested whether the regional hypometabolism is associated with FA in the angular bundle and regional amyloid-β deposition. In the AD patients, [ 18 F]FDG hypometabolism in the striatum, mesiobasal temporal, orbitofrontal, precuneus, and cingulate cortices were associated with the interaction between high levels of [ 18 F]Florbetapir standard uptake value ratios (SUVR) in these regions and low FA in the angular bundle. We found that the interaction between, rather than the independent effects of, high levels of amyloid-β deposition and WM integrity disruption determined limbic hypometabolism in patients with AD. This finding highlights a more integrative model for AD, where the interaction between partially independent processes determines the glucose hypometabolism.