Regional multimodal relationships between tau, hypometabolism, atrophy, and fractional anisotropy in atypical Alzheimer's disease

• Published in: Human brain mapping Vol. 40; no. 5; pp. 1618 - 1631
• Main Authors: Sintini, Irene, Schwarz, Christopher G., Martin, Peter R., Graff‐Radford, Jonathan, Machulda, Mary M., Senjem, Matthew L., Reid, Robert I., Spychalla, Anthony J., Drubach, Daniel A., Lowe, Val J., Jack, Clifford R., Josephs, Keith A., Whitwell, Jennifer L.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.04.2019
• Subjects: Aged; Aged, 80 and over; Alzheimer Disease - diagnostic imaging; Alzheimer Disease - metabolism; Alzheimer's disease; Anisotropy; Aphasia, Primary Progressive - diagnostic imaging; Aphasia, Primary Progressive - metabolism; Atrophy; atypical Alzheimer's disease; Brain Mapping; Cingulum; Corpus callosum; Correlation analysis; Cortex; Degeneration; Diffusion Tensor Imaging; DTI; FDG; Female; Fluorine isotopes; Fluorodeoxyglucose F18; Humans; Hypometabolism; Image Processing, Computer-Assisted; Magnetic resonance imaging; Male; Medical imaging; Metabolism; Middle Aged; MRI; multimodal imaging; multivariate analysis; Neural networks; Neurodegeneration; Neurodegenerative diseases; Neuroimaging; Neurology; Patients; Positron emission; Positron emission tomography; Radiation; Radiopharmaceuticals; Substantia alba; Substantia grisea; tau; Tau protein; Tauopathies - diagnostic imaging; Tauopathies - metabolism; Tensors; Thalamus; Tomography; White Matter - diagnostic imaging; MRI; atypical Alzheimer's disease; DTI; FDG; tau; multimodal imaging; multivariate analysis
• ISSN: 1065-9471; 1097-0193
• DOI: 10.1002/hbm.24473

Alzheimer's disease (AD) can present with atypical clinical forms where the prominent domain of deficit is not memory, that is, atypical AD. Atypical AD patients show cortical atrophy on MRI, hypometabolism on [18F]fluorodeoxyglucose (FDG) PET, tau uptake on [18F]AV‐1451 PET, and white matter tract degeneration on diffusion tensor imaging (DTI). How these disease processes relate to each other locally and distantly remains unclear. We aimed to examine multimodal neuroimaging relationships in individuals with atypical AD, using univariate and multivariate techniques at region‐ and voxel‐level. Forty atypical AD patients underwent MRI, FDG‐PET, tau‐PET, beta‐amyloid PET, and DTI. Patients were all beta‐amyloid positive. Partial Pearson's correlations were performed between tau and FDG standardized uptake value ratios, gray matter MRI‐volumes and white matter tract fractional anisotropy. Sparse canonical correlation analysis was applied to identify multivariate relationships between the same quantities. Voxel‐level associations across modalities were also assessed. Tau showed strong local negative correlations with FDG metabolism in the occipital and frontal lobes. Tau in frontal and parietal regions was negatively associated with temporoparietal gray matter MRI‐volume. Fractional anisotropy in a set of posterior white matter tracts, including the splenium of the corpus callosum, cingulum, and posterior thalamic radiation, was negatively correlated with parietal and occipital tau, atrophy and, predominantly, with hypometabolism. These results support the view that tau is the driving force behind neurodegeneration in atypical AD, and that a breakdown in structural connectivity is related to cortical neurodegeneration, particularly hypometabolism.