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Distinct tau PET patterns in atrophy-defined subtypes of Alzheimer's disease
Rik Ossenkoppele 1 2, Chul Hyoung Lyoo 3, Carole H Sudre 4 5 6, Danielle van Westen 7, Hanna Cho 3, Young Hoon Ryu 7, Jae Yong Choi 8 9, Ruben Smith 1, Olof Strandberg 1, Sebastian Palmqvist 1, Eric Westman 10, Richard Tsai 11, Joel Kramer 11, Adam L Boxer 10, Maria L Gorno-Tempini 11, Renaud La Joie 11, Bruce L Miller 11, Gil D Rabinovici 11, Oskar Hansson 1 12
Abstract:
Introduction: Differential patterns of brain atrophy on structural magnetic resonance imaging (MRI) revealed four reproducible subtypes of Alzheimer's disease (AD): (1) "typical", (2) "limbic-predominant", (3) "hippocampal-sparing", and (4) "mild atrophy". We examined the neurobiological characteristics and clinical progression of these atrophy-defined subtypes.
Methods: The four subtypes were replicated using a clustering method on MRI data in 260 amyloid-β-positive patients with mild cognitive impairment or AD dementia, and we subsequently tested whether the subtypes differed on [18 F]flortaucipir (tau) positron emission tomography, white matter hyperintensity burden, and rate of global cognitive decline.
Results: Voxel-wise and region-of-interest analyses revealed the greatest neocortical tau load in hippocampal-sparing (frontoparietal-predominant) and typical (temporal-predominant) patients, while limbic-predominant patients showed particularly high entorhinal tau. Typical patients with AD had the most pronounced white matter hyperintensity load, and hippocampal-sparing patients showed the most rapid global cognitive decline.
Discussion: Our data suggest that structural MRI can be used to identify biologically and clinically meaningful subtypes of AD.
Methods: The four subtypes were replicated using a clustering method on MRI data in 260 amyloid-β-positive patients with mild cognitive impairment or AD dementia, and we subsequently tested whether the subtypes differed on [18 F]flortaucipir (tau) positron emission tomography, white matter hyperintensity burden, and rate of global cognitive decline.
Results: Voxel-wise and region-of-interest analyses revealed the greatest neocortical tau load in hippocampal-sparing (frontoparietal-predominant) and typical (temporal-predominant) patients, while limbic-predominant patients showed particularly high entorhinal tau. Typical patients with AD had the most pronounced white matter hyperintensity load, and hippocampal-sparing patients showed the most rapid global cognitive decline.
Discussion: Our data suggest that structural MRI can be used to identify biologically and clinically meaningful subtypes of AD.
PMID: 31672482
Free Full-Text: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7012375/
