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Amyloid staging models showed that regional abnormality occurs before global positivity. Several studies assumed that the trajectory of amyloid spread is homogeneous, but clinical evidence suggests that it is highly heterogeneous. We tested whether different amyloid-β (Aβ) patterns exist by applying clustering on negative scans and investigating their demographics, clinical, cognitive, and biomarkers correlates, and cognitive trajectories. 151 individuals from Geneva and Zurich cohorts with T1-MRI, negative Aβ positron emission tomography (PET,centiloid<12) and clinical assessment were included. N=123 underwent tau PET, and N=65 follow-up neuropsychological assessment. We performed k-means clustering using 33 Aβ regional Standardized Uptake Vales ratio. Demographics, clinical, cognitive, and biomarkers differences were investigated. Longitudinal cognitive changes by baseline cluster status were estimated using a linear mixed model. The cluster analysis identified two clusters: temporal predominant (TP) and cingulate predominant (CP). TP tau deposition was higher than CP. A trend for a higher cognitive decline in TP compared to CP was observed. This study suggests the existence of two Aβ deposition patterns in the earliest phases of Aβ accumulation, differently prone to tau pathology and cognitive decline.
Amyloid, 610 Medicine & health, 2717 Geriatrics and Gerontology, tau Proteins, 1309 Developmental Biology, 618.97, 1302 Aging, Tau Proteins, Alzheimer Disease, Humans, Amyloid-β, Cognitive Dysfunction / diagnostic imaging, Cognitive Dysfunction, Positron-Emission Tomography / methods, Amyloid beta-Peptides, 616.0757, Alzheimer Disease / pathology, 2800 General Neuroscience, 10181 Clinic for Nuclear Medicine, 11359 Institute for Regenerative Medicine (IREM), Alzheimer's disease, 2728 Neurology (clinical), Data-driven approach, Positron emission tomography (PET), Positron-Emission Tomography, Biomarkers
Amyloid, 610 Medicine & health, 2717 Geriatrics and Gerontology, tau Proteins, 1309 Developmental Biology, 618.97, 1302 Aging, Tau Proteins, Alzheimer Disease, Humans, Amyloid-β, Cognitive Dysfunction / diagnostic imaging, Cognitive Dysfunction, Positron-Emission Tomography / methods, Amyloid beta-Peptides, 616.0757, Alzheimer Disease / pathology, 2800 General Neuroscience, 10181 Clinic for Nuclear Medicine, 11359 Institute for Regenerative Medicine (IREM), Alzheimer's disease, 2728 Neurology (clinical), Data-driven approach, Positron emission tomography (PET), Positron-Emission Tomography, Biomarkers
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