Greater amyloid burden in cognitive networks in preclinical Alzheimer's disease

Background In preclinical Alzheimer's disease (pAD), regional patterns of amyloid-β (Aβ) deposition are well characterized but have not been systematically compared across functional networks. Objective Determine how Aβ accumulation in functional networks (“network-amyloid burden” [NAB]) varies by age, network type (cognitive versus non-cognitive), and Aβ status (Aβ+/Aβ-), and relates to cognition. Methods 157 cognitively unimpaired adults (45–84 years; n = 28 Aβ+ per neuroradiological read) underwent brain MRI, amyloid PET ( 18 F-florbetapir), and neuropsychological testing. NAB was calculated as the mean standard uptake value ratio within 7 networks categorized as cognitive (fronto-parietal, default mode, ventral and dorsal attention, limbic) or non-cognitive (somato-motor, visual). Linear mixed models tested how NAB varies across age, networks (by type and each separately), Aβ status, and their interactions, and relationships between NAB and cognition. Results NAB increased with age, most prominently in fronto-parietal and default mode networks. NAB was higher in cognitive than non-cognitive networks, and this difference was more pronounced in Aβ+ individuals. NAB was not significantly associated with cognition. Conclusions Cognitive brain networks are more vulnerable to amyloid accumulation with aging and in pAD than non-cognitive networks. Cognitive NAB may be useful for early detection and as a target for intervention in pAD.