期刊
NEURON
卷 104, 期 5, 页码 856-+出版社
CELL PRESS
DOI: 10.1016/j.neuron.2019.08.037
关键词
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资金
- NIH [K01AG055698, P50AG023501, P01AG019724]
- Tau Consortium
- Bluefield Project to Cure FTD
- Larry L. Hillblom Network Grant for the Prevention of Age-Associated Cognitive Decline [2014-A-004-NET]
- National Institute on Aging (NIA) [U24 AG21886]
Neurodegenerative diseases appear to progress by spreading via brain connections. Here we evaluated this transneuronal degeneration hypothesis by attempting to predict future atrophy in a longitudinal cohort of patients with behavioral variant frontotemporal dementia (bvFTD) and semantic variant primary progressive aphasia (svPPA). We determined patient-specific epicenters at baseline, located each patient's epicenters in the healthy functional connectome, and derived two region-wise graph theoretical metrics to predict future atrophy: (1) shortest path length to the epicenter and (2) nodal hazard, the cumulative atrophy of a region's first-degree neighbors. Using these predictors and baseline atrophy, we could accurately predict longitudinal atrophy in most patients. The regions most vulnerable to subsequent atrophy were functionally connected to the epicenter and had intermediate levels of baseline atrophy. These findings provide novel, longitudinal evidence that neurodegeneration progresses along connectional pathways and, further developed, could lead to network-based clinical tools for prognostication and disease monitoring.
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