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- W4256146280 abstract "Neurodegeneration in Alzheimer's Disease appears more closely related to regional deposition of tau than amyloid. What is unclear is how local and global tau combine to drive subsequent atrophy. Here we tested whether a network-based model of tau could improve our prediction of longitudinal gray matter atrophy based on a baseline Flortaucipir PET scan. 21 patients who met NIA-AA criteria for AD dementia likely due to AD were studied (age = 63 ± 9, MMSE = 24 ± 4 at baseline). At baseline, patients received structural MRI and PET scans for Flortaucipir and PIB. All patients received followup structural MRI (448+-102 days). PET Standard Uptake Volume Ratio (SUVR) values were calculated by normalizing to cerebellar cortex for PIB/inferior cerebellar cortex for Flortaucipir. Structural MRIs were assessed for longitudinal atrophy using SPM12 serial registration. To perform network modeling, we derived the average functional connectome from task-free fMRI of 75 healthy older subjects (age = 68), calculating the timeseries correlation between 214 regions from the Brainnetome atlas. We determined each patient's tailored disease “epicenter” by calculating the mean Flortaucipir for the 214 regions and correlating this vector with a simulated model of network spread into all regions, originating from a single region. We labeled the region with the maximal correlation as the epicenter. We used a unified mixed effect model (214 regions x 21 subjects = 4494 entries) to predict regional longitudinal atrophy based on baseline Flortaucipir and shortest network pathlength to the epicenter, with covariates for age, sex, clinical dementia rating, interscan interval, and Euclidean distance from epicenter, with random intercepts for node identity and subject identity. Epicenters were identified in the medial temporal lobe (hippocampus and parahippocampal gyrus), inferior temporal lobe, and orbitofrontal cortex (Figure 1). Our model was a highly accurate predictor of regional atrophy (r2=0.68) with significant contributions from regional baseline Flortaucipir (t=-26.12) and only a minor contribution from shortest path to epicenter (t=1.99)." @default.
- W4256146280 created "2022-05-12" @default.
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- W4256146280 date "2018-07-01" @default.
- W4256146280 modified "2023-10-16" @default.
- W4256146280 title "IC‐P‐029: PATIENT‐TAILORED PREDICTIONS OF GRAY MATTER ATROPHY IN ALZHEIMER'S DISEASE BASED ON BASELINE FLORTAUCIPIR AND CONNECTOME‐BASED SPREAD" @default.
- W4256146280 doi "https://doi.org/10.1016/j.jalz.2018.06.2093" @default.
- W4256146280 hasPublicationYear "2018" @default.
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