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In Alzheimer's & dementia : the journal of the Alzheimer's Association

INTRODUCTION : Machine learning models were used to discover novel disease trajectories for autosomal dominant Alzheimer's disease.

METHODS : Longitudinal structural magnetic resonance imaging, amyloid positron emission tomography (PET), and fluorodeoxyglucose PET were acquired in 131 mutation carriers and 74 non-carriers from the Dominantly Inherited Alzheimer Network; the groups were matched for age, education, sex, and apolipoprotein ε4 (APOE ε4). A deep neural network was trained to predict disease progression for each modality. Relief algorithms identified the strongest predictors of mutation status.

RESULTS : The Relief algorithm identified the caudate, cingulate, and precuneus as the strongest predictors among all modalities. The model yielded accurate results for predicting future Pittsburgh compound B (R2  = 0.95), fluorodeoxyglucose (R2  = 0.93), and atrophy (R2  = 0.95) in mutation carriers compared to non-carriers.

DISCUSSION : Results suggest a sigmoidal trajectory for amyloid, a biphasic response for metabolism, and a gradual decrease in volume, with disease progression primarily in subcortical, middle frontal, and posterior parietal regions.

Luckett Patrick H, McCullough Austin, Gordon Brian A, Strain Jeremy, Flores Shaney, Dincer Aylin, McCarthy John, Kuffner Todd, Stern Ari, Meeker Karin L, Berman Sarah B, Chhatwal Jasmeer P, Cruchaga Carlos, Fagan Anne M, Farlow Martin R, Fox Nick C, Jucker Mathias, Levin Johannes, Masters Colin L, Mori Hiroshi, Noble James M, Salloway Stephen, Schofield Peter R, Brickman Adam M, Brooks William S, Cash David M, Fulham Michael J, Ghetti Bernardino, Jack Clifford R, Vöglein Jonathan, Klunk William, Koeppe Robert, Oh Hwamee, Su Yi, Weiner Michael, Wang Qing, Swisher Laura, Marcus Dan, Koudelis Deborah, Joseph-Mathurin Nelly, Cash Lisa, Hornbeck Russ, Xiong Chengjie, Perrin Richard J, Karch Celeste M, Hassenstab Jason, McDade Eric, Morris John C, Benzinger Tammie L S, Bateman Randall J, Ances Beau M


Pittsburgh compound B (PiB), “autosomal dominant Alzheimers disease (ADAD)”, fluorodeoxyglucose (FDG), machine learning, magnetic resonance imaging (MRI)