Citations 3
Regional effects of gantenerumab on neuroimaging biomarkers in the DIAN‐TU‐001 trial
Chen, Charles D., Jack, Clifford R. , Koeppe, Robert, Hornbeck, Russ C. , Koudelis, Deborah, Keefe, Sarah , Aggarwal, Neelum T. , Bird, Thomas D. , Black, Sandra E., Chhatwal, Jasmeer P. , Day, Gregory S. , Farlow, Martin R. , Gauthier, Serge , Honig, Lawrence S., Xiong, Chengjie , Masellis, Mario, Méndez, Patricio Chrem, Ringman, John M. , Snider, B. Joy, Salloway, Stephen, Dyck, Christopher H. van , Klein, Gregory , Clifford, David B. , Hassenstab, Jason , Mills, Susan L., Perrin, Richard J., Supnet, Charlene , Wang, Guoqiao , Xiong, Chengjie , Team, for the DIAN‐TU Study, Jack, Clifford R , Day, Gregory S , Xiong, Chengjie , Chen, Charles D , Hassenstab, Jason , Supnet-Bell, Charlene , McCullough, Austin , Gordon, Brian A. , Joseph‐Mathurin, Nelly , McKay, Nicole S. , Hobbs, Diana A. , Flores, Shaney , Allegri, Ricardo , Berman, Sarah , Black, Sandra E. , Brooks, William S. , Fox, Nick C. , Honig, Lawrence S. , Hsiung, Ging‐Yuek Robin , Jucker, Mathias , Masters, Colin L. , Schofield, Peter R. , Shimada, Hiroyuki , Suzuki, Kazushi , Cruchaga, Carlos , Li, Yan , McDade, Eric , Morris, John C. , Bateman, Randall J. , Benzinger, Tammie L.S. , Team, for the DIAN‐TU Study
Alzheimer's & Dementia | July 15, 2025 | Volume: 21 | Issue: 7 | Pages: No page available
Abstract INTRODUCTION Monoclonal anti‐amyloid therapies are now accessible, but how these treatments influence changes within the brain is still not clear. We investigated overall and regional change in amyloid removal, glucose metabolism, and atrophy in trial participants with dominantly inherited Alzheimer's disease (DIAD). METHODS In the DIAN‐TU‐001 trial, 92 carriers received gantenerumab or placebo and underwent serial neuroimaging assessments including [ 11 C]‐Pittsburgh compound‐B (PiB) positron emission tomography (PET), [ 18 F]‐fluoro‐2‐deoxyglucose (FDG) PET, and magnetic resonance imaging (MRI). RESULTS Gantenerumab significantly reduced PiB‐PET uptake overall and in most regions and showed no changes in FDG‐PET or MRI measures. Drug effects were associated with baseline PiB‐PET uptake, and the largest effects occurred in medial regions. DISCUSSION Treated DIAD participants, and especially those with higher amyloid burden, showed a decrease in PiB‐PET uptake, which was more pronounced in the basal ganglia and medial frontal structures. These results may inform patient response and future drug trial design. Highlights Gantenerumab unevenly decreased Aβ burden as measured by PiB‐PET across brain regions. The strongest decrease in PiB‐PET uptake was in basal ganglia and medial frontal structures. Variable drug effect on Aβ was partly due to the amount of burden present before treatment. There was no regional effect on FDG‐PET metabolism or MRI volumetrics after 4 years.
Longitudinal cognitive performance of participants with sporadic early onset Alzheimer's disease from LEADS
Hammers, Dustin B. , Eloyan, Ani , Taurone, Alexander, Thangarajah, Maryanne, Gao, Sujuan , Polsinelli, Angelina J. , Kirby, Kala, Dage, Jeffrey L. , Aisen, Paul, Reman, Rema, Joie, Renaud La , Clark, David W. , Day, Gregory S. , Duara, Ranjan , Graff‐Radford, Neill R. , Grant, Ian , Honig, Lawrence S., Johnson, Erik C. B. , Masdeu, Joseph C. , Mendez, Mario F. , Onyike, Chiadi U. , Riddle, Meghan , Rogalskı, Emily , Salloway, Steven, Sha, Sharon J. , Turner, Raymond Scott , Wingo, Thomas S. , Carrillo, Marı́a C., Rabinovici, Gil D. , Apostolova, Liana G. , Carrillo, María C. , Day, Gregory S , La Joie, Renaud , Rabinovici, Gil D , Wingo, Thomas S , Dage, Jeffrey L , Hammers, Dustin B , Beckett, Laurel , Kirby, Kala, Nudelman, Kelly , Reman, Rema, Lagarde, Julien , Atri, Alireza , Duara, Ranjan , Honig, Lawrence S. , Jones, David T. , Masdeu, Joseph C , Womack, Kyle , Musiek, Erik , Salloway, Steve , Wolk, S. J. , Dickerson, Bradford Clark
Alzheimer's & Dementia | December 23, 2024 | Volume: 21 | Issue: 2 | Pages: No page available
Abstract INTRODUCTION Early‐onset Alzheimer's disease (EOAD) manifests prior to the age of 65, and affects 4%–8% of patients with Alzheimer's disease (AD). The current analyses sought to examine longitudinal cognitive trajectories of participants with early‐onset dementia. METHODS Data from 307 cognitively normal (CN) volunteer participants and those with amyloid‐positive EOAD or amyloid‐negative cognitive impairment (EOnonAD) were compared. Cognitive trajectories across a comprehensive cognitive battery spanning 42 months were examined using mixed‐effects modeling. RESULTS The EOAD group displayed worse cognition at baseline relative to EOnonAD and CN groups, and more aggressive declines in cognition over time. The largest effects were observed on measures of executive functioning domains, while memory declines were blunted in EOAD. DISCUSSION EOAD declined 2–4× faster than EOnonAD, and EOAD pathology is not restricted to memory networks. Early identification of deficits is critical to ensure that individuals with sporadic EOAD can be considered for treatment using disease‐modifying medications. Highlights Represents the most comprehensive longitudinal characterization of sporadic EOAD to date. The trajectory of cognitive declines was steep for EOAD participants and worse than for other groups. Executive functioning measures exhibited the greatest declines over time in EOAD.
Hexanucleotide repeat expansions in C9ORF72 in the spectrum of motor neuron diseases
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Neurology | July 27, 2012 | Volume: 79 | Issue: 9 | Pages: 878-882