Tau and atrophy: domain-specific relationships with cognition.
Leonardino A. Digma,John Madsen,Emilie T. Reas,Anders M. Dale,James B. Brewer,Sarah J. Banks,Alzheimer’s Disease Neuroimaging Initiative +6 more
TLDR
The findings indicate that AD-related decline in domain-specific cognitive performance reflects underlying progression of tau and atrophy into associated brain circuits, and suggest that tau-PET may have better sensitivity to this decline than MRI-derived measures of cortical thickness.Abstract:
Late-onset Alzheimer’s disease (AD) is characterized by primary memory impairment, which then progresses towards severe deficits across cognitive domains. Here, we report how performance in cognitive domains relates to patterns of tau deposition and cortical thickness. We analyzed data from 131 amyloid-β positive participants (55 cognitively normal, 46 mild cognitive impairment, 30 AD) of the Alzheimer’s Disease Neuroimaging Initiative who underwent magnetic resonance imaging (MRI), flortaucipir (FTP) positron emission tomography, and neuropsychological testing. Surface-based vertex-wise and region-of-interest analyses were conducted between FTP and cognitive test scores, and between cortical thickness and cognitive test scores. FTP and thickness were differentially related to cognitive performance in several domains. FTP-cognition associations were more widespread than thickness-cognition associations. Further, FTP-cognition patterns reflected cortical systems that underlie different aspects of cognition. Our findings indicate that AD-related decline in domain-specific cognitive performance reflects underlying progression of tau and atrophy into associated brain circuits. They also suggest that tau-PET may have better sensitivity to this decline than MRI-derived measures of cortical thickness.read more
Citations
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The Cortical Signature of Alzheimer's Disease: Regionally Specific Cortical Thinning Relates to Symptom Severity in Very Mild to Mild AD Dementia and is Detectable in Asymptomatic Amyloid-Positive Individuals
Bradford C. Dickerson,Akram Bakkour,David H. Salat,Eric Feczko,Jenni Pacheco,Douglas N. Greve,Fran Grodstein,Christopher I. Wright,Christopher I. Wright,Deborah Blacker,H. Diana Rosas,Reisa A. Sperling,Alireza Atri,John H. Growdon,Bradley T. Hyman,John C. Morris,Bruce Fischl,Bruce Fischl,Randy L. Buckner,Randy L. Buckner +19 more
TL;DR: Results demonstrate a reliably quantifiable in vivo signature of abnormal cortical anatomy in AD, which parallels known regional vulnerability to AD neuropathology, and may provide a powerful methodological framework for studies of neuropsychiatric diseases.
Journal ArticleDOI
Patient-centered connectivity-based prediction of tau pathology spread in Alzheimer's disease
Nicolai Franzmeier,Anna Dewenter,Lukas Frontzkowski,Martin Dichgans,Martin Dichgans,Anna Rubinski,Julia Neitzel,Ruben Smith,Olof Strandberg,Rik Ossenkoppele,Rik Ossenkoppele,Katharina Buerger,Katharina Buerger,Marco Duering,Oskar Hansson,Michael Ewers,Michael Ewers +16 more
TL;DR: A connectivity-based, patient-centered tau spreading model improved the assessment of tau accumulation rates compared to Braak stage–specific readouts and reduced sample sizes by ~40% in simulated tau-targeting interventions, demonstrating utility in clinical trials.
Journal ArticleDOI
Tauvid™: The First FDA-Approved PET Tracer for Imaging Tau Pathology in Alzheimer’s Disease
TL;DR: The approval of Tauvid marks a step forward in the field of AD research and opens up opportunities for second-generation tau tracers to advance tau PET imaging in the clinic.
Journal ArticleDOI
Spatial Relationships between Molecular Pathology and Neurodegeneration in the Alzheimer's Disease Continuum.
Leonardo Iaccarino,Renaud La Joie,Lauren Edwards,Amelia Strom,Daniel R. Schonhaut,Daniel R. Schonhaut,Rik Ossenkoppele,Rik Ossenkoppele,Julie Pham,Taylor J. Mellinger,Mustafa Janabi,Suzanne L. Baker,David N Soleimani-Meigooni,David N Soleimani-Meigooni,Howard J. Rosen,Bruce L. Miller,William J. Jagust,William J. Jagust,Gil D. Rabinovici +18 more
TL;DR: Molecular pathology and neurodegeneration showed a progressive overlap along AD course, indicating shared vulnerabilities or synergistic toxic mechanisms.
Journal ArticleDOI
Tau pathology and relative cerebral blood flow are independently associated with cognition in Alzheimer’s disease
Denise Visser,Emma E. Wolters,Sander C.J. Verfaillie,Emma M. Coomans,Tessa Timmers,Hayel Tuncel,Juhan Reimand,Ronald Boellaard,Albert D. Windhorst,Philip Scheltens,Wiesje M. van der Flier,Rik Ossenkoppele,Rik Ossenkoppele,Bart N.M. van Berckel +13 more
TL;DR: Tau pathology and low rCBF were both independently associated with worse cognitive performance and indicate that each biomarker may independently contribute to cognitive impairment in Alzheimer’s disease.
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NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease
Clifford R. Jack,David A. Bennett,Kaj Blennow,Maria C. Carrillo,Billy Dunn,Samantha Budd Haeberlein,David M. Holtzman,William J. Jagust,Frank Jessen,Jason Karlawish,Enchi Liu,José Luis Molinuevo,Thomas J. Montine,Creighton H. Phelps,Katherine P. Rankin,Christopher C. Rowe,Philip Scheltens,Eric Siemers,Heather M. Snyder,Reisa A. Sperling,Cerise L Elliott,Eliezer Masliah,Laurie M. Ryan,Nina Silverberg +23 more
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