Journal Article10.1002/alz.13160
Profiling baseline performance on the Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) cohort near the midpoint of data collection.
Dustin B Hammers,Ani Eloyan,Alexander J. Taurone,Laurel A. Beckett,Su Gao,P. Aisen,Jeffrey L. Dage,Tatiana Foroud,P. Griffin,Lea T. Grinberg,Clifford R. Jack,Joel H. Kramer,Robert A. Koeppe,Walter A. Kukull,N. Mundada,Renaud La Joie,David N Soleimani-Meigooni,Leonardo Iaccarino,Melissa E. Murray,Kelly N.H. Nudelman,Angelina J. Polsinelli,Malia Rumbaugh,Arthur W. Toga,Alexandra Touroutoglou,Prashanthi Vemuri,Alireza Atri,Gregory S. Day,Ranjan Duara,Neill R. Graff-Radford,Lawrence S. Honig,David T. Jones,Joseph C. Masdeu,Mario F. Mendez,Kyle B. Womack,Erik S. Musiek,Chiadi U. Onyike,Meghan Riddle,Emily Rogalski,Stephen Salloway,Sharon J. Sha,R. Scott Turner,Thomas S. Wingo,David A. Wolk,Maria C. Carrillo,Bradford C. Dickerson,Gil D. Rabinovici,Liana G. Apostolova +46 more
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TL;DR: The most comprehensive baseline characterization of sporadic early-onset Alzheimer's disease (EOAD) in the United States to date is presented in this article , showing that cognitive performance was worse for EOAD than other groups, and EOAD participants were apolipoprotein E (APOE) ε4 homozygotes at higher rates.
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Abstract: OBJECTIVE
The Longitudinal Early-Onset Alzheimer's Disease Study (LEADS) seeks to provide comprehensive understanding of early-onset Alzheimer's disease (EOAD; onset <65 years), with the current study profiling baseline clinical, cognitive, biomarker, and genetic characteristics of the cohort nearing the data-collection mid-point.
METHODS
Data from 371 LEADS participants were compared based on diagnostic group classification (cognitively normal [n = 89], amyloid-positive EOAD [n = 212], and amyloid-negative early-onset non-Alzheimer's disease [EOnonAD; n = 70]).
RESULTS
Cognitive performance was worse for EOAD than other groups, and EOAD participants were apolipoprotein E (APOE) ε4 homozygotes at higher rates. An amnestic presentation was common among impaired participants (81%), with several clinical phenotypes present. LEADS participants generally consented at high rates to optional trial procedures.
CONCLUSIONS
We present the most comprehensive baseline characterization of sporadic EOAD in the United States to date. EOAD presents with widespread cognitive impairment within and across clinical phenotypes, with differences in APOE ε4 allele carrier status appearing to be relevant.
HIGHLIGHTS
Findings represent the most comprehensive baseline characterization of sporadic early-onset Alzheimer's disease (EOAD) to date. Cognitive impairment was widespread for EOAD participants and more severe than other groups. EOAD participants were homozygous apolipoprotein E (APOE) ε4 carriers at higher rates than the EOnonAD group. Amnestic presentation predominated in EOAD and EOnonAD participants, but other clinical phenotypes were present.
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Citations
Amyloid and tau-PET in early-onset AD: Baseline data from the Longitudinal Early-onset Alzheimer's Disease Study (LEADS).
Hanna Cho,N. Mundada,Liana G. Apostolova,Maria C. Carrillo,Ranjani Shankar,Alinda N Amuiri,Ehud Zeltzer,Charles Windon,David N Soleimani-Meigooni,Jeremy A. Tanner,Courtney Lawhn Heath,Orit H. Lesman-Segev,P. Aisen,Ani Eloyan,Hye Sun Lee,Dustin B Hammers,Kala Kirby,Jeffrey L. Dage,Anne Fagan,Tatiana Foroud,Lea T. Grinberg,Clifford R. Jack,Joel Kramer,Walter A. Kukull,Melissa E. Murray,Kelly N.H. Nudelman,Arthur W. Toga,Prashanthi Vemuri,Alireza Atri,Gregory S. Day,Ranjan Duara,Neill R. Graff-Radford,Lawrence S. Honig,David T. Jones,Joseph Masdeu,Mario F. Mendez,Erik S. Musiek,Chiadi U. Onyike,Meghan Riddle,Emily Rogalski,Stephen Salloway,Sharon Sha,R. Scott Turner,Thomas S. Wingo,David A. Wolk,Robert A. Koeppe,Leonardo Iaccarino,Bradford C. Dickerson,Renaud La Joie,Gil D. Rabinovici +49 more
TL;DR: Baseline amyloid- and tau-PET data from LEADS provide evidence for amyloid- and tau-PET positivity in a majority of EOAD participants and highlight the potential utility of tau-PET in characterizing disease heterogeneity and advancing therapeutic interventions.
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Longitudinal clinical, cognitive, and biomarker profiles in dominantly inherited versus sporadic early-onset Alzheimer’s disease.
Jorge J. Llibre-Guerra,Leonardo Iaccarino,Dean W. Coble,Lauren Edwards,Yan Li,Eric McDade,Amelia Strom,Brian A. Gordon,N. Mundada,Suzanne E. Schindler,Elena Tsoy,Yinjiao Ma,Ruijin Lu,Anne M Fagan,Tammie L.S. Benzinger,David N Soleimani-Meigooni,Andrew J. Aschenbrenner,Zachary A. Miller,Guoqiao Wang,Joel H Kramer,Jason Hassenstab,Howard J. Rosen,John C Morris,Bruce L. Miller,Chengjie Xiong,R. Perrino,Ricardo F. Allegri,Patricio Chrem,Ezequiel Surace,Sarah B. Berman,Jasmeer P. Chhatwal,C. L. Masters,Marty Farlow,Mathias Jucker,Johannes Levin,Nick C. Fox,Gregory S. Day,Maria Luisa Gorno-Tempini,Adam L. Boxer,Renaud La Joie,Gil D Rabinovici,Randall J. Bateman +41 more
TL;DR: Sporadic early onset is best distinguished from dominantly inherited by later age at onset, high frequency of atypical clinical presentations and worse executive performance at baseline, and shared pathways in longitudinal clinical decline and CSF biomarkers suggest potential common therapeutic targets for both populations.
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Medial temporal lobe atrophy patterns in early- versus late-onset amnestic Alzheimer’s disease
Anika Wuestefeld,Alexa Pichet Binette,Danielle van Westen,Olof Strandberg,Erik Stomrud,Niklas Mattsson-Carlgren,Shorena Janelidze,Ruben Smith,Sebastian Palmqvist,Hannah Baumeister,David Berron,Paul A. Yushkevich,Oskar Hansson,Nicola Spotorno,Lem Wisse +14 more
TL;DR: MTL atrophy patterns in early- versus late-onset amnestic Alzheimer’s disease show similarities across groups, although LOAD exhibits thinner entorhinal cortices and lower white matter hyperintensity.
Medial temporal lobe atrophy patterns in early-versus late-onset amnestic Alzheimer’s disease
Anika Wuestefeld,Alexa Pichet Binette,Danielle van Westen,Olof Strandberg,Erik Stomrud,Niklas Mattsson-Carlgren,Shorena Janelidze,Ruben Smith,Sebastian Palmqvist,Hannah Baumeister,David Berron,Paul A. Yushkevich,Oskar Hansson,Nicola Spotorno,Laura E M Wisse +14 more
TL;DR: This study examines medial temporal lobe atrophy in early-onset versus late-onset amnestic Alzheimer's disease, finding similar atrophy patterns and levels of tau pathology across both groups, with differences in specific subregions and co-pathologies.
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