Nicholas M Vogt1, Jack F V Hunt1, Nagesh Adluru2, Yue Ma1, Carol A Van Hulle1, Douglas C Dean Iii2,3,4, Steven R Kecskemeti2, Nathaniel A Chin1, Cynthia M Carlsson1,5, Sanjay Asthana1,5, Sterling C Johnson1,5, Gwendlyn Kollmorgen6, Richard Batrla7, Norbert Wild6, Katharina Buck6, Henrik Zetterberg8,9,10,11, Andrew L Alexander2,4, Kaj Blennow8,9, Barbara B Bendlin1. 1. Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA. 2. Waisman Laboratory for Brain Imaging and Behavior, Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA. 3. Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA. 4. Department of Medical Physics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA. 5. Geriatric Research Education and Clinical Center, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin, USA. 6. Roche Diagnostics GmbH, Penzberg, Germany. 7. Roche Diagnostics International AG, Rotkreuz, Switzerland. 8. Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden. 9. Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden. 10. Department of Neurodegenerative Disease, UCL Institute of Neurology, London, UK. 11. UK Dementia Research Institute, University College London, London, UK.
Abstract
INTRODUCTION: Neurite orientation dispersion and density imaging (NODDI), a multi-compartment diffusion-weighted imaging (DWI) model, may be useful for detecting early cortical microstructural alterations in Alzheimer's disease prior to cognitive impairment. METHODS: Using neuroimaging (NODDI and T1-weighted magnetic resonance imaging [MRI]) and cerebrospinal fluid (CSF) biomarker data (measured using Elecsys® CSF immunoassays) from 219 cognitively unimpaired participants, we tested the main and interactive effects of CSF amyloid beta (Aβ)42 /Aβ40 and phosphorylated tau (p-tau) on cortical NODDI metrics and cortical thickness, controlling for age, sex, and apolipoprotein E ε4. RESULTS: We observed a significant CSF Aβ42 /Aβ40 × p-tau interaction on cortical neurite density index (NDI), but not orientation dispersion index or cortical thickness. The directionality of these interactive effects indicated: (1) among individuals with lower CSF p-tau, greater amyloid burden was associated with higher cortical NDI; and (2) individuals with greater amyloid and p-tau burden had lower cortical NDI, consistent with cortical neurodegenerative changes. DISCUSSION: NDI is a particularly sensitive marker for early cortical changes that occur prior to gross atrophy or development of cognitive impairment.
INTRODUCTION: Neurite orientation dispersion and density imaging (NODDI), a multi-compartment diffusion-weighted imaging (DWI) model, may be useful for detecting early cortical microstructural alterations in Alzheimer's disease prior to cognitive impairment. METHODS: Using neuroimaging (NODDI and T1-weighted magnetic resonance imaging [MRI]) and cerebrospinal fluid (CSF) biomarker data (measured using Elecsys® CSF immunoassays) from 219 cognitively unimpaired participants, we tested the main and interactive effects of CSF amyloid beta (Aβ)42 /Aβ40 and phosphorylated tau (p-tau) on cortical NODDI metrics and cortical thickness, controlling for age, sex, and apolipoprotein E ε4. RESULTS: We observed a significant CSF Aβ42 /Aβ40 × p-tau interaction on cortical neurite density index (NDI), but not orientation dispersion index or cortical thickness. The directionality of these interactive effects indicated: (1) among individuals with lower CSF p-tau, greater amyloid burden was associated with higher cortical NDI; and (2) individuals with greater amyloid and p-tau burden had lower cortical NDI, consistent with cortical neurodegenerative changes. DISCUSSION: NDI is a particularly sensitive marker for early cortical changes that occur prior to gross atrophy or development of cognitive impairment.
Authors: Victor Montal; Eduard Vilaplana; Daniel Alcolea; Jordi Pegueroles; Ofer Pasternak; Sofia González-Ortiz; Jordi Clarimón; María Carmona-Iragui; Ignacio Illán-Gala; Estrella Morenas-Rodríguez; Roser Ribosa-Nogué; Isabel Sala; María-Belén Sánchez-Saudinós; Maite García-Sebastian; Jorge Villanúa; Andrea Izagirre; Ainara Estanga; Mirian Ecay-Torres; Ane Iriondo; Montserrat Clerigue; Mikel Tainta; Ana Pozueta; Andrea González; Eloy Martínez-Heras; Sara Llufriu; Rafael Blesa; Pascual Sanchez-Juan; Pablo Martínez-Lage; Alberto Lleó; Juan Fortea Journal: Alzheimers Dement Date: 2017-10-31 Impact factor: 21.566
Authors: Clifford R Jack; Heather J Wiste; Terry M Therneau; Stephen D Weigand; David S Knopman; Michelle M Mielke; Val J Lowe; Prashanthi Vemuri; Mary M Machulda; Christopher G Schwarz; Jeffrey L Gunter; Matthew L Senjem; Jonathan Graff-Radford; David T Jones; Rosebud O Roberts; Walter A Rocca; Ronald C Petersen Journal: JAMA Date: 2019-06-18 Impact factor: 56.272
Authors: Jordi Pegueroles; Eduard Vilaplana; Victor Montal; Frederic Sampedro; Daniel Alcolea; Maria Carmona-Iragui; Jordi Clarimon; Rafael Blesa; Alberto Lleó; Juan Fortea Journal: Alzheimers Dement Date: 2016-09-28 Impact factor: 21.566
Authors: Stephen M Smith; Mark Jenkinson; Heidi Johansen-Berg; Daniel Rueckert; Thomas E Nichols; Clare E Mackay; Kate E Watkins; Olga Ciccarelli; M Zaheer Cader; Paul M Matthews; Timothy E J Behrens Journal: Neuroimage Date: 2006-04-19 Impact factor: 6.556
Authors: Philip S J Weston; Ivor J A Simpson; Natalie S Ryan; Sebastien Ourselin; Nick C Fox Journal: Alzheimers Res Ther Date: 2015-07-01 Impact factor: 6.982
Authors: Andreana Benitez; Jens H Jensen; Kathryn Thorn; Siddhartha Dhiman; Stephanie Fountain-Zaragoza; William J Rieter; Maria Vittoria Spampinato; Eric D Hamlett; Paul J Nietert; Maria de Fatima Falangola; Joseph A Helpern Journal: Ann Neurol Date: 2022-03-30 Impact factor: 11.274
Authors: Akram Zamani; Adam K Walker; Ben Rollo; Katie L Ayers; Raysha Farah; Terence J O'Brien; David K Wright Journal: Neuroimage Clin Date: 2022-04-22 Impact factor: 4.891