Jordi Pegueroles1, Eduard Vilaplana1, Victor Montal1, Frederic Sampedro2, Daniel Alcolea1, Maria Carmona-Iragui1, Jordi Clarimon1, Rafael Blesa1, Alberto Lleó1, Juan Fortea3. 1. Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau- Biomedical Research Institute Sant Pau-Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Spain. 2. Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau- Biomedical Research Institute Sant Pau-Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Spain; Nuclear Medicine Department, Hospital de la Santa Creu i Sant Pau-Biomedical Research Institute Sant Pau-Universitat Autònoma de Barcelona, Barcelona, Spain. 3. Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau- Biomedical Research Institute Sant Pau-Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, CIBERNED, Spain. Electronic address: jfortea@santpau.cat.
Abstract
INTRODUCTION: Brain structural changes in preclinical Alzheimer's disease (AD) are poorly understood. METHODS: We compared the changes in cortical thickness in the ADNI cohort during a 2-year follow-up between the NIA-AA preclinical AD stages defined by cerebrospinal fluid (CSF) biomarker levels. We also analyzed the correlation between baseline CSF biomarkers and cortical atrophy rates. RESULTS: At follow-up, stage 1 subjects showed reduced atrophy rates in medial frontal areas and precuneus compared to stage 0 subjects, whereas stage 2/3 subjects presented accelerated atrophy in medial temporal structures. Low CSF Aβ1-42 levels were associated with reduced atrophy rates in subjects with normal tau levels and high CSF tau levels with accelerated atrophy only in subjects with low Aβ1-42 levels. DISCUSSION: Our longitudinal data confirm a biphasic trajectory of changes in brain structure in preclinical AD. These have implications in AD trials, both in patient selection and the use of MRI as a surrogate marker of efficacy.
INTRODUCTION: Brain structural changes in preclinical Alzheimer's disease (AD) are poorly understood. METHODS: We compared the changes in cortical thickness in the ADNI cohort during a 2-year follow-up between the NIA-AA preclinical AD stages defined by cerebrospinal fluid (CSF) biomarker levels. We also analyzed the correlation between baseline CSF biomarkers and cortical atrophy rates. RESULTS: At follow-up, stage 1 subjects showed reduced atrophy rates in medial frontal areas and precuneus compared to stage 0 subjects, whereas stage 2/3 subjects presented accelerated atrophy in medial temporal structures. Low CSF Aβ1-42 levels were associated with reduced atrophy rates in subjects with normal tau levels and high CSF tau levels with accelerated atrophy only in subjects with low Aβ1-42 levels. DISCUSSION: Our longitudinal data confirm a biphasic trajectory of changes in brain structure in preclinical AD. These have implications in AD trials, both in patient selection and the use of MRI as a surrogate marker of efficacy.
Authors: Jian W Dong; Ileana O Jelescu; Benjamin Ades-Aron; Dmitry S Novikov; Kent Friedman; James S Babb; Ricardo S Osorio; James E Galvin; Timothy M Shepherd; Els Fieremans Journal: Neurobiol Aging Date: 2020-01-23 Impact factor: 4.673
Authors: Claire André; Stéphane Rehel; Elizabeth Kuhn; Brigitte Landeau; Inès Moulinet; Edelweiss Touron; Valentin Ourry; Gwendoline Le Du; Florence Mézenge; Clémence Tomadesso; Robin de Flores; Alexandre Bejanin; Siya Sherif; Nicolas Delcroix; Alain Manrique; Ahmed Abbas; Natalie L Marchant; Antoine Lutz; Olga M Klimecki; Fabienne Collette; Eider M Arenaza-Urquijo; Géraldine Poisnel; Denis Vivien; Françoise Bertran; Vincent de la Sayette; Gaël Chételat; Géraldine Rauchs Journal: JAMA Neurol Date: 2020-06-01 Impact factor: 18.302
Authors: Brett M Frye; Suzanne Craft; Thomas C Register; Rachel N Andrews; Susan E Appt; Mara Z Vitolins; Beth Uberseder; Marnie G Silverstein-Metzler; Haiying Chen; Christopher T Whitlow; Jeongchul Kim; Richard A Barcus; Samuel N Lockhart; Siobhan Hoscheidt; Brandon M Say; Sarah E Corbitt; Carol A Shively Journal: Alzheimers Dement Date: 2020-12-03 Impact factor: 21.566
Authors: Nicholas M Vogt; Jack F V Hunt; Nagesh Adluru; Yue Ma; Carol A Van Hulle; Douglas C Dean Iii; Steven R Kecskemeti; Nathaniel A Chin; Cynthia M Carlsson; Sanjay Asthana; Sterling C Johnson; Gwendlyn Kollmorgen; Richard Batrla; Norbert Wild; Katharina Buck; Henrik Zetterberg; Andrew L Alexander; Kaj Blennow; Barbara B Bendlin Journal: Alzheimers Dement Date: 2021-05-13 Impact factor: 16.655
Authors: Amanda Jimenez; Jordi Pegueroles; María Carmona-Iragui; Eduard Vilaplana; Victor Montal; Daniel Alcolea; Laura Videla; Ignacio Illán-Gala; Adriana Pané; Anna Casajoana; Olivia Belbin; Jordi Clarimón; Violeta Moizé; Josep Vidal; Alberto Lleó; Juan Fortea; Rafael Blesa Journal: Oncotarget Date: 2017-10-31
Authors: Eduard Vilaplana; Elena Rodriguez-Vieitez; Daniel Ferreira; Victor Montal; Ove Almkvist; Anders Wall; Alberto Lleó; Eric Westman; Caroline Graff; Juan Fortea; Agneta Nordberg Journal: Neurology Date: 2020-04-14 Impact factor: 9.910