Cortical asymmetry in autosomal dominant Alzheimer’s disease progression

The cortical asymmetry index evaluates the cortical thickness asymmetry between hemispheres. We investigated cortical asymmetry index in asymptomatic and symptomatic mutation carriers of autosomal dominant Alzheimer's disease to explore the brain asymmetry within the Alzheimer's disease continuum. Sixty baseline T1-weighted MRI scans were obtained from the Clinic Barcelona cohort. Baseline and longitudinal MRI data from 564 participants within the dominantly inherited Alzheimer network observational study were used as an independent, confirmatory cohort. Cerebrospinal fluid and plasma neurofilament light chain levels were included when available. Cortical thickness was calculated using Freesurfer and cortical asymmetry index was calculated via an open-source pipeline. Cross-sectional analyses examined cortical asymmetry index differences based on clinical classification and <i>APOE</i> ε<i>4</i> status, adjusting for age, sex and estimated years from onset, while correlations were assessed with age, estimated years from onset, mini-mental state examination scores, and neurofilament light. Longitudinal cortical asymmetry index evolution was modelled using generalized additive models in the dominantly inherited Alzheimer network observational study cohort, incorporating age, sex, and the interaction between group and estimated years from onset. The cortical asymmetry index successfully distinguished asymptomatic mutation carrier and symptomatic mutation carriers from healthy controls in the Clinic Barcelona cohort and symptomatic mutation carriers from controls in dominantly inherited Alzheimer network observational study. Higher cortical asymmetry index in mutation carriers (asymptomatic mutation carrier and symptomatic mutation carriers combined) and in symptomatic mutation carriers were associated with higher plasma neurofilament light levels, a closer proximity to symptom onset, and lower mini-mental state examination in the Clinic Barcelona cohort. In the dominantly inherited Alzheimer network observational study cohort, mutation carriers exhibited increased cortical asymmetry index compared to controls and correlated with elevated neurofilament light (plasma and Cerebrospinal fluid), lower mini-mental state examination, and a closer proximity to symptom onset. <i>APOE3/3</i> carriers showed greater asymmetry than other <i>APOE</i> genotypes and significant cortical asymmetry index differences between asymptomatic mutation carrier and symptomatic mutation carriers. Longitudinally, cortical asymmetry index increased over time significantly in symptomatic mutation carriers. These findings underscore brain asymmetry as a potential biomarker for early Alzheimer's disease progression in autosomal dominant Alzheimer's disease, with implications for detection and monitoring tracking disease-related neuroanatomical changes.

Authors

Institutions

Publication Details

Journal
Brain Communications
Published
2025-12-18
DOI
https://doi.org/10.1093/braincomms/fcaf488
Primary Topic
Functional Brain Connectivity Studies
Type
article
Field-Weighted Citation Impact
0.00
Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
OCT
article

Cortical asymmetry in autosomal dominant Alzheimer’s disease progression

Yamile Bocanegra, Stephen Salloway, James M. Noble, Nicole S. McKay et al.
Brain Communications
Functional Brain Connectivity Studies
article

Cortical asymmetry in autosomal dominant Alzheimer’s disease progression

Yamile Bocanegra, Stephen Salloway, James M. Noble, Nicole S. McKay, Neus Falgàs, Jacqui Smith, Allan Levey, Celeste M M. Karch, Jessica Banks, Richard J. Perrin, Manu S. Goyal, Ezequiel Surace, Paolo Vitali, Emma Devenney, Ana Baena, Nicholas T. Seyfried, Randall John Bateman, Sarah Berman, Christian la Fougère, Anne M. Fagan, Erin Franklin, Yoshiki Niimi, Kelley Jackson, Jonathan Vöglein, Andrei G. Vlassenko, Jinbin Xu, Mariana Martin, David Fernando Aguillon, Johannes Levin, Christoph Laske, Ulrike Obermueller, Takanobu Ishiguro, Charlene Supnet, David M. Cash, Takeshi Ikeuchi, Austin McCullough, Kensaku Kasuga, Cortaiga Hellm, William S. Brooks, Alisha Daniels, Joyce Nicklaus, Colin L. Masters, Francisco Lopera, Bryce Baker, Deborah Koudelis, Parinaz Massoumzadeh, Ellen Ziegemeier, Snežana Ikonomović, Patricio Chrem, Gina Jerome, Elke Kuder-Buletta, Matthew Minton, Gregory Scott Day, Emily Gremminger, Ricardo Allegri, Eric McDade, Nicolas R. Barthélemy, Danielle M. Picarello, Martin R. Farlow, Sarah Keefe, Diana A. Hobbs, Carlos C Cruchaga, Edward D. Huey, Yan Li, Brian Fulton‐Howard, Charles D. Chen, Natalie S. Ryan, John M. Ringman, Jalen Scott, Andrew J. Aschenbrenner, Jasmeer P. Chhatwal, David M. Holtzman, Russ C. Hornbeck, Christine Pulizos, Edita Sabaredzovic, Diana Esteller-Gauxax, Jae Hong Lee, Yuzheng Nie, Ashlee Simmons, Jacqueline Rizzo, Patricio Chrem Méndez, Brian A. Gordon, Beatriz Muries Bosch, Neill R Graff-Radford, Guoqiao Wang, Ana Luisa Sosa Ortíz, Ralph Martins, Núria Bargalló, Yudy Milena Leon, Courtney Maa, Yvonne Rödenbeck, Karina Skrbec, Reda Timofejavaite, Angela Ziegemeier, Jamie Bartzel, Mathias Jucker, Raquel Sánchez-Valle, John C Morris, Chengie Xiong, Sergi Borrego-Écija, Yong Wang, Hiroshi Mori, Guadalupe Fernández-Villullas, Michio Senda, Agnès Pérez-Millan, Nick C Fox, Nelly Joseph-Mathurin, Silvia Vazquez, Laura Ramirez, Jason Hassenstab, Albert Lladó, Jacob Marsh, Alan E Renton, Susanne Graber-Sultan, Sarah Stout, Kenji Ishii, Xiong Xu, Jonathan Vӧglein, Laura Courtney, Tammie L S Benzinger, Alison M Goate, Qing Wang, Shaney Flores, Erik C B Johnson, Laura Serna, Gerald Reischl, Jennifer Stauber, Jorge J Llibre-Guerra, Adrià Tort-Merino, Ruijin Lu, Laura Ibanez, Anna Antonell, Allison Chen, The Dominantly Inherited Alzheimer Network (DIAN), Jee Hoon Roh, Jacob A Bechara, Peter R Schofield, Mircea Balasa
article en

Abstract

The cortical asymmetry index evaluates the cortical thickness asymmetry between hemispheres. We investigated cortical asymmetry index in asymptomatic and symptomatic mutation carriers of autosomal dominant Alzheimer's disease to explore the brain asymmetry within the Alzheimer's disease continuum. Sixty baseline T1-weighted MRI scans were obtained from the Clinic Barcelona cohort. Baseline and longitudinal MRI data from 564 participants within the dominantly inherited Alzheimer network observational study were used as an independent, confirmatory cohort. Cerebrospinal fluid and plasma neurofilament light chain levels were included when available. Cortical thickness was calculated using Freesurfer and cortical asymmetry index was calculated via an open-source pipeline. Cross-sectional analyses examined cortical asymmetry index differences based on clinical classification and <i>APOE</i> ε<i>4</i> status, adjusting for age, sex and estimated years from onset, while correlations were assessed with age, estimated years from onset, mini-mental state examination scores, and neurofilament light. Longitudinal cortical asymmetry index evolution was modelled using generalized additive models in the dominantly inherited Alzheimer network observational study cohort, incorporating age, sex, and the interaction between group and estimated years from onset. The cortical asymmetry index successfully distinguished asymptomatic mutation carrier and symptomatic mutation carriers from healthy controls in the Clinic Barcelona cohort and symptomatic mutation carriers from controls in dominantly inherited Alzheimer network observational study. Higher cortical asymmetry index in mutation carriers (asymptomatic mutation carrier and symptomatic mutation carriers combined) and in symptomatic mutation carriers were associated with higher plasma neurofilament light levels, a closer proximity to symptom onset, and lower mini-mental state examination in the Clinic Barcelona cohort. In the dominantly inherited Alzheimer network observational study cohort, mutation carriers exhibited increased cortical asymmetry index compared to controls and correlated with elevated neurofilament light (plasma and Cerebrospinal fluid), lower mini-mental state examination, and a closer proximity to symptom onset. <i>APOE3/3</i> carriers showed greater asymmetry than other <i>APOE</i> genotypes and significant cortical asymmetry index differences between asymptomatic mutation carrier and symptomatic mutation carriers. Longitudinally, cortical asymmetry index increased over time significantly in symptomatic mutation carriers. These findings underscore brain asymmetry as a potential biomarker for early Alzheimer's disease progression in autosomal dominant Alzheimer's disease, with implications for detection and monitoring tracking disease-related neuroanatomical changes.

Brain CommunicationsVol. 8(1)
Montreal Neurological Institute and Hospital (CA), Universitat Oberta de Catalunya (ES), Washington University in St. Louis (US), Brown University (US), Instituto de Salud Carlos III (ES), German Center for Neurodegenerative Diseases (DE), Jacksonville College (US), LMU Klinikum (DE), Universidad de Antioquia (CO), Biomedical Research Networking Center on Neurodegenerative Diseases (ES), Centro de Investigación Biomédica en Red de Salud Mental (ES), Departament de Salut (ES), Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia (AR), Hospital Clínic de Barcelona (ES), Neurological Research Institute (US), Vietnam National Children's Hospital (VN), Hertie Institute for Clinical Brain Research (DE), Fundació Clínic per a la Recerca Biomèdica (ES), Korea University (JP), Niigata University (JP), Ludwig-Maximilians-Universität München (DE), Neuroscience Research Australia (AU)
Good health and well-being
Openalex Percentile: Top 34%
Functional Brain Connectivity Studies
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.