Cortical thickness across the lifespan in a Colombian cohort with autosomal-dominant Alzheimer's disease: A cross-sectional study.

Introduction: Cortical thinning is a marker of neurodegeneration in Alzheimer's disease (AD). We investigated the age-related trajectory of cortical thickness across the lifespan (9-59 years) in a Colombian kindred with autosomal dominant AD (ADAD).
Methods: Two hundred eleven participants (105 presenilin-1 [ PSEN1 ] E280A mutation carriers, 16 with cognitive impairment; 106 non-carriers) underwent magnetic resonance imaging. A piecewise linear regression identified change-points in the age-related trajectory of cortical thickness in carriers and non-carriers.
Results: Unimpaired carriers exhibited elevated cortical thickness compared to non-carriers, and thickness more negatively correlated with age and cognition in carriers relative to non-carriers. We found increased cortical thickness in child carriers, after which thickness steadied compared to non-carriers prior to a rapid reduction in the decade leading up to the expected age at cognitive impairment in carriers.
Discussion: Findings suggest that cortical thickness may fluctuate across the ADAD lifespan, from early-life increased thickness to atrophy proximal to clinical onset.
Competing Interests: Mr. Fox‐Fuller was supported by the National Institute on Aging (NIA F31AG062158) and was the member‐at‐large for the International Neuropsychological Society's Student Liaison Committee. Dr. Quiroz was supported by grants from the National Institutes of Health (NIH) Office of the Director (DP5OD019833), the NIA (R01 AG054671]), the Alzheimer's Association, and Massachusetts General Hospital Executive Committee on Research (ECOR). Mr. d'Oleire Uquillas was supported by the National Science Foundation, NSF GRFP (disbursed to institution) and the Ford Foundation National Academies of Sciences, Medicine and Engineering Predoctoral Fellowship (disbursed to institution). Dr. Kewei Chen was supported by the NIH (to the institute State of Arizona and to the institute) and was a paid consultant (unrelated to this manuscript) to the following: Green Valley Pharmaceutical, Shanghai, China; Beijing Normal University, Beijing, China; and The sixth people's hospital, Shanghai, China. In addition, Dr. Kewei Chen holds a patent regarding use of multi‐modal linkage (multi‐modal partial least square) to link and co‐analyze multi‐modal data (https://patents.google.com/patent/US20060074290). Dr. Su was supported on this work by R01AG055444 (funding was made to Banner Health) and was also supported by the following grants: NIH/NIA R01AG069453, NIH/NIA R21AG065942, NIH/NIA R42AG053149, NIH/NIA P30AG019610, NIH/NIA R01AG031581, NIH/NIA U19AG024904, NIH/NIBIB R21EB024366 BrightFocus ADR A2017272S, Alzheimer's Association AARG‐17‐532945 State of Arizona All grants were made to institution. Dr. Su is also a paid consultant (unrelated to this work) to Green Valley Pharmaceutical LLC. Dr. Jacobs received support (unrelated to this work) from the following: NIA‐NIH R01 AG 062559, R01 AG 068062‐01A1, and from Alzheimer Nederland (the Netherlands): AN‐19021. In addition, Dr. Jacobs is vice‐chair of the Neuromodulatory Subcortical Systems professional interest area of International Society to Advance Alzheimer's Research and Treatment (ISTAART; Alzheimer's Association). Dr. Guzmán‐Vélez was supported by funding from the National Institute on Aging (NIA) K23AG061276, the Massachusetts General Hospital ECOR Fund for Medical Discovery Clinical Fellowship Award, and the NIH Research Supplement for Diversity (DP5OD019833); she also received honoraria for a presentation at a Missouri University of Science and Technology departmental colloquium (unrelated to this work). Dr. Vila‐Castelar is supported by a grant from the Alzheimer's Association (2019A005859) and serves as co‐chair for the Sex Differences Special Interest Group, Diversity and Disparities Professional Interest Area‐PIA of ISTAART. Dr. Reiman has received support from the following grants: NIH grants R01 AG069453, R01 AG031581, P30 AG019610, R01 AG055444, R01 AG054671, R01 AG058468, U01 NS093334, OT2 OD026549, PO1 AG052350, U19 AG024904, U54 MD000507, U01 AG0169765 and AG016976, and R01 AG054671; Arizona Department of Health Services; and Banner Alzheimer's Foundation, Flinn Foundation, Anonymous Foundations, NOMIS Foundation, Alzheimer's Association, and GHR Foundation. Dr. Reiman's institution has received consulting fees for his work with: Alkahest, Alzheon, Aural Analytics, Denali, Green Valley, Retromer Therapeutics, and Vaxxinity. Dr. Reiman is an inventor, with a patent issued to Banner Health, related to biomarker strategies involved in the accelerated evaluation of AD prevention therapies. Dr. Reiman is on the Board of Directors, Flinn Foundation, and is a Member of the National Advisory Council on Aging (NACA). Dr. Reiman is also Cofounder and shareholder of ALZPath. Dr. Sperling was supported by the following grants: R01AG058825 from the NIH, payment made to Brigham and Women's Hospital (BWH); R01AG063689 from NIH, payment made to BWH R01AG053184; from NIH, payment made to BWH; P01AG036694 from NIH, payment made to Massachusetts General Hospital (MGH); R01AG063689 from NIH (subcontract with USC), payment made to MGH R01AG061848; from NIH, payment made to MGH R01AG058468; from NIH (subcontract with Banner Alzheimer's Institute), payment made to MGH; from a research grant from the Alzheimer's Association, payment made to MGH ; and research funding Eisai, Eli Lilly, Janssen, clinical research funding. Dr. Sperling received Honorarium payments (unrelated to this work) made directly to her from: Shionogi, Genentech, Oligomerix, Inc., Cytox, Prothena, Acumen, JOMDD, Renew, Alnylam Pharmaceuticals, Neuraly, Janssen, Neurocentria, AC Immune, Biogen, Eisai, Roche, and Takeda. Dr. Sperling also reports a financial relationship for my spouse Dr. Keith Johnson regarding the following: Cerveau, Janssen, AC Immune, Novartis (these are all honorarium consulting payments). Dr. Sperling received the following additional honoraria (unrelated to this work): 2018 Duke Lectureship; 2018 UCLA Talk; 2018 Alzheimer Research Roundtable; 2018 ADRC Talk; 2019 ACTC Scottdale; 2019 ADPD Symposium; 2019 University of Tokyo Roundtable; 2019 Biogen: ARIA State of the Art Meeting; 2019 University of Pittsburgh Distinguished Scientist Lecture; 2019 University of Cincinnati Lurie Lecture; 2019 CTAD San Diego; 2019 CT Research Academy Talk; 2020 UC Irvine Distinguished Lecture on the Brain; 2020 Virtual Rhode Island IDeA Symposium; 2020 IMPACT‐AD Course; 2020 University of Chicago DOM Weekly Grand Rounds Seminar Series; 2020 Adler Foundation Symposium; San Diego 2020 ACTC; and San Diego 2020 UC Irvine Lecture. Dr. Sperling has also received travel support for the following conferences (unrelated to this work): 2018 ACTC Atlanta; 2018 CTAD Spain; 2018 Harvard HUBWeek Panel; 2018 Japan JSNM; 2019 Palm Beach Reversing the Tide of Alzheimer's Fundraiser; 2019 HAI Meeting; 2019 ACTC Philadelphia; 2019 GHR Board of Directors in DC; 2019 Marr Family Race; 2019 ACTC St. Louis; 2019 FDA Type C Meeting; 2019 Marc Diamond UT Southwestern Symposium; and 2020 HAI Miami. Dr. Sperling reports the following leadership positions: 2014‐2018 National Institute on Aging, Standing Council Member; National Advisory Council on Aging 2018‐2019 Chair, Division of Neuroscience Review Committee; National Institute on Aging 2018‐Present Journal of Prevention of Alzheimer's Disease; Editorial Board 2020‐2021 Chair, Preclinical Alzheimer's Disease Biomarker Disclosure Workshop Committee, National Academies of Science, Engineering and Medicine. Dr. Lopera reports support from the COLBOS project to himself and his Institution and received funds from an NIH Subcontract with Massachusetts General Hospital. Dr. Lopera reports receiving funds from NIH to participate in various Alzheimer's‐related conferences. Dr. Keith Johnson reports research support from NIH (unrelated to this work) and received personal consulting fees from Novartis. Dr. Brad Dickerson reports research support from NIA, NIDCD, and NIMH, as well as royalties/licenses with Oxford University Press, Cambridge University Press, and Elsevier. Dr. Dickerson reports personal consulting fees received from: Acadia, Alector, Arkuda, Biogen, Novartis, Takeda, and Wave. Dr. Dickerson received honoraria from InTouch Medical and Biogen and was on the Data Safety/Advisory Boards for: Acadia, Alector, Arkuda, Biogen, Novartis, Takeda, and Wave. Dr. Dickerson is also Chair elect of the Association for FTD.
(© 2021 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)