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. 2024 Mar 26;102(6):e208053.
doi: 10.1212/WNL.0000000000208053. Epub 2024 Feb 20.

Association Between Years of Education and Amyloid Burden in Patients With Subjective Cognitive Decline, MCI, and Alzheimer Disease

Merle Hönig  1 , Daniele Altomare  1 , Camilla Caprioglio  1 , Lyduine Collij  1 , Frederik Barkhof  1 , Bart Van Berckel  1 , Philip Scheltens  1 , Gill Farrar  1 , Mark R Battle  1 , Hendrik Theis  1 , Kathrin Giehl  1 , Gerard N Bischof  1 , Valentina Garibotto  1 , José Luis L Molinuevo  1 , Oriol Grau-Rivera  1 , Julien Delrieu  1 , Pierre Payoux  1 , Jean Francois Demonet  1 , Agneta K Nordberg  1 , Irina Savitcheva  1 , Zuzana Walker  1 , Paul Edison  1 , Andrew W Stephens  1 , Rossella Gismondi  1 , Frank Jessen  1 , Christopher J Buckley  1 , Juan Domingo Gispert  1 , Giovanni B Frisoni  1 , Alexander Drzezga  1 ; AMYPAD Consortium  1
Collaborators, Affiliations

Association Between Years of Education and Amyloid Burden in Patients With Subjective Cognitive Decline, MCI, and Alzheimer Disease

Merle Hönig et al. Neurology. .

Abstract

Objectives: Higher-educated patients with Alzheimer disease (AD) can harbor greater neuropathologic burden than those with less education despite similar symptom severity. In this study, we assessed whether this observation is also present in potential preclinical AD stages, namely in individuals with subjective cognitive decline and clinical features increasing AD likelihood (SCD+).

Methods: Amyloid-PET information ([18F]Flutemetamol or [18F]Florbetaben) of individuals with SCD+, mild cognitive impairment (MCI), and AD were retrieved from the AMYPAD-DPMS cohort, a multicenter randomized controlled study. Group classification was based on the recommendations by the SCD-I and NIA-AA working groups. Amyloid PET images were acquired within 8 months after initial screening and processed with AMYPYPE. Amyloid load was based on global Centiloid (CL) values. Educational level was indexed by formal schooling and subsequent higher education in years. Using linear regression analysis, the main effect of education on CL values was tested across the entire cohort, followed by the assessment of an education-by-diagnostic-group interaction (covariates: age, sex, and recruiting memory clinic). To account for influences of non-AD pathology and comorbidities concerning the tested amyloid-education association, we compared white matter hyperintensity (WMH) severity, cardiovascular events, depression, and anxiety history between lower-educated and higher-educated groups within each diagnostic category using the Fisher exact test or χ2 test. Education groups were defined using a median split on education (Md = 13 years) in a subsample of the initial cohort, for whom this information was available.

Results: Across the cohort of 212 individuals with SCD+ (M(Age) = 69.17 years, F 42.45%), 258 individuals with MCI (M(Age) = 72.93, F 43.80%), and 195 individuals with dementia (M(Age) = 74.07, F 48.72%), no main effect of education (ß = 0.52, 95% CI -0.30 to 1.58), but a significant education-by-group interaction on CL values, was found (p = 0.024) using linear regression modeling. This interaction was driven by a negative association of education and CL values in the SCD+ group (ß = -0.11, 95% CI -4.85 to -0.21) and a positive association in the MCI group (ß = 0.15, 95% CI 0.79-5.22). No education-dependent differences in terms of WMH severity and comorbidities were found in the subsample (100 cases with SCD+, 97 cases with MCI, 72 cases with dementia).

Discussion: Education may represent a factor oppositely modulating subjective awareness in preclinical stages and objective severity of ongoing neuropathologic processes in clinical stages.

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Conflict of interest statement

This communication reflects the views of the authors and neither IMI nor the European Union and EFPIA are liable for any use that may be made of the information contained in this study. M. Hoenig, D. Altomare, C. Caprioglio, P. Scheltens, B.N.M. van Berckel, G.N. Bischof, H. Theis, K. Giehl, J.L. Molinuevo, O. Grau-Rivera, J.F. Demonet, A. Nordberg, I. Savitcheva, and F. Jessen report no relevant conflicts of interest related to this work. L. Collij has received research support from GE Healthcare (paid to institution). F. Barkhof received payment and honoraria from Bayer, Biogen-Idec, Merck, Novartis, Roche, IXICO Ltd, Combinostics, and Prothena for consulting, steering committee, or IDMC membership and research support through grants from EU/EFPIA Innovative Medicines Initiative Joint Undertaking (AMYPAD consortium), UK MS Society, PICTURE (IMDI-NWO), NIHR UCLH Biomedical Research Centre (BRC), and ECTRIMS-MAGNIMS. G. Farrar is a full-time employee of GE Healthcare. M. Battle is a full-time employee of GE Healthcare. V. Garibotto received financial support for research and/or speaker fees through her institution from Siemens Healthineers, GE Healthcare, and Novo Nordisk. O. Grau-Rivera has received financial support for a research project by Roche Diagnostics and F- Hoffmann La Roche (paid to institution) and speaker fees from Roche Diagnostics. J. Delrieu has received payment/honoraria from Biogen (presentation for Biogen in 2021) and has participated on a Data Safety Monitoring Board or Advisory Board for French board for Roche in 2020–2022. P. Payoux received research support and consultancy fees from GE Healthcare. Z. Walker received research support and consultancy fees from GE Healthcare. P. Edison was funded by the Medical Research Council and now by Higher Education Funding Council for England (HEFCE). He has also received grants from Alzheimer's Research, UK, Alzheimer's Drug Discovery Foundation, Alzheimer's Society, UK, Alzheimer's association, US, Medical Research Council, UK, Novo Nordisk, Piramal Life Sciences, and GE Healthcare. He is a consultant to Roche, Pfizer, and Novo Nordisk. He has received speaker fees from Novo Nordisk, Pfizer, Nordea, and Piramal Life Sciences. He has received educational and research grants from GE Healthcare, Novo Nordisk, Piramal Life Science/Life Molecular Imaging, Avid Radiopharmaceuticals and Eli Lilly. He was an external consultant to Novo Nordisk and a member of their Scientific Advisory Board. A.W. Stephens is a full-time employee of Life Molecular Imaging, GmbH. R. Gismondi is a full-time employee of Life Molecular Imaging, GmbH. C. Buckley is a full-time employee of GE Healthcare. J.D. Gispert has received research support from GE Healthcare, Roche Diagnostics, and Hoffmann-La Roche, given lectures in symposia sponsored by General Electric, Philips, and Biogen and has served as a consultant for Roche Diagnostics and Prothena. G.B. Frisoni has received unrestricted grants and support for event organization from ROCHE Pharmaceuticals, OM Pharma, EISAI Pharmaceuticals, and Biogen Pharmaceuticals. GBF Competitive research projects have been funded by H2020, Innovative Medicines Initiative (IMI), IMI2, Swiss National Science Foundation, and VELUX Foundation. He reports that the Centre de la mémoire at Geneva University Hospitals is funded by the following private donors under the supervision of the Private Foundation of Geneva University Hospitals: A.P.R.A. - Association Suisse pour la Recherche sur la Maladie d’Alzheimer, Genève; Fondation Segré, Genève; Race Against Dementia Foundation, London, UK; Fondation Child Care, Genève; Fondation Edmond J. Safra, Genève; Fondation Minkoff, Genève; Fondazione Agusta, Lugano; McCall Macbain Foundation, Canada; Nicole et René Keller, Genève; and Fondation AETAS, Genève. A. Drzezga reports the following conflicts of interest: research support—Siemens Healthineers, Life Molecular Imaging, GE Healthcare, AVID Radiopharmaceuticals, Sofie, Eisai, and Novartis/AAA; speaker honorary/advisory boards—Siemens Healthineers, Sanofi, GE Healthcare, Biogen, Novo Nordisk, Invicro, Novartis/AAA, and Bayer Vital; stock: Siemens Healthineers and Lantheus Holding; patents: patent for 18F-PSMA7 (PSMA PET imaging tracer). 2-Alkoxy-6-[18F]Fluoronicotinoyl substituted Lys-C(O)-Glu derivatives as efficient probes for imaging of PSMA expressing tissues (Patent No.: EP3765097A1; Date of patent: Jan. 20, 2021). Go to Neurology.org/N for full disclosures.

Figures

Figure
Figure. Association Between Years of Education and Centiloid Value for Potential Preclinical Stages (SCD+) and Clinical Stages (MCI and Dementia) of AD
See this image and copyright information in PMC

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