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Published on: May 19, 2022
Association Between Years of Education and Amyloid Burden in Patients With Subjective Cognitive Decline, MCI, and
Merle Hönig1, Daniele Altomare1, Camilla Caprioglio1
1From the Department of Nuclear Medicine, Faculty of Medicine and University Hospital Cologne (M.H., H.T., K.G., G.N.B., A.D.), University of Cologne; Institute of Neuroscience and Medicine (INM-2) (M.H., K.G., A.D.), Molecular Organization of the Brain, Forschungszentrum Jülich, Germany; Neurology Unit (D.A.), Department of Clinical and Experimental Sciences, University of Brescia, Italy; Laboratory of Neuroimaging of Aging (LANVIE) (D.A.), University of Geneva; Geneva Memory Center (D.A., C.C., G.B.F.), Geneva University Hospitals, Switzerland; Amsterdam UMC (L.C., F.B., B.V.B., P.S.), Location VUmc, Radiology; Amsterdam Neuroscience (L.C., F.B., B.V.B., P.S.), Brain Imaging, the Netherlands; Queen Square Institute of Neurology and Centre for Medical Image Computing (F.B.), University College London; GE Healthcare (G.F., M.R.B., C.J.B.), Pharmaceutical Diagnostics, Amersham, United Kingdom; Department of Neurology (H.T.), Faculty of Medicine and University Hospital Cologne, University of Cologne, Germany; Division of Nuclear Medicine and Molecular Imaging (V.G.), Diagnostic Department, University Hospitals of Geneva; Laboratory of Neuroimaging and Innovative Molecular Tracers (NIMTLab) (V.G.), Faculty of Medicine, Department of Radiology, University of Geneva; Center for Biomedical Imaging (CIBM) (V.G.), Geneva, Switzerland; Barcelonaβeta Brain Research Center (BBRC) (J.L.L.M., O.G.-R., J.D.G.), Pasqual Maragall Foundation, Barcelona, Spain; Gérontopôle (J.D., P.P., J.F.D.), Department of Geriatrics, Toulouse University Hospital; Maintain Aging Research Team (J.D.), CERPOP, Inserm, Université Paul Sabatier, Toulouse; ToNIC (P.P.), Toulouse NeuroImaging Center, Université de Toulouse, Inserm, UPS, France; Center for Alzheimer Research (A.K.N.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet; Theme Inflammation and Aging (A.K.N.), Karolinska University Hospital, Stockholm; Medical Radiation Physics and Nuclear Medicine (I.S.), Karolinska University Hospital, Sweden; Division of Psychiatry (Z.W.), University College London, London and Essex Partnership University NHS Foundation Trust; Department of Brain Sciences (P.E.), Imperial College London, United Kingdom; Life Molecular Imaging (A.W.S., R.G.), Berlin; Department of Psychiatry (F.J.), Faculty of Medicine and University Hospital Cologne, University of Cologne; and German Center for Neurodegenerative Diseases (DZNE) (F.J., A.D.), Bonn-Cologne, Germany.
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.
