Subtle executive deficits are associated with higher brain amyloid burden and lower cortical volume in subjective cognitive decline: the FACEHBI cohort

Alba Pérez‐Cordón ,Marta Marquié,Ana Mauleón,Luis Tárraga,Francisco Lomeña,Sergi Valero,Maitée Rosende-Roca ,Assumpta Vivas,Francisco Ramos Campos ,Ángela Sanabria ,Gemma C Monté-Rubio ,Merçé Boada ,Liliana Vargas,Alba Benaque,Ana Espinosa,Gemma Ortega,Marta Gómez-Chiari ,Isabel Hernández ,Carla Abdelnour,Octavio Rodríguez-Gómez ,Juan Pablo Tartari,Agustín Ruiz ,Silvia Gil,Montserrat Alegret

doi:10.1038/s41598-020-74704-7

Abstract

To determine whether lower performance on executive function tests in subjective cognitive decline (SCD) individuals are associated with higher levels of brain amyloid beta (Aβ) deposition and regional volumetric reduction in areas of interest for Alzheimer’s disease (AD). 195 individuals with SCD from the FACEHBI study were assessed with a neuropsychological battery that included the following nine executive function tests: Trail Making Test A and B (TMTA, TMTB), the Rule Shift Cards subtest of BADS, the Automatic Inhibition subtest of the Syndrom Kurz Test (AI-SKT), Digit Span Backwards and Similarities from WAIS-III, and the letter, semantic, and verb fluency tests. All subjects underwent an 18F-Florbetaben positron emission tomography (FBB-PET) scan to measure global standard uptake value ratio (SUVR), and a magnetic resonance imaging (MRI). A multiple regression analysis, adjusted for age, was carried out to explore the association between global SUVR and performance on executive tests. Then, on those tests significantly associated with amyloid burden, a voxel-based morphometry (VBM) analysis was carried out to explore their correlates with grey matter volume. Multiple regression analysis revealed a statistically significant association between Aβ deposition and performance on one of the executive tests (the AI-SKT). Moreover, VBM analysis showed worse AI-SKT scores were related to lower volume in bilateral hippocampus and left inferior frontal regions. In conclusion, in SCD individuals, worse automatic inhibition ability has been found related to higher cerebral Aβ deposition and lower volume in the hippocampus and frontal regions. Thus, our results may contribute to the early detection of AD in individuals with SCD.

Highlights

To determine whether lower performance on executive function tests in subjective cognitive decline (SCD) individuals are associated with higher levels of brain amyloid beta (Aβ) deposition and regional volumetric reduction in areas of interest for Alzheimer’s disease (AD). 195 individuals with SCD from the Fundació ACE Healthy Brain Initiative (FACEHBI) study were assessed with a neuropsychological battery that included the following nine executive function tests: Trail Making Test A and B (TMTA, Trail Making Test B (TMTB)), the Rule Shift Cards subtest of Behavioral Assessment of the Dysexecutive Syndrome (BADS), the Automatic Inhibition subtest of the Syndrom Kurz Test (AI-SKT), Digit Span Backwards and Similarities from WAIS-III, and the letter, semantic, and verb fluency tests
The aims of this study were (1) to determine whether lower performance on executive function tests in subjective cognitive decline (SCD) individuals are associated with higher levels of brain Aβ deposition; and (2) in those executive function tests correlated with amyloid burden, to elucidate if worse performance is associated with a specific grey matter (GM) topology in regions known to be sensitive to AD
The results of the present study reinforce the importance of assessing executive functioning in the early detection of AD in individuals with SCD

Summary

Introduction

To determine whether lower performance on executive function tests in subjective cognitive decline (SCD) individuals are associated with higher levels of brain amyloid beta (Aβ) deposition and regional volumetric reduction in areas of interest for Alzheimer’s disease (AD). 195 individuals with SCD from the FACEHBI study were assessed with a neuropsychological battery that included the following nine executive function tests: Trail Making Test A and B (TMTA, TMTB), the Rule Shift Cards subtest of BADS, the Automatic Inhibition subtest of the Syndrom Kurz Test (AI-SKT), Digit Span Backwards and Similarities from WAIS-III, and the letter, semantic, and verb fluency tests. To determine whether lower performance on executive function tests in subjective cognitive decline (SCD) individuals are associated with higher levels of brain amyloid beta (Aβ) deposition and regional volumetric reduction in areas of interest for Alzheimer’s disease (AD). The work presented is part of the Fundació ACE Healthy Brain Initiative (FACEHBI)[22], a broad study based on a cohort of 200 middle-aged adults with SCD and focused on increasing the understanding of AD’s preclinical stages It is a longitudinal study involving a multimodal biomarker approach intended to capture the more relevant molecular, structural and functional processes present in the earliest phases of AD combined with a comprehensive and sensitive neuropsychological protocol

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