Abstract

BackgroundThe Cognitive Reserve (CR) theory posits that brains with higher reserve can cope with more cerebral damage to minimize clinical manifestations. The aim of this study was to examine the effect of education (CR proxy) on brain structure and function in Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI) patients and in cognitively healthy elderly (HC) individuals.MethodsFifty-seven AD patients, 57 aMCI patients and 48 HCs were included to investigate the relationships between education years and gray matter volume (GMV), regional homogeneity (ReHo) and functional connectivity (FC) in brain regions to show associations with both structure and function. Taking the severity of the disease into account, we further assessed the relationships in AD stratified analyses.ResultsIn AD group, the GMV of the dorsal anterior cingulate cortex (dACC) and ReHo in the left inferior temporal cortex (ITC) were inversely associated with education years, after adjustment for age, sex, Mini-Mental State Examination (MMSE), and total intracranial volume or head motion parameters. Seed-based FC analyses revealed that education years were negatively correlated with the FC between the left anterior ITC and left mid frontal cortex as well as right superior frontal cortex and right angular gyrus. Stratified analyses results indicated that this negative relation between education and GMV, ReHo, FC was mainly present in mild AD, which was attenuated in moderate AD and aMCI groups.ConclusionsOur results support the CR theory, and suggest that CR may be protective against AD related brain pathology at the early stage of clinical dementia. These findings could provide the locus of CR-related functional brain mechanisms and a specific time-window for therapeutic interventions to help AD patients to cope better with the brain pathological damage by increasing CR.

Highlights

  • The Cognitive Reserve (CR) theory posits that brains with higher reserve can cope with more cerebral damage to minimize clinical manifestations

  • Correlations between gray matter volume (GMV) and education years Controlling for age, sex, Mini-Mental State Examination (MMSE), and total intracranial volume (TIV), significant negative correlations were observed between education years and the GMV of the dorsal anterior cingulate cortex in Alzheimer’s disease (AD) patients

  • No significant negative correlations were observed in amnestic mild cognitive impairment (aMCI) patients or Cognitively healthy elderly (HC), and no positive correlations were observed in any of the groups

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Summary

Introduction

The Cognitive Reserve (CR) theory posits that brains with higher reserve can cope with more cerebral damage to minimize clinical manifestations. The aim of this study was to examine the effect of education (CR proxy) on brain structure and function in Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI) patients and in cognitively healthy elderly (HC) individuals. Higher educated individuals seem to withstand more severe brain damage It is not a perfect measurement of CR, education has been used widely with diverse populations and in various studies, reinforcing the rationale for testing its connection to dementia. Cerebrospinal fluid (CSF) Aβ42, CSF tau, FDG-PET, and structural and functional MRI have been suggested as biomarkers of AD-related pathology [20]. The measures of AD-related pathology we used here were MRI-based measures of brain structure and function

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