Cognitive Reserve Proxies Relate to Gray Matter Loss in Cognitively Healthy Elderly with Abnormal Cerebrospinal Fluid Amyloid-β Levels

Abstract

Cognitive reserve capacity may increase tolerance of neurodegenerative processes. However, its role regarding amyloid-β (Aβ₄₂) deposition in cognitively normal subjects is not well understood. We aimed to investigate the association between areas showing Aβ₄₂-related structural changes and cognitive reserve proxies in cognitively intact subjects showing normal or abnormal Aβ₄₂ cerebrospinal fluid (CSF) concentrations. Thirty-three subjects (aged 55–85) underwent lumbar puncture and high resolution anatomical magnetic resonance imaging analyzed by voxel-based morphometry and cortical thickness procedures. Subjects with abnormal Aβ₄₂ CSF levels showed significant left hippocampal atrophy and greater cortical thinning in parietal, temporal, and frontal regions (including the supramarginal and the anterior cingulate gyrus) compared to subjects with normal Aβ₄₂ CSF levels. Using a multivariate general linear model, we investigated the relationship between these areas and cognitive reserve proxies. We found a significant relationship between decreased volume of the left hippocampus or decreased cortical thickness of the right supramarginal gyrus and higher cognitive reserve proxies only in the group with abnormal Aβ₄₂ CSF levels. Thus, subjects with abnormal Aβ₄₂ CSF levels (which may be at a higher risk of developing Alzheimer's disease) and with high scores on cognitive reserve proxies may be tolerating a more advanced neurodegenerative process in critical cortical and subcortical regions. The present results emphasize the relevance of evaluating cognitive reserve proxies, as well as the importance of using neuroimaging techniques for early diagnosis in individuals with higher reserve.