The concept of cognitive reserve (CR); most commonly estimated through the use of ‘proxies’ such as years of education (YoE); addresses inter-individual differences in the adaptability and susceptibility of cognitive abilities or day-to-day function to brain aging, pathology or insult. Neuroimaging studies of cognitively normal older individuals have revealed positive associations between CR proxies and measures of brain integrity.
These associations are primarily observed in limbic, paralimbic, and heteromodal cortical association areas; particularly within the prefrontal cortex, and have typically interpreted as reflecting a higher capacity for plastic change; which may increase the adaptability of higher educated individuals to age- or disease-related brain changes. This interpretation is by functional imaging studies that have demonstrated differential patterns of the brain; activation in these latter regions that are suggestive of greater neural efficiency and capacity in highly educated individuals.
Inter-individual variations in anatomy
Neuroimaging investigations have revealed inter-individual variations in anatomy, metabolism, activity, and connectivity of specific cortical association areas through which years of education; as a common proxy of cognitive reserve, may operate in the face of age- or brain changes. However, the associated molecular properties of YoE-related brain regions and the biological pathways involved remain poorly understood.
In the present study, they first identified brain areas that showed an association between cortical thickness and YoE amongst 122 cognitively healthy older human individuals. They subsequently the molecular properties of these regions by studying brain-wide microarray measurements of regional gene expression. In accordance with previous studies, they observed that YoE with higher cortical thickness in medial prefrontal, anterior cingulate and orbitofrontal areas.
Compared to the rest of the cortex; these regions exhibited a distinct gene expression profile by relative up-regulation of gene sets implicated in ionotropic and metabotropic neurotransmission; as well as activation of an immune response. Our genome-wide expression profile analysis of YoE-related brain regions points to distinct molecular pathways that may underlie a higher capacity for plastic changes in response to lifetime intellectual enrichment and potentially also a higher resilience to age-related pathologic brain changes.
Therefore they combined a neuroimaging-based analysis with a transcriptome-wide gene expression approach to investigate the molecular-functional properties of cortical regions with educational attainment; as a commonly used proxy for cognitive reserve, in older individuals. The strongest association with education was observed in specific areas of the medial prefrontal cortex; these areas exhibited a distinct gene expression profile by relative up-regulation of gene sets implicated in neurotransmission and immune responses.
These findings complement previous neuroimaging studies in the field and point to novel biological pathways that may mediate the beneficial effects of high educational attainment on adaptability to cope with or prevent, age-related brain changes. The identified genes and pathways now warrant further exploration in mechanistic studies.