Different reserve proxies confer overlapping and unique endurance to cortical thinning in healthy middle-aged adults

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To investigate different proxies of brain and cognitive reserve as potential mediators of the effect of cortical thinning on cognition in healthy middle-aged adults.


Eighty-two middle-aged individuals were included (mean(SD) age = 45.1(3.9) years). Cortical thickness was calculated for multiple brain regions using FreeSurfer. Cognitive measures sensitive to early cognitive decline were selected, including Block Design from the Wechsler Adult Intelligence Scale-III (WAIS-III), Judgment of Line Orientation Test (JLOT), Color Trails Test (CTT), and first learning trial of TAVEC (the Spanish version of the California Verbal Learning Test, CVLT). Brain reserve was operationalized as total intracranial volume (TIV); and cognitive reserve was estimated by means of Years of Education, WAIS-III Vocabulary subtest, WAIS-III Information subtest, and a Cognitive Reserve Questionnaire (CRQ). Mediation effects were investigated with multiple linear regression and bootstrapping analysis.


Information and Vocabulary showed the greatest mediation capacity. All the observed mediations were positive indicating that higher levels of reserve attenuate the effect of reduced cortical thickness on cognition. Information, Vocabulary and TIV buffered the effect of frontal thinning on Block Design; Vocabulary and Years of Education buffered the effect of frontal thinning on JLOT; and CRQ buffered the effect of temporal thinning on CTT.


Higher reserve buffers the effect of cortical thinning on cognition in healthy middle-aged adults. The investigated proxies might be underpinned by slightly different neural networks. Advancing in the understanding of the influences of reserve in healthy middle-aged adults is crucial to facilitate early interventions.

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