Different reserve proxies confer overlapping and unique endurance to cortical thinning in healthy middle-aged adults.
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.
Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, 14186 Stockholm, Sweden. Electronic address: daniel.ferreira.padilla@ki.se.
Daniel
D
Ferreira
Departament de Psiquiatria i Psicobiologia Clínica, Facultat de Medicina, Campus Casanova-Clínic, Universitat de Barcelona, 08036 Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain.
David
D
Bartrés-Faz
Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, 14186 Stockholm, Sweden.
Linn
L
Nygren
Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, 14186 Stockholm, Sweden.
Leigh J
LJ
Rundkvist
Faculty of Psychology, University of La Laguna, 38205 La Laguna, Tenerife, Spain.
Yaiza
Y
Molina
Faculty of Psychology, University of La Laguna, 38205 La Laguna, Tenerife, Spain.
Alejandra
A
Machado
Departament de Psiquiatria i Psicobiologia Clínica, Facultat de Medicina, Campus Casanova-Clínic, Universitat de Barcelona, 08036 Barcelona, Spain; Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), 08036 Barcelona, Spain.
Carme
C
Junqué
Faculty of Psychology, University of La Laguna, 38205 La Laguna, Tenerife, Spain.
José
J
Barroso
Department of Neurobiology, Care Sciences and Society, Center for Alzheimer Research, Division of Clinical Geriatrics, Karolinska Institutet, 14186 Stockholm, Sweden.
Eric
E
Westman
D000328:Adult; D000375:Aging / Q000473:pathology* / Q000523:psychology*; D002540:Cerebral Cortex / Q000000981:diagnostic imaging* / Q000473:pathology; D058245:Cognitive Reserve; D004522:Educational Status; D005260:Female; D006801:Humans; D007807:Language Tests; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009483:Neuropsychological Tests; D009929:Organ Size; D014888:Wechsler Scales
Brain reserve; Cognitive reserve; Cortical thickness; Mediation analysis; Middle-age; Normal aging