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The Relationship Between Frontal Gray Matter Volume and Cognition Varies Across the Healthy Adult Lifespan

From the Department of Psychiatry and Human Behavior (MEZ, RHP, DFT, RAC, MSA), Brown Medical School, Providence, Rhode Island; Taub Institute for Research on Alzheimer’s Disease and the Aging Brain (AMB), Columbia University Medical Center, New York, NY; The Brain Resource International Database (SMG, EG), The Brain Resource Company, Ultimo, Australia; the Department of Psychology (JG), Kent State University, Kent, Ohio; The Brain Dynamics Centre (LMW, TJW), Westmead Millenium Institute, Westmead Hospital and University of Sydney, Westmead, Australia; the Discipline of Psychological Medicine (LMW), and School of Psychology (TJW), University of Sydney, Sydney, Australia; and the School of Psychology (CRC), Flinders University, Adelaide, Australia.

Objective: Age-associated decline in gray matter brain volume and cognitive function in healthy adults has been reported in the literature. The goal of the current study is to examine the relationship between age-related changes in regional gray matter volumes and cognitive function in a large, cross-sectional sample of healthy adults across the lifespan.

Methods: Magnetic resonance imaging and cognitive assessment were conducted on 148 adults aged 21–76 years. Multiple regression analyses examining the effect of age were performed on magnetic resonance image-derived gray matter brain volumes and standardized cognitive summary scores of attention and executive function. Regression was also performed to test the effect of age, gray matter volumes, and their interaction on the prediction of cognitive performance.

Results: Age significantly predicted performance on tests of attention (F [1, 146]=50.97, p <0.01, R²=0.26) and executive function (F [1, 146]=126.19, p <0.01, R²=0.46) and gray matter volumes for frontal subregions (lateral, medial, orbital), hippocampus, amygdala, and putamen (F [2, 145]=45.34–23.96, p <0.01–0.02). Lateral frontal (ß=-1.53, t=-2.16, df=131, p <0.03) and orbital frontal (ß=1.24, t=2.08, df=131, p <0.04) regions significantly predicted performance on tests of attention. Lateral frontal (ß=-1.69, t=-2.83, df=131, p <0.01) and the interaction between age and lateral frontal volume (ß=3.76, t=2.49, df=131, p <0.02) significantly predicted executive function.

Conclusions: The findings confirm age-associated decline in cognitive function and gray matter volumes, particularly in anterior cortical brain regions. Furthermore, the association between lateral frontal gray matter volume and the ability to successfully plan, organize, and execute strategies varies as a function of age across the healthy adult lifespan.

Key Words: Aging • healthy adults • magnetic resonance imaging • gray matter • cognitive function

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