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Soma and Neurite Density Imaging (SANDI), a novel biophysical model of diffusion MRI, provides estimates of cell body (soma) radius and density, and neurite density in gray matter. The goal of this cross\u2010sectional study was to assess the sensitivity of high\u2010gradient diffusion MRI toward age\u2010related alterations in cortical microstructure across the adult lifespan using SANDI. Seventy\u2010two cognitively unimpaired healthy subjects (ages 19\u201385\u2009years; 40 females) were scanned on the 3T Connectome MRI scanner with a maximum gradient strength of 300mT\/m using a multi\u2010shell diffusion MRI protocol incorporating 8 <jats:italic>b<\/jats:italic>\u2010values and diffusion time of 19\u2009ms. Intra\u2010soma signal fraction obtained from SANDI model\u2010fitting to the data was strongly correlated with age in all major cortical lobes (<jats:italic>r<\/jats:italic>\u2009=\u2009\u22120.69 to \u22120.60, FDR\u2010<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Intra\u2010soma signal fraction (<jats:italic>r<\/jats:italic>\u2009=\u20090.48\u20130.63, FDR\u2010<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and soma radius (<jats:italic>r<\/jats:italic>\u2009=\u20090.28\u20130.40, FDR\u2010<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.04) were significantly correlated with cortical volume in the prefrontal cortex, frontal, parietal, and temporal lobes. The strength of the relationship between SANDI metrics and age was greater than or comparable to the relationship between cortical volume and age across the cortical regions, particularly in the occipital lobe and anterior cingulate gyrus. In contrast to the SANDI metrics, all associations between diffusion tensor imaging (DTI) and diffusion kurtosis imaging metrics and age were low to moderate. 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