However, in humans, it is unknown whether cognitive function and brain structure are affected by GHRD. SIGNIFICANCE STATEMENT People and mice with growth hormone receptor deficiency (GHRD or Laron syndrome) are protected against age-related diseases including cancer and diabetes. Further investigation may lead to improved understanding of underlying mechanisms and could contribute to the identification of treatments for age-related cognitive deficits. The results suggest that, compared with controls, GHRD subjects have brain structure and function that are more consistent with those observed in younger adults reported in previous studies. Furthermore, they had greater functional synchronicity of activity between the precuneus and the rest of the default mode network at rest. The GHRD group showed enhanced cognitive performance and greater task-related activation in frontal, parietal, and hippocampal regions compared with controls. They had lower mean diffusivity in the genu of the corpus callosum and the anterior thalamic tracts. The GHRD group had larger surface areas in several frontal and cingulate regions and showed trends toward larger dentate gyrus and CA1 regions of the hippocampus. We also evaluated brain activity at rest and during a hippocampal-dependent pattern separation task. We assessed differences in white matter microstructural integrity, hippocampal volume, subregional volumes, and cortical thickness and surface area of selected regions. Using MRI, we compared brain structure, function, and connectivity between 13 people with GHRD and 12 unaffected relatives. Whereas GHRD mice show improved age-dependent cognitive performance, the effect of GHRD on human cognition remains unknown. Previous studies in mice and humans suggested that GHRD has protective effects against age-related diseases, including cancer and diabetes. Growth hormone receptor deficiency (GHRD) results in short stature, enhanced insulin sensitivity, and low circulating levels of insulin and insulin-like growth factor 1 (IGF-1).
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