Mechanisms contributing to age-related cognitive decline are poorly defined. Thus, we used canine microarrays to compare gene expression profiles of brain tissue from geriatric and young adult dogs. Cerebral cortex samples were collected from six geriatric (12-year old) and six young adult (1-year old) female beagles after being fed one of two diets (animal protein-based versus plant-protein based) for 12 months. RNA samples were hybridized to Affymetrix GeneChip® Canine Genome Arrays. Statistical analyses indicated that the age had the greatest impact on gene expression, with 963 transcripts differentially expressed in geriatric dogs. Although not as robust as age, diet affected mRNA abundance of 140 transcripts. As demonstrated in aged rodents and humans, geriatric dogs had increased expression of genes associated with inflammation, stress response, and calcium homeostasis and decreased expression of genes associated with neuropeptide signaling and synaptic transmission. In addition to its existing strengths, availability of gene sequence information and commercial microarrays make the canine a powerful model for studying the effects of aging on cognitive function.