Octreotide treatment improves multiple domains of cognitive performance in aged beagle dogs

Samenvatting

Aging in dogs is accompanied by progressive cognitive decline and neuropathological changes that parallel key features of human brain aging and dementia, making canines a highly valuable naturally occurring model for studying aging and neurodegenerative disease. Across species, reduced growth hormone/insulin-like growth factor-1 (GH/IGF-1) signaling is associated with extended lifespan and preserved late-life cognition, whereas chronically elevated somatotropic activity is linked to deficits in memory, attention, and executive function. The effects of pharmacologic GH/IGF-1 suppression on cognition in naturally aging animal models remain unclear. We investigated whether attenuation of IGF-1 signaling with the long-acting somatostatin analog octreotide improves cognitive performance in aged dogs. Twenty-eight aged beagle dogs (7–15 years) experienced in neuropsychological testing were enrolled in a randomized, placebo-controlled study. After a 28-day baseline, dogs received either long-acting octreotide (Sandostatin LAR, 10 mg, i.m.) or placebo, followed by a wash-in interval and 28 days of post-treatment testing. A validated cognitive battery assessed executive function and cognitive flexibility (discrimination reversal), selective attention (variable oddity), and visuospatial working memory (variable delayed non-matching to position). Treated dogs demonstrated significantly improved performance relative to placebo across the three behavioral paradigms with the primary effect being reductions in response latency and task engagement. Pharmacologic IGF-1 suppression with octreotide improves cognitive response efficiency and engagement in aged dogs, particularly in executive and attentional domains. These results support a functional role for somatotropic signaling in late-life cognition and highlight the aged canine as a valuable translational model for geroscience-based interventions targeting age-related cognitive decline.