Unveiling the significance of dog domestication in cognitive dysfunction: Are wolves protected?

Over the course of their long coexistence with humans, dogs have developed a stronger bond with humans than with any other domestic species. This close relationship has promoted notable parallels in both genetics and lifestyle, thereby facilitating the development of comparable pathological conditions, including several central nervous system disorders. Canine cognitive dysfunction (CCD) is a spontaneous model of neurodegeneration that shares clinical features, neuropathological characteristics, and risk factors with human Alzheimer's disease (AD). However, the potential role of dog domestication in increasing CCD susceptibility remains poorly explored. In this sense, the gray wolf (Canis lupus), a direct ancestor of the domestic dog (Canis lupus familiaris), represents a comparative model of great interest, as the information available on its neuropathology and behavior associated with aging is very limited. To provide a preliminary framework for assessing how domestication may have shaped vulnerability to cognitive decline in canids, this study employed a database-driven analytical approach to evaluate the degree of impact of various risk factors shared by AD and CCD-including aging, oxidative stress, inflammation, sleep disturbances, and periodontal disease-in domestic dogs and gray wolves kept in captivity or semi-captivity. Our results indicate that domestic dogs have more pronounced key risk factors for CCD than captive or semi-captive gray wolves. This finding suggests that wolves may be less vulnerable to age-related cognitive dysfunction, possibly reflecting differences in evolutionary or domestication processes. Nevertheless, given the scarcity of neuropathological and behavioral data on aged wolves, these conclusions should be interpreted with caution, and further direct investigations are warranted. Domestication may have increased susceptibility to age-related cognitive dysfunction in dogs by enhancing exposure to key risk factors, as oxidative stress, inflammation, and lifestyle-related conditions. Recognizing these domestication-linked vulnerabilities highlights the need for preventive health strategies in dogs and provides a valuable comparative framework for understanding neurodegenerative processes across species within a One Health perspective.