Measures of spatial memory, peripheral inflammation and negative emotional state predict social-cognitive skills in healthy aging cats

Abstract

Aging is a complex, multidimensional process. Normative aging is typically accompanied by declines in several cognitive domains, including memory and social cognition. As aging progresses, the often-overlooked early manifestations of cognitive decline can advance, leading to an inability to adapt to new situations and environments. Potential mechanisms influencing cognitive decline remain elusive, but, among other mechanisms, inflammaging, an age-related increase in the chronic production of pro-inflammatory mediators, and emotional stress are implicated. Cognitive function in cats is under-researched, with no studies on the link between potential risk factors and cognitive signs in aging subjects. Understanding this link is essential as it may facilitate the early identification of cognitive decline and encourage preventative, individualized interventions. We carried out a citizen science study to investigate, for the first time, the relationship between cognitive functions, stress, and the inflammatory markers interleukin (IL)-1β and IL-10 in 44 healthy, privately owned pet cats (7–14 years of age), who underwent standardized testing in their home environment. A task was employed to test spatial memory, requiring the cat to recall the location of a food-baited container. An unsolvable task was used to assess cats' social cognition and cognitive flexibility by measuring how they used referential communication (i.e., gaze alternation between the apparatus and the caregivers) compared to their persistence in trying to obtain food which was out of reach. Generalized linear regression analysis, conducted while adjusting for demographic factors and stress behaviors, revealed: 1) a predictive positive relationship connecting spatial memory and the use of social referencing with the caregiver (more gaze alternation) in the unsolvable task, highlighting the importance of the interplay between cognitive domains in sustaining complex behaviors, and 2) a reduced engagement in social referencing toward caregivers (less gaze alternation) in the presence of higher serum levels of IL-1β in the unsolvable task, especially as cats get older. A cat’s social cognitive performance was also negatively predicted by stress-related behaviors, which is not surprising given that cats are sentient creatures whose everyday behavior is also influenced by emotional states. These findings provide new insights into the crosstalk between different cognitive domains during aging and the potential contributions of emotions and inflammation to cognitive changes in healthy aging cats. Further research using this multidimensional approach will help explore these mechanisms of cognitive aging and potential markers for early detection of cognitive changes in older cats, which is critical for timely interventions.