Abstract: Background - Companion dogs, like humans, experience age-related cognitive decline and mobility loss. These changes begin at a molecular level and targeting cellular senescence and NAD+ depletion, both molecular hallmarks of aging, may delay clinical progression in senior dogs.Hypothesis/Objectives - A combination of senolytic and NAD+ precursor (LY-D6TM) will improve cognition and activity over a three month period. Animals - Seventy companion dogs (age >10 years) with mild to moderate cognitive impairment.Methods - This randomized controlled clinical trial tested two doses of LY-D6TM (half, full) against placebo. Primary outcomes were change in Canine Cognitive Dysfunction Rating (CCDR) score (completed by caregiver) and in physical activity monitor counts. Dogs were evaluated at baseline, 1,3 and 6 months, with 3 months as the primary endpoint. Repeated measures ANOVA was used to compare changes in outcome over time with p< 0.05 indicating significance. Covariates were incorporated when significant. Results - After enrollment, two dogs died and nine dogs were excluded from analysis ( noncompliance, significant health changes and inability to complete visits), leaving 20 dogs in the placebo group, 21 in half dose, and 18 in full dose at 3 months. There was a significant difference in CCDR score over time across treatment groups, with those receiving LY-D6TM decreasing more than placebo. (Table 1). There was no difference between groups in activity level across time. (Table 2).Conclusions and clinical importance - A combination of NAD+ precursor and senolytic shows evidence of improving cognitive health in aged dogs.
