A randomized, controlled clinical trial demonstrates improved owner-assessed cognitive function in senior dogs receiving a senolytic and NAD+ precursor combination.

Age-related decline in mobility and cognition are associated with cellular senescence and NAD + depletion in dogs and people. A combination of a novel NAD + precursor and senolytic, LY-D6/2, was examined in this randomized controlled trial. Seventy dogs with mild to moderate cognitive impairment were enrolled and allocated into placebo, low or full dose groups. Primary outcomes were change in cognitive impairment measured with the owner-reported Canine Cognitive Dysfunction Rating (CCDR) scale and change in activity measured with physical activity monitors. Fifty-nine dogs completed evaluations at the 3-month primary endpoint, and 51 reached the 6-month secondary endpoint. There was a significant difference in CCDR score across treatment groups from baseline to the primary endpoint (p = 0.02) with the largest decrease in the full dose group. No difference was detected between groups using in house cognitive testing. There were no significant differences between groups in changes in measured activity. The proportion of dogs that improved in frailty and owner-reported activity levels and happiness was higher in the full dose group than other groups, however this difference was not significant. Adverse events occurred equally across groups. All groups showed improvement in cognition, frailty, and activity suggesting placebo effect and benefits of trial participation. We conclude that LY-D6/2 improves owner-assessed cognitive function over a 3-month period and may have broader, but more subtle effects on frailty, activity and happiness as reported by owners.

Longitudinal Analysis of Canine Oral Microbiome Using Whole Genome Sequencing in Aging Companion Dogs.

Aged companion dogs have a high prevalence of periodontal disease and canine cognitive dysfunction syndrome (CCDS) and the two disorders are correlated. Similarly, periodontal disease and Alzheimer's Disease are correlated in people. However, little is known about the oral microbiota of aging dogs. The goal of this project was to characterize the longitudinal changes in oral microbiota in aged dogs. Oral swabs were taken from ten senior client-owned dogs on 2-3 occasions spanning 24 months and they underwent whole genome shotgun (WGS) sequencing. Cognitive status was established at each sampling time. A statistically significant increase in alpha diversity for bacterial and fungal species was observed between the first and last study visits. Bacteroidetes and proteobacteria were the most abundant bacterial phyla. Porphyromonas gulae was the most abundant bacterial species (11.6% of total reads). The species Lactobacillus gasseri had a statistically significant increase in relative abundance with age whereas Leptotrichia sp. oral taxon 212 had a statistically significant positive longitudinal association with cognition score. There is an increased fungal and bacterial alpha diversity in aging dogs over time and nearly universal oral dysbiosis. The role of the oral microbiota, particularly Leptotrichia and P. gulae and P. gingivalis, in aging and CCDS warrants further investigation.

Sustained Gaze Is a Reliable In-home Test of Attention for Aging Pet Dogs.

Canine Cognitive Dysfunction Syndrome (CCDS) is a syndrome of progressive cognitive decline comparable to Alzheimer's Disease. The sustained gaze test captures attention loss associated with CCDS in laboratory settings, and adapting the sustained gaze test for use by owners at home could greatly increase the data generated on CCDS. We hypothesized that it would be feasible for owners to perform the sustained gaze test at home, and that results would be reliable over repeated trials. Training materials were developed and dog owners underwent training and performed the test in triplicate at weekly intervals for 3 weeks. Gaze videos and a CAnine DEmentia Scale (CADES) questionnaire were submitted each week. Videos were examined for inclusion and duration of gaze was recorded. One observer repeated video assessments twice, 1 week apart; five different observers assessed videos once. Outcome measures included the relationship between CADES and gaze duration, test-retest reliability of owner-performed sustained gaze testing, and intra- and inter-rater reliability. Twenty dogs aged 7-15.5 years completed testing. The majority of videos were acceptable (162/183). Within dog test-retest reliability was excellent (ICC = 0.96). Intra- and interobserver reliability for determining video validity for inclusion were substantial (k = 0.76 and 0.78, respectively); for duration of gaze these were excellent (ICC = 0.99 and 0.96, respectively). Gaze duration was significantly associated with CADES (p = 0.0026). We conclude that owners can perform the sustained gaze test at home and that data generated are reliable and correlate to CADES, a validated measure of dementia.

Evaluation of repeated dosing of a dexmedetomidine oromucosal gel for treatment of noise aversion in dogs over a series of noise events.

BACKGROUND: Noise aversion is a common behavioural disorder in dogs; affected dogs show fear behaviours in response to noise stimuli. Pharmacological treatment is effective for many dogs; clinical reports suggest anxiolytic treatment lowers the need for treatment over time. We aimed to evaluate the effect of dexmedetomidine oromucosal gel for dogs with noise aversion over a series of noise events. Furthermore, we evaluated burden of care for owners of dogs with noise aversion via questionnaire. METHODS: Owners of enrolled dogs completed records for 10 noise events indicating whether their dog received dexmedetomidine gel and pretreatment and post-treatment anxiety scores; adverse events were noted. Owners were queried about burden of care. RESULTS: Twenty-two client-owned dogs completed recordings for 10 events. Logistic regression results showed a significant effect for time of event with decreased probability of receiving treatment for subsequent events (OR=0.75, P=0.0017). Within an event, significant improvement in anxiety was seen (median improvement 11 points; paired Wilcoxon; P<0.0001). We found overall burden of care was manageable, yet many owners agreed with statements regarding frustration (42 per cent), stress (46 per cent), guilt (42 per cent) and sadness (75 per cent) about their dog's condition. CONCLUSIONS: Repeated use of dexmedetomidine gel for noise events resulted in decreased need for administration. Burden of care is important to discuss with clients.

Use of oral trazodone for sedation in cats: a pilot study.

OBJECTIVES: Resistance to transportation and stressful veterinary visits are major causes for a decrease in feline veterinary care. Few options exist for oral sedatives to reduce cats' anxiety prior to veterinary visits. The purpose of this study was to evaluate the safety and efficacy of oral trazodone for use as a single dose agent for sedation in cats. METHODS: Six laboratory cats were given single 50, 75 and 100 mg doses of trazodone and placebo. Trazodone 100 mg and placebo treatments were randomized. Pre- and post-study laboratory values and physical examinations were compared. During each 4 h period post-treatment, sedation was measured via accelerometers and video observations scored by an observer blinded to treatment. Examinations were performed on the cats 90 mins after treatment, and their behavioral responses scored by the same blinded observer. RESULTS: No adverse effects or changes in physical examinations or laboratory values were detected as a result of trazodone administration. Accelerometer data showed trazodone 50, 75 and 100 mg caused sedation as measured by activity reduction (83%, 46% and 66%, respectively). In contrast, there was a 14% activity increase after placebo. There was a significant reduction in video observation scores when cats were given trazodone 100 mg compared with placebo. Mean latency to peak sedation for trazodone 100 mg occurred at 2 h. Scores for behavioral response to examination, performed at 90 mins post-treatment, were not significantly different between cats receiving trazodone 100 mg and placebo. CONCLUSIONS AND RELEVANCE: Trazodone was well tolerated in this population of cats and caused appreciable sedation at all doses. Behavior during examination was not significantly different when cats received trazodone 100 mg compared with placebo. Further studies are recommended to investigate the use of oral trazodone in cats for the purpose of decreasing anxiety assocaited with transportation and examination.

The Use of an Open Field Model to Assess Sound-Induced Fear and Anxiety Associated Behaviors in Labrador Retrievers.

Previous studies have shown that the playing of thunderstorm recordings during an open-field task elicits fearful or anxious responses in adult beagles. The goal of our study was to apply this open field test to assess sound-induced behaviors in Labrador retrievers drawn from a pool of candidate improvised explosive devices (IED)-detection dogs. Being robust to fear-inducing sounds and recovering quickly is a critical requirement of these military working dogs. This study presented male and female dogs, with 3 minutes of either ambient noise (Days 1, 3 and 5), recorded thunderstorm (Day 2), or gunfire (Day 4) sounds in an open field arena. Behavioral and physiological responses were assessed and compared to control (ambient noise) periods. An observer blinded to sound treatment analyzed video records of the 9-minute daily test sessions. Additional assessments included measurement of distance traveled (activity), heart rate, body temperature, and salivary cortisol concentrations. Overall, there was a decline in distance traveled and heart rate within each day and over the five-day test period, suggesting that dogs habituated to the open field arena. Behavioral postures and expressions were assessed using a standardized rubric to score behaviors linked to canine fear and anxiety. These fear/anxiety scores were used to evaluate changes in behaviors following exposure to a sound stressor. Compared to control periods, there was an overall increase in fear/anxiety scores during thunderstorm and gunfire sound stimuli treatment periods. Fear/anxiety scores were correlated with distance traveled, and heart rate. Fear/anxiety scores in response to thunderstorm and gunfire were correlated. Dogs showed higher fear/anxiety scores during periods after the sound stimuli compared to control periods. In general, candidate IED-detection Labrador retrievers responded to sound stimuli and recovered quickly, although dogs stratified in their response to sound stimuli. Some dogs were robust to fear/anxiety responses. The results suggest that the open field sound test may be a useful method to evaluate the suitability of dogs for IED-detection training.

Acquisition of a visual discrimination and reversal learning task by Labrador retrievers.

Optimal cognitive ability is likely important for military working dogs (MWD) trained to detect explosives. An assessment of a dog's ability to rapidly learn discriminations might be useful in the MWD selection process. In this study, visual discrimination and reversal tasks were used to assess cognitive performance in Labrador retrievers selected for an explosives detection program using a modified version of the Toronto General Testing Apparatus (TGTA), a system developed for assessing performance in a battery of neuropsychological tests in canines. The results of the current study revealed that, as previously found with beagles tested using the TGTA, Labrador retrievers (N = 16) readily acquired both tasks and learned the discrimination task significantly faster than the reversal task. The present study confirmed that the modified TGTA system is suitable for cognitive evaluations in Labrador retriever MWDs and can be used to further explore effects of sex, phenotype, age, and other factors in relation to canine cognition and learning, and may provide an additional screening tool for MWD selection.