Characterizing dog cognitive aging using spontaneous problem-solving measures: development of a battery of tests from the Dog Aging Project.

Companion dogs are a valuable model for aging research, including studies of cognitive decline and dementia. With advanced age, some dogs spontaneously develop cognitive impairments and neuropathology resembling features of Alzheimer's disease. These processes have been studied extensively in laboratory beagles, but the cognitive assays used in that context-which rely on time-consuming operant procedures-are not easily scalable to large samples of community-dwelling companion dogs. We developed a battery of five short-form tasks targeting three aspects of cognition that are impaired in Alzheimer's disease: spatial memory, executive functions, and social cognition. In Experiment 1, we tested a cross-sectional sample of dogs (N = 123) and estimated associations between age and task performance. Older dogs scored lower on measures of spatial learning, memory, and response flexibility, and spent less time near, but more time gazing at, the experimenter. We found no differences in associations between age and performance across dogs of different body masses, a proxy for expected lifespan. In Experiment 2, we demonstrated the feasibility of these measures in clinical settings (N = 35). Dogs meeting clinical criteria for moderate or severe cognitive impairment scored lower, on average, than dogs characterized as mildly impaired and healthy agers, although these distributions overlapped. However, few dogs in our study cohort met the criteria for moderate or severe impairment. The measures presented here show promise for deployment in large-scale longitudinal studies of companion dogs, such as the Dog Aging Project.

The efficacy and safety of cannabidiol as adjunct treatment for drug-resistant idiopathic epilepsy in 51 dogs: A double-blinded crossover study.

BACKGROUND: Approximately 30% of dogs with idiopathic epilepsy (IE) are drug-resistant. Recent studies have suggested cannabidiol (CBD) may be an effective anticonvulsant in dogs with IE. OBJECTIVE: To evaluate the addition of CBD to antiseizure drugs (ASDs) on seizure frequency and to report adverse events in dogs with drug-resistant IE. ANIMALS: Fifty-one dogs. Dogs having at least 2 seizures per month while receiving at least 1 ASD were included in the trial. METHODS: Double-blinded placebo-controlled crossover study. The 5 mg/kg/day dosage met futility requirements after 12 dogs, and a dosage of 9 mg/kg/day was used in the next 39 dogs. Dogs were randomly assigned to receive CBD or placebo for 3 months, with a 1-month washout period between oils. Total numbers of seizures and seizure days were recorded. Diagnostic testing was performed periodically throughout the trial. RESULTS: At the 9 mg/kg/day dose, the decrease in total seizure frequency was significant compared with placebo. A 24.1% decrease in seizure days occurred in dogs receiving CBD and a 5.8% increase occurred in dogs receiving placebo (P ≤ .05). No significant difference was found in the number of responders (≥50% decrease in total seizures or seizure days). Liver enzyme activities increased at both dosages. Decreased appetite and vomiting were more common in the CBD phase (P ≤ .05). CONCLUSIONS AND CLINICAL IMPORTANCE: Cannabidiol decreased total seizures and seizure days compared to placebo when administered to dogs PO at 9 mg/kg/day. Liver enzymes should be monitored with administration of CBD in dogs.

Activated gliosis, accumulation of amyloid ß, and hyperphosphorylation of tau in aging canines with and without cognitive decline.

Canine cognitive dysfunction (CCD) syndrome is a well-recognized naturally occurring disease in aged dogs, with a remarkably similar disease course, both in its clinical presentation and neuropathological changes, as humans with Alzheimer's disease (AD). Similar to human AD patients this naturally occurring disease is found in the aging canine population however, there is little understanding of how the canine brain ages pathologically. It is well known that in neurodegenerative diseases, there is an increase in inflamed glial cells as well as an accumulation of hyperphosphorylation of tau (P-tau) and amyloid beta (Aß1-42). These pathologies increase neurotoxic signaling and eventual neuronal loss. We assessed these brain pathologies in aged canines and found an increase in the number of glial cells, both astrocytes and microglia, and the activation of astrocytes indicative of neuroinflammation. A rise in the aggregated protein Aß1-42 and hyperphosphorylated tau, at Threonine 181 and 217, in the cortical brain regions of aging canines. We then asked if any of these aged canines had CCD utilizing the only current diagnostic, owner questionnaires, verifying positive or severe CCD had pathologies of gliosis and accumulation of Aß1-42 like their aged, matched controls. However uniquely the CCD dogs had P-tau at T217. Therefore, this phosphorylation site of tau at threonine 217 may be a predictor for CCD.

Pharmacokinetics of escalating single-dose administration of cannabidiol to cats.

This study aimed to assess the single-dose pharmacokinetics and tolerability of a cannabidiol (CBD) isolate in sunflower oil with escalating oral doses in eight healthy, purpose-bred cats. Eight cats were randomized into six dosing groups of four cats each. Cats were administered a single 2.5, 5, 10, 20, 40, or 80 mg/kg dose orally with at least a two-week washout in between doses. Behavior scoring, complete blood count, serum biochemistry analysis, physical examination, and CBD plasma levels were evaluated before and after dosing. All cats successfully completed the study. CBD was measured in the plasma of all cats dosed with CBD oil. The Cmax and AUC increased in a dose-proportional fashion across all dosing groups. There were no major bloodwork or behavioral changes although the BUN and creatinine values decreased after treatment across all doses. No adverse effects were observed, and behavioral changes were limited to head shaking, lip smacking, and hypersalivation immediately following dose administration. Single orally administered CBD doses up to 80 mg/kg were safe and well tolerated in this cohort of cats and display dose-proportional pharmacokinetics across a broad concentration.

Assessment of risk factors in dogs with presumptive advanced canine cognitive dysfunction.

Objectives: The aim of this study was to investigate the potential risk factors involved in the development of presumptive advanced canine cognitive dysfunction (pACCD). Materials and methods: A questionnaire was developed to identify dogs with presumptive canine cognitive dysfunction (CCD) based on an adapted Canine Dementia Scale and to evaluate for potential risk factors among the presumptive advanced cognitive dysfunction group. The questionnaire was distributed to 7,574 owners of dogs (≥8 years of age) who presented to the CSU VTH between 2017 and 2020. Dogs were classified into four groups based on the Canine Dementia Scale score (normal, mild, moderate, and severe cognitive impairment) and two subgroups for the cognitively impaired groups based on the presence or absence of underlying medical conditions. Comparisons between normal and presumptive advanced cognitively impaired groups, with and without underlying medical conditions, were made against various risk factors. Chi-square tests and logistic regression analysis were used to determine associations between categorical variables and a p-value of <0.05 was considered indicative of evidence of association. Results: The completed response rate for the questionnaire was 14.2% (1,079/7,574). Among those, 231 dogs were classified as having presumptive advanced cognitive dysfunction. The prevalence of presumptive advanced cognitive dysfunction in the included age groups was 8.1% in ages 8 to <11 years, 18.8% in ages 11 to <13 years, 45.3% in ages 13 to <15 years, 67.3% in ages 15 to <17 years, and 80% in ages >17 years. Dogs with a thin body condition score had the largest contribution to the chi-square statistic. Based on the logistic regression model, both age (p < 0.001) and BCS (p = 0.0057) are associated with presumptive ACCD. Conclusion and relevance: The chi-square test and logistic regression analysis both suggested an association between a thin body condition and an increased chance of cognitive decline. However, it is difficult to determine if the thin BCS in this group could be secondary to another confounding factor. The prevalence of cognitive dysfunction rapidly increased with age in this study. These findings warrant continued studies including veterinary evaluations to explore risk factors of canine dementia.