@article{colon_early_munana_olby_mariani_mancini_fefer_li_briley_bailey_et al._2024, title={Pharmacokinetics of subcutaneous ketamine administration via the Omnipod® system in dogs}, volume={3}, ISSN={["1365-2885"]}, DOI={10.1111/jvp.13440}, abstractNote={Ketamine is an injectable anesthetic agent with analgesic and antidepressant effects that can prevent maladaptive pain. Ketamine is metabolized by the liver into norketamine, an active metabolite. Prior rodent studies have suggested that norketamine is thought to contribute up to 30% of ketamine's analgesic effect. Ketamine is usually administered as an intravenous (IV) bolus injection or continuous rate infusion (CRI) but can be administered subcutaneously (SC) and intramuscularly (IM). The Omnipod® is a wireless, subcutaneous insulin delivery device that adheres to the skin and delivers insulin as an SC CRI. The Omnipod® was used in dogs for postoperative administration of ketamine as a 1 mg/kg infusion bolus (IB) over 1 hour (h). Pharmacokinetics (PK) showed plasma ketamine concentrations between 42 and 326.1 ng/mL. The median peak plasma concentration was 79.5 (41.9-326.1) ng/mL with a Tmax of 60 (30-75) min. After the same infusion bolus, the corresponding norketamine PK showed plasma drug concentrations between 22.0 and 64.8 ng/mL. The median peak plasma concentration was 43.0 (26.1-71.8) ng/mL with a median Tmax of 75 min. The median peak ketamine plasma concentration exceeded 100 ng/mL in dogs for less than 1 h post infusion. The Omnipod® system successfully delivered subcutaneous ketamine to dogs in the postoperatively.}, journal={JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS}, author={Colon, Claudia and Early, Peter and Munana, Karen and Olby, Natasha and Mariani, Christopher and Mancini, Shelby and Fefer, Gilad and Li, Zhong and Briley, Jessica and Bailey, Kate and et al.}, year={2024}, month={Mar} }
 @article{khan_mondino_russell_case_fefer_woods_olby_gruen_2023, title={A novel task of canine olfaction for use in adult and senior pet dogs}, volume={13}, ISSN={["2045-2322"]}, url={https://europepmc.org/articles/PMC9908929}, DOI={10.1038/s41598-023-29361-x}, abstractNote={While much work has been done in the field of canine olfaction, there has been little exploration of hyposmia or anosmia. This is partly due to difficulties in reducing confounds like training history and environmental distraction. The current study describes a novel olfaction test using spontaneous search behavior in dogs to find a hidden food treat in a three-choice task with both light-phase and dark-phase conditions. The study was performed in 18 adult control dogs, 18 senior/geriatric dogs enrolled in a longitudinal aging study, and a single dog with severe nasal pathology. In the senior/geriatric and control groups, dogs performed with higher accuracy (p < 0.0001) and were less likely to show biased selection strategy (p < 0.01) in the dark-phase than light-phase. While senior/geriatric dogs performed above chance, they had lower accuracy in the dark-phase compared to controls (p = 0.036). Dogs who scored higher on an owner questionnaire of cognitive decline showed a positive correlation with performance in the dark-phase; performance on additional cognitive tests did not correlate with performance in the dark-phase. This task can be used to quantify canine olfaction using clearly defined endpoints and spontaneous behaviors thus making it feasible to compare between and within groups of pet dogs.}, number={1}, journal={SCIENTIFIC REPORTS}, author={Khan, Michael Z. and Mondino, Alejandra and Russell, Katharine and Case, Beth and Fefer, Gilad and Woods, Hope and Olby, Natasha and Gruen, Margaret}, year={2023}, month={Feb} }
 @article{salzman_merten_panek_fefer_mondino_westermeyer_gruen_olby_mowat_2023, title={Age-associated changes in electroretinography measures in companion dogs}, volume={6}, ISSN={["1573-2622"]}, url={https://doi.org/10.1007/s10633-023-09938-7}, DOI={10.1007/s10633-023-09938-7}, abstractNote={[[{:Label=>"PURPOSE", :NlmCategory=>"OBJECTIVE"}, "To determine the association between age and retinal full-field electroretinographic (ERG) measures in companion (pet) dogs, an important translational model species for human neurologic aging."], [{:Label=>"METHODS", :NlmCategory=>"METHODS"}, "Healthy adult dogs with no significant ophthalmic abnormalities were included. Unilateral full-field light- and dark-adapted electroretinography was performed using a handheld device, with mydriasis and topical anaesthesia. Partial least squares effect screening analysis was performed to determine the effect of age, sex, body weight and use of anxiolytic medication on log-transformed ERG peak times and amplitudes; age and anxiolytic usage had significant effects on multiple ERG outcomes. Mixed model analysis was performed on data from dogs not receiving anxiolytic medications."], [{:Label=>"RESULTS", :NlmCategory=>"RESULTS"}, "In dogs not receiving anxiolytics, median age was 118 months (interquartile range 72-140 months, n = 77, 44 purebred, 33 mixed breed dogs). Age was significantly associated with prolonged peak times of a-waves (dark-adapted 3 and 10 cds/m", {:sup=>"2"}, " flash p < 0.0001) and b-waves (cone flicker p = 0.03, dark-adapted 0.01 cds/m", {:sup=>"2"}, " flash p = 0.001). Age was also significantly associated with reduced amplitudes of a-waves (dark-adapted 3 cds/m", {:sup=>"2"}, " flash p < 0.0001, 10 cds/m", {:sup=>"2"}, " flash p = 0.005) and b-waves (light-adapted 3 cds/m", {:sup=>"2"}, " flash p < 0.0001, dark-adapted 0.01 cds/m", {:sup=>"2"}, " flash p = 0.0004, 3 cds/m", {:sup=>"2"}, " flash p < 0.0001, 10 cds/m", {:sup=>"2"}, " flash p = 0.007) and flicker (light-adapted 30 Hz 3 cds/m", {:sup=>"2"}, " p = 0.0004). Within the Golden Retriever breed, these trends were matched in a cross-sectional analysis of 6 individuals that received no anxiolytic medication."], [{:Label=>"CONCLUSIONS", :NlmCategory=>"CONCLUSIONS"}, "Aged companion dogs have slower and reduced amplitude responses in both rod- and cone-mediated ERG. Consideration of anxiolytic medication use should be made when conducting ERG studies in dogs."]]}, journal={DOCUMENTA OPHTHALMOLOGICA}, author={Salzman, Michele M. and Merten, Natascha and Panek, Wojciech K. and Fefer, Gilad and Mondino, Alejandra and Westermeyer, Hans D. and Gruen, Margaret E. and Olby, Natasha J. and Mowat, Freya M.}, year={2023}, month={Jun} }
 @article{templeton_fefer_case_roach_azcarate-peril_gruen_callahan_olby_2023, title={Longitudinal Analysis of Canine Oral Microbiome Using Whole Genome Sequencing in Aging Companion Dogs}, volume={13}, ISSN={["2076-2615"]}, DOI={10.3390/ani13243846}, abstractNote={Simple Summary The prevalence of dental disease and cognitive decline in elderly dogs is extremely high, and, given the known relationship between dental disease and Alzheimer’s Disease in people, this study sought to describe the changes in oral microbiota in aged pet dogs over time. By sequencing oral swabs, we were able to identify bacterial and fungal populations in the dogs’ mouths. The most common bacterial species present, Phorphorymonas spp. is known to produce factors that cause neurodegeneration. Moreover, Leptotrichia, another bacterial species present, correlated to cognition scores in these dogs. We conclude that this small exploratory study shows the importance of defining the oral microbiota in aged dogs with a view to understanding potential therapeutic targets. Larger prospective studies should be undertaken as a priority. Abstract 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.}, number={24}, journal={ANIMALS}, author={Templeton, Ginger B. and Fefer, Gilad and Case, Beth C. and Roach, Jeff and Azcarate-Peril, M. Andrea and Gruen, Margaret E. and Callahan, Benjamin J. and Olby, Natasha J.}, year={2023}, month={Dec} }
 @article{khan_mondino_russell_case_fefer_woods_olby_gruen_2023, title={Relationship between engagement with the impossible task, cognitive testing, and cognitive questionnaires in a population of aging dogs}, volume={9}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2022.1052193}, abstractNote={Introduction The aim of this study was to evaluate the engagement of aging dogs with a cognitively challenging and potentially frustrating task (the impossible task). Based on previous observations, we predicted that dogs showing signs of cognitive impairment in other cognitive tests and owner-completed questionnaires would show reduced engagement with the task. Methods In this task, dogs were shown a piece of food in a clear container that they could not open; time spent interacting with the container and the experimenter was measured. While the impossible task has not been used as a measure of frustration, the parameters of the test design creates a potential frustrate state, making this assessment appropriate. Thirty-two dogs enrolled in a longitudinal aging study participated in the study. Owners were asked to complete two cognitive dysfunction screening questionnaires (Canine Dementia Scale [CADES] and Canine Cognitive Dysfunction Rating Scale [CCDR]) as well a questionnaire assessing general frustration. Dogs participated in multiple measures of cognitive function as well the impossible task. Results Latency to disengage from the impossible task was faster for dogs with higher total (more impaired) CADES (p = 0.02) and total CCDR (p = 0.04) scores. Latency to disengage also correlated with decreased performance in cognitive tests observing social cues (p = 0.01), working memory (p ≤ 0.001), spatial reasoning and reversal learning (p = 0.02), and sustained attention (p = 0.02). Discussion The high correlation with several cognitive measures and the ease of administration of this test makes it a useful tool in evaluating canine cognitive dysfunction syndrome, however it is unclear if increased frustration or other cognitive processes are contributing to the observed changes.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Khan, Michael Z. and Mondino, Alejandra and Russell, Katharine and Case, Beth and Fefer, Gilad and Woods, Hope and Olby, Natasha J. and Gruen, Margaret E.}, year={2023}, month={Jan} }
 @article{mondino_khan_case_fefer_panek_gruen_olby_2023, title={Winning the race with aging: age-related changes in gait speed and its association with cognitive performance in dogs}, volume={10}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2023.1150590}, abstractNote={Introduction In humans, gait speed is a crucial component in geriatric evaluation since decreasing speed can be a harbinger of cognitive decline and dementia. Aging companion dogs can suffer from age-related mobility impairment, cognitive decline and dementia known as canine cognitive dysfunction syndrome. We hypothesized that there would be an association between gait speed and cognition in aging dogs. Methods We measured gait speed on and off leash in 46 adult and 49 senior dogs. Cognitive performance in senior dogs was assessed by means of the Canine Dementia Scale and a battery of cognitive tests. Results We demonstrated that dogs' food-motivated gait speed off leash is correlated with fractional lifespan and cognitive performance in dogs, particularly in the domains of attention and working memory. Discussion Food-motivated gait speed off leash represents a relatively easy variable to measure in clinical settings. Moreover, it proves to be a more effective indicator of age-related deterioration and cognitive decline than gait speed on leash.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Mondino, Alejandra and Khan, Michael and Case, Beth and Fefer, Gilad and Panek, Wojciech K. and Gruen, Margaret E. and Olby, Natasha J.}, year={2023}, month={Jun} }
 @article{fefer_khan_panek_case_gruen_olby_2022, title={Relationship between hearing, cognitive function, and quality of life in aging companion dogs}, volume={8}, ISSN={["1939-1676"]}, url={https://doi.org/10.1111/jvim.16510}, DOI={10.1111/jvim.16510}, abstractNote={Abstract Background Elderly people with presbycusis are at higher risk for dementia and depression than the general population. There is no information regarding consequences of presbycusis in dogs. Objective Evaluate the relationship between cognitive function, quality of life, and hearing loss in aging companion dogs. Animals Thirty‐nine elderly companion dogs. Methods Prospective study. Hearing was evaluated using brainstem auditory evoked response (BAER) testing. Dogs were grouped by hearing ability. Owners completed the canine dementia scale (CADES) and canine owner‐reported quality of life (CORQ) questionnaire. Cognitive testing was performed, and cognitive testing outcomes, CADES and CORQ scores and age were compared between hearing groups. Results Nineteen dogs could hear at 50 dB, 12 at 70 dB, and 8 at 90 dB with mean ages (months) of 141 ± 14, 160 ± 16, and 172 ± 15 for each group respectively (P = .0002). Vitality and companionship CORQ scores were significantly lower as hearing deteriorated (6.6‐5.4, 50‐90 dB group, P = .03 and 6.9‐6.2, 50‐90 dB group, P = .02, respectively). Cognitive classification by CADES was abnormal in all 90 dB group dogs and normal in 3/12 70 dB group and 11/19 50 dB group dogs (P = .0004). Performance on inhibitory control, detour and sustained gaze tasks decreased significantly with hearing loss (P = .001, P = .008, P = .002, respectively). In multivariate analysis, higher CADES score was associated with worse hearing (P = .01). Conclusions and Clinical Importance Presbycusis negatively alters owner‐pet interactions and is associated with poor executive performance and owner‐assessed dementia severity.}, journal={JOURNAL OF VETERINARY INTERNAL MEDICINE}, author={Fefer, Gilad and Khan, Michael Z. and Panek, Wojciech K. and Case, Beth and Gruen, Margaret E. and Olby, Natasha J.}, year={2022}, month={Aug} }
 @article{fefer_panek_khan_singer_westermeyer_mowat_murdoch_case_olby_gruen_2022, title={Use of Cognitive Testing, Questionnaires, and Plasma Biomarkers to Quantify Cognitive Impairment in an Aging Pet Dog Population}, volume={87}, ISSN={["1875-8908"]}, DOI={10.3233/JAD-215562}, abstractNote={BACKGROUND
Aging dogs suffer from canine cognitive dysfunction syndrome (CCDS), a condition in which cognitive decline is associated with amyloid pathology and cortical atrophy. Presumptive diagnosis is made through physical examination, exclusion of systemic/metabolic conditions, and completion of screening questionnaires by owners.


OBJECTIVE
This study aimed to determine whether cognitive function could be quantified in aging pet dogs, and to correlate cognitive testing with validated questionnaires and plasma neurofilament light chain (pNfL) concentration in aging dogs.


METHODS
Thirty-nine dogs from fifteen breeds were recruited (9.3 to 15.3 years). Owners completed the Canine Dementia Scale (CADES) and Canine Cognitive Dysfunction Rating scale (CCDR). Executive control and social cues were tested, and pNfL was measured with single molecule array assay. Comparisons were made between cognitive testing scores, CADES, CCDR scores, and pNfL.


RESULTS
CADES scoring classified five dogs as severe CCDS, six as moderate, ten as mild, and eighteen as normal. CCDR identified seven dogs at risk of CCDS and thirty-two as normal. Cognitive testing was possible in the majority of dogs, although severely affected dogs were unable to learn tasks. CADES score correlated with sustained attention duration (r = -0.47, p = 0.002), inhibitory control (r = -0.51, p = 0.002), detour (r = -0.43, p = 0.001), and pNfL (r = 0.41, p = 0.025). Concentration of pNfL correlated with inhibitory control (r = -0.7, p≤0.001). The CCDR scale correlated with performance on inhibitory control (r = -0.46, p = 0.005).


CONCLUSION
Our findings suggest that a multi-dimensional approach using a combination of questionnaires, specific cognitive tests, and pNfL concentration can be used to quantify cognitive decline in aging pet dogs.}, number={3}, journal={JOURNAL OF ALZHEIMERS DISEASE}, author={Fefer, Gilad and Panek, Wojciech K. and Khan, Michael Z. and Singer, Matthew and Westermeyer, Hans D. and Mowat, Freya M. and Murdoch, David M. and Case, Beth and Olby, Natasha J. and Gruen, Margaret E.}, year={2022}, pages={1367–1378} }
 @article{hoel_templeton_fefer_case_shah_gruen_olby_2021, title={Sustained Gaze Is a Reliable In-home Test of Attention for Aging Pet Dogs}, volume={8}, ISSN={["2297-1769"]}, DOI={10.3389/fvets.2021.819135}, abstractNote={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.}, journal={FRONTIERS IN VETERINARY SCIENCE}, author={Hoel, Jane A. and Templeton, Ginger B. and Fefer, Gilad and Case, Beth C. and Shah, Anshu and Gruen, Margaret E. and Olby, Natasha J.}, year={2021}, month={Dec} }