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.

Clinical and imaging findings in dogs with nerve root signature associated with cervical intervertebral disc herniation.

BACKGROUND: Intervertebral disc herniation (IVDH) is the most common spinal cord disease in dogs. Little information is available regarding the clinical presentation of nerve root signature (NRS) associated with cervical IVDH. HYPOTHESIS/OBJECTIVE: To detail the clinical and magnetic resonance imaging (MRI) findings in dogs with NRS associated with cervical IVDH. ANIMALS: Forty-seven client-owned dogs presenting with thoracic limb NRS and MRI confirmed IVDH. METHODS: Medical records from 2010 to 2020 were retrospectively reviewed for dogs that met inclusion criteria. Imaging studies were evaluated by 2 individuals to characterize location and severity of neural tissue compression. RESULTS: Chondrodystrophoid dogs comprised the majority of the study cohort, with dachshund the most common breed (n = 10). Three-quarters of dogs were ≥7 years of age. Interobserver agreement was moderate or good for all of the imaging variables evaluated. The C6-C7 intervertebral disc space was significantly overrepresented (P = .01), comprising 32% (15/47) of the affected discs. However, 42% (20/47) of cases involved C2-C3 though C4-C5 disc sites. Disc material was more frequently located laterally compared to medially within the vertebral canal (P = .0005), and to be associated with compression of the nerve root at the level of the intervertebral foramen (P = .012). CONCLUSION/CLINICAL IMPORTANCE: NRS is most commonly associated with lateralized or foraminal cervical disc herniations. It is most prevalent with C6-C7 intervertebral disc involvement, suggesting that there might be unique anatomic factors that contribute to development of NRS at this site, but can be a clinical manifestation of IVDH occurring anywhere along the cervical spine.

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.

Magnetic resonance imaging characteristics of atlanto-axial subluxation in 42 dogs: Analysis of joint cavity size, subluxation distance, and craniocervical junction anomalies.

Background: Atlanto-axial (AA) subluxation can be a complex syndrome in dogs. Accurate identification and assessment of this condition are key to providing treatment and resolution. Aim: The purpose of this retrospective study was to describe the magnetic resonance imaging (MRI) characteristics of AA subluxation and associated neurologic deficits. Methods: A multicenter review of dogs with a diagnosis of AA subluxation was conducted, evaluating signalment, neurologic grade, duration of signs, and MRI characteristics. MRI characteristics included degree of spinal cord compression and joint subluxation, integrity of odontoid ligaments, presence of a dens, spinal cord signal intensity, and presence of syringohydromyelia, hydrocephalus, and Chiari-like malformation. A control population with normal AA joints was also evaluated. MR images of 42 dogs with AA subluxation were compared to 26 age and breed-matched control dogs. Results: Affected dogs had a median age of 27 months and a median weight of 2.7 kg, and the most commonly affected breed was the Yorkshire terrier (47.5%). Spinal cord signal hyperintensity, increased AA joint size, and cross-sectional cord compression at the level of the dens and mid-body C2 were associated with AA subluxation. No associations were found between cord compression, the appearance of the dens, or cord signal intensity and neurologic grade. Affected dogs did not have a higher incidence of Chiari-like malformation, syringohydromyelia, or hydrocephalus than control dogs, and their neurologic grade was not associated with MRI findings. Lack of dens and/or odontoid ligaments was associated with larger subluxations. Conclusion: Dogs with clinical signs of AA subluxation were significantly more likely to have intramedullary hyperintensity at the level of compression ( p = 0.0004), an increased AA joint cavity size ( p = 0.0005), and increased spinal cord compression at the level of dens and mid-body C2 (p ≤ 0.05). The authors suggest an AA joint cavity size >1.4 mm and a subluxation distance >2.5 mm as cutoffs for MRI diagnosis of AA subluxation in dogs. No differences were noted between dogs with AA subluxation and control dogs regarding syringohydromyelia, hydrocephalus, and Chiari-like malformation.

Diagnosis and management of dogs with degenerative myelopathy: A survey of neurologists and rehabilitation professionals.

BACKGROUND: Antemortem diagnosis of degenerative myelopathy (DM) in dogs is presumptive and there are no accepted guidelines for the management of this condition. HYPOTHESIS/OBJECTIVES: Describe current practices of neurology clinicians and physical rehabilitation professionals in the diagnosis and management of DM. ANIMALS: None. METHODS: Online surveys examining diagnosis and management of DM were constructed and distributed via neurology and rehabilitation listservs. RESULTS: One hundred ninety neurology and 79 rehabilitation professionals from 20 countries participated. Most neurology (142/189) and rehabilitation (23/39) respondents required genetic testing for the superoxide dismutase 1 (SOD1) mutation and 82/189 neurologists also required spinal magnetic resonance imaging (MRI) for presumptive DM diagnosis. Most neurology respondents recommended exercise (187/190) and physical rehabilitation (184/190). Over 50% (102/190) of neurology respondents perform rechecks on dogs diagnosed with DM. Rehabilitation respondents reported preservation or improvement of strength (78/79) and coordination (77/79) as therapeutic goals. At-home exercises (75/79), underwater treadmill (64/79), gait training (55/79), and strength building exercises (65/79) were used to maintain strength (58/79), coordination (56/79), muscle mass (56/79), and improve overall wellbeing (54/79). Neurology respondents reported that owners elect euthanasia when dogs become nonambulatory paraparetic whereas rehabilitation respondents report euthanasia when paraplegia and incontinence develop. CONCLUSION AND CLINICAL IMPORTANCE: The majority of dogs diagnosed with DM have not undergone advanced imaging, the combination of history, neurological findings, and genetic testing is heavily relied upon. Whereas the diagnosis of DM is frequently made by veterinary neurologists, continued care is often performed by rehabilitation professionals or primary veterinarians.

Winning the race with aging: age-related changes in gait speed and its association with cognitive performance in dogs.

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.

A review of frailty instruments in human medicine and proposal of a frailty instrument for dogs.

Over the last few decades, frailty has become a pillar of research and clinical assessment in human gerontology. This complex syndrome, characterized by loss of physiologic reserves leading to decreased resilience to stressors, is of critical importance because it predicts higher risks of poor health outcomes, including mortality. Thus, identifying frailty among the elderly human population has become a key focus of gerontology. This narrative review presents current scientific literature on frailty in both humans and animals. The authors discuss the need for an accessible frailty instrument for companion dogs suitable for general use in veterinary medicine and the advances that would be facilitated by this instrument. A phenotypic frailty instrument for companion dogs, utilizing components that are easily collected by owners, or in the general practice setting, is proposed. The authors elaborate on the domains (physical condition, physical activity, mobility, strength, cognitive task performance, and social behavior), factors that will be included, and the data from the Dog Aging Project that inform each domain.

Age-associated changes in electroretinography measures in companion dogs.

PURPOSE: 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. 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. 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/m2 flash p < 0.0001) and b-waves (cone flicker p = 0.03, dark-adapted 0.01 cds/m2 flash p = 0.001). Age was also significantly associated with reduced amplitudes of a-waves (dark-adapted 3 cds/m2 flash p < 0.0001, 10 cds/m2 flash p = 0.005) and b-waves (light-adapted 3 cds/m2 flash p < 0.0001, dark-adapted 0.01 cds/m2 flash p = 0.0004, 3 cds/m2 flash p < 0.0001, 10 cds/m2 flash p = 0.007) and flicker (light-adapted 30 Hz 3 cds/m2 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. 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.

Sleep and cognition in aging dogs. A polysomnographic study.

Introduction: Sleep is fundamental for cognitive homeostasis, especially in senior populations since clearance of amyloid beta (key in the pathophysiology of Alzheimer's disease) occurs during sleep. Some electroencephalographic characteristics of sleep and wakefulness have been considered a hallmark of dementia. Owners of dogs with canine cognitive dysfunction syndrome (a canine analog to Alzheimer's disease) report that their dogs suffer from difficulty sleeping. The aim of this study was to quantify age-related changes in the sleep-wakefulness cycle macrostructure and electroencephalographic features in senior dogs and to correlate them with their cognitive performance. Methods: We performed polysomnographic recordings in 28 senior dogs during a 2 h afternoon nap. Percentage of time spent in wakefulness, drowsiness, NREM, and REM sleep, as well as latency to the three sleep states were calculated. Spectral power, coherence, and Lempel Ziv Complexity of the brain oscillations were estimated. Finally, cognitive performance was evaluated by means of the Canine Dementia Scale Questionnaire and a battery of cognitive tests. Correlations between age, cognitive performance and sleep-wakefulness cycle macrostructure and electroencephalographic features were calculated. Results: Dogs with higher dementia scores and with worse performance in a problem-solving task spent less time in NREM and REM sleep. Additionally, quantitative electroencephalographic analyses showed differences in dogs associated with age or cognitive performance, some of them reflecting shallower sleep in more affected dogs. Discussion: Polysomnographic recordings in dogs can detect sleep-wakefulness cycle changes associated with dementia. Further studies should evaluate polysomnography's potential clinical use to monitor the progression of canine cognitive dysfunction syndrome.

Presumed pituitary apoplexy in 26 dogs: Clinical findings, treatments, and outcomes.

BACKGROUND: Pituitary apoplexy refers to hemorrhage or infarction within the pituitary gland resulting in acute neurological abnormalities. This condition is poorly described in dogs. OBJECTIVES: To document presenting complaints, examination findings, endocrinopathies, magnetic resonance imaging (MRI), treatments, and outcomes of dogs with pituitary apoplexy. ANIMALS: Twenty-six client-owned dogs with acute onset of neurological dysfunction. METHODS: Retrospective case series. Dogs were diagnosed with pituitary apoplexy if MRI or histopathology documented an intrasellar or suprasellar mass with evidence of hemorrhage or infarction in conjunction with acute neurological dysfunction. Clinical information was obtained from medical records and imaging reports. RESULTS: Common presenting complaints included altered mentation (16/26, 62%) and gastrointestinal dysfunction (14/26, 54%). Gait or posture changes (22/26, 85%), mentation changes (18/26, 69%), cranial neuropathies (17/26, 65%), cervical or head hyperpathia (12/26, 46%), and hyperthermia (8/26, 31%) were the most frequent exam findings. Ten dogs (38%) lacked evidence of an endocrinopathy before presentation. Common MRI findings included T1-weighted hypo- to isointensity of the hemorrhagic lesion (21/25, 84%), peripheral enhancement of the pituitary mass lesion (15/25, 60%), brain herniation (14/25, 56%), and obstructive hydrocephalus (13/25, 52%). Fifteen dogs (58%) survived to hospital discharge. Seven of these dogs received medical management alone (median survival 143 days; range, 7-641 days) and 8 received medications and radiation therapy (median survival 973 days; range, 41-1719 days). CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with pituitary apoplexy present with a variety of acute signs of neurological disease and inconsistent endocrine dysfunction. Dogs that survive to discharge can have a favorable outcome.

MRI features can help to confirm a diagnosis of progressive myelomalacia, but may not be accurate in dogs lacking characteristic clinical signs at the time of imaging.

Progressive myelomalacia (PMM) is a fatal sequela of acute thoracolumbar intervertebral disc extrusion in dogs, with unpredictable onset in the days after the inciting injury. No single reliable diagnostic test is currently available. Magnetic resonance imaging (MRI) features such as T2-weighted spinal cord hyperintensity and loss of subarachnoid signal in a half-Fourier single-shot turbo spin echo (HASTE) sequence have been associated with PMM, but are sometimes present in other dogs with severe deficits. Magnetic resonance imaging findings in 22 dogs with a clinical or histopathologic diagnosis of PMM and 38 deep pain-negative paraplegic dogs were compared in a retrospective case-control study. Length of T2-weighted hyperintense spinal cord change and HASTE signal loss were significantly associated with clinically evident PMM (P = .0019 and P = .0085), however, there were no significant differences between groups when analysis was restricted to dogs not yet showing clinical signs of PMM. The PMM group also had significantly shorter compressive lesions than the control group (P = 0.026), suggesting a possible role of more severe focal pressure at the extrusion site. A segment of total loss of contrast enhancement in the venous sinuses and meninges, a feature not previously described, was more common in the PMM group and the difference approached significance (P = 0.054). Findings show that MRI features can support the diagnosis in dogs with clinical evidence of PMM, and absence of these features supports absence of PMM at time of imaging. However, their absence does not reliably differentiate dogs with imminent progressive myelomalacia from other dogs with severe deficits following intervertebral disc extrusion.

Relationship between hearing, cognitive function, and quality of life in aging companion dogs.

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.

A novel mutation of the CLCN1 gene in a cat with myotonia congenita: Diagnosis and treatment.

CASE DESCRIPTION: A 10-month-old castrated male domestic longhair cat was evaluated for increasing frequency of episodic limb rigidity. CLINICAL FINDINGS: The cat presented for falling over and lying recumbent with its limbs in extension for several seconds when startled or excited. Upon examination, the cat had hypertrophied musculature, episodes of facial spasm, and a short-strided, stiff gait. DIAGNOSTICS: Electromyography (EMG) identified spontaneous discharges that waxed and waned in amplitude and frequency, consistent with myotonic discharges. A high impact 8-base pair (bp) deletion across the end of exon 3 and intron 3 of the chloride voltage-gated channel 1 (CLCN1) gene was identified using whole genome sequencing. TREATMENT AND OUTCOME: Phenytoin treatment was initiated at 3 mg/kg po q24 h and resulted in long-term improvement. CLINICAL RELEVANCE: This novel mutation within the CLCN1 gene is a cause of myotonia congenita in cats and we report for the first time its successful treatment.

ACVIM consensus statement on diagnosis and management of acute canine thoracolumbar intervertebral disc extrusion.

BACKGROUND: Thoracolumbar intervertebral disc extrusion (TL-IVDE) is the most common cause of acute paraparesis and paraplegia in dogs; however, guidelines on management of the condition are lacking. OBJECTIVES: To summarize the current literature as it relates to diagnosis and management of acute TL-IVDE in dogs, and to formulate clinically relevant evidence-based recommendations. ANIMALS: None. METHODS: A panel of 8 experts was convened to assess and summarize evidence from the peer-reviewed literature in order to develop consensus clinical recommendations. Level of evidence available to support each recommendation was assessed and reported. RESULTS: The majority of available literature described observational studies. Most recommendations made by the panel were supported by a low or moderate level of evidence, and several areas of high need for further study were identified. These include better understanding of the ideal timing for surgical decompression, expected surgical vs medical outcomes for more mildly affected dogs, impact of durotomy on locomotor outcome and development of progressive myelomalacia, and refining of postoperative care, and genetic and preventative care studies. CONCLUSIONS AND CLINICAL IMPORTANCE: Future efforts should build on current recommendations by conducting prospective studies and randomized controlled trials, where possible, to address identified gaps in knowledge and to develop cost effectiveness and number needed to treat studies supporting various aspects of diagnosis and treatment of TL-IVDE.

Novel subcutaneous cytarabine infusion with the Omnipod system in dogs with meningoencephalomyelitis of unknown etiology.

OBJECTIVE: To investigate the feasibility and pharmacokinetics of cytarabine delivery as a subcutaneous continuous-rate infusion with the Omnipod system. ANIMALS: 6 client-owned dogs diagnosed with meningoencephalomyelitis of unknown etiology were enrolled through the North Carolina State University Veterinary Hospital. PROCEDURES: Cytarabine was delivered at a rate of 50 mg/m2/hour as an SC continuous-rate infusion over 8 hours using the Omnipod system. Plasma samples were collected at 0, 4, 6, 8, 10, 12, and 14 hours after initiation of the infusion. Plasma cytarabine concentrations were measured by high-pressure liquid chromatography. A nonlinear mixed-effects approach generated population pharmacokinetic parameter estimates. RESULTS: The mean peak plasma concentration (Cmax) was 7,510 ng/mL (range, 5,040 to 9,690 ng/mL; SD, 1,912.41 ng/mL), average time to Cmax was 7 hours (range, 4 to 8 hours; SD, 1.67 hours), terminal half-life was 1.13 hours (SD, 0.29 hour), and the mean area under the curve was 52,996.82 hours X µg/mL (range, 35,963.67 to 71,848.37 hours X µg/mL; SD, 12,960.90 hours X µg/mL). Cmax concentrations for all dogs were more than 1,000 ng/mL (1.0 µg/mL) at the 4-, 6-, 8-, and 10-hour time points. CLINICAL RELEVANCE: An SC continuous-rate infusion of cytarabine via the Omnipod system is feasible in dogs and was able to achieve a steady-state concentration of more than 1 µg/mL 4 to 10 hours postinitiation of cytarabine and a Cmax of 7,510 ng/mL (range, 5,040 to 9,690 ng/mL; SD, 1,912.41 ng/mL). These are comparable to values reported previously with IV continuous-rate infusion administration in healthy research Beagles and dogs with meningoencephalomyelitis of unknown etiology.

Stereotactic radiotherapy (10 Gy X 3) for canine nonlymphomatous intranasal tumors is associated with prolonged survival and minimal risk of severe radiotoxicity.

OBJECTIVE: To describe oncologic outcomes following administration of a uniform stereotactic radiotherapy protocol (SRT; 10 Gy X 3) for canine intranasal tumors and to identify whether any clinical or dosimetric factors were predictive of event-free or overall survival time (EFST or OST). ANIMALS: 129 dogs. PROCEDURES: In this single-institution retrospective study, the medical records database was searched for canine nonlymphomatous intranasal tumors treated with 10 Gy X 3 SRT between August 2013 and November 2020. Findings regarding adverse effects and outcomes were analyzed overall, for dogs grouped on the basis of life stage (mature adult, senior, or end of life), and for treatment-related or tumor-related variables to identify potential predictors of outcome. RESULTS: After SRT, most dogs clinically improved with minimal acute radiotoxicity. The median EFST was 237 days; median OST was 542 days. Receipt of other tumor-directed therapies before or after SRT was associated with improved EFST in senior dogs (hazard ratio [HR], 0.416) and improved OST in mature adult (HR, 0.241) and senior dogs (HR, 0.348). In senior dogs, administration of higher near-minimum radiation doses was associated with improved EFST (HR, 0.686) and OST (HR, 0.743). In senior dogs, chondrosarcoma was associated with shorter OST (HR, 7.232), and in dogs at end of life, having a squamous cell or transitional carcinoma was associated with worse EFST (HR, 6.462). CLINICAL RELEVANCE: This SRT protocol results in improved quality of life and prolonged OST for dogs of all life stages. Radiation protocol optimization or use of multimodal therapy may further improve outcomes.

Canine Geriatric Syndrome: A Framework for Advancing Research in Veterinary Geroscience.

Biological aging is the single most important risk factor for disease, disability, and ultimately death in geriatric dogs. The effects of aging in companion dogs also impose significant financial and psychological burdens on their human caregivers. The underlying physiologic processes of canine aging may be occult, or early signs of aging may be ignored because of the misconception that biological aging is natural and therefore inevitable. The ability to detect, quantify, and mitigate the deleterious processes of canine aging would greatly enhance veterinary preventative medicine and animal welfare. In this paper we propose a new conceptual framework for aging in dogs, the Canine Geriatric Syndrome (CGS). CGS consists of the multiple, interrelated physical, functional, behavioral, and metabolic changes that characterize canine aging as well as the resulting clinical manifestations, including frailty, diminished quality of life, and age-associated disease. We also identify potential key components of a CGS assessment tool, a clinical instrument that would enable veterinarians to diagnose CGS and would facilitate the development and testing of interventions to prolong healthspan and lifespan in dogs by directly targeting the biological mechanisms of aging. There are many gaps in our knowledge of the mechanisms and phenotype of aging in dogs that must be bridged before a CGS assessment tool can be deployed. The conceptual framework of CGS should facilitate identifying these gaps and should stimulate research to better characterize the processes and effects of aging in dogs and to identify the most promising preventative strategies to target these.

Use of Cognitive Testing, Questionnaires, and Plasma Biomarkers to Quantify Cognitive Impairment in an Aging Pet Dog Population.

BACKGROUND: Aging dogs may 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. 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.

Developing a predictive model for spinal shock in dogs with spinal cord injury.

BACKGROUND: Reduced pelvic limb reflexes in dogs with spinal cord injury typically suggests a lesion of the L4-S3 spinal cord segments. However, pelvic limb reflexes might also be reduced in dogs with a T3-L3 myelopathy and concurrent spinal shock. HYPOTHESIS/OBJECTIVES: We hypothesized that statistical models could be used to identify clinical variables associated with spinal shock in dogs with spinal cord injuries. ANIMALS: Cohort of 59 dogs with T3-L3 myelopathies and spinal shock and 13 dogs with L4-S3 myelopathies. METHODS: Data used for this study were prospectively entered by partner institutions into the International Canine Spinal Cord Injury observational registry between October 2016 and July 2019. Univariable logistic regression analyses were performed to assess the association between independent variables and the presence of spinal shock. Independent variables were selected for inclusion in a multivariable logistic regression model if they had a significant effect (P ≤ .1) on the odds of spinal shock in univariable logistic regression. RESULTS: The final multivariable model included the natural log of weight (kg), the natural log of duration of clinical signs (hours), severity (paresis vs paraplegia), and pelvic limb tone (normal vs decreased/absent). The odds of spinal shock decreased with increasing weight (odds ratio [OR] = 0.28, P = .09; confidence interval [CI] 0.07-1.2), increasing duration (OR = 0.44, P = .02; CI 0.21-0.9), decreased pelvic limb tone (OR = 0.04, P = .003; CI 0.01-0.36), and increased in the presence of paraplegia (OR = 7.87, P = .04; CI 1.1-56.62). CONCLUSIONS AND CLINICAL IMPORTANCE: A formula, as developed by the present study and after external validation, could be useful for assisting clinicians in determining the likelihood of spinal shock in various clinical scenarios and aid in diagnostic planning.