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Funding Pressing Research Needs for the Health of Senior Dogs
Janet C. Patterson-Kane BVSc, PhD

ABBREVIATIONS
AD: Alzheimer’s disease
ALS: Amyotrophic lateral sclerosis
CDS: Cognitive dysfunction syndrome
BCS: Body condition score
MCS: Muscle Condition Score
DM: Degenerative myelopathy
FDA: Food and Drug Administration
GOLPP: Geriatric onset laryngeal paralysis polyneuropathy
QoL: Quality of life

The Mark L. Morris Jr. Investigator Award was established by Morris Animal Foundation to honor the legacy and vision of the veterinary scientist Dr. Mark L. Morris Jr., DVM, PhD. The aim of this award is to satisfy an urgent and unmet need in canine or feline veterinary science where there is a realistic expectation of making rapid and meaningful progress. Our own survey data and expert opinion led us to choose senior dog health as the topic for this third call for the award. Ages at which dogs are considered “senior” and their expected lifespans are breed/size dependent — for example epigenetic (methylome) analysis indicated that Labrador retrievers are senior over 7 years of age, with an expected lifespan of 12 years.1 Senior dogs are plagued by a litany of poorly studied but significant diseases and conditions that, for whatever reason, have been largely neglected in terms of research. This commentary presents feedback from our blue-ribbon panel, subdivided into discussion categories, as a guide for applicants in preparing their submissions for this call. The call opens on February 22, 2022.

Nutrition Including Weight Management
More than half of dogs (in the United States and other comparable westernized countries) are overweight or obese, particularly older dogs, which increases their risk of other diseases. BCS is commonly used to determine (subcutaneous) fat accumulation but can be overly subjective when performed by pet owners. MCS evaluates muscle mass and is not directly related to BCS. We know dogs benefit from an early focus on nutrition to facilitate healthy aging, as shown by the longevity gains from slight caloric restriction. Unfortunately, we lack evidence-based guidelines for food or supplements for senior dogs, including those with CDS who might benefit from nutrition-based interventions. Underweight geriatric dogs with undiagnosed sarcopenia represent a further cohort worthy of study.

Potential Research Questions

  • Specific nutritional and/or supplement requirements for seniors.
  • Dietary modifications to slow CDS including early intervention.
  • Techniques directed by primary care veterinarians and/or veterinary technicians to help owners optimize BCS and MCS for their pets throughout all life stages.
  • Effects of different feeding methods on BCS and overall health inclusive of behavior and cognition.
  • Improved definition of age-related sarcopenia using non-invasive imaging.
  • Determination of links between nutrition and/or exercise, and age-related sarcopenia.

Cognitive Decline and Other Neurological Conditions
CDS is a major issue in terms of pathology, QoL, and preservation of the human-animal bond, with a diagnosis based on exclusion (guided by history) and clues from imaging. Typically, euthanasia becomes an option once the family’s emotional, time, and/or physical budgets are exhausted and the dog’s QoL is irreversibly diminished. In human patients, anesthesia has been linked to accelerated progression of AD, the human equivalent of CDS, although inflammation provoked by surgical tissue trauma might be the culprit.2 Either way, any link between surgery and cognitive decline is an obvious worry for owners and veterinarians.

Senior dogs and their owners urgently need treatments for CDS and tools to recognize it early. Tracking lifelong behavior and mobility using wearable technology might flag early disease and buy time for interventions such as group classes that can mitigate CDS.3 Canine CDS research could also piggy-back developments in the field of AD. An FDA-approved melatonin receptor agonist (tasimelteon) used to treat circadian rhythm disorders in people, might also translate to canine medicine, given appropriate trial data.    

Another poorly understood but common disease for seniors is GOLPP, a polyneuropathy that can cause a variety of symptoms — although owners tend to focus on the obvious breathing and regurgitation issues. Esophageal dysfunction is poorly understood in GOLPP and represents a significant safety issue for the anesthesia needed for corrective surgery. “Tie-back” surgery is rarely recommended or available, although anecdotal owner-reported outcomes are largely positive. Progressive weakness and mobility issues may be slowed by physical therapy.  

DM is a third problem disease for senior dogs for which we need evidence-based treatments to extend survival and QoL; aggressive physical therapy is the only current treatment. DM is a significant issue in working dogs where follow-up potential can be high. These dogs may constitute a useful study cohort. The roles of inflammaging and behavioral health in disease development are unknown and, as for CDS, there may be value in translating advances for the equivalent human disease i.e., ALS. 

Potential Research Questions

  • Systematic approaches to diagnose CDS as early as possible including specific, sensitive, and validated pre-screening tools (e.g., app-based and/or wearable technology) that can be used longitudinally and pre-appointment by owners.
  • Breed/size-specific age ranges where CDS screening/intervention is beneficial.
  • Trials of behavioral, pharmacological, or other interventions to manage/slow CDS progression. These might include testing the effects of melatonin/melatonin receptor agonists on the circadian cycle, sleep duration and sleep quality.
  • Investigation into the effects of anesthesia (general/local/different duration) and surgical procedures on CDS onset and progression. This includes development of standardized cognition tests to identify at-risk patients through pre-screens, particularly those facing longer anesthesia e.g., for dental procedures.
  • Applying advances in AD or ALS research to canine CDS and DM respectively.
  • Prevalence of GOLPP in general pet populations including breed-specific data.
  • Outcomes and prognosis for surgical and other interventions to treat GOLPP.
  • A clinical trial to test the efficacy of sildenafil (a smooth-muscle relaxant) on esophageal function and clinical symptoms of GOLPP.

Mobility
Mobility is a senior dog’s greatest asset for extending QoL (healthspan) and lifespan, and the owner’s mental and physical health. Loss of mobility is a common reason to consider euthanasia, particularly for larger breeds whose health issues might exceed the owner’s physical budget. Behavioral issues may include house soiling with overlapping comorbidities including sensory, cognitive (disorientation), and frailty issues. Differentiation of the causes of mobility loss are critical, including neurologic, age-related sarcopenia, and lack of exercise/disuse.   

Creating senior dog-friendly environments is important in veterinary practices with potential collateral benefits for staff and clients. Senior-friendly practices in the same vein as cat friendly or “Fear Free” practices might improve client confidence and encourage an uptick in the repeat visits needed for these dogs. Adaptations in the home environment and more predictable daily routines can also help. Examples include food bowl locations, non-slippery surfaces, and sensor activated guide-lights when vision deteriorates.

Some specific physical causes include unrecognized cruciate ligament injuries and poorly trimmed toenails; the latter affecting posture, gait, proprioception and, if chronic, predisposing to later mobility problems. Joint laxity, even when affecting mobility at a subclinical level, has been associated with excitability and can be a key trait in anxiety-related disorders.4 As a generality, lack of mobility causes anxiety — with potential downstream systemic effects that are ill-defined.

Potential Research Questions

  • Effects of subclinical/clinical mobility issues on behavioral and physical health including chronic inflammation and immunocompetence.
  • Breed-specific relationships between age-related sensory perception and mobility.
  • Impacts of nail trimming on pain and mobility, ideally including force plate analysis.

Frailty
The frailty-related phenotype is poorly defined in animals. Other than a frailty phenotype described for aged guide dogs,5 there remains a need for validated breed/size-specific metrics that would allow us to meaningfully test interventions. The potential use of such information by owners and veterinarians would need to be clearly defined. Frailty is complex, multifactorial and, in common with other species, can overlap with mobility issues and pain. Measurements of frailty could include walking speed, as commonly seen for human patients, and muscle imaging to define sarcopenia. Clinical approaches once the phenotype is defined could address protein deficiency, including supplements (e.g., omega-3 fatty acids) to enhance skeletal muscle anabolism and use of pharmacological appetite stimulants.

Potential Research Questions

  • Development of a consensus statement to define canine frailty by an expert international task force, with a focus on assisting veterinarians in primary care practice.
  • Breed/size-specific frailty phenotype scoring systems applicable in general practice that support the testing of interventions to increase healthspan.
  • Better definition of age-related sarcopenia.
  • Nutritional and/or pharmacological interventions to normalize muscle mass or body composition and associated frailty.

Inflammaging and Immunosenescence
The process of aging involves cellular and tissue deterioration that can lead to chronic inflammation. Validated age-specific biomarkers or panels for inflammatory processes are needed, particularly for early detection of animals experiencing accelerated biologic aging. Immune system senescence also limits an individual’s responses to stress and disease including cancer. Collectively, these processes influence both physical and behavioral health including cognition.

Potential Research Questions

  • Clinically relevant, validated, life stage-specific biomarkers/panels for inflammatory load, particularly those that might be detected in urine or saliva i.e., amenable to patient-side diagnostic screening.
  • Data on age-related inflammatory and immune system alterations in dogs with interventions to slow/mitigate progression.
  • Differences in responses to vaccination in senior versus younger animals including the long-term effects of vaccinating at an early age or repetitive vaccine boosters.

Owner and Veterinarian Awareness of Specific Needs
Primary care practitioners are time-poor and standard clinic visits generally ill-suited to the more nuanced consultation needed to advise on dietary or home environment changes that might benefit senior dogs. Screening tools could assist in directing clients to more specialized assistance (e.g., nutritional), which might be veterinarian or technician led. Prevention and early detection should be the focus, with an emphasis on the importance of good care at earlier life stages to prolong healthspan. Currently gerontology is taught in a haphazard fashion in veterinary schools, despite our heavy caseloads of senior pets. General practitioners are well placed to navigate complex medical and emotional situations, financial realities, and act as an advocate for their patients. Keeping a focus on “just because we can doesn’t mean we should” is as important as ensuring that palliative/hospice care (as appropriate) is seen as a positive option. The influence of pet insurance on these choices is an unknown.

Potential Research Questions

  • Surveys of veterinarians/owners to determine awareness and confidence in dealing with senior dog issues and any mismatches in perceptions.
  • Screening tools, potentially app-based, to assist owners and veterinarians in early identification of senior life-stage issues.
  • Development of a consensus statement for senior dog health care by an expert international task force, with a focus on assisting veterinarians in primary care practice.
  • Determining the role for telehealth in assisting with senior dog issues including supporting pets and their owners who might need more frequent consultations.

End-of-Life Care
Owners remain unsure as to the difference between palliative and hospice care and this should be addressed. With terminal disease (which might require hospice care), experience with human patients has shown the value of accepting that prognosis and focusing on QoL. Veterinarians probably need to bring up the word “euthanasia” sooner and be the first to do so, such that patient care is optimized. Misconceptions remain as to what constitutes a “natural death” which can lead to welfare issues if unassisted. Other huge issues for owners and their veterinarians are anticipatory grief or conversely, the shock of an animal suddenly requiring euthanasia versus a more planned situation involving chronic health issues.  

Communication missteps that inadvertently traumatize owners when their pet is euthanized might not be recognized by veterinarians. Interestingly, veterinarians who work with organizations that provide euthanasia services report happy and fulfilling careers, without the time constraints of general practice; owner experience with this specialist practitioner group may differ.

Potential Research Questions

  • Effective communication methods related to euthanasia, including determining potential touchpoints to prevent inadvertent owner guilt or psychological trauma.
  • Pharmacological studies to develop euthanasia protocols (including pre-euthanasia sedation) with fewer/minimal side effects.
  • More effective and holistic QoL assessment tools to assist with euthanasia decisions including behavioral issues.

Conclusions
Our panel agreed that “general practitioners are the gerontologists” of the veterinary world. Meaningful research for senior dogs must concretely address their needs, those of their owners, and those of their veterinarians. Studies should account for the sizes/breeds of dogs involved in terms of life stages and aging, which must be biologically defined. Research might also focus on “subphases” for seniors i.e., early, mid-phase (and experiencing clinical problems), and end-of-life care. We prefer collaborative projects with the potential to rapidly translate to the clinic. The suggestions for possible research questions accurately reflect our interests and we anticipate that successful projects will take these or very closely related approaches. We will not fund off-topic. Relevant projects involving more than one of the discussed areas are also welcome.

Acknowledgements
The author declares that there were no conflicts of interest.

References

  1. Wang T, Ma J, Hogan AN, et al. Quantitative translation of dog-to-human aging by conserved remodeling of the DNA methylome. Cell Syst 2020;11:176-185.
  2. Feng X, Valdearcos M, Uchida Y, et al. Microglia mediate postoperative hippocampal inflammation and cognitive decline in mice. JCI Insight 2017;2;e91229.
  3. O’Brien ML, Herron ME, Smith AM, et al. Effects of a four-week group class created for dogs at least eight years of age on the development and progression of signs of cognitive dysfunction syndrome. J Am Vet Med Assoc 2021;259:637-643.
  4. Bowen J, Fatjó J, Serpell JA, et al. First evidence for an association between joint hypermobility and excitability in a non-human species, the domestic dog. Sci Rep 2019;16:8629.
  5. Hua J, Hoummady, S, Muller C, et al. Assessment of frailty in aged dogs. Am J Vet Res 2016;77:1357-1365.

Blue-Ribbon Panel

Julie Buzby, DVM, CVA, CAVCA, Dr. Buzby’s Innovations, LLC
Areas of Expertise: Veterinary chiropractic, dog traction and mobility

Julie Churchill, DVM, PhD, DACVIM (Nutrition), University of Minnesota
Areas of Expertise: Veterinary nutrition

Heidi Lobprise, DVM, DAVDC, Cibolo Creek Veterinary Hospital
Areas of Expertise: Dentistry, senior care

Talisha Moore, DVM, DACVIM, University of Tennessee
Areas of Expertise: Neurology, neurosurgery, neuro-imaging

Sheilah Robertson, BVMS (Hons), PhD, DACVAA, DECVAA, DACAW, DECAWBM (WSEL), CVA, MRCVS, Lap of Love Veterinary Hospice Inc., and University of Florida
Areas of Expertise: Analgesia, acute and chronic pain management, acupuncture, euthanasia, quality of life assessment, chronic painful diseases, veterinary medical ethics, end of life care, palliative care, hospice care

Carlo Siracusa, DVM, MS, PhD, DACVB, DECAWBM, University of Pennsylvania
Areas of Expertise: Small animal behavior and stress assessment

Dean Vicksman, DVM, Evans East Animal Hospital and Denver Cat Hospital
Areas of Expertise: Veterinary medicine and practice management