Literature Review: Canine Cognitive Dysfunction
Just like their human caretakers, pet dogs are reaping the benefits of medical advancements and are living longer than ever before (Katina et al., 2016; McGreevy & Bennett, 2010). While a longer lifespan is viewed as a positive by most owners, a dog’s golden years can come with a host of age-related medical and behavioral challenges. Canine cognitive dysfunction (CCD), similar to Alzheimer’s Disease in humans, is one such condition affecting a notable proportion of the country’s approximately 30 million senior and geriatric dogs (Madari et al., 2015). The frequency of CCD in dogs is estimated to range between 14 and 67% in senior dogs (usually defined as dogs older than 8 years of age), with the percentage of dogs affected increasing with age. With upwards of one in five senior-aged companion dogs experiencing impaired cognitive function, it is critical that we work to better understand, identify, treat, and manage CCD in our aging pets to ensure their later years are as comfortable and low stress as possible.
In this article, I will review the behavioral indicators of CCD along with the underlying neurobiological mechanisms associated with the condition. I will examine factors that increase a dog’s risk of developing CCD, review current tools and techniques used for diagnosis, and evaluate the efficacy of current treatment options for CCD. Finally, I will discuss future research opportunities with a focus on increasing rates of diagnosis, exploring effects of combining multiple treatment types, and providing support to owners of dogs with CCD.
Defining canine cognitive dysfunction
Beyond normal aging: Behavioral indicators of CCD
Canine cognitive dysfunction is a progressive, age-related, neurodegenerative condition that affects cognitive function. The impairments of memory function and learning ability caused by CCD are marked by changes in behavior that include altered social interactions, changes in the sleep/wake cycle, confusion and disorientation, house training issues, increased anxiety, and changes in overall activity level (Fast et al., 2013; Madari et al., 2015). The most common clinical symptoms of CCD include (Fast et al. 2013; Cory, 2013; Schutt et al., 2015):
- Sleeping during the day and being restless at night
- Showing a decrease in social interaction with the owner and other familiar people and pets
- Becoming disoriented in the home
- Displaying increased anxiety in a variety of situations
- Failure to recognize familiar people and pets
- Aimless wandering and pacing
- Getting “lost” in corners and behind furniture
- Staring into space
- Engaging in repetitive or incomplete behaviors
- Failure to perform previously known obedience behaviors
- Avoidance of petting, or an increased desire for contact and attention from the owner.
Canine cognitive dysfunction is a progressive disorder, meaning behavioral symptoms will worsen over time; however, the rate of prevalence of various symptoms and the rate of cognitive decline will vary greatly based on the individual (Schutt et al., 2015).
In a study of 64 senior dogs of various breeds, ages, and sizes, CCD symptoms progressed as follows over a 12- to 14-month period: at first measurement, six to eight months after baseline, 42% of subjects diagnosed as having normal cognitive function had progressed to showing mild cognitive impairment, 24% of those dogs that started with mild cognitive impairment progressed to showing moderate cognitive impairment, and 85% of those that started off diagnosed as having moderate cognitive impairment remained in the “moderate” category. After an additional six months, 71.4% of the dogs who were originally classified as having normal cognitive function were found to have mild cognitive impairment, and 50% of the dogs who were “mildly” impaired at baseline had progressed to moderate cognitive impairment (Madari et al., 2015).
Neurobiological changes involved in CCD
There are a number of neurodegenerative changes associated with CCD. A certain degree of cortical atrophy is normal in an aging brain, but CCD is associated with a greater-than-normal degree of cortical atrophy (Cotman & Head, 2008; Fast et al., 2013). Neuronal loss, decreased neurogenesis, and changes to neurotransmitter pathways, including the serotonergic pathway, are also present to a greater degree in the brains of dogs with CCD (Cory, 2013; Cotman & Head, 2008; Fast et al., 2013).
Cotman and Head (2008) hypothesized that both neuronal loss and cortical atrophy may be caused, at least in part, by an accumulation of pathological proteins like amyloid-β (Aβ). Indeed, an abundance of research has examined the role of Aβ in CCD, in terms of both the extent and location of deposits, and many studies indicate that an increased presence of Aβ is associated with increased cognitive impairment, particularly with regard to deficits in discrimination learning, reversal learning, and spatial learning (Cummings et al., 1996; Fahnestock et al., 2012; Fast et al., 2013; Schutt et al., 2015).
A study involving dogs aged 10 years and older (Ozawa et al., 2016) found that levels of amyloid-β deposits may in fact be an indirect consequence, rather than a direct causal factor, in CCD. However, treatments that aim at reducing behavioral symptoms of CCD by reducing levels of amyloid-β in the brain have been shown to be effective, suggesting there is still much we don’t know about the relationship between Aβ and CCD.
Oxidative damage caused by free radicals is a widely accepted contributing factor in cognitive decline (Cotman & Head, 2008). Looking more closely at oxidative damage, Snigdha et al. (2011) hypothesize that caspase activation and ceramide accumulation in the frontal cortex contribute to both oxidative damage (due to an increased presence of free radicals) and increased Aβ production.
Other potential factors associated with an increased prevalence of CCD include a decreased concentration of vitamin E (Fast et al., 2013; Skoumalova, 2003), and changes in intracellular calcium regulation (Milgram et al., 2015).
Detecting canine cognitive dysfunction in senior dogs
Symptoms of CCD can potentially progress relatively quickly and can have severe negative impacts on a dog’s quality of life. However, owners may confuse CCD symptoms for regular behavior changes related to old age—a likely factor in explaining why CCD has a high rate of under-diagnosis (Hamnilrat et al., 2015). Despite there being an assortment of effective, readily available techniques to diagnose the condition, many owners whose dogs display behaviors consistent with CCD do not think their dogs have a problem with cognitive function, and as many as one in seven cases go undiagnosed by a veterinarian (Salvin et al., 2010).
Further complicating matters is the fact that certain behavioral symptoms associated with CCD are similar to symptoms of other medical problems, so CCD is identified through differential diagnosis.
Identifying at-risk individuals
Age is the number one predictor of whether a dog develops CCD, with likelihood of both prevalence and severity of symptoms increasing as a dog ages (Katina et al., 2016). Although I did not find definitive data regarding typical age of onset of CCD symptoms, most studies I reviewed examined dogs aged 8 years and older.
There is conflicting evidence about whether sex, reproductive status, or body size are associated with prevalence of cognitive decline. One study showed significant differences between male vs. female, intact vs. neutered/spayed, and small breeds vs. large breeds, but data collection was based entirely on owner surveys and did not include clinical evaluations of the dogs’ behavioral symptoms (Askona et al., 2009). Two studies that relied instead on clinical observation in addition to owner accounts of behavior, found that sex, weight, and reproductive status were not significantly correlated with cognitive decline (Fast et al., 2013; Katina et al., 2016).
Dietary factors, as well as levels of physical exercise and cognitive activity, appear correlated with a dog’s long-term cognitive health (Cory, 2013; Pop et al., 2010). A study of senior dogs of varying ages examined the link between nutrition and cognitive health, and found that dogs that consumed a controlled diet (classified as a quality commercial food, wet or dry, made for a specific breed, age, or life stage) were 2.8 times less likely to develop CCD than dogs fed an uncontrolled diet (classified as a diet comprised of scraps and a variety of different foods, including low-quality commercial food) (Katina et al., 2016).
In addition to internal factors such as age, diet, exercise, and cognitive activity, a dog’s external environment can also put them more at risk of developing CCD. Cory (2013) points to evidence that feral dogs that live in high air pollution areas show increased oxidative damage and increased levels of amyloid-β at an early age. Exposure to noise pollution, and residing in an impoverished environment with little novelty or cognitive enrichment may also correlate negatively with cognitive impairment.
Based on the information above, it seems reasonable that veterinarians begin to actively screen their canine patients for signs of CCD at 8 years of age. Particular attention may be paid to those dogs that are in poor body condition (potentially indicating a poor diet and/or lack of exercise), and those dogs that reside in areas with greater degrees of noise and air pollution.
Behavior-based diagnostic tools
Owner-completed questionnaires are an important first step in identifying dogs with CCD. Several questionnaires have proven to be effective, reliable diagnostic tools; some are intended for dogs displaying multiple symptoms and/or moderate to severe symptoms of CCD, and others are for mild to moderate impairment (Schutt et al., 2015).
The canine cognitive dysfunction rating scale (CCDR) (Salvin, 2011) was created using 27 previously validated behavioral indicators of CCD (Salvin, 2010) and comprises 13 behavioral items, three of which relate to determining severity of the condition. Despite the exclusion of questions asking about anxiety and changes in sleep/wake cycle—two of the four most commonly reported clinical signs of CCD—the the CCDR showed 98.9% diagnostic accuracy, making it a valuable and convenient screening tool that owners can complete in their homes, or behavior consultants can give to clients. The CCDR is available online as a PDF, here.
Neurological and biochemical diagnostic tools
Canine cognitive dysfunction shares similar symptoms with other medical and functional diseases, so veterinarians will often conduct an assortment of tests including blood count, thyroid profiles, urinalysis, and more, to rule out other conditions and arrive at a differential diagnosis of CCD (Schutt et al., 2015). There are specific tests available to definitively diagnose CCD, but they are limited, expensive, and often invasive to the animal.
Magnetic resonance imaging (MRI) is an effective diagnostic tool that can quickly identify whether a dog is affected by CCD, while also ruling out the presence of other diseases (Pugliese et al., 2010). A CCD-affected brain will show visible cortical atrophy, specifically in the medial temporal lobe, entorhinal cortex, and hippocampus (Cory, 2013). While effective, an MRI is often prohibitively expensive for owners, as well as risky for senior dogs because it must be performed under general anesthetia (Pugliese et al., 2010).
Visual evoked potential (VEP) tests that evaluate the optic nerve pathway are used in the diagnosis of Alzheimer’s disease, but are less established as a neurological diagnostic tool for CCD. However, the VEP’s proven ability to confirm the presence or absence of brain atrophy could make it a promising and less costly alternative to an MRI. A study of 28 Pomeranian dogs showed that VEPs were not significantly different for “normal” dogs of all ages; VEP patterns indicated cortical atrophy in eight of ten CCD-symptomatic dogs; and, especially promising, VEP patterns for the remaining two of ten CCD-symptomatic dogs were different from all other groups, and further diagnostic testing confirmed these two dogs had brain tumors (Hamnilrat, 2015).
Treatment of Canine Cognitive Dysfunction
Treatments for CCD fall into one of three primary categories: Special diets and dietary supplements; environmental and behavioral enrichment; and pharmacological intervention. Generally, dogs with CCD show an increased sensitivity to change. They have a harder time coping with ordinary life stressors, and show a decreased ability to adapt to unexpected situations (Fast et al., 2013). For this reason, it is important for owners to understand that, in addition to the specific treatments discussed below, any changes to environment and routine should be introduced gradually whenever possible; even the implementation of new enrichment activities designed to improve cognitive function could be stressful if introduced too quickly (Cory, 2013; Landsberg, 2005).
Dietary interventions for CCD involve the inclusion of ingredients that target free radicals, reduce inflammation, protect cell health, enhance signaling in the brain, enhance metabolism, target amyloid-β, or more rarely, work to increase levels of ketone bodies in the blood to improve brain function (Heath et al., 2007; Fahenstock et al., 2012; Landsberg et al., 2005; Pan, 2011; Pop et al, 2010).
It has been proposed that an appropriate diet throughout a dog’s lifetime can prevent or slow cognitive impairment later in life (Katina et al., 2016). Research also shows that a specially formulated diet can enhance cognitive function once cognitive impairment is present. The efficacy of Hills Pet Nutrition Prescription diet® Canine b/d, a diet specially formulated to improve cognitive function and widely available via veterinarians for the treatment of CCD, was assessed over a two-year period via clinical trials (Milgram et al., 2005). Compared to baseline measures, dogs showed significantly improved performance on cognitive tests after between two and eight weeks on the diet. The specialized diet claims to reduce production and toxic effects of free radicals, protect cell health, and reduce inflammation via incorporation of a broad range of antioxidants, vitamin E and C supplements, and an increased amount of omega-3 fatty acids (Milgram et al., 2005).
Two vitamin supplements, Aktivait® and Senilife®, join Hills b/d as clinically tested, broadly available dietary treatment options for CCD; Aktivait works to improve quality of life through increased social interaction and decreased repetitive behavior, while Senilife works to improve memory and learning ability in dogs displaying more mild CCD symptoms (Cory, 2013). In a study of senior dogs showing signs of CCD, dogs in an Activait treatment group showed significant improvements in social interactions, spent significantly more time awake during the day, experienced significantly fewer instances of lack of recognition, and showed significant improvements in house soiling compared to a control group after 42 days of treatment (Heath et al., 2007). Used primarily in the United Kingdom, Aktivait ingredients include DHA, vitamins C and E, l-carnitine, coQ10, selenium, and more (VetPlus, 2016). A smaller study with dogs older than 7 years of age showed that Senilife significantly improved dogs’ CCD symptoms of disorientation, impaired social and environmental interaction, disrupted sleep/wake cycles, house soiling, and general changes in activity level, though it should be noted that dogs in the study displayed relatively mild symptoms of CCD (Osella et al., 2007). Most prevalent in North America, Senilife ingredients include phosphatidylserine, pyridoxine, and d-alpha-tocopheral (Ceva Animal Health, 2015).
Various studies have looked more deeply at how these dietary supplements, particularly those rich in antioxidants, promote cognitive health. Fahnestock et al. (2007) showed that an antioxidant-enriched diet increased levels of brain-derived neurotrophic factor (BDNF), a protein that promotes brain plasticity through its role in the growth and maintenance of neurons in the brain and spinal cord. BDNF levels are inversely correlated with amyloid-β levels. Snigdha et al. (2011) noted that activation of caspase and accumulation of ceramide in the frontal cortex play a notable role in oxidative damage caused by free radicals, and also in amyloid-β production. They found that, when combined with behavioral enrichment, an antioxidant-enriched diet significantly reduced both caspase and ceramide levels.
While antioxidants have proven themselves a powerful component in improving cognitive health in dogs with CCD, limitations exist, including research suggests that antioxidants may not be effective at increasing neurogenesis in the brain (Pan, 2011). Medium-chain triglycerides (MCT), however, have proven successful in improving brain function in humans with Alzheimer’s disease by increasing levels of ketone bodies in the blood, which act as a source of energy for the brain (Pan, 2011). A study of cognitively normal senior beagles tested the effects of an MCT-enhanced diet compared to a control diet over 240 days, and found that dogs on the MCT diet showed significant improvement in cognitive capabilities with regard to attention, memory, spatial learning, and executive function. Cognitive improvements were apparent 15 to 30 days into treatment (Pan, 2011). MCT is not currently a component of common dietary treatments for CCD, but its use warrants further investigation, especially considering that digestible sources of MCT, such as coconut oil, are readily available to most owners.
Other various herbs, extracts, and nutraceuticals such as Dog Appeasing Pheromone (DAP®), melatonin, and valerian root are purported to increase calmness and reduce general anxiety, though there is no published research that shows the efficacy of these products in improving symptoms related to cognitive decline (Landsberg, 2005).
A multitude of studies confirm that the provision of cognitive and environmental enrichment opportunities can both prevent (or delay) and improve symptoms of cognitive decline (Cory, 2013; Cotman & Head, 2008; Fahnestock et al., 2012; Landsberg, 2005; Pop et al., 2010; Snigdha et al., 2011). A longitudinal, two-year study of senior dogs showed that a control group receiving no environmental enrichment showed significant and dramatic cognitive decline compared to the enrichment group (Landsberg, 2005).
Behavioral enrichment can include:
- Cognitive stimulation in the form of food puzzles, access to novel toys, training and practicing simple behaviors, and working on more complex cognitive tasks such as discrimination and concept training;
- Social enrichment in the form of access to and positive interaction with conspecific friends and human friends;
- Physical exercise by way of leash walks and off-leash playtime (Landsberg, 2005; Pop et al., 2010).
With all behavioral enrichment treatments, it is important to provide enough variety that the activity is, in fact, enriching, but to keep the amount of novelty and change at a level appropriate for the individual dog—dogs with mild cognitive impairment may be able to handle more than dogs with more severe levels of dysfunction. Behavioral enrichment is important not only for the related benefits to cognitive function, but also to help the dog maintain or reclaim a more normal sleep/wake cycle by providing enough activity and stimulation during the day so the dog can sleep at night (Landsberg, 2005).
It is of critical importance to note that, in nearly all studies examining both enhanced diets and behavioral enrichment treatments, a pronounced and significant additive effect on cognitive function occurred when both treatment types were used together (Cotman & Head, 2008; Fahnestock et al., 2012; Milgram et al., 2005; Pop et al., 2010; Snigdha et al., 2011), compared to either being used alone.
Selegiline is the only drug approved specifically for the treatment of CCD (Landsberg, 2005). A selective, irreversible monoamine oxidase-B (MAO-B) inhibitor, it works to improve levels of dopamine and serotonin in the brain, while also providing neuronal protection and reducing production of free radicals (Head et al., 1996; Landsberg, 2005). Some studies have shown the drug to be widely variable in its effectiveness, depending on dosage and on the individual, producing only minimal or modest results among study participants (Head et al., 1996; Studzinski et al., 2005); others showed that administration of selegiline significantly improved behavior in senior dogs showing symptoms of CCD, most notably after 30 days of treatment (Campbell et al., 2001; Ruehl et al., 1995). The discrepancy in findings appears to stem from varying emphases across studies: Those studies that reported highly varied results and minimal effectiveness were focused on measuring memory and learning ability, while those studies that confirmed the drug’s effectiveness showed noted improvements in sleep/wake cycle and disorientation.
There is some evidence that intracellular calcium regulation may contribute to the structural—and in turn, behavioral—changes involved in CCD. A study examining the use of apoaequorin, a calcium-binding protein found in jellyfish, on cognitively healthy senior beagles showed greater improved performance on attention tasks and discrimination learning tasks for dogs taking apoaequorin compared to dogs taking selegiline (Milgram et al., 2015). This finding supports my hypothesis that selegiline may not be highly effective at improving learning ability, but instead provides relief to CCD-affected dogs by way of improved sleep patterns and reduced disorientation.
Anti-inflammatory medications, anxiolytics, and antidepressants can all play a useful primary or supporting role in treatment by helping to reduce the anxiety that often accompanies CCD (Cotman & Head, 2008; Landsberg, 2005).
Canine cognitive dysfunction is a progressive, neurodegenerative, age-related condition that presents a serious welfare concern for our senior canine companions. Disruptions to the sleep/wake cycle, feelings of disorientation, increased anxiety, and failure to recognize beloved family members are just some of the heart-wrenching behavioral symptoms associated with CCD (Cory, 2013). Although the disease cannot be cured, its progress can be slowed, and the dog’s quality of life can be improved. More can be done the earlier the disease is diagnosed, so education efforts will be required to raise awareness about the condition.
In addition to targeted dietary, behavioral, and pharmacological treatments, it is important to provide dogs with CCD with a predictable routine and low-stress environment due to their reduced coping abilities and often increased anxiety (Cory, 2013; Landsberg, 2005).
While CCD does not appear to affect life span, it does present a serious risk to quality of life, both to the dogs affected and to the owners caring for dogs with CCD. From my research, I have identified three important areas that deserve additional attention in CCD-related research and practical applications, as they have the potential to significantly, positively impact quality of life for both senior dogs living with CCD and their owners:
- Increasing the rate of diagnosis.
- Conducting further research on novel treatment approaches that consider lines of research being conducted for treatment of human Alzheimer’s disease, and, examining the efficacy of multiple treatment types used together.
- Conducting research on and providing resources to owners whose personal welfare is impacted by caring for a dog with CCD.
Increasing the rate of diagnosis of CCD is imperative to improving the wellbeing of those dogs that go undiagnosed for two reasons. First, if dogs go undiagnosed, they are not receiving treatment and management interventions to improve cognitive function, decrease anxiety levels, and slow rate of cognitive decline. Second, owners may interpret certain CCD symptoms as general bad behavior, especially in cases of inappropriate social interactions, house soiling, and destructive behavior, and thus attempt to punish the dog for behavior that is beyond their control. Education will be critical to improve diagnosis rates of CCD; I suggest that veterinarians incorporate standard “senior cognitive checks” into examinations for dogs aged 8 years and up. Further, educational messaging about identifying signs of CCD should be disseminated via veterinary clinics, kennel clubs, rescue groups and shelters, and online to dog-related social media groups.
Novel lines of research exploring behavioral, dietary, and pharmacological treatments will hopefully result in new, more effective treatment options for CCD. Milgram et al.’s (2015) focus on intracellular calcium regulation and Pan’s (2011) focus on the use of dietary medium-chain triglycerides to promote brain neurogenesis in senior dogs are to be commended for their investigations into previously unexplored options to improve cognitive health in aging canine brains.
Researchers have already documented the additive benefits of combining dietary enhancement with behavioral enrichment in the treatment of CCD. Additional research that explores the effectiveness of combining multiple treatment types—including pharmacological interventions—could prove invaluable in helping veterinarians arrive at general best practice treatment plans for CCD.
A diagnosis of canine cognitive dysfunction is one that may test and strain an owner’s relationship with their dog. The stress of seeing a loved companion lose cognitive faculties, potentially withdraw from previously enjoyed attention and activities, and display disruptive and concerning behaviors is disturbing in and of itself; but living with a dog with CCD can impact other areas of an owner’s life as well. Altered sleep/wake cycles in the dog, potentially accompanied by vocalizations and repetitive movements, can affect an owner’s quality and quantity of sleep; an increased desire for contact and decreased ability to cope with changes and separation may restrict an owner’s ability to travel or be flexible in work and social endeavors. Certainly, the role of CCD caregiver deserves attention both in research and in support-focused practical applications. The formation of specialized group training classes that offer age-appropriate behavioral enrichment for cognitively impaired senior dogs could be beneficial not only to the dog, but also to the owner as an ongoing source of community and support.
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Sarah Fraser, CDBC, KPA-CTP, CPDT-KA, is Co-Founder of Instinct Dog Behavior & Training in NYC, and Co-CEO of Instinct Dog Training Inc. Sarah has worked with hundreds of NYC owners and dogs with aggression, fear, and anxiety issues. Her primary role with Instinct is oversight of training & behavior programming, marketing & social media, and implementation of Instinct’s mission to provide help and hope to every dog and owner through kind, practical dog behavior & training resources. Sarah holds a Bachelor of Commerce in Marketing Management from Dalhousie University, and is an MA Candidate, Animal Behavior & Conservation at Hunter College/CUNY. She lives in NYC with Co-Founder Brian Burton, and their 5 adopted Helper Dogs, dogs, Buster, Mozeez, Will, Jacky, and Joey.