What is Cognitive Dysfunction Syndrome (CDS)?
Cognitive Dysfunction Syndrome or commonly referred to as Canine Cognitive Dysfunction in dogs is a neurobehavioral disorder that causes an age-related decline in cognitive functioning in senior dogs and cats. Cognitive functions include: perception, awareness, learning and memory. The disorder can be compared to dementia in humans. Similarly to humans, it’s devastating to experience your pet displaying these progressive behavioral changes. Pets who develop CDS often require increased care and environment alterations to accommodate their needs and make them comfortable.
Pathophysiology of Cognitive Dysfunction Syndrome
Cognitive Dysfunction Syndrome is very similar to Alzheimer’s disease in humans. There are many theories about the pathology of both Alzheimer’s and Cognitive Dysfunction Syndrome. The two main theories are:
- toxic plaques build up around brain cells (neurons) resulting in cognitive dysfunction
- accumulation of reactive oxygen species damages neurons resulting in cognitive dysfunction
Amyloid-beta and neurofibrillary tangles (composed of TAU proteins) are protein plaques that are toxic to neurons. Build up of these plaques causes neuronal damage leading to cognitive dysfunction. In dogs, it has been shown that build up of TAU causes weakening of signaling between neurons.
Aging has been associated with the increased production of reactive oxygen species. When the body creates energy, the by-products (reactive oxygen species) of that process can cause damage to cells, fats and proteins. Protective mechanisms that fight reactive oxygen species begin to fail with age. Antioxidants are molecules that fight reactive oxygen species to prevent them from damaging cells. They are produced within the body and also come from your dog’s diet. Reduction in antioxidants has been associated with aging.
How Common is Cognitive Dysfunction Syndrome?
Cognitive Dysfunction Syndrome is actually quite common, but undiagnosed. It is often overlooked because symptoms exhibited are often thought to be a part of the normal aging process. While cognitive dysfunction is associated with the aging process, there are therapeutic treatments to slow down progression and often improve symptoms. Early diagnosis and treatment increases the prognosis of slowing down the disease progression. Prevalence of CDS in dogs 11-12 years old is 28% and 68% in dogs 15-16 years old. Prevalence of CDS in cats 11- 21 years old is 36%. Data collected from a questionnaire study estimated that around 14.2% of pets displayed symptoms of CDS and only 1.9% were diagnosed by a veterinarian.
How is Cognitive Dysfunction Syndrome Diagnosed?
Cognitive Dysfunction Syndrome (CDS) is diagnosed by exclusion of other pathologies. Since animals are unable to tell us what’s wrong it’s important to rule out all possible disease processes that cause behavior changes. There are several disease processes that can cause behavior changes, including: endocrinopathies, degenerative joint disease, central nervous system disorders, renal (kidney) disease, bladder and urinary infections, dental disease and hypertension (high blood pressure), Before diagnosing CDS, a veterinarian will perform a thorough physical examination, pain assessment, complete blood panel, biochemistry panel and urinalysis. Diagnostic imaging, such as radiographs, ultrasound and an MRI as well as endocrine tests that measure specific hormone levels may be recommended depending on the patient’s history, presentation and clinical symptoms. A general practice veterinarian may provide you with a referral to a veterinary neurologist because they specialize in neurological conditions that are also responsible for behavioral changes. In addition, general practice clinics typically do not have CT and MRI testing equipment.
Animals show pain differently than humans. Oftentimes, pets attempt to hide their pain. Prior to domestication, hiding pain was advantageous to their survival. Wild animals who display signs of pain are viewed as weak and vulnerable by others. Although dogs have been domesticated for many years now, some dogs still have this inherited trait of survival. This can be confusing and disheartening to owners, especially when pain is detected on an annual examination to which the owner was not aware. Pets may or may not vocalize when they are in pain. Contrary to popular belief, vocalization is the least specific indicator of pain. The best indicator of pain is changes in behavior and body language. For this reason, it’s extremely important to rule out potential pain before diagnosing CDS.
Listed below are some common behavior changes seen in pets, however, any shift in behavior can be indicative of pain and should be evaluated by a veterinarian.
- Decreased activity, sleeping more than usual
- Compulsive licking and teeth grinding
- Staring at the wall or ceiling
- Increased clinginess or seeking attention
- Aggression or guarding
- Submissive behavior
- Decreased desire for attention or social interaction
- Refusal to move
- Lacking interest in playtime or walks
- New or abnormal body posture
- Anxious behaviors: worried facial expression, pacing, restlessness, self-mutilation from chronic licking or biting and hiding
- Decreased appetite
The Canine Dementia Scale or CADES is a statistically validated assessment tool used to diagnose Cognitive Dysfunction Disorder and evaluate the efficacy of therapeutic methods. The scale is broken down into four distinct categories of cognitive functioning, which are spatial orientation, social interactions, sleep-wake cycles and house soiling.
Symptoms of Cognitive Dysfunction Syndrome
- Pacing back and forth, circling and wandering aimlessly
- Getting lost in familiar places and failing to recognize familiar people
- Appearing confused or staring at the wall or ceiling
- Getting stuck behind furniture
- Failure to greet you at the door when you come home
- Diminished reaction in response to their name
- Decreased interest in their favorite activities
- Decreased desire for attention
- Sleeping throughout the day and waking up frequently throughout the night (termed “sundowning”)
- Failure to remember routines
- Barking or howling at night and restlessness
A research study published in the Journal of Veterinary Medical Science in 2019 collected data through an online questionnaire to better understand the physical disturbances related to canine cognitive dysfunction. They obtained 726 responses, in which vision impairment, smell disturbance, tremor, swaying or falling and head ptosis (drop neck) were frequently experienced in dogs with cognitive dysfunction.
Treatment for Cognitive Dysfunction Syndrome
Cognitive Dysfunction Syndrome (CDS) is a progressive disease. Unfortunately there is no cure, however there are effective treatment options to slow down progression and improve clinical symptoms. Treatment consists of nutrition and pharmacologic intervention as well as enrichment and environmental management. Foods rich in antioxidants aid in counteracting the negative effects of toxic free radicals and boost immunity. There are several antioxidants, some include vitamin C, vitamin E and beta-carotene that are found in many fruits and vegetables.
Omega 3 fatty acids are essential fats. They are present in the neuronal membrane and aid in synaptic transmission and neuroprotection. Alpha-linolenic acid (ALA) is a type of omega 3 fatty acids that is found in plant oils, such as flaxseed and walnut. Hill’s b/d prescription diet is filled with antioxidants and omega-3 fatty acids. Medium chain triglycerides (MCT) are another form of fatty acids, but have shorter carbon chains. This allows MCT to quickly be converted by the liver to ketones, a bioavailable fuel source. Glucose is the main fuel source of neurons, but the aging process reduces glucose metabolism and ketones act as an additional fuel source. Purina Pro Plan Bright Mind Adult 7+ and Purina One Smartblend Vibrant Maturity 7+ formula contain MCTs. There are currently no therapeutic diets available for CDS in cats. There are foods available with antioxidants and essential fatty acids, such as Hill’s j/d prescription diet which is designed for the management of feline arthritis. Other dietary supplementations that may be effective at improving symptoms of canine cognitive dysfunction include: phosphatidylerine (Senilife), apoequorin (Neutricks) and S-Adenosyl-L-Methionine (Denosyl).
Selegiline hydrochloride is FDA approved for the use in dogs to manage progression and symptoms of canine cognitive dysfunction. It is a selective, irreversible monoamine oxidase B (MAO-B) inhibitor that is used in humans to treat Parkinson’s disease and major depressive disorder. MAO-B is an enzyme that is responsible for breaking down several chemicals in the brain, including dopamine, norepinephrine and serotonin. An MAO-B inhibitor, inhibits the breakdown of these chemicals. In doing this, the levels of these chemicals increase. It also decreases formation of toxic free radicals. The onset of action is not immediate. It can take anywhere from 1 to 3 months to see results. While there is not an approved drug for use in cats, selegiline can be used off-label in cats with cognitive dysfunction syndrome.
Possible side effects include…
- Agitation or aggression
- Vomiting and diarrhea
- Repetitive movements
- Excessive drooling
- Excessive licking
- Decreased appetite
- Panting more than usual
Let your veterinarian know if your pet experiences any of the above side effects. The most common side effects are GI upset, including vomiting, diarrhea and loss of appetite. Drug tolerance varies from patient to patient and the dose may need to be lowered if your pet is experiencing these symptoms. Speak with your veterinarian IMMEDIATELY if your pet begins excessively panting or pacing. These side effects are rare, but could be a sign of drug toxicity.
Selegiline should not be used in combination with other MAO inhibitors as it increases the chances of side effects and may result in a life threatening disorder called serotonin syndrome. Types of medications include: antidepressants (Prozac, Zoloft, Paxil, etc.), phenylpiperidine opioids (methadone, tramadol, Demeral®), phenylpropanolamine (Proin®), alpha 2 agonists (SILEO®), trazodone or buspirone (Buspar®). If visiting a new veterinary clinic or specialty center, be sure to let the veterinarian know that your pet is taking selegiline as it interacts with several drugs administered for anesthetic procedures.
Symptoms of serotonin syndrome depend on the severity of the condition and include:
- Vomiting and diarrhea
- Agitation or depression
- Muscle rigidity (stiffness)
- Sweating and shivering
- Hypersalivation (excessive drooling)
- Ataxia (impaired balance and coordination)
- Hyperthermia (elevated body temperature)
- Hyperesthesia (excessive physical sensitivity)
- Mydriasis (dilated pupils)
- Tachypnea (increased respiratory rate)
- Tachycardia (increased heart rate)
- Hypertension (elevated blood pressure)
- Transient blindness (short-lived)
Cholinesterase inhibitors, tactrine, donepezil and rivastigmine, is a drug class approved for use in humans to treat Alzheimer’s disease. This drug class increases the amount of acetylcholine in the brain which increases synaptic input in neurons. Memantine is an NMDA receptor antagonist that blocks activity of glutamate, which can have neurotoxic effects if excessive. It has been used in dogs to treat obsessive compulsive disorder. Donepezil and memantine have been used in experiments with dogs to evaluate their efficacy in which improvement of clinical symptoms have been noted.
In addition, nicergoline and propentofylline are two other drugs that are occasionally prescribed to dogs with canine cognitive dysfunction. These drugs have neuroprotective effects by increasing blood flow to the brain and reducing the production of toxic free radicals.
Melatonin may be helpful for pets who experience disruption in their sleep-wake cycle. Melatonin helps to maintain circadian rhythm. Circadian rhythms are 24 hour cycles that can be thought of as one’s “internal clock” which regulate the sleep-wake cycle. Melatonin production decreases with age and can be responsible for sleep disruption commonly seen in pets with cognitive dysfunction syndrome.
Anti-anxiety (anxiolytics) medications, such as benzodiazepines (diazepam, alprazolam, etc.) may be prescribed to decrease anxiety that frequently accompanies cognitive dysfunction syndrome. However, there are other alternative methods of treating anxiety that I recommend trying before starting medication.
Environmental enrichment is achieved through mental and physical stimulation. Providing regular environmental enrichment can help your pet maintain cognitive functioning. Listed below are ideas to help you provide an enriched environment for your pet.
Oftentimes environmental modification will be needed to accommodate your pet’s changing needs. You may need to provide your dog with more opportunities to go outside and use the bathroom and place pee pads down and litter boxes around the house. Accidents in the house may be unavoidable. Patience and understanding are critical. If your pet is sundowning (sleeping during the day and waking up at night), increase physical activity during the day and remove distractions in the evening to encourage regular sleep cycles. Pets with cognitive dysfunction syndrome are less tolerant of children and other animals because they easily become anxious and overwhelmed. It’s important to provide your pet with a safe, quiet and convenient location that they can go to get away from chaos. If sensory dysfunction is significant, you may need to alter how you communicate with your pet. For example, replacing verbal cues with tactile cues or hand signals. In addition, you may need to provide a little encouragement at feeding time and may consider using high-value food rewards as a motivator.