Managing common behavioral problems in old dogs and cats (Proceedings)

Definite personality changes and behavioral problems can be extremely challenging to the practitioner and extremely frustrating to the client. Some problems are mild and acceptable, while others are major concerns initiating euthanasia discussions. General behavioral changes are elderly patient's desire more attention, are more jealous, are more irritable, are less mentally alert, and have altered sleep cycles.

According to an AAHA sponsored study, 60% of dogs and cats sleep in the owner's bed or in their bedroom. As a result, any sleep cycle disturbance poses an inconvenience for both the pet and the owner(s). Altered sleep patterns are common geriatric "behavioral" dilemmas especially in those situations where the owner is affected. For those pets that sleep in a dog house or garage, the owners would be unaware of a problem.

With sleep cycle disturbances, the owners report one or more of the following complaints; night crying (cats); routine nightly pacing of the bed room or entire house; periods of panting as if they were anxious or hot; they awaking the owners to go outside for no obvious reason; the pet seems to be unable to get comfortable as they are either up and down or constantly "fluffing up" their bed. Various causes of sleep cycle disturbances have been postulated include; an underling painful condition such as dental disease, osteoarthritis, spondylosis or a chronic IVD; sleeping on a hard surface; an altered biological clock where the patient sleeps all day then can't get to sleep at night; the patient is cold from either poor circulation or a lowered basal metabolic rate associated thermoregulation issue; or a simple phobia of the dark associated with decreased night vision. In some cases, a sleep cycle complaint can also be a manifestation of Cognitive Dysfunction Syndrome in dogs and cats. The author would advocate any or all of the following options; a warm soft bed; a night light; a radio playing softly; a brief 10 minute walk before bedtime; hydroxyzine 1-3 mg/kg (to effect) prior to bedtime; melatonin 1-3 mg / dog PO SID; and/or a 1 week trial of a short term pain management program to rule out a "painful" condition.

Many of these common "old dog or old cat" behaviors are often grouped into a syndrome called Cognitive Dysfunction Syndrome (CDS). CDS is a progressive disease syndrome of older dogs and cats associated with various brain pathology and /or neuro-transmitter imbalances that results in commonly recognized groups of related behavioral changes. Impairments in memory, learning, perception and/or awareness are common findings of CDS. These clinical behaviors in older patients are related to impaired mental function often referred to as senility, dementia, or canine / feline Alzheimer's disease". CDS is a progressive disease of the brain seen in a high percentage of older dogs and cats and is associated with persistent changes in behavior.

What is actual incidence of CDS in older dogs and cats? In one recent study, 75% of owners of dogs that were over 7 years of age, reported at least one symptom consistent with CDS, however only 7% had reported it to their veterinarian, thinking the observed behavior was "normal" part of aging. While the incidence of CDS in cats is also unknown, there is growing evidence that it is actually much more common than previously thought although the onset occurs later in life. In a recent study of feline CDS, when carefully questioned, 50% of owners of cats over 12 years of age reported at least one symptom compatible with CDS, but less than 1% had reported it to their veterinarian. In addition there are some significant differences in the age of onset and symptoms in cats compared to dogs; the older age of onset in cats; the cat owners lack of recognition/interpretation of the specific clinical signs of CDS. These two factors combine with less frequent veterinary visits of cats, all contribute to the lack of CDS clinical knowledge.

All of the causes on CDS in dogs or cats have not been identified or proven. Much of what is known comes from extrapolating the research done in humans, primates, and rats. Some of our current knowledge has come from research and some from the perceived clinical benefits observed in various clinical trials or clinical experiences.

The current thinking suggests pathogenesis of CDS is complex and is associated with four general categories of causative agents that initiate specific brain pathology that results in altered behavior. The pathogenesis of CDS is complex and is associated with four general categories of pathology each resulting in altered behavior. Initially any of the four pathological agents will initiate varying degrees of neuronal dysfunction that can possibly be reversible when treated early. Unfortunately no one treatment is effective against each pathologic cause. Except with alterations in neurotransmitters levels, over time, the damaged neurons will eventually die leading to permanent abnormal behaviors. This is one explanation of why some various treatment options may be not be beneficial at all or following some improvement, become less effective with time.

Multi-modal therapy advocates the use of several management options instead of a single selection. The two benefits of this approach are; 1. Since CDS is a chronic progressive disease, eventually no one single medication will be entirely effective, therefore "poly- pharmacy" approach will be essential in the long term patient care. By using multiple options, with each positive benefit being additive, the chance for toxicity decreases; and 3. Since the exact cause(s) is usually not known, the "shotgun" strategy improves the chances of improving the patient's condition in the shortest amount of time when compared to the "try this for 30 days and let me know" method. While there is always a chance of adverse drug interactions, in general, multi-modal therapies provides a safer and more effective management of those chronic / progressive diseases associated with aging including CDS.

One of the major causes of CDS in both dogs and cats is the accumulation of metabolic waste products in the neurons. The primary infiltrate in humans, dogs and cats is beta amyloid. Beta amyloid exhibits characteristic brown plaques when viewed on histopathology brain sections. Initially the behavioral changes associated with beta amyloid can be attributed to reversible neuronal inflammatory dysfunction, however over time the affected cells will die.

Another category of causative agents is cerebral hypoxia usually from decreased cerebral blood flow. Decreased oxygenation of neurons will initially result in neuronal dysfunction soon followed by neuron death. The hypoxia can result from decreased cardiac output, chronic pulmonary disease or vascular compromise from arterial constriction or non-lipid arteriolosclerosis.

Another area of current CDS research focuses on the age-related decreases in various CNS neuro-transmitter levels i.e. ACH, GABA, dopamine, nor-epinephrine, or serotonin. Since assessment of CNS neurotransmitter levels are currently not practical, the confirmatory diagnosis of a specific neurotransmitter deficiency is based on the patient's behavioral response to any replacement therapy.

The deceased utilization of glucose by the CNS neurons is another emerging area of interest and one reason the use of dietary medium chained triglycerides (MCT) are advocated by some authors. As the utilization of glucose by the neurons decreases, the MCT provide the energy the neurons need to adequately function.

The final category of causative agents for CDS involves the deleterious effect of oxygen derived free radical on CNS neuronal function. There has been considerable animal research into the positive effects of anti-oxidants therapy on brain function in dogs with CDS. Antioxidant packages are becoming common place in most quality senior diets and prescription diets. There are a number of studies demonstrating the positive effects of Hills Prescription diet b/d and other nutritional supplements in improving the symptoms of dogs with CDS. In addition, antioxidants are currently being investigated as possible preventatives for many of the age-related diseases in animals.

The traditional clinical signs of canine Cognitive Dysfunction Syndrome fall into four distinct categories found in the acronym DISH. The D= disorientation / confusion: the I = decreased interactions with family or housemates; the S= Sleep cycle disturbances; and the H= house soiling. It is important to note that most cases of CDS have symptoms in only one or two of the four categories. Since most dogs will have a symptom in only one or two of the four categories, comprehensive questioning in each category is essential in arriving at the diagnosis.

Canine

As cats are not small dogs, that acronym is still appropriate, but some exceptions. AS stated previously, in felines, onset of signs starts at a much later time frame; 12 – 15 years of age as compared to dogs; 7 -10 years. The common clinical signs of CDS include DISH plus one or more of the following; aggressions to owners or housemates; increased vocalization (night criers); excessive grooming; hiding / reclusiveness. It is important to note that most cases of CDS in cats also have only one or two symptoms listed above.

Unfortunately certain metabolic diseases, endocrinopathy, sensory dysfunction, or brain tumors can also present with similar if not identical symptoms. Any suspected case of CDS should undergo a complete work up prior to initiation of any CDS therapy. The absolute minimum data base for possible CCD case should include; a complete behavior history; a complete physical examination; a neurological examination; plus diagnostic testing to include a CBC, a chemistry profile, complete UA, and thyroid evaluation. An adrenal screen test may also be in order as some of the symptoms of canine Cushing's disease resemble that of CDS. Brain imaging is also recommended to rule out other causes of organic brain disease especially brain tumors.

Feline

Obviously the overall success is proportional to the specific therapy used to counteract the specific pathological cause. Unfortunately that is difficult to determine ante-mortem, so a multi-modal approach to therapy is often implemented to "cover all the bases". One of the various management strategies of CDS involves increasing the oxygen to the brain by increasing cerebral blood flow. Until the advent of Selegiline, the management of CDS was extremely frustrating. In the mid 1980's, several authors advocated mild exercise in older dogs to combat canine "senility". Various clinical reports surmised that mild forced exercise was conducive to increased alertness, plus improved the dog's spirit and enthusiasm in response to human socialization. During that same time period, Dr. Jacob Mosier at Kansas State University reported the positive clinical cognitive benefits of placing affected dogs in an oxygen cage for 3 – 4 hours on a weekly schedule.

The current strategies involve various methods of increasing the blood flow to the brain. There are several drugs approved for use in Europe including Propentofylline (Vivitonin) that increases the blood flow to the brain and therefore the oxygen supply without increasing the brain's glucose demand. Another European product Nicergolin (Fitergol) is a competitive antagonist to norepinephrin at the alpha-adrenergic receptors. This drug effectively increases the cerebral blood flow via decreasing the vasoconstriction associated with excessive norepinephrin production. One positive effect of ginkgo biloba is increased blood flow to the brain, as one proposed mechanism for improving memory in humans.

Numerous approved and non-approved veterinary labeled products advocate some degree of efficacy as neuro-protectants. As a group, they may help slow the progression of the neuropathology in CDS. Neuro-protectants are those nutritional supplements or drugs that protect the neurons from the effects of oxygen derived free radicals or beta amyloid deposits. The list includes vitamins E, C and zinc, fatty acids DHA & EPA, SAMe, lipoic Acid and l-carnitine, carotenoids and Flavonoids; anabolic steroids; and Selegiline. Other therapies such as Selegiline, Nicergolin, Cholodin® & Dynaload® alter specific neurotransmitter levels often associated with CDS.

Selegiline also known as L deprenyl is a specific B monoamine oxidase inhibitor (MOA-B). The animal form of selegilline is marketed as Anipryl by Pfizer Animal Health and is approved for use in dogs only. There are also several generic products available from various compounding pharmacies. In some dogs and cats with signs of CDS, prolonged selegilline therapy resulted in significant clinical improvements in greeting behavior, client / patient interactions, inappropriate urination and defecation, activity levels, confusion/disorientation, and/or sleep cycle disturbances. These positive behavioral effects are usually attributed to restoration of depleted dopamine levels via MOA activity and/or the facilitation of dopaminergic transmission by some other related mechanism. However, another suggested mechanism of action includes the CNS stimulatory action of two of the metabolites, L-amphetamine and L-methamphetamine. Selegiline also has some neuro-protecting properties against amyloid deposition and the deleterious effects of oxygen derived free radicals on neurons.

Regardless of the exact mechanism(s) of action, selegilline can be beneficial in managing certain age-related behavioral problems in dogs. The initial minimum dosage of Anipryl for use in both canine and feline Cognitive Dysfunction Syndrome is 1.0 mg/kg PO SID each morning for at least a 60-day trial. Adverse reactions including restlessness, vomiting, diarrhea, diminished hearing, pruritis, shivering/shaking/trembling and disorientation are much more commonly reported at the 2.0 mg/kg PO SID range or when given at bedtime. Regardless of the exact mechanism(s) of action, Selegiline can also be beneficial in managing certain age-related behavioral problems in cats. The initial off label dosage of Anipryl for use in CDS is the same as in dogs; 1.0 mg/kg PO SID each morning for at least a 60-day trial. Adverse reactions including restlessness, vomiting, diarrhea, diminished hearing, pruritis, shivering/shaking/trembling and disorientation. The contraindications of Anipryl therapy include concurrent use with meperidine (and other Apodes), tramadol, or use in combination with other MOA inhibitors. Expense will become a major issue with the lifelong administration.

Recently the use of dietary "anti-oxidants" combined with essential fatty acids (Hills Prescription b/d) has been shown to be effective in the managing some clinical aspects of CDS especially when used in combination with environmental enrichment activities. Oral antioxidant supplements may also be of benefit in selected cases.

One of the theories of brain aging in humans and rats in the decreasing levels of the amino acid S-addenosylmethionine (SAMe). While the exact mechanism is unknown, supplementing SAMe may improve monoamine neurotransmitters levels and neuronal membrane fluidity. The benefit of increased membrane fluidity is the increased movement of receptor proteins through the membranes to better couple with the neurotransmitters. SAMe also is a precursor of the production of glutathione, a major cellular antioxidant.

Phosphatidylserine (PS) is a phospholipids compound found in cell membranes thus facilitating neuronal activities dependent on cell membrane. In addition, PS can "normalize" the levels of specific neurotransmitter ACH and Dopamine.

Pyridoxine (vitamin B6) is a co-enzyme for the synthesis of the neurotransmitters serotonin, noradrenalin and dopamine. Ginkgo biloba is a Neuro-protectants helping to block the effects of free radicals and beta-amyloid on neurons. Ginkgo may also act as monoamine oxidase inhibitor prolonging the availability of Dopamine. As mentioned earlier, Ginkgo can increase the blood flow (oxygen) to the brain counteracting hypoxia. Resveratrol is a phenol compound that protects the neurons form the effects of free radical and beta amyloid.

Non-specific nutritional supplements therapies such as Cholodin® alter acetylcholine neurotransmitter levels occasionally often associated with CDS. Cholodin phosphatidylcholine, choline, dl-methionine, inositol, zinc, niacinamide, vitamin E, thiamine, riboflavin, pyridoxine, and vitamin ±2.

As with all supplements, there are quality control and label claim issues. When used, always allow a significant time lag between initiation of therapy and observed favorable clinical responses. To determine if they are beneficial, a 30-90 day trial is usually recommended.