Veterinarians have found canine cognitive dysfunction syndrome may be progressive.
Improved nutrition and medical care have prolonged life spans in both people and their pets. Current estimates suggest that there are approximately 20 to 30 million senior and geriatric dogs over the age of 7 years in the North America.
However, longer life may lead to an increased prevalence of age-related behavioral and cognitive problems.
Canine cognitive dysfunction syndrome (CDS) is the name proposed to describe the behavioral changes associated with brain aging in senior dogs. In examining the cases referred to veterinary behaviorists, the most common complaints of owners of senior dogs included separation anxiety, aggression to people, anxiety and phobias, housesoiling, night waking and vocalization. However, these cases do not accurately reflect the magnitude of the problem at the general practice level.
For example, using an owner-based observational questionnaire, 28 percent of the otherwise healthy dogs between the ages of 11 and 12, and 68 percent between the ages of 15 to 16 had signs of CDS in at least one of the following categories: disorientation, housesoiling, social interactions, sleep-wake cycles or activity levels.
Further, CDS may be progressive. Many aged dogs with impairments in one behavioral category were found to have impairments in two or more categories within 12 to 18 months.
The aged canine brain exhibits several key features that can also be observed in the aging human brain.
Aged canine brains display a number of morphological changes similar to those observed in aged human brains, including cortical atrophy and ventricular widening, myelin degeneration in the white matter, accumulation of degraded proteins, DNA damage and reduction of endogenous antioxidants.
The aged canine brain also accumulates proteins within and around neurons that may be toxic. Accumulation of diffuse proteinaceous plaques has received the most attention in aged dogs because it is thought to play a causative role in development of human Alzheimer's disease.
Plaques contain a number of proteins, but the primary constituent is the β-amyloid peptide (Aβ), which has identical amino acid sequences in both people and dogs.
The extent of Aβ deposition in the canine brain is linked to the severity of cognitive deficits and behavioral changes.
A mechanism that may contribute to neuron dysfunction and progressive accumulation of neuropathologic lesions in aged brains is oxidative damage due to reactive oxygen species, which are formed as by-products of cellular metabolism.
Aerobic metabolism in mitochondria has been implicated in the production of the majority of reactive oxygen species.
As mitochondrian age or become dysfunctional from disease or stress, more reactive oxygen species form, which may then undergo further uncontrolled reactions within the cell. Brain aging is a cumulative response to these alterations and the associated neuropathology accounts for age-associated cognitive and behavioral changes.
The brain may be especially vulnerable to cumulative oxidative damage and aging due to its high metabolic rate (i.e., high demand for oxygen) and limited antioxidant defense and repair capabilities. The aging process also appears to be accompanied by a decreased ability to fight the effects of oxidative stress and decreased mitochondrial function, resulting in greater oxidative damage.
The advanced learning ability of dogs is well known as evidenced by their use as assistance companions (e.g. guide dogs) and working animals (e.g. military, search and rescue dogs).
Learning and memory can be tested systematically in dogs using tasks developed for use in nonhuman primates.
In parallel with human and primate studies, tasks are selected that are sensitive to the function of specific brain cortical circuits or regions. All testing is conducted using food rewards, which sufficiently motivate dogs to learn each task.
Use of these testing procedures has shown that aged dogs are on average, able to learn simple associative tasks such as visual discrimination (learning that one of two different objects covers a food reward), at the same level as younger dogs. Significant impairment is seen, however, on more complex discrimination learning problems, such as when the objects become increasingly similar or in reversal tasks, where the pet first learns under which object the food is located and then must learn that the reward has been moved to the previously unrewarded object.
In addition to learning ability, memory is also compromised in aged dogs.
Aged dogs seem to fall into one of three categories based on learning and memory testing: (1) unimpaired or successful agers; (2) age-impaired; (3) severely impaired. These clusters of aged dogs may be analagous to declines along a "cognitive continuum" in people with mild age-associated memory impairment followed by cognitive decline and dementia.
The decline in learning and memory documented in laboratory studies to arise as early as 6 to 7 years of age is consistent with behavioral changes observed in dogs with CDS.
Careful questioning of the owner is the best way for veterinarians to detect early signs of cognitive impairment, since many of the early signs are subtle and might otherwise not be reported. A questionnaire is a useful diagnostic tool and an excellent means of tracking changes and response to therapy (Table 1).
Table 1: Behaviors evaluated in dogs to assess age-related cognitive decline*
A series of studies were initiated to test the hypothesis that a food enriched with complex mixtures of antioxidants and mitochondrial cofactors could result in improvements in learning and memory and reduce the extent of pathology that accumulates in aged canine brains.
A longitudinal investigation of the effects of dietary management on cognitive function of Beagles has recently been completed. The experimental subjects are groups of aged Beagle dogs (10 to 13 years old) and young dogs (3 to 5 years old). The study was conducted as a randomized controlled clinical trial with each animal assigned to an extruded senior dog food (control) or an enriched food. No differences in cognitive ability existed between groups prior to dietary intervention
The enriched food was supplemented with Vitamins E and C, a mixture of fruits and vegetables rich in carotenoids and flavonoids and mitochondrial cofactors (L-carnitine, dl-α-lipoic acid). Vitamin E is a lipid-soluble vitamin that protects cell membranes from oxidative damage, while vitamin C is a water-soluble vitamin that helps replenish vitamin E cellular levels. L-carnitine is a precursor to acetyl-L-carnitine, which is involved in mitochondrial lipid metabolism and maintaining efficient mitochondrial function.
Lipoic acid is an antioxidant nutrient capable of redox recycling of other antioxidants and raising intracellular glutathione levels. Glutathione is the major intracellular water-soluble antioxidant.
In one example from the study, dogs were fed the control or enriched food for six months and tested on four oddity discrimination learning tasks that became increasingly difficult. Aged dogs made significantly more errors than young dogs in all tasks. This would seem to support the adage that "you can't teach old dogs new tricks."
However, old dogs receiving the enriched food performed better on all tasks than old dogs eating the control food. The enriched food produced the most significant improvement in the ability of old dogs to learn complex tasks.
Another component of this study was to determine the effect of environmental enrichment on learning ability in old dogs.
Half of the control diet dogs and half of the enriched diet dogs were given an enriched lifestyle with an increase in daily walks, new toys and a regular cognitive testing.
At the end of two years, the dogs with the combination of enriched environment and enriched food scored statistically better in the learning tasks than those dogs given an enriched environment or enriched food alone.
In addition to the extensive laboratory testing reported above, a randomized, double-blind, controlled clinical trial was conducted to evaluate effects of dietary enrichment in dogs with age-related behavioral changes.
The study evaluated 125 pet dogs 7 years of age or older that were recognized by the owner as exhibiting at least two behavioral characteristics of age-related cognitive decline.
The mean enrollment age of the dogs was 12 years (range 7-20 years). During the 60-day feeding period, significant improvement occurred in 14 of 16 (88 percent) individual behavioral attributes for the Canine b/d (Hill's Pet Nutrition) group and four of 16 (25 percent) for the control group.
In addition, a significant advantage existed in favor of the enriched food compared to the control food at day 60 for individual attributes of agility, recognition of family members and recognition of other animals.
Dogs in the Canine b/d group also showed significant improvement for compulsive behaviors. These findings are consistent with the premise that dogs with age-related cognitive decline benefit significantly from the nutritional management offered by feeding a food enriched in antioxidants and mitochondrial cofactors.
Dogs develop age-related neuropathologic changes which are associated with impaired cognitive function and behavioral changes.
These changes parallel many of the alterations seen in aged people with memory deficits, cognitive impairment and dementia.
Oxidative damage and behavioral changes associated with brain aging in dogs can be mitigated, in part, by nutritional management with food enriched with antioxidants and mitochondrial cofactors. Veterinarians should therefore be proactive in screening for behavioral changes in senior pets, to ensure that dietary and behavioral intervention can be implemented as soon as clinical signs begin to emerge.
Dr. Landsberg is a diplomate of the American College of Veterinary Behaviorists and is the incoming president. He is partner in two companion animal practices in Thornhill, Ontario, as well as his behavior referral practice. Dr. Landsberg is a consultant on VIN, is on the advisory board of a number of veterinary journals and is co-author of the Handbook of Behavior Problems of the Dog and Cat (Saunders 2003), a set of client handouts from AAHA and a CD of client behavior handouts from Lifelearn. In 2000 he received the AAHA companion animal behavior award. For more info go to www.doncasteranimalclinic.com.
Dr. Roudebush received his DVM degree from Purdue University in 1975 and did a medical residency at the University of Missouri. He has been in private practice, a faculty member at Mississippi State University and joined Hill's Pet Nutrition in 1989. He is the veterinary fellow in the technical information services department. He is a diplomate of the American College of Veterinary Internal Medicine and is an adjunct professor at Kansas State University in the department of clinical sciences.
Employed by Hill's Pet Nutrition.