Effectiveness of Interventions in Modifying Cognitive Function of Aged Dogs

Behavioral Enrichment and Antioxidant Supplementation

According to the free radical theory of aging, compounds that the body makes, known as antioxidants, are critical to the prevention of cellular changes that account for various aging processes, including age-dependent deficits in learning and memory. In support of this hypothesis, we have shown that adding a broad spectrum of antioxidants to food can improve cognitive function in aged dogs, and retard the development of cognitive dysfunction.

Oddity task figure

The figure to the left illustrates the results from a study in which aged dogs were separated into two groups, based on food provided. The animals provided with the antioxidant supplemented diet showed more rapid learning, particularly on the most difficult tasks, which showed statistically significant differences.

Aged dogs, on a three-year longitudinal study, were treated with a combination of behavioral enrichment and a food fortified with antioxidants and mitochondrial cofactors. The combination of interventions delayed the development of cognitive decline as assessed by discrimination and reversal learning. Administration of the fortified food improved long-term retention and short-term working memory. In addition, the fortified food slowed the progression of beta-amyloid deposition (Milgram et al., 2005). Clinical trials in humans using antioxidants are currently underway.

Acetylcholinesterase inhibitors

Aged dogs administered an acetylcholinesterase inhibitor showed an improvement in visuospatial memory ability compared to stable baseline performance. Cholinesterase inhibitors are the only drugs currently approved for use in Alzheimer's patients in North America.

Adrafinil

At a dose of 20 mg/kg, adrafinil improved discrimination learning. By contrast, the same dose impaired visuospatial memory performance. Adrafinil is currently approved for attentional problems in geriatric patients in France.

l-deprenyl

Our model has demonstrated limited efficacy with l-deprenyl. In several studies using various cognitive measures, l-deprenyl was found to have small, but inconclusive effects in aged dogs. Clinical trials in humans also proved to be inconclusive. Consequently l-deprenyl has not been approved for use in people.

Ineffective Therapies

Initial tests of the following have not demonstrated efficacy in the dog.

Ampakines
Vasopressin Analogs
Nicergoline
Estrogen
Propentophyline

Treatments that modify brain metabolism

Modification of serotonergic transmission