one approved treatment for cognitiv

one approved treatment for cognitive dysfunction, selegiline, has been shown to increase levels of superoxide dismutase in the brain (Carillo et al, 1994).This compensatory mechanism appears to be compromised in older dogs (Kiatipattanasakul et al,1997).It has also been shown that oxidative damage to proteins (Head et al,2002) and lipids (Rofina et al,2004) accumulates in older dogs. These findings, in combination with agerelated cognitive dysfunction and pathologic changes, suggest that decreasing oxidative damage in the brain might improve cognitive function in older dogs. Thus, dietary interventions that decrease specific types of oxidative damage may slow the progression of age-related cognitive decline in dogs. Key Nutritional Factors A longitudinal laboratory-based study and a randomized,controlled clinical field trial of the effects of a food enriched in a broad spectrum of antioxidants were conducted as described below.Subjects were assigned to receive either an enriched food (test food) or an extruded senior food (control food). The enriched food was supplemented with vitamins C and E,selenium, L-carnitine, α-lipoic acid, omega-3 fatty acids and a mixture of fruits and vegetables.Key nutritional factors for cognitive dysfunction are listed in Table 35-3 and discussed in more detail below.Antioxidants and Mitochondrial Cofactors Antioxidants are substances that scavenge ROS and decrease the overall number of oxidants in a system (Ames et al, 1993; De Ruvo et al, 2000). Many antioxidant compounds such as vitamin E, vitamin C and trace minerals (e.g., selenium) are derived from food sources. Vitamin C is a water-soluble vitamin that helps replenish vitamin E. Mitochondrial cofactors (α-lipoic acid and L-carnitine) act to enhance the function of aged mitochondria so that fewer ROS are produced during aerobic respiration (i.e.,they work to increase mitochondrial efficiency). L-carnitine is involved in lipid metabolism within mitochondria;α-lipoic acid participates in redox reactions and increases intracellular concentrations of glutathione, a primary water-soluble antioxidant within cells. Fruits and vegetables contain flavonoids and carotenoids, which have antioxidant activities as well. One hypothesis is that adding increased amounts of these components to a food would reduce the amount of oxidative damage in two ways,by:1) decreasing the production of ROS and 2) increasing the capacity to clear ROS,and that this would slow the progression of age-related pathologic changes and cognitive decline by reducing overall oxidative damage. A longitudinal laboratory-based study and a blinded veterinary clinical field trial were conducted to assess the effectiveness of a food supplemented with antioxidants and mitochondrial cofactors in ameliorating cognitive decline in older dogs (Dodd et al,2003).Results were used as grade 1 evidence-based nutritional research for the development of a commercial, antioxidant-enriched food.a Investigators conducting the clinical field trial recruited dogs over seven years of age that had clinical signs in two or moreDISH categories. The dogs were randomly assigned to two groups:one that was fed a commercial control food (n = 64) and one that was fed an antioxidant fortified test dog fooda(n = 61). Owners rated their pet’s behaviors before and on Days 30 and 60 of the dietary intervention. After 30 days of dietary intervention, owners reported significant improvements in the following categories:disorientation,interactive changes,sleep patterns and house soiling.By Day 60,owners reported that dogs receiving the test food improved in all four DISH categories (plus activity) whereas those fed the control food improved in only two categories. Dogs receiving the fortified food had improvements in awareness of their surroundings, family and animal recognition and interaction,enthusiasm in greeting and agility,and were reported to circle and house soil less frequently.Overall,the test food was better than the control food;dogs receiving it improved in 13 of 15 behaviors (87%) compared to four of 15 behaviors (27%) for dogs in the control group (Dodd et al,2003;Zicker,2005). The laboratory-based study included 48 aged beagles (10 to 13 years old) and 17 young dogs (three to five years).Each age group was divided into an enriched food group (antioxidant) and a control food group; both groups were balanced for age and initial cognitive performance.The enriched food consisted of a variety of antioxidants, mitochondrial cofactors and dried fruits and vegetables. The control food was an identical base food adequate for senior dogs;however,it was not fortified with additional antioxidants and mitochondrial cofactors.Dogs were tested at several time points over two years after initiation of dietary intervention. Old dogs receiving the antioxidant food had improved learning and memory as measured by several cognitive tasks. The oddity discrimination task was administered,as described abov