Strategies that might slow the progression and improve the signs of CDS, include drugs, functional foods and nutritional supplements focused on reducing the effects of oxidative stress, correcting metabolic changes associated with cognitive decline, and improving mitochondrial function, neuronal health and signaling. In addition, the combination of behavioral enrichment and nutrition has been demonstrated to slow the progression and improve the clinical signs of cognitive dysfunction.¹ A reduction in reactive oxygen species (ROS) is reported in humans after exercise.

Environmental Enrichment

When considering the type and level of enrichment for senior pets, provide for the pet’s needs within the limitations of its physical and mental health. Shorter, slower, more limited or less frequent physical activities might need to be provided. Reward based training and shaping and other forms of mental stimulation (e.g., scent work, hide and seek, activity puzzles) can provide ongoing enrichment even if mobility and stamina are reduced.

Dietary Therapy and Nutritional Supplements in Dogs

Studies in both laboratory models and clinical trials have demonstrated a beneficial effect of nutrition on improving signs and slowing the progression of cognitive dysfunction in dogs. In fact, in one recent study dogs fed high quality commercial diets designed for age, size, or health, were 2.8x less likely to develop CDS than dogs fed low quality commercial food or table scraps.² Although single ingredient supplements may be beneficial, the greatest effect was demonstrated with a combination of ingredients.^1,3,4 This is supported by human studies in which diets containing fruits, vegetables, seeds, legumes, nuts and fish oils as in a Mediterranean diet, and a diet with both omega-3 fatty acids and B vitamins have been shown to reduce cognitive decline.

A diet supplemented with botanic oils containing medium chain triglycerides (MCT) to provide ketone bodies as an alternate source of energy for aging neurons improved memory in AD patients.⁵ Studies in dogs have demonstrated a significant reduction in cerebral glucose metabolism in 6-year-old dogs compared to one year of age.⁶ In dogs fed a diet supplemented with 5.5% MCT over 8 months, there was significantly better performance over a placebo diet in a variety of neuropsychological tests. The group supplemented with MCT had significantly elevated levels of the ketone body, β-hydroxybutyrate (BHB).⁷ Most recently Nestlé Purina assessed a diet supplemented with MCT combined with a brain protection blend (BPB) of nutrients in a clinical trial in dogs presenting with signs of DISHAA. The blend was selected to address risk factors for cognitive decline including arginine (to enhance nitrous oxide synthesis to reduce blood pressure, improve circulation and cognition); antioxidants including vitamins C, E and selenium; B vitamins; and fish oil containing DHA and EPA for anti-inflammatory effects. In humans, a combination of high omega-3 and B vitamins reduced cognitive decline in human subjects with mild cognitive impairment. In a study in dogs aged 9 to 11.5 years, and a study in cats aged 5.5 to 8.7 years, a BPB-enhanced diet has been demonstrated to enhance cognitive function and slow aging-induced decline in learning tasks.^4,13 In the clinical trial, dogs supplemented with 6.5% MCT and BPB (Purina® Pro Plan® Veterinary Diets NC Neurocare™) improved all 6 categories of DISHAA significantly after 90 days compared to the control diet for which 4 of the 6 categories improved (but not social interactions or disorientation). After 30 days, 5 categories improved in the MCT + BPB diet but only 3 categories in the control group.⁸

A senior diet (Hills® Prescription Diet® b/d® Canine) supplemented with fatty acids, antioxidants (vitamins C and E, beta carotene, selenium, flavonoids, carotenoids), and dl-alpha-lipoic acid and l-carnitine to enhance mitochondrial function has been shown to improve signs and slow the progress of cognitive decline in laboratory models and in clinical trials.^1,9 The highest cognitive scores were seen in the dogs that received both the antioxidant diet and added enrichment.^1,9 However, a reduction in beta amyloid pathology, reactive oxygen species and improved mitochondrial function was seen with dietary therapy but not with enrichment alone while enrichment protected against neuronal loss in the hippocampus.^1,9

Another diet that might enhance senior pet cognitive function contains phosphatidylserine, tryptophan and a blend of antioxidants (Royal Canin® Veterinary Canine Mature Consult).

Nutritional supplements that might be effective for CDS include a mix of phosphatidyserine, gingko biloba, resveratrol, vitamin E and B₆ (Senilife®); a mix of phosphadylserine, omega-3 fatty acids, vitamins E and C, l-carnitine, alpha-lipoic acid, coenzyme Q and selenium (Activait®); and S-adenosylmethionine (SAMe, Novifit®), a methyl donor that might improve membrane fluidity.

Pharmacological Therapy

Selegiline is the only drug licensed for treatment of CDS in North America. It is a monoamine oxidase B inhibitor that may improve signs of CDS by increasing 2-phenylethylamine and other catecholamines in the cortex and hippocampus and by decreasing production and increasing clearance of free radicals. The dose is 0.5 to 1.0 mg /kg in the morning.¹⁰ In some European countries, both propentofylline, a xanthine derivative and nicergoline, an alpha-adrenergic antagonist have been licensed for treatment of age-related behaviour changes, perhaps by improving cerebral blood flow. Although feline use is off label, beneficial effects have been reported in cats selegiline for signs of disorientation, vocalization, and decreased interest in affection. In addition, there are anecdotal reports of efficacy of propentofylline.

As the elderly are particularly susceptible to the effects of anticholinergic drugs, it is prudent to avoid drugs with anticholinergic effects. In fact, anticholinergic drugs might potentially contribute to further cognitive impairment. Therefore, drugs that enhance cholinergic transmission such as donepezil and phenserine might theoretically improve signs.

References

1.  Milgram NW et al. Long-term treatment with antioxidants and a program of behavioural enrichment reduces age-dependant impairment in discrimination and reversal learning in beagle dogs. Exp Gerentol. 2004;39:753–765

2.  Katina S et al. Risk factors for canine cognitive dysfunction syndrome in Slovakia. Acta Vet Scand. 2016;58:17.

3.  Araujo JA, Studzinski CM, Head E, et al. Assessment of nutritional interventions for modification of age-associated cognitive decline using a canine model of human aging. AGE. 2005;27:27–37.

4.  Pan Y, Kennedy AD, Jönsson TJ, et al. Cognitive enhancement in old dogs from dietary supplementation with a nutrient blend containing arginine, antioxidants, B vitamins and fish oil. Br J Nutr. 2018 doi.org/10.1017/S0007114517003464.

5.  Reger MA, Henderson ST, Hale C, et al. Effects of beta-hydroxybutyrate on cognition in memory-impaired adults. Neurobiol Aging. 2004;25:311–314.

6.  London ED, Ohata M, Takei H, et al. Regional cerebral metabolic rate for glucose in beagle dogs of different ages. Neurobiol Aging. 1983;4:121–126.

7.  Pan Y, Larson B, Araujo JA, et al. Dietary supplementation with medium-chain TAG has long-lasting cognition-enhancing effects in aged dogs. Br J Nutr. 2010;103:1746–54.

8.  Pan Y, Landsberg G, Mougeot I, et al. Efficacy of a therapeutic diet on dogs with signs of cognitive dysfunction syndrome (CDS): a prospective double blinded placebo controlled clinical trial. Front Nutr. 2018: doi.org/10.3389/fnut.2018.00127.

9.  Head E et al. Effects of age, dietary, and behavioral enrichment on brain mitochondria in a canine model of human aging. Expl Neurol. 2009;220:171–176.

10.  Ruehl WW, Bruyette DS, DePaoli A, et al. Canine cognitive dysfunction as a model for human age-related cognitive decline, dementia and Alzheimer’s disease: clinical presentation, cognitive testing, pathology and response to l-deprenyl therapy. Progr Brain Res. 1995:106:217–225.