Nutritional supplementation in cases of canine cognitive dysfunction—A clinical trial

Abstract

Canine cognitive dysfunction (CCD) is a clinical condition, which impacts significantly on the lives of elderly dogs and their owners. It is hypothesised that nutritional supplementation can be used in the management of the condition and this trial was designed to investigate the therapeutic effects of a specific supplement when compared to a placebo. The trial was conducted in a clinical context and involved 20 UK veterinary practices, giving geographical spread across the country. The duration of the trial was 56 days, including a baseline period of 7 days and a post trial period of 7 days. There was a significant difference between the treated and the placebo groups in relation to improvement in their scores for disorientation, changes in interaction and house soiling behaviour at day 21, day 28 and day 42. These results support the clinical practice of nutritional supplementation as a valuable component of the therapeutic approach in cases of canine cognitive dysfunction.

Introduction

Canine cognitive dysfunction (CCD) is a clinical condition, which is primarily identified by behavioural changes in the aged patient. The prevalence within the UK has not been accurately established, but a recent survey of 981 owners of dogs over 7 years of age (Vetplus Ltd., 2005 Survey of owners of geriatric pets) suggested that approximately one third of dogs showed signs of confusion, restlessness and less enjoyment of life, while one in five exhibited an increased incidence of house soiling problems. A study in the USA involving 97 spayed female and 83 castrated male dogs aged between 11 and 16 years aimed to determine the prevalence of age-related behavioural impairment in a randomly chosen population of dogs. The results of this study showed that 28% (22/80) of 11–12-year-old dogs demonstrated impairment in one or more categories of behavioural signs associated with CCD and 10% (8/80) had impairment in two or more behavioural categories. In contrast 68% (23/24) of 15–16-year-old dogs had impairment in one or more categories and 35% (12/34) had impairments in two or more categories (Neilson et al., 2001). CCD is a neurodegenerative disorder resulting in a decline in higher brain functions, including those involved in memory and learning. It is believed to resemble Alzheimer-type dementia in humans in both its symptomology and pathophysiology (Cummings et al., 1996). For example, the brains of 20 old dogs aged between 8 and 18 years of age were compared with the brains of 10 younger dogs and revealed pathological changes affecting the meninges, choroid plexi, meningeal and parenchymal vessels, neurons and glial cells. The authors noted the similarities between the age-related changes in canine and human brains and concluded that the dog could be used as a natural model for the study of ageing and neurodegenerative disease in humans (Borras et al., 1999). Similarities in underlying pathology have been reflected in a similar approach to treatment for the canine and human conditions of age related pathology and since, in human medicine, single ingredient supplements have proven successful in aiding symptoms that are normally associated with Alzheimer's disease it has been hypothesised that nutritional manipulation can also be used in the management of the canine condition. Research in the human field has indicated that increased vulnerability to oxidative stress is associated with the ageing process and that among the most effective agents that counteract the effects of that process are fruit derived polyphenolics with high antioxidant activity (Joseph et al., 2000). A range of other human studies have also supported the efficacy of nutritional manipulation as a treatment modality for cases of age related behaviour changes in humans (Prasad et al., 2000, Kontush and Schekatolina, 2004, Youdim et al., 2000). Similarly a variety of studies in the veterinary field have supported the proposal of nutritional manipulation, particularly with anti-oxidants as part of the treatment regime in cases of CCD and reported significant effects of modified diets in laboratory based studies (Milgram et al., 2001, Milgram et al., 2002a, Milgram et al., 2002b, Milgram et al., 2004). They also found that the improvement related to the test food was clearest in the most difficult cognitive tasks. However, in a clinical setting it is recognised that owners of older dogs are often reluctant to alter their pet's diet and that the presence of systemic disease may also limit the use of diets specifically designed for the control of CCD. The proposal of a nutritional supplement is therefore of clinical interest and the aim of this study was to assess the efficacy of such a product in a clinical field trial.

In this study the use of a nutritional supplement (Aktivait^®, VetPlus Ltd., Lytham St Anne's, UK), rather than an alternative diet, was investigated. Constituents of Aktivait^® (see Table 1) include a range of antioxidants and free radical scavengers including N-acetyl cysteine, which is a primary precursor to glutathione (Pocernich et al., 2000), α-lipoic acid, Vitamins C and E (Zandi et al., 2004), l-carnitine and Co-enzyme Q10. Essential fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are also included, both of which have been shown to be beneficial in influencing the effects of brain ageing in humans (Horrocks and Yeo, 1999, Kyle et al., 1999, Otsuka, 2000). In addition Aktivait^® contains phosphatidylserine, which is a natural phospholipid, the main physiological effect of which is to enhance and maintain the cell activities based on the functionality of the plasma membrane (Samson, 1987). Clinical studies have demonstrated the role of phosphatidylserine in cognitive function of human patients (Cenacchi et al., 1993) and in experimental animals, administration of phosphatidylserine rapidly induced dose-dependent improvements during learning and memory tests (Suzuki et al., 2001).