Treatment of Canine Dementia
Current treatment options for CCD target prevention, slowing and/or improving the cognitive decline in dogs. Some drugs or food supplements are available for senior dogs and might act neuroprotective. Some enhance the blood flow into the brain, others work as antioxidants and more effort is now directed to slowing the progression of the disease instead of providing only symptomatic treatment. One commonly prescribed drug for cognitive impaired dogs is selegiline, which acts as an inhibitor of monoamine oxidase B (MAOB), thus reducing degradation of several neurotransmitters in the brain, and may have neuroprotective effects on dopaminergic, noradrenergic and cholinergic neurons (Landsberg, 2005; Magyar, 2011). Another drug that is occasionally used is nicergoline, which increases the blood flow through the brain. It may enhance neuronal transmission and act neuroprotective, increase dopamine and noradrenaline turnover and inhibit platelet aggregation (Landsberg, 2005). Propentofylline also has a neuroprotective role as it inhibits the production of free radicals and reduces the activation of microglial cell, thus acting anti-inflammatory (Frampton et al., 2003). Antidepressants such as selective serotonin reuptake inhibitors fluoxetine and sertraline, amitriptyline, paroxetine and anxiolytics benzodiazepines, gabapentin, valproic acid and buspirone can also be used to treat the anxiety and aggression which may accompany CCD. Clomipramin is an antidepressant commonly prescribed for dogs with anxiety (Landsberg, 2005), but these are all symptomatic treatments and do not treat the disease itself. S-adenosylmethionine tosylate supplementation was reported to be safe and effective in improving signs of age-related mental decline in dogs (Rème et al., 2008).
There are also some nutraceutical preparations available for dogs, which are based on natural products and/or supplement formulations. Behavioral enrichment alongside with antioxidant-rich diet and exercise is an approach for maintaining cognitive function and slowing the progression of CCD in senior pets. As means of preventative intervention, aging beagles were fed a diet rich in antioxidant, which improved cognition, maintained cognition and reduced oxidative damage and Aβ pathology in treated dogs (Milgram et al., 2004; Dowling and Head, 2012). Another longitudinal survey in beagles looked at the proteomic changes following administration of antioxidant-rich diet in combination with behavioral enrichment (Opii et al., 2008). Following treatment, the levels of oxidative stress biomarkers decreased and the increased expression levels of Cu/Zn superoxide dismutase, fructose-bisphosphate aldolase C, creatine kinase, glutamate dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase correlated with improved cognition (Opii et al., 2008). In addition, some other studies implicated the nutrition as cognition modifying factor in dogs (Araujo et al., 2005a; Siwak et al., 2005; Osella et al., 2007; Christie et al., 2009; Head et al., 2009; Snigdha et al., 2011, 2012; Katina et al., 2016; Chapagain et al., 2018), highlighting combination of nutraceutical supplements directed at several mechanisms of pathological aging, in combination with behavioral enrichment, as more effective (Araujo et al., 2005a, 2008). Dogs receiving both an antioxidant-rich diet and environmental enrichment showed increased levels of brain-derived neurotrophic factor (BDNF) mRNA when compared to untreated aged dogs. As a result of increase in BDNF mRNA, the cognitive performance improved and the amount of cortical Aβ deposits decreased (Fahnestock et al., 2012). Interesting is the finding that neuronal loss in the hippocampus, occurring in the aged dogs, could be partially reversed by more engagement with the dog, i.e., with stimulation of brain function (Siwak et al., 2000).