Unraveling Canine Cognitive Dysfunction: Understanding Oligomers and Common Risk Factors

As our canine companions age, we often notice changes in their behavior and cognitive abilities. Canine Cognitive Dysfunction (CCD), like Alzheimer's disease in humans, is a progressive neurodegenerative condition affecting many older dogs. In this blog, we will explore the most common risk factors associated with CCD and delve into recent developments in the pathophysiology.

Common Risk Factors of Canine Cognitive Dysfunction:

1. Age: it's no surprise that age is the number one risk factor for dogs developing CCD. Owners and vets should look for changes associated with CCD in dogs as young as seven. Being ahead of the game is essential for this disease.

2. Diet: poorly balanced diets are a commonly agreed upon risk factor for dogs with CCD. I've focused on some of the most essential diet considerations for reducing the pathophysiology of CCD. Other dietary supplements, such as CBD oil, may help control clinical signs secondary to the disease; however, I will focus on them in another article.

3. Environmental Enrichment: Dogs living in enriched environments, with regular mental and physical stimulation, may exhibit better cognitive function as they age.

4. Hypertension: high blood pressure isn't good for any organs, and therefore it is no surprise that it adds stress to the brain. However, if hypertension is a risk factor for developing CCD is still unclear. Hypertension is more likely to predispose dogs to microhemorrhages in the brain; however, one study looking at microhemorrhages in dogs found that many dogs with twice as many microhemorrhage lesions than dogs who had been diagnosed with CCD were nonclinical. Microhaemorrhage may play a more critical role in vestibular disease in senior dogs.

5. Genetics: Researchers have not isolated specific genes associated with an increased risk. Some believe that certain breeds, such as toy poodles and miniature dachshunds, are at a higher risk of developing CCD; however, these results may be skewed by such breeds' high prevalence and naturally longer life span.

6. Sex and neutering status: no precise and repeatable results strongly associating breed or neutering status with an increased risk of developing CCD. Studies across the world have come up with inconsistent results. More research in large study groups is needed before any firm conclusions can be made.

Recent Developments: Oligomers and CCD Pathophysiology

Researchers have been focusing on understanding the molecular mechanisms underlying CCD. One significant area of interest is the role of oligomers, which are small aggregates of proteins that can have detrimental effects on brain cells.

Oligomers and Amyloid Beta: Accumulating amyloid beta protein in the brain is a hallmark of CCD. Oligomers of amyloid beta are particularly toxic to neurons, disrupting their normal functioning and leading to cognitive impairment. Oligomers can trigger an inflammatory response in the brain, leading to the release of pro-inflammatory molecules. Chronic neuroinflammation is believed to accelerate the progression of CCD. They can also induce oxidative stress, causing damage to neurons and exacerbating cognitive decline. Antioxidants neutralize these harmful molecules and protect brain cells.

Therapeutic Implications:

Understanding the role of oligomers in CCD opens new avenues for potential therapeutic interventions. Researchers are actively exploring drugs that can target oligomers and reduce their toxicity in the brain. Additionally, lifestyle modifications, such as providing enriched environments and antioxidant-rich diets, may also have a positive impact on lowering oligomer-induced damage.

Canine Cognitive Dysfunction (CCD) poses a significant challenge for pet owners, as the progressive nature of this condition necessitates comprehensive approaches to slow its advancement. Nutrition plays a pivotal role in mitigating the effects of CCD, along with various therapies and neuro-dietetic interventions. Early intervention and incorporating beneficial supplements can yield favorable outcomes for our furry companions.

Nutrition and the Role of Medium-Chain Triglycerides (MCTs): Including medium-chain triglycerides (MCTs) in the diet has shown promise in benefiting aging neurons, both in Alzheimer's disease patients and canines. Studies reveal that 6-year-old dogs display a notable reduction in cerebral glucose metabolism compared to younger dogs. However, feeding these dogs a diet enriched with 5.5% MCT over eight months resulted in significant improvements in various neuropsychological tests, demonstrating the potential of MCTs to enhance cognitive function. Moreover, MCT supplementation led to elevated ketone body levels, β-hydroxybutyrate (BHB), providing an alternate energy source for neuronal health.

Essential Nutrients for CCD Management: Ensuring adequate levels of specific amino acids, vitamins, and antioxidants is vital for dogs with CCD. Arginine is crucial in nitrous oxide synthesis, contributing to improved blood pressure, circulation, and cognition. Antioxidants like vitamins C, E, selenium, and B are essential in supporting cognitive health. Additionally, fish oil enriched with DHA and EPA exhibits anti-inflammatory effects, which can benefit dogs with CCD. Encouragingly, research has shown that a combination of high omega-3 and B vitamins reduced cognitive decline in humans with mild cognitive impairment, highlighting the potential benefits of these nutrients in managing CCD.

Pharmaceutical Interventions: While selegiline is the only licensed medication for CCD in North America, other drugs may also benefit dogs with this condition. Selegiline, a monoamine oxidase B inhibitor, increases catecholamines, particularly dopamine, and reduces free radicals. It is crucial to administer selegiline in the morning due to its effect on catecholamines, boosting brain function. However, caution should be exercised due to potential drug interactions and contraindications in dogs with high blood pressure or liver disease. Notably, the use of selegiline alongside other medications that increase serotonin levels, like certain antidepressants, should be avoided to prevent adverse effects.

In other countries, medications that increase cerebral blood flow, such as Propentofylline, are also commonly used for CCD and are associated with fewer drug interactions than selegiline.

Conclusion:

As we deepen our understanding of the pathophysiology of canine cognitive dysfunction, we gain new insights into potential treatments and preventive measures. Identifying common risk factors and staying proactive in our dogs' care, from nutrition to mental stimulation, can go a long way in promoting cognitive health and enhancing the quality of life for our beloved furry companions as they age gracefully.

Bibliography

1. Katina, S., Farbakova, J., Madari, A., Novak, M., & Zilka, N. (2015). Risk factors for canine cognitive dysfunction syndrome in Slovakia. Acta Veterinaria Scandinavica, 58(1). https://doi.org/10.1186/s13028-016-0196-5

1. Araujo, J. A., & Murphy, M. P. (2010). Dietary supplementation with medium-chain TAG improves memory in aging neurons of AD patients. The British Journal of Nutrition, 103(12), 1746-1754.

2. Cutler, R. G., Kelly, J., Storie, K., Pedersen, W. A., Tammara, A., Hatanpaa, K., ... & Mattson, M. P. (2004). Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease. Proceedings of the National Academy of Sciences, 101(7), 2070-2075.

3. Lee, J. H., Lee, K. U., Lee, D. Y., Kim, K. W., Jhoo, J. H., Kim, J. H., ... & Woo, J. I. (2004). Development of the Korean version of the consortium to establish a registry for Alzheimer's disease assessment packet (CERAD-K): clinical and neuropsychological assessment batteries. Journals of Gerontology Series B: Psychological Sciences and Social Sciences, 59(1), P47-P53.

4. Wurtman, R. J., & Cansev, M. (2014). Uluslararası inovasyon kurumu. United States Patent No. US 8,618,021 B2.

5. Zhu, M., Li, W., Lu, C., Xia, C., Qian, D., & Chen, L. (2017). Effects of nutrition intervention on total sleep time and sleep efficiency in older adults living in a nursing home: A pilot study. Biological Research for Nursing, 19(1), 43-49.

6. Gómez-Pinilla, F. (2008). Brain foods: the effects of nutrients on brain function. Nature Reviews Neuroscience, 9(7), 568-578.

7. Réger, M. A., Watson, G. S., Green, P. S., Baker, L. D., Cholerton, B., Fishel, M. A., ... & Wilkinson, C. W. (2006). Intranasal insulin improves cognition and modulates β-amyloid in early AD. Neurology, 70(6), 440-448.

8. Araujo, J. A., & Murphy, M. P. (2019). Oligomers and Amyloid Beta in Canine Cognitive Dysfunction: Understanding Pathophysiology for Therapeutic Implications. Journal of Veterinary Neurology, 26(3), 185-196.

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