Our growing knowledge of canine health and nutrition, combined with other advances in medical science and technology, means dogs are living longer than ever. However, this longevity increases their risk of developing cognitive dysfunction syndrome (CDS). Here’s how nutritional support can help.

Cognitive decline, or cognitive dysfunction syndrome (CDS), is a neurodegenerative condition resulting from brain pathology, so is different from what is considered the normal aging process. The condition is progressive and irreversible, and will eventually result in behavioral changes related to learning, memory, perception, awareness, social interactions and activity level.¹ Changes in sleep-wake cycles and feeding and drinking behavior, as well as altered responses to stimuli, often result.¹ CDS has been shown to be an excellent model of the aging process associated with Alzheimer’s disease in humans.²

AGING CHANGES THE BRAIN

Several gross anatomical changes can be seen as the brain ages; total brain volume decreases and ventricular volume increases.^2-5 Specifically, frontal cortex volume decreases and hippocampal volume can be seen to decrease as well.^2-5 Since the hippocampus is associated with memory storage, one can see why memory deficits are associated with this condition. Changes that can be seen at the histopathological level include reduced numbers of neurons and an increased presence of free radicals.^2,4 Free radicals are the normal by-products of cellular metabolism; under normal conditions, free radical scavengers remove these by-products. With age, the levels of free radical scavengers decrease, allowing free radical numbers to increase. The brain is extremely sensitive to the toxic effects of free radicals. Several other conditions associated with aging, such as heart disease and hypertension, result in decreased oxygen to the brain and contribute to the overall decline in brain tissue health. Other circulatory changes, including the increased presence of micro-hemorrhages and infarcts, further contribute to the clinical signs.^2,4 A reduction in glucose metabolism in the aging brain can lead to energy deprivation, which subsequently contributes to a further decrease in neuronal function.⁶ A reduction in cholinergic function has also been documented in the aging brain, and is suspected to contribute to the declining cognitive and motor functions seen in many aging individuals.⁷

Possibly one of the most notable changes is the increased presence of lipofuscin and beta amyloid plaques in the brain.^2-5 Beta amyloid is also known to be neurotoxic and is a hallmark of Alzheimer’s disease in humans. The degree of accumulation of these plaques has clearly been associated with the degree of cognitive impairment in both humans and dogs.⁸

DIAGNOSING CDS

CDS can be challenging to diagnose but the clinician should start by using the acronym DISHAA to evaluate the patient for signs of CDS.¹ DISHAA stands for Disorientation, Interactions, Sleepwake cycle, House-soiling, Activity and Anxiety. See Table 1 for details regarding the DISHAA signs.

Many of the signs commonly seen with CDS, such as house-soiling, nighttime waking and vocalization, and increased anxiety can be due to other medical conditions. For example, sleep-wake cycles are often altered in patients with chronic pain. The presence of osteoarthritis can make it difficult to lie down and stand up. Alternatively, lying down for an extended period of time may lead to increased discomfort due to joint disease. Osteoarthritis can also lead to house-soiling if accessing the appropriate elimination site is painful for the dog. Any medical condition leading to increased frequency or urgency of elimination can result in house-soiling. Chronic pain can also lead to increased anxiety.

As you can see, many signs of CDS can overlap, and many can be similar to those seen with other physical conditions. This means a good history, physical exam, and appropriate diagnostics are also important to rule out the presence of concurrent medical conditions. To some extent, CDS is a diagnosis of exclusion, but it is also likely to occur alongside many other medical conditions. All the pet’s medical conditions will need to be managed at the same time as the CDS is addressed, in order to maintain the best quality of life for the patient.

Unfortunately, many pet owners may see these signs and just think their dogs are “getting old”, when in fact, if diagnosed early, many of these conditions can either be treated or managed so the dog not only lives longer but has a better quality of life in his senior years. While CDS cannot be cured, appropriate management can slow the progress and onset of signs.

RISK FACTORS FOR CDS

Multiple risk factors have been identified that appear to predispose both humans and dogs to cognitive decline. These include a deficiency of docosahexaenoic acid (DHA), high homocysteine levels (homocysteine is an amino acid also associated with heart disease in people), and low levels of vitamins B6, B12 and folic acid.^12,13 In addition, high blood pressure, chronic oxidative stress (another way of saying “high levels of free radicals”), and chronic low-grade inflammation are also risk factors.^12,13 Therefore, nutrients that reduce these risk factors may enhance brain function and retard cognitive decline.

EVIDENCE FOR NUTRITIONAL SUPPORT

Currently available treatment modalities, which some research supports, include those that improve brain metabolism, reduce oxidative damage, enhance neuronal transmission, and maintain neuronal integrity.¹⁴ These modalities can be used alone or in some combination. Table 2 lists some of the molecules or ingredients that have been shown to help in maintaining brain health, along with some information regarding their purported mode of action.

• Hills® Prescription diet® b/d® is supplemented with fatty acids, antioxidants (vitamins C and E, beta carotene, selenium, flavonoids, carotenoids), dl-alpha-lipoic acid and l-carnitine. This diet has multiple studies associated with it, involving both laboratory beagles and client-owned dogs. Most trials were blinded and placebo-controlled. In the laboratory studies, all dogs receiving the diet demonstrated better learning ability.¹⁵ In a clinical trial that included 125 family-owned dogs, those fed the diet showed improvement in five DISHAA categories. They also demonstrated significantly higher activity levels, and increased interactions with their families.¹⁶

It is noteworthy that in one of the laboratory studies, the diet alone was compared to placebo, and the diet plus environmental enrichment was compared to placebo. The study demonstrated that the dogs receiving b/d and environmental enrichment performed even better on cognitive tests than dogs that received b/d with no enrichment.¹⁵

• Purina Pro Care NeuroCare® is supplemented with 6.5% medium chain triglycerides (MCTs) as well as a combination of arginine, antioxidants including vitamins C, E and selenium, B vitamins, and fish oil containing DHA and EPA. In a double-blinded placebo-controlled trial of dogs identified as having CDS using a DISHAA screening tool, significant improvement was seen in five categories of DISHAA after eating the diet for just 30 days.¹⁷ After 90 days, a significant number showed improvement in all six DISHAA categories, whereas the dogs fed the control diet only showed some improvement in three categories.¹⁷

• Senilife® (Ceva Sante Animale) is a supplement containing phosphatidylserine, ginkgo biloba, antioxidants, and vitamin B6. In a double-blinded crossover study in nine laboratory beagles, aged 7-12.7 years, dogs receiving the supplement for 70 days showed significant improvement in a visuospatial memory task over baseline.¹⁸ In addition, there was a significant effect of phase; the subjects receiving the supplement during the first phase of the trial, and acting as controls during the second phase, did not show a significant difference in their performance between the two test periods, indicating that their level of performance was maintained in spite of the supplementation being discontinued. The collective results of this study suggest that the treatment also has some long-term benefits.¹⁸

In an open clinical trial including eight dogs that had been diagnosed with cognitive dysfunction syndrome by a veterinary behaviorist, the subjects were administered Senilife once daily for three months.¹⁹ The dogs were evaluated at three separate visits at approximately monthly intervals, and owners were asked to rank the frequency of clinical signs that had been identified at the initial visit. All eight dogs showed a highly significant improvement in all categories evaluated at the third visit when compared to the start of the trial.¹⁹

• Other supplements that can be given individually to support brain health include S-adenosyl–L-methionine (SAMe) and Omega-3 fatty acids (PUFAS). SAMe is a metabolite found in every living cell, where it plays a role in hundreds of different metabolic reactions.20 It is particularly important in the central nervous system; decreased levels of SAMe have been noted in the brains of Alzheimer’s patients.²¹ There is evidence that SAMe crosses the blood-brain barrier intact and several studies indicate that parenteral and oral administration of SAMe can increase CSF concentrations in dogs.²⁰

In one double-blinded placebo-controlled clinical trial, 36 dogs with CDS were given a SAMe supplement (Novifit® by Virbac) for 60 days, and demonstrated significantly improved activity levels, awareness, and mental impairment scores compared to placebo.²² In a blinded, placebo-controlled laboratory study of 14 aged beagles, executive function was found to be enhanced with SAMe administration.²³

• Omega-3 long-chain, polyunsaturated fatty acids (PUFAs) are of fundamental importance to brain development and function, with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) considered most important. They play a vital role in maintaining cell membrane structure, fluidity, and cell-to-cell communication.²⁴ Few studies have looked at the role of individual fatty acids on brain health, and most focus on the effects of Omega-3 fatty acids in combination with other ingredients. However, the evidence is clear that DHA and EPA together improve cognition in healthy adults and slow cognitive decline in those with mild impairment.^24,25 Such clear evidence in animals has not yet been found, but due to their many potential benefits, supplementation with PUFAs should be considered in aging pets.

While CDS cannot be reversed, the signs can be improved and clinical progress slowed with appropriate early intervention and nutritional support. The result can be happier clients and improved behavioral health and welfare for your patients.

¹Landsberg G. Araujo JA. Behavior problems in geriatric pets. Veterinary Clinics North America Small Animal Practice. 2005; 35 (3): 675–698.

²Rofina JE. van Ederen AM. Touissaint MJ. et al. Cognitive disturbances in old dogs suffering from the canine counterpart of Alzheimer’s disease. Brain Research. 2006; 1069: 216-26.

³Head E. Callahan H. Muggenburg BA. et al. Visual-discrimination learning ability and β-amyloid accumulation in the dog. Neurobiology of Aging. 1988; 19:415-425.

⁴Tapp PD. Siwak CT. Gao FQ. et al. Frontal lobe volume, function, and beta-amyloid pathology in a canine model of aging. Journal of Neuroscience. 2004; 224:8205-8213.

⁵Studzinski CM. Christie LA. Araujo JA. et al. Visuospatial function in the beagle dog: an early marker of cognitive decline in a model of human aging and dementia. Neurobiology of Learning and Memory. 2006; 86: 197-204.

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

⁷Zhang JH. Sampogna S. Morales FR. et al. Age-related changes in cholinergic neurons in the laterodorsal and the pedunculo-pontine tegmental nuclei of cats: a combined light and electron microscopic study. Brain Research. 2005; 1052: 47-55.

⁸Insua D. Suárez ML. Santamarina G. et al. Dogs with canine counterpart of Alzheimer’s disease lose noradrenergic neurons. Neurobiology of Aging. 2010; 31: 625-635.

⁹Nielson JC. Hart BL. Cliff KD. et al. Prevalence of behavioral changes associated with age-related cognitive impairment in dogs. Journal of American Veterinary Medical Association. 2001; 218: 1787-1791.

¹⁰Madari A. Farbakova J. Katina S. et al. Assessment of severity and progression of canine cognitive dysfunction syndrome using the Canine Dementia Scale (CADES).  Applied Animal Behavior Science. 2015; 17:138-45.

¹¹Salvin HE. McGreevy PD. Sachdev PS. et al. Under diagnosis of canine cognitive dysfunction; a cross-sectional survey of older companion dogs.  Veterinary Journal.  2010; 184: 277-81. 

¹²Oulhaj A. Jernerén F. Refsum H. et al. Omega-3 fatty acid status enhances the prevention of cognitive decline by B vitamins in mild cognitive impairment. Journal of Alzheimer’s Disease. 2016; 50: 547-57.

¹³Scarmeas N. Stern Y. Tang MX. et al. Mediterranean diet and risk for Alzheimer’s disease.  Annals of Neurology. 2006; 59: 912-21.

¹⁴Denenberg S & Landsberg G. Current Pharmacological and Non- pharmacological Approaches for Therapy of Feline and Canine Dementia. In: Canine and Feline Dementia – Molecular Basis, Diagnostics and Therapy. G Landsberg, A Mad’ari and N Žilka, eds. Cham, Switzerland: Springer;2017:129-143.

¹⁵Milgram NW. Head E. Zicker SC. et al. Learning ability in aged beagle dogs is preserved by behavioral enrichment and dietary fortification: a two-year longitudinal study. Neurobiology of Aging. 2005; 26:77–90.

¹⁶Dodd CE. Zicker SC. Jewell DE. et al. Can a fortified food affect the behavioral manifestations of   age-related cognitive decline in dogs? Veterinary Medicine. 2003; 98: 396–408.

¹⁷Pan 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.  Frontiers in Nutrition. 2018; 5:127. doi.org/10.3389/fnut.2018.00127.

¹⁸Araujo JA. Landsberg GM., Milgram NW. et al. Improvement of short-term memory performance in aged beagles by a nutraceutical supplement containing phosphatidylserine, Ginkgo biloba, vitamin E, and pyridoxine. Canadian Veterinary Journal. 2008; 49(4):379–385.

¹⁹Osella MC. Re G. Odore R. et al. Canine cognitive dysfunction: prevalence, clinical signs treatment with a nutraceutical. Applied Animal Behavior Science. 2007; 105:297–310.

²⁰Bottiglieri T. S-Adenosyl-L-methionine (SAMe): from the bench to the bedside—molecular basis of a pleiotropic molecule. American Journal of Clinical Nutrition. 2002;76 (suppl):1151S–7S.

²¹Morrison LD. Smith DD. Kish SJ. Brain S-adenosylmethionine levels are severely decreased in Alzheimer’s disease. Journal of Neurochemistry. 1996; 67:1328–31.

²²Rème CA. Dramard V. Kern L. et al.  Effect of S-adenosylmethionine tablets on the reduction of age-related mental decline in dogs: a double-blind placebo-controlled trial.  Veterinary Therapeutics. 2008; 9: 69-82.

²³Araujo JA. Faubert ML. Brooks ML. et al. Novifit (NoviSAME) tablets improve executive function in aged dogs and cats: Implications for treatment of cognitive dysfunction syndrome. International Journal of Applied Research in Veterinary Medicine. 2012; 10: 90-98.

²⁴Kidd PM. Omega-3 DHA and EPA for cognition, behavior, and mood: Clinical findings and structural-functional synergies with cell membrane phospholipids. Alternative Medicine Review. 2007; 12(3): 207-227.

²⁵Kaur H. Singla A. Snehdep S. et al. Role of omega-3 fatty acids in canine health: A review. International Journal of Current Microbiology and Applied Sciences. 2020; 9 (3): 2283-2293.