Doggy Dementia- Canine Brain Ageing

It’s more common than you might think

It has lots of names: doggy dementia, canine Alzheimer’s, canine brain ageing, canine senility or canine cognitive dysfunction syndrome (CDS).  This can get confusing – especially for owners – but they all mean the same thing and CDS, which is how I will refer to it in this article, is more common than you might think.  It’s just maybe that your owners are not mentioning it to you…

A neurodegenerative disorder

CDS is a progressive neurodegenerative disorder of senior dogs characterised by a gradual loss of memory and learning, and reduced problem-solving ability. The clinical signs are insidious and progressive, and often not easily diagnosed at consultation. In fact, the behavioural changes associated with CDS are likely to be more obvious to the pet owner at home than they are to the veterinarian.¹

The brains of older dogs develop similar neuro-pathological features to the brains of elderly people.¹ Many of these features are similar to the early pathology seen in normal human brain ageing, those with mild cognitive impairment and in Alzheimer’s Disease (AD).¹ As in humans, the brains of older dogs accumulate senile plaques between neurons, which are thought to be neurotoxic. The primary constituent of these proteinaceous plaques is β-amyloid. Accumulation of these plaques has received a lot of attention as they are believed to play a causative role in development of Alzheimer’s disease in elderly humans.² 

Nevertheless, the fact remains that, despite decades of research into AD in people, the causes of its onset and progression remain unclear, including whether or not it reflects systemic disease as well as being a disease of the brain.³

β-amyloid deposits

The extent of β-amyloid deposition in older canine brains is linked to the severity of cognitive deficits and behavioural changes.^4,5 Not all brain regions are equally vulnerable to β-amyloid associated pathological changes. Deposits of β-amyloid are evident in the prefrontal cortex at an earlier age and in a more consistent manner than in other cortical areas.⁵ This pattern of deposition in older dogs parallels that seen in people.⁶ 

Accumulation of β-amyloid deposits occurs late in the disease process,⁶ however the development of age-related oxidative damage may be one of the earlier pathological events. The free radical theory of ageing, first published in 1956,⁷ proposes that as the body ages the mitochondria become less efficient at producing ATP, resulting in less efficient energy production and increased free radical generation (i.e. increased production of reactive oxygen species formed as by-products of cellular metabolism).

The brain is particularly susceptible to free radical attack and oxidative damage because:¹

• It has a high rate of metabolism requiring a high uptake of O2
• It has a high polyunsaturated fat content, which makes it especially vulnerable to free radical attack
• It contains limited antioxidant defences, and in the aged canine brain the activity of antioxidant enzymes is significantly reduced
• Brain tissue has limited ability for repair

There is increased oxidative damage to brain lipids prior to overt β-amyloid deposition, which provides evidence that oxidative damage is an early event.⁸ Production of free radicals leads to oxidative damage to proteins, lipids and nucleotides, which may contribute substantially to neuronal dysfunction, and, ultimately, neuronal death. This results in an obvious reduction in the amount of functional brain tissue as evidenced by cortical atrophy and enlarged lateral ventricles, changes that are clearly visible on an MRI.^1,9 This loss of brain function in turn results in impaired learning and memory, and leads to certain behavioural changes.¹

The behavioural signs of cognitive dysfunction in dogs are identified by the acronym “DISH”

A study of dog owners undertaken to determine the levels of DISH behaviours among dogs aged 7 or over 10 years found that 75% of owners noticed at least one DISH sign, 37% observed one or more signs at least several times a week, and 32% reported three or more signs, but only 12% had discussed the signs with their veterinarian.¹⁰

The progressive nature of the syndrome is evidenced by the finding that older dogs with impairment in one behavioural category subsequently developed impairments in two or more categories within 12-18 months.^11,12 Thus it appears that many owners can recognise the signs of CDS easily, but few do anything about it, believing that they are an inevitable part of normal ageing.  But there are definitely things we can do to help these patients and improve their quality of life!

Nutrition can help

References

1. Roudebush P, Zicker SC, Cotman CW et al. Nutritional management of brain aging in dogs. J Am Vet Med Assoc 2005; 227:722-728.
2. Selkoe DJ. Amyloid beta protein and the genetics of Alzheimer’s disease. J Biol Chem 1996:271:18295.
3. Bin-Lu Sun, Wei-Wei Li, Chi Zhu,et al. Clinical Research on Alzheimer’s Disease: Progress and Perspectives. Neurosci Bull 2018; 34: 1111–1118.
4. Cummings BJ, Head E, Afagh AJet al. Beta-amyloid accumulation correlates with cognitive dysfunction in the aged canine. Neurobiol Learn Mem 1996:66:11.
5. Colle MA, Hauw JJ, Crespeau F et al. Vascular and parenchymal Abeta deposition in the aging dog: correlation with behavior. Neurobiol Aging 2000:21:695.
6. Head E, McCleary R, Hahn FF et al. Region-specific age at onset of beta-amyloid in dogs. Neurobiol Aging 2000:21:89.
7. Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol 1956; 11:298-300. 
8. Pratico D, Uryu K, Leight S et al. Increased lipid peroxidation precedes amyloid plaque formation in an animal model of Alzheimer amyloidosis. J Neurosci 2001; 21: 4183-4187.
9. Cotman CW, Head E. The neuropathology of Alzheimer’s disease. Hill’s European Symposium on Canine Brain Ageing,2002.
10. U.S. Marketing Research Summary. Omnibus Study on Aging Pets. November, 2000. Data on File. Hill’s Pet Nutrition, Inc.
11. Neilson JC, Hart BL, Cliff KD, Ruehl WW. Prevalence of behavioral changes associated with age-related cognitive impairment in dogs. J Am Vet Med Assoc 2001:218:1787.
12. Bain MJ, Hart BL, Cliff KD, Ruehl WW. Predicting behavioral changes associated with age-related cognitive impairment in dogs. J Am Vet Med Assoc 2001:218:1792-1795.
13. Dodd CE, Zicker SC , Jewell DE, Fritsch DA, Lowry SR, Allen TA. Can a fortified food affect behavioural manifestations of age-related cognitive decline in dogs? Veterinary Medicine. 2002; 98: 396-408
14.  Milgram NW, Head E, Cotman CW, Muggenburg B, Zicker Sc. Age dependent cognitive dysfunction in canines: Dietary intervention. In: Overall KL, Mill DS, Heath SE, Horwitz D (editors), Proceedings of the Third International Congress on Veterinary Behavioural Medicine. Universities Federation for Animal Welfare, Wheathampstead, UK. 2001; 53-57.

(HIMA-JE-171337D0)