Cognitive dysfunction syndrome

From Dog
(Redirected from Cognitive dysfunction)
Canine cognitive rating scale[1]

Cognitive dysfunction syndrome (CDS) is a neurobehavioural syndrome affecting older dogs characterized by neurological changes.

This syndrome umbrellas a wide range of under-diagnosed cognitive deficits associated with the aging brain including learning deficits or degeneration, loss of memory and spatial awareness, aimless or changes in behaviour, loss of curiosity directed toward novel stimuli, inappropriate incontinence and sleep irregularities[2].

Cognitive dysfunction is exacerbated in dogs with concurrent hypothyroidism, hyperlipidemia, hypercholesterolemia and/or atherosclerosis which collectively result in microvascular ischemia, increased viscosity and hypercoagulability, with subsequent greater risk of thromboembolism[3].

Each dog with cognitive dysfunction has unique clinical presenting signs (designer disease) but common underlying neuropathology. Although the rate of onset and severity are individual within each dog, once cognitive decline begins it is generally a progressively predictable disorder.

CDS is a degenerative process of beta-amyloid plaque deposition within the basal forebrain (parietal cortex and hippocampus), with subsequent loss of cholinergic system activity (increased sensitivity to scopolamine impairment and decreased muscarinic receptor density[4]) and coordination, similar to what is seen with Alzheimer's disease in humans[5].

The plaque deposition (akin to canine amyloidosis) is primarily due to inflammatory deposition of Aβ1-42 and Aβ42/40 amyloid protein in the parietal cortex and hippocampus[6] of aged dogs[7], resulting in neuronal dysfunction. The underlying causes of oxidative stress which leads to neuronal amyloidosis are manifold[8], including chronic exposure to environmental pollutants[9], dietary chemicals and other, often unrelated, chronic inflammatory diseases.

The consequences of these neuropathic changes include thickening and calcification of the meninges, decreased cerebral blood flow and glucose utilization[10], reduced frontal lobe volume and demyelination of neurones and glial cells, leading to overt neurological and behavioral changes which can be observed clinically.

Typical clinical signs include anxiety, confusion, disorientation, reduced activity, changes to sleep patterns, loss of appetite (despite any obvious underlying disease process), inappropriate elimination, inappropriate vocalization, forgetting familiar people in the dog's home. A canine cognitive rating scale is often employed to assess canine patients clinically[1].

A ready reckoner is also available online to assist in individual cases.

Diagnosis of CDS is based on presenting clinical size, age of dog and breed, and elimination of any underlying metabolic disease, neoplastic or musculoskeletal disease that may be attributed to the symptoms.

The physical size of the dog (referable to breed) is not a reliable indicator of disease onset[11], although there is a suggestion that brain pathology, including the age of onset and extent may vary across breeds[12].

In humans, the use of statins to lower blood cholesterol has shown increased cognitive function in the early stages of Alzheimer disease and this has been mirrored in canine models, emphasizing the importance of minimizing cerebral amyloidosis as a preventative measure against age-related cognitive disorders. However, in geriatric dogs with existing amyloid plaques, statins and statin-immunotherapy have been shown to decrease cognitive function[13][14] and although they do reduce circulating cholesterol in dogs, may not play an important role in management of this disease in dogs[15]

Nutritional supplementation is an important aspect of management of this condition, as it is with other age-onset diseases (e.g. obesity, arthritis)[16]. The use of antioxidants (vitamins E and C, fruits and vegetables), mitochondrial cofactors (e.g. Co-Q10, S-adenosylmethionine[17], lipoic acid and carnitine)[18][19] and nutriceuticals such as pyridoxine, Ginkgo biloba and vitamin E[20] have been shown to significantly improve cognitive function in aged dogs.

Pharmacotherapy with ergot-drivative drugs such as selegiline, and possibly nicergoline, have shown anecdotal benefits in clinical settings and should be considered as an adjunct therapy in advanced clinical cases[21].

Quality of life is essential in the treatment and maintenance of this generally progressive disease, and compassion must be directed to a dog which is neurologically challenged but often strongly bonded to its owner(s) and lifestyle.

Euthanasia is not recommended unless other disease(s) accompany this condition and consequently result in rapidly diminishing, poor or absent quality of life parameters.

References

  1. 1.0 1.1 Salvin HE et al (2011) The canine cognitive dysfunction rating scale (CCDR): a data-driven and ecologically relevant assessment tool. Vet J 188(3):331-336
  2. Salvin HE et al (2010) Under diagnosis of canine cognitive dysfunction: a cross-sectional survey of older companion dogs. Vet J 184(3):277-281
  3. Garosi L (2005) Ischaemic stroke stroke in dogs and humans: a comparative review. J Small Anim Pract 46:521-529
  4. Araujo JA et al (2011) Aged dogs demonstrate both increased sensitivity to scopolamine impairment and decreased muscarinic receptor density. Pharmacol Biochem Behav 98(2):203-209
  5. Insua D et al (2012) Expression of p75(NTR), a marker for basal forebrain cholinergic neurons, in young and aged dogs with or without cognitive dysfunction syndrome. J Alzheimers Dis 28(2):291-296
  6. Yu CH et al (2011) Histopathological and immunohistochemical comparison of the brain of human patients with Alzheimer's disease and the brain of aged dogs with cognitive dysfunction. J Comp Pathol 145(1):45-58
  7. González-Martínez Á et al (2011) Plasma β-amyloid peptides in canine aging and cognitive dysfunction as a model of Alzheimer's disease. Exp Gerontol 46(7):590-596
  8. Head E et al (2008) Oxidative stress, aging, and central nervous system disease in the canine model of human brain aging. Vet Clin North Am Small Anim Pract 38(1):167-178
  9. Calderón-Garcidueñas L et al (2008) Air pollution, cognitive deficits and brain abnormalities: a pilot study with children and dogs. Brain Cogn 68(2):117-127
  10. Irimajiri M et al (2010) Cerebral metabolism in dogs assessed by (18)F-FDG PET: a pilot study to understand physiological changes in behavioral disorders in dogs. J Vet Med Sci 72(1):1-6
  11. Landsberg GM et al (2012) Cognitive dysfunction syndrome: a disease of canine and feline brain aging. Vet Clin North Am Small Anim Pract 42(4):749-768
  12. Head E (2011) Neurobiology of the aging dog. Age (Dordr) 33(3):485-496
  13. Vasilevko V & Head E (2009) Immunotherapy in a natural model of Abeta pathogenesis: the aging beagle. CNS Neurol Disord Drug Targets 8(2):98-113
  14. Martin SB et al(2011) Coenzyme Q10 and cognition in atorvastatin treated dogs. Neurosci Lett 501(2):92-95
  15. Murphy MP et al (2010) Changes in cognition and amyloid-β processing with long term cholesterol reduction using atorvastatin in aged dogs. J Alzheimers Dis 22(1):135-150
  16. Laflamme DP (2012) Nutritional care for aging cats and dogs. Vet Clin North Am Small Anim Pract 42(4):769-791
  17. Rème CA et al (2008) Effect of S-adenosylmethionine tablets on the reduction of age-related mental decline in dogs: a double-blinded, placebo-controlled trial. Vet Ther 9(2):69-82
  18. Head E et al (2009) Effects of age, dietary, and behavioral enrichment on brain mitochondria in a canine model of human aging. Exp Neurol 220(1):171-176
  19. Manteca X et al (2011) Nutrition and behavior in senior dogs. Top Companion Anim Med 26(1):33-36
  20. Araujo JA et al (2008) Improvement of short-term memory performance in aged beagles by a nutraceutical supplement containing phosphatidylserine, Ginkgo biloba, vitamin E, and pyridoxine. Can Vet J 49(4):379-385
  21. Mills D & Ledger R (2001) The effects of oral selegiline hydrochloride on learning and training in the dog: a psychobiological interpretation. Prog Neuropsychopharmacol Biol Psychiatry 25(8):1597-1613