Cognitive dysfunction syndrome (CDS) is a neurodegenerative disorder of senior dogs and cats characterized by gradual and progressive cognitive decline. Advancing brain pathology is expressed behaviorally by signs related to learning, memory, perception, awareness, social interactions, sleep and activity. The diagnosis is based on clinical signs described by the acronym DISHAA, including disorientation, altered social interactions and sleep–wake cycles, and loss of housetraining and other learned behaviors, altered activity (including an increase in spontaneous activity with greater severity of CDS), and anxiety. Other signs might include altered responsiveness to stimuli, altered appetite or self-hygiene and altered feeding or drinking.

While a decline in learning and memory may be the hallmark signs, the average pet may appear minimally challenged until the dysfunction becomes severe. However, using neuropsychological tests, executive function, attention, and memory impairment can be objectively quantified in the laboratory.^1-3 These tests also provide a mechanism by which the effect of therapeutic agents can be assessed. While pet owners most commonly report changes associated with cognitive decline beginning around 11 years or older, deficits in learning and memory in both dogs and cats have been demonstrated as early as 6 years of age.^2,3

Prevalence

Both prevalence and severity of signs increase with age. In one study of 28% of dogs aged 11–12 years had at least 1 category of DISHA and 10% had 2 or more categories, while in dogs aged 15–16, 68% had 1 category and 36% had 2 or more.4 In another study of 479 dogs using online screening with a validated CCDR questionnaire, the overall prevalence was 14.2% with 41% of dogs over 14 affected.5 More recently in a prospective screening study prevalence ranged from 13–16% in dogs 8–11 to almost 100% of dogs >13.6 Over the course of 6 months, 42% with no impairment progressed to mild impairment and 24% with mild progressed to moderate. Over 1 year, 71% converted from none to mild and 50% from moderate to severe.⁵ The most common reported signs in dogs with CDS were sleeping more during the day and restlessness at night (57%), altered social interactions (51%), disorientation (49%) and anxiety (46%).⁶ For dogs with mild CDS, the principal sign was increased daytime sleep (70%) and anxiety 11%. By contrast anxiety was reported in only 4% of dogs with no CDS.⁷

Biannual Screening

As initial signs of cognitive decline may be subtle, most cases go undiagnosed until signs become sufficiently problematic for the pet or the owner, with mild signs seldom reported.⁵ In one study that identified a prevalence of CDS of 14.2% in dogs over 8 using a validated questionnaire (CCDR), only 13% had been diagnosed.⁷ As signs can emerge or progress over the course of 6 months, and behavioral signs may be the first or only indication of disease and pain, senior dogs should be scheduled for twice yearly visits and owners counselled on prompt reporting any change in health or behavior. While the CCDR and CADES questionnaires have been validated for diagnosis of CDS, the DISHAA questionnaire may provide a more sensitive tool to identify all clinical signs that might be caused by CDS.^5,6

The combination of behavioral screening (owner identified signs), physical examination (veterinary identified signs and blood, urine and blood pressure screening (laboratory identified signs) offers a comprehensive approach to early identification and diagnosis and treatment of health and welfare In fact, physical examination and laboratory screening in senior pets can identify abnormalities before they are clinically apparent. In a recent trial of 100 healthy senior and geriatric dogs, 53 had increased systolic blood pressure, 22 had heart murmurs, over 20% had hypophosphatemia, leukopenia, increased serum creatinine, ALT, or alkaline phosphatase, leukopenia, and 4 had bacterial cystitis. Platelets were significantly higher and temperature, HCT, albumin and TT4 were lower in geriatric compared to senior dogs.⁸

Age-related Pathology and Risk Factors

With increasing age in dogs, frontal and temporal lobe volume decreases, ventricular size increases and there is meningeal calcification, a reduction in neurons, and an increase in toxic free radicals.^1,2,9,10 Circulatory changes in dogs and cats, including microhemorrhage and infarcts, may also be responsible for signs of CDS. As in humans, impairment in cholinergic function has also been identified which may contribute to declining cognitive and motor function and a disruption in sleep–wake cycles. In dogs, cats, and humans there is an accumulation of diffuse beta amyloid plaques and perivascular infiltrates with increased age.^1,2,9-10 In dogs, the amount and location of Ab plaque deposition may be linked to the severity of cognitive deficits.^1,10

Soluble A can also be measured in the cerebrospinal fluid (CSF) of dogs making it a useful marker for aging and cognition studies.

A recent study found that high levels of CSF A in dogs coincide with lower cognitive performance prior to amyloid deposition. Cognitive decline has also been shown in dogs to be related to tau hyperphosphorylation.¹¹ Taken together, the pathological changes, clinical signs, learning and memory impairment and age-related progression, are analogous to the changes seen in the aging human brain and in early Alzheimer’s disease. However, in contrast to humans, there is an absence of senile plaques, neurofibrillary tangles are rare and CDS seldom progresses to mortality.^1,9,11

Risk Factors

Multiple risk factors have been associated with accelerated brain aging and risk of AD, including DHA deficiency, high homocysteine, low vitamin B₆, vitamin B₁₂, and folic acid, high blood pressure, chronic oxidative stress, and chronic low-grade inflammation. Therefore, nutrients which reduce risk factors might enhance brain function and retard decline.

Diagnosis

With the identification of any behavioral signs of CDS, a diagnosis is made by exclusion of all possible medical causes of the signs. Neurological disorders, sensory decline, endocrine and metabolic disorders and pain such as with musculoskeletal or gastrointestinal disease are the primary rule-outs. In one study, of 300 dogs visiting the veterinary clinic for preventive care or health complaints, 85 were excluded with underlying medical problems and 159 (53%) had displayed signs of CDS.⁷ In a clinical trial in which 100 senior dogs were identified with signs of cognitive dysfunction on DISHAA screening, 15 had markedly abnormal laboratory findings including 6 with significantly increased alkaline phosphatase and/or ALT, 3 with kidney disease, 5 with bacterial cystitis, and 1 with marked hypercalcemia.² In addition, as medical health conditions are increasingly more common with advancing age (including but not limited to sensory decline, osteoarthritis, elevated alkaline phosphatase and heart murmurs) a concurrent diagnosis of cognitive dysfunction must also be considered. For a comprehensive reference on the science of canine and feline dementia, see Landsberg, G.M., Madari, Al, Zilka, N. (eds). Canine and Feline Dementia. Molecular Basis, Diagnostics, and Therapy. Cham, Switzerland: Springer, 2017.

References

1.  Head E, Callahan H, Muggenburg BA, et al. Visual-discrimination learning ability and -amyloid accumulation in the dog. Neurobiol Aging. 1988;19:415–425.

2.  Studzinski 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. Neurobiol Learn Mem. 2006;86:197–204

3.  Araujo JA, Studzinski CM, Head E, et al. Assessment of nutritional interventions for modification of age-associated cognitive decline using a canine model of human aging. AGE. 2005;27:27–37.

4.  Nielson JC, Hart BL, Cliff KD, et al. Prevalence of behavioral changes associated with age-related cognitive impairment in dogs. J Am Vet Med Assoc. 2001;218:1787–1791.

5.  Salvin HE, McGreevy PD, Sachdev PS, et al. Under diagnosis of canine cognitive dysfunction; a cross-sectional survey of older companion dogs. Vet J. 2010; 184, 277–81.

6.  Madari A, Farbakova J, Katina S, et al. Assessment of severity and progression of canine cognitive dysfunction syndrome using the Canine Dementia Scale (CADES). Appl Anim Behav Sci. 2015;17:138–45.

7.  Fast R, Schutt T, Toft N, et al. An observational study with long-term follow-up of canine cognitive dysfunction: clinical characteristics, survival and risk factors. J Vet Intern Med. 2013;27:822–29.

8.  Willems A, Paepe D, Marynissen S, et al. Results of screening apparently healthy senior and geriatric dogs. J Vet Intern Med. 2017;31:81–92.

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

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

11.  Smolek T, Madari A, Farbakova J, et al. Tau hyperphosphorylation in synaptosomes and neuroinflammation are associated with canine cognitive impairment. J Comp Neurol. 2016;524;874–95.