The life expectancy of pet cats is increasing and there are increasing numbers with signs of apparent senility. These behavioural changes may result from many different disorders (Figure 1). Diagnosis involves a full investigation looking for underlying illness (Figure 2) and assessment for behavioural problems. Once these have been ruled out cognitive dysfunction syndrome (CDS) should be considered, although, ante-mortem, this is a diagnosis of exclusion.

It can be difficult to differentiate the changes caused by CDS and osteoarthritis; both conditions often occur concurrently and some of the treatments help both conditions.

Signs of Cognitive Dysfunction Syndrome

The most common changes include spatial or temporal disorientation (e.g., getting trapped in corners, or forgetting they have been fed), altered learning and memory, house-soiling with inappropriate urination/defecation, altered interaction with the family (e.g., increased attention seeking, aggression, irritability or anxiety, or decreased responsiveness), changes in sleep-wake cycles, changes in activity (e.g., aimless wandering or pacing, or reduced activity), altered interest in food (typically decreased), decreased grooming and/or inappropriate vocalisation (e.g., loud crying at night). Recent studies suggest 28% of pet cats aged 11-14 years develop at least one geriatric-onset behaviour problem; increasing to >50% for cats of >15 years of age.

Aetiology

The cause of CDS is unknown, but compromised cerebral blood flow and chronic free radical damage are believed to be important.

Cerebral Blood Flow

Vascular changes include a decrease in cerebral blood flow, small haemorrhages around blood vessels, and a form of arteriosclerosis. Further compromise to blood flow and hypoxia may result from heart disease, anaemia, blood clotting defects, or hypertension.

Chronic Free Radical Damage

A small amount of the oxygen that is used by cells in normal energy production is normally converted to free radicals. As cells age they become less efficient, producing less energy and more free radicals. Normally, these free radicals are removed by the body's natural antioxidant defenses, including a number of special enzymes and free radical scavengers, such as vitamins A, C and E. The balance between the production and removal of free radicals can be upset by disease, age, and stress. Excessive free radicals can lead to damage and the brain is particularly susceptible because it has high fat content, high demand for oxygen, and limited ability to repair. Chronic damage can eventually lead to disease processes similar to those seen in humans with Alzheimer's disease (AD), with alteration of proteins within nerve cells (e.g., tau hyperphosphorylation) and deposition of protein plaques (made from β-amyloid protein) outside the nerve cells.

Management

While there are no published studies relating to the treatment of cats with CDS it is possible to extrapolate from studies of humans with AD and dogs with CDS.

Dietary Modification and Environmental Management

Diets enriched with antioxidants and other supportive compounds (e.g., vitamin E, β-carotene, and essential fatty acids) are believed to reduce oxidative damage, so reducing β-amyloid production, and improving cognitive function. In humans, studies have shown that high intake of fruits, vegetables, vitamins E and/or C, folate and/or B₁₂ may improve cognition (although excessive intake of some of these compounds can be harmful). In addition, α-lipoic acid and l-carnitine enhance mitochondrial function, and omega-3 fatty acids promote cell membrane health and have, in humans, been found to be beneficial in the treatment of dementia. In general, combinations of these compounds are believed to work best.

There have been a number of studies investigating the potential benefit of various supplements in dogs with CDS. For example, a study of dogs >6 years of age, when given a supplement containing omega-3 fish oils, vitamins E and C, L-carnitine, α-lipoic acid, coenzyme Q, phosphatidylserine and selenium (combination sold in the UK as Aktivait®; VetPlus) over a 2 month period resulted in significant improvements in signs of disorientation, social interaction, and house soiling. Unfortunately, a different formula is needed for cats as α-lipoic acid is toxic in this species. While there is a new feline-safe version of Aktivait, trials in cats still need to determine its efficacy.

Environmental enrichment can lead to an increase in nerve growth factors, the growth and survival of nerves and an increase in cognitive function. The combination of environmental stimulation (e.g., toys, company, interaction, and food hunting games) and a diet enriched with antioxidants is believed to have a synergistic action in improving cognitive function. In aged dogs, a 4 year study on the use of an antioxidant-enriched diet (e.g., vitamins E and C, selenium, fruit and vegetable extract [β-carotene, other carotenoids, flavonoids]), mitochondrial cofactors (dl-lipoic acid and l-carnitine), and essential fatty acids (omega-3 fatty acids) (Hill's b/d®), plus environmental enrichment (e.g., toys, kennel mate, walks, and cognitive experience testing) revealed rapid (2-8 weeks into treatment) and significant improvements in learning and memory. Interestingly, while there was no reversal of existing pathology, the antioxidants appeared to prevent the deposition of more β-amyloid while the environmental enrichment did not.

While a similar study showing improvement of CDS in cats in response to dietary supplementation is not yet available, a 5 year study feeding healthy old cats (7-17 years old; n=90) a diet (Nestlé Purina Pro Plan Age 7+®) supplemented with antioxidants (vitamin E and β-carotene), essential fatty acids (omega-3 and 6 fatty acids) and dried whole chicory root (which contains the prebiotic inulin to modify intestinal flora) resulted in the supplemented cats living significantly longer (and more healthily) than the un-supplemented ones. Other similarly supplemented diets are now on the market (e.g., Hill's Feline j/d which is actually designed for cats with arthritis--it is supplemented with a mixture of anti-oxidants (e.g., vitamins C and E, and β-carotene), essential fatty acids, chondroprotectants (e.g., methionine, glycosaminoglycans, glucosamine, and chondroitin sulphate), and L-carnitine and lysine [to aid obesity management and the build-up of lean muscle]: in a 2 month study of 75 cats of 12 years of age or older, that were not selected for signs of CDS or (osteoarthritis), where owners were asked to complete questionnaires >70% improved in one or more signs of cognitive function (and >50% improved in one or more signs of mobility).

Unfortunately, once cats develop significant clinical signs of CDS, instigating environmental change can actually have a negative effect. This is because affected cats often become very stressed and cope poorly with change; whether in their environment, daily routine, diet, or members of the household. The cat's response to this stress is to show more obvious signs of CDS (e.g., anorexia, hiding, and/or upset of toileting habits). For these cats, where possible, change should be kept to a minimum, and when it cannot be avoided it should be made slowly and with reassurance. Some cats may become so demented and cope so poorly with change that they may benefit from having their area of access reduced in size (e.g., to a single room containing everything they need); this core territory can then be kept safe and constant. Environmental application of synthetic feline appeasement pheromone (Feliway®; Ceva) can also help in reducing feline anxiety.

Potential Drug Therapies

There are a number of possible drug options for AD. These include various cholinesterase inhibitors (to increase the availability of acetyl choline at the neuronal synapses), selegiline (to manipulate the monoaminergic system), antioxidants (e.g., Vitamin E), and non-steroidal anti-inflammatory drugs (to reduce neuronal damage). There are no drugs licensed for the treatment of CDS in cats. However, selegiline (Selgian®; Pfizer: suggested dose 0.25-1.0 mg/kg PO q24h), propentofylline (Vivitonin®; Intervet: suggested dose 12.5 mg/cat PO q24h) and nicergoline (Fitergol®; Merial: suggested dose quarter of a 5mg q24h), have all been used in cat with varying degrees of success, e.g., a small open trial using selegiline showed a positive effect and the American Association of Feline Practitioners supports the use of this drug for the treatment of CDS. Other drugs that have been used to treat particular signs of CDS in cats include anxiolytic drugs, such as buspirone and benzodiazepines (e.g., diazepam--although hepatotoxicity is a risk with this drug), or antidepressants (that lack anticholinergic effects) such as fluoxetine.

Figure 1. Potential causes of behavioural changes in geriatric cats.

 Arthritis (pain and/or dysfunction of arthritis is often under-recognised in elderly cats)*

 Systemic hypertension (primary or secondary to hyperthyroidism, renal failure, diabetes mellitus, acromegaly or hyperadrenocorticism)

 Hyperthyroidism

 Chronic kidney disease

 Diabetes mellitus

 Urinary tract infection

 Gastrointestinal disease

 Liver disease

 Neurological defects (either sensory or motor deficits)

 Reduced vision or hearing

 Brain tumours

 Infectious disease (e.g., FIV, FeLV, toxoplasmosis, FIP)

 Periodontal disease

 Pain and inflammation in general

 True behavioural problems (e.g., separation anxiety)

 CDS

* The importance of arthritis should not be overlooked. Radiographic evidence of degenerative joint disease is present in 70-90% of cats >10 years of age. Associated pain and/or dysfunction can result in reduced activity and mobility, aggression, altered interactions with the family, and/or loss of litter box training. Owners can help their arthritic cats by adjusting their house; for example, by moving food and water bowls to lower surfaces, adding ramps to allow easier access to favoured sleeping areas, providing deep comfortable bedding that will support and protect the cat's joints (heated beds can be particularly soothing), and placing low-sided litter boxes within easy cat reach.

Figure 2. Investigations.

Initial investigation:

 History, including the possibility of previous trauma (risk of arthritis), potential exposure to toxins or drugs, recent environmental changes (in the household, family members, diet, etc.). Asking specific questions about alterations in the cat's behaviour can help in determining how the cat has changed (Figure 3).

 Physical examination (including body weight, body condition score, retinal examination and neurological examination).

 Systemic blood pressure.

 Haematology and serum biochemistry, including thyroid hormone level.

 Urine analysis (including urine protein to creatinine ratio and bacterial culture).

Further investigation may include:

 Serological testing for FeLV, FIV, toxoplasmosis or FIP.

 Thoracic, abdominal or skeletal radiography, abdominal ultrasound examination, ECG, echocardiography, intestinal endoscopy / exploratory laparotomy and biopsy collection, as indicated.

 Head CT or MRI.

Figure 3. Mobility / cognitive dysfunction questionnaire.

References

References are available upon request.