Although there are no published studies relating to the treatment of cats with CDS, it is possible to consider potential treatment options by extrapolation from studies of humans with AD and dogs with CDS. Potential interventions therefore include dietary modification, environmental management and drug therapies (reviewed in Landsberg 2006).
Dietary modification and environmental management
Diets enriched with antioxidants and other supportive compounds (for example, vitamin E, β-carotene and essential fatty acids) are believed to reduce oxidative damage, so reducing Aβ production and improving cognitive function. In humans, studies have shown that high intakes of fruits, vegetables, vitamins E and/or C, folate and/or B12 may improve cognition (although excessive intakes of antioxidants can have a pro-oxidant effect). In addition, alpha-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 (Ikeda-Douglas and others 2004; reviewed in Head and Zicker 2004, Roudebush and others 2005, Landsberg 2006). For example, a study of dogs over six years of age, when given a supplement containing omega-3 fish oils, vitamins E and C, l-carnitine, alpha-lipoic acid, coenzyme Q, phosphotidylserine and selenium (this supplement is sold in the UK as Aktivait® from VetPlus) over a two-month period resulted in significant improvements in signs of disorientation, social interaction and house-soiling (Heath and others 2007). Unfortunately, a different formula is needed for cats as alpha lipoic acid is toxic in this species (Hill and others 2004) so products containing it should not be given. While the new feline-safe version of Aktivait is now on the market, trials in cats still need to determine its efficacy, as they have for the other supplements that have also recently become available, such as Feli-Age® from Vetri-Science.
Environmental enrichment can lead to an increase in neuronal growth factors, the growth and survival of neurons and an increase in cognitive function. The combination of environmental stimulation (for example, 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 four-year study on the use of an antioxidant-enriched diet (for example, vitamins E and C, selenium, fruit and vegetable extract [β-carotene, other carotenoids, flavinoids]), mitochondrial cofactors (dl-lipoic acid and l-carnitine) and essential fatty acids (omega-3 fatty acids) (Hill’s b/d®), plus environmental enrichment (for example, toys, kennel mate, walks and cognitive experience testing), revealed rapid (two to eight 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 Aβ, while the environmental enrichment did not (Milgram and others 2004, 2005).
While a similar study showing improvement of CDS in cats in response to dietary supplementation is not yet available, a five-year study feeding healthy old cats (seven to 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 than the unsupplemented ones (Cupp and others 2006). Other similarly supplemented diets will soon be on the market (for example, Hill’s Science Plan Feline Mature Adult 7+®).
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, their daily routine, their diet or the members of the household with which they live. The cat’s response to this stress is to show more obvious signs of CDS (for example, anorexia, hiding and/or upset of toileting habits) (Houpt and Beaver 1981). 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 much 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 (for example, to a single room containing everything they need); this small area 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 growing 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 (for example, vitamin E) and non-steroidal anti-inflammatory drugs (to reduce neuronal damage). While there are no drugs licensed for the treatment of CDS in cats, selegiline, propentofylline and nicergoline have all been used in this species with varying degrees of success (see below) (Landsberg and others 2003, Landsberg and Araujo 2005, Studzinski and others 2005, Landsberg 2006). Anecdotally, other drugs that have been used to treat particular signs of CDS in cats include anxiolytic drugs, such as buspirone and benzodiazepines (although hepatotoxicity is a particular risk with the latter), or antidepressants (that lack anticholinergic effects) such as fluoxetine.
Selegiline (l-deprenyl; Selgian® in the UK, Anipryl® in the USA; Pfizer) is licensed to treat dogs with CDS in the USA. It is a selective and irreversible MAOB inhibitor, which leads to an increase in 2-phenylethylamine and enhances the effects of dopamine. While its exact mechanism of action is still unclear, it may also have an antioxidant effect by increasing the effect of SOD. There have been a number of studies on its use in geriatric dogs, with up to 80 per cent of the dogs (n≥600 in different studies) showing improvement after being medicated for longer than a month. Improvements are typically seen in disorientation, sleep-wake cycles and interaction with the family, but are less marked in the most severely affected cases, and the disease continues to progress in all cases (Ruehl and others 1995, Campbell and others 2001). While selegiline is not approved for use in cats with CDS, anecdotally evidence is supportive, as was a small open trial (Landsberg 2006), and the American Association of Feline Practitioners has supported its use for this disorder (suggested dose 0·25 to 1·0 mg/kg orally every 24 hours; dog dose 0·5 to 1·0 mg/kg orally every 24 hours).
Propentofylline (Vivitonin®; Intervet) is licensed for the treatment of CDS in dogs in Europe. It is a xanthine derivative that is purported to increase blood supply to the brain, particularly the cerebral tissues, without increasing oxygen demand. It is also supposed to inhibit platelet aggregation, thrombus formation, inflammation and excessive activation of microglia, and decrease the formation of free radicals, cytokines and abnormal amyloid precursor proteins (Parkinson and others 1994). While studies show some benefit in dogs with CDS, increasing general demeanour, alertness and willingness to exercise (Siwak and others 2000), there is only weak evidence that it slows the progression of AD in people. Anecdotally, it has been used to treat cats with CDS (suggested dose 12·5 mg/cat orally every 24 hours; dog dose 3 to 5 mg/kg orally every 8 to 12 hours).
Nicergoline (Fitergol®; Merial) is licensed to treat CDS in dogs in Europe. It is an ergoline derivative that acts as an α1 and α2 adrenergic agonist. It increases cerebral blood flow, has a neuroprotective effect on neurons, and inhibits platelet aggregation. It may also act as a scavenger of free radicals and even increases appetite (Siwak and others 2000). Anecdotally, it has been used to treat cats with CDS (suggested dose quarter of a 5 mg every 24 hours: dog dose 0·25 to 0·5 mg/kg orally every 24 hours).
|Cerebral amyloid angiopathy||The accumulation of Aβ around meninges and blood vessels|
|Caudate area of the brain||Nucleus located within the basal ganglia in the brain. The caudate, originally thought to be primarily involved with control of voluntary movement, is now known to be an important part of the brain’s learning and memory system|
|Caudate dysfunction||Occurs when the caudate area of the brain is not functioning correctly, and can result in alterations in movement, learning and memory|
|Cognitive dysfunction syndrome||Describes an age-related decline of cognitive abilities; it is characterised by behavioural changes that are not attributable to other medical conditions|
|Classical conditioning||Also termed Pavlovian conditioning is a type of associative learning in which a response is elicited by a neutral stimulus which has previously been repeatedly presented in conjunction with the stimulus that originally elicited the response|
|Cognition||The operation of the mind by which we become aware of objects of thought or perception; it includes all aspects of perceiving, thinking and remembering|
|Habituation||The gradual adaptation to a stimulus or to the environment|
|Locus coereleus||An area on the floor of the fourth ventricle of the brain; it is involved in vigilance and autonomic activity|
|Neurofibillary tangles||Made from hyperphosphorylated tau protein (tau is a intraneuronal microtubule-associated protein that in its unphosphorylated form is involved in forming the cytoskeleton of neurons)|
|Senile plaques||Made from the extracellular accumulation of Aβ|