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Dog dementia - the 3 main miracle pharmaceuticals used to treat & prevent
My dog Archie is nearly eight. At 7 is when most dog food companies market mature dog food to you, and some include supplements to help brain function and mobility. Most science paper tests for older humans and dogs seem to rely on the three same drugs, each with their own effects. However I have managed to find a few other chemicals that might help prevent your dogs brain from ageing.
As always your vet should have the final say, but here are some of the dog drugs that I found in the science papers and what their effects are.
This blog concentrates on the three (plus Adrafinil) or so main prescription chemicals used in dog senile treatment as well as two new promising Non prescription options.
Canine Cognitive Dysfunction Syndrome (CDS) Behaviour are usually caused by brain issues in older dogs, They are often categorised into 4 main areas where behavioural changes are seen:
- decreased social interaction
- inappropriate elimination (urine and faeces)
- changes in the sleep-wake activity cycle.
Dementia in senior dogs is now often being found to be a form of Alzheimer's Disease (AD)
In senile dogs a correlation exists between the quantity of beta-amyloid accumulation and the degree of cognitive decline.
The reason for the decline is said to be " neuronal death neurotransmitter dysfunction also contributes to changes seen in the older brain. Monoamine oxidase B (MAO-B) activity is increased, while the concentration of the neuromodulator 2-phenylethylamine is decreased. A consequence of increased MAO-B is decreased dopamine function, which in turn leads to increased production of free radicals, the neurotoxic by-products of dopamine metabolism, which leads to further degeneration and are hypothesised to be contributing factors in the development of CDS." (hills pet)
There are a number of physical reasons (arthritis, glandular, organ failure) that can contribute to dogs' seeming like they have dementia, but when these are ruled out medicine is usually prescribed by a vet.
The three most common drugs prescribed are:
1. Nicergoline - has been recommended for dogs showing signs consistent with aging related behavioural disorders (canine cognitive dysfunction syndrome (CDS)) and cerebral insufficiency of vascular origin. It is an alpha-adrenergic antagonist and it is used in humans for the prevention and treatment of cerebrovascular disorders and arteriosclerotic diseases.
Nicergoline is an ergoloid mesylate derivative (akin to Hydergine), that is currently being used in the battle to treat senile dementia. It has been found to improve mental agility more through enhancing clarity, perception and vigilance. Whereas Hydergine (improves oxygen stability and increases mental ability - by extending the period of useful mental workload, (IQ booster) and provides brain dendrite stimulation).
Nicergoline alpha-adrenolytic action activates the brain's metabolism and improves arterial flow, lowers vascular resistance and improves the use of glucose and oxygen. It also inhibits platelet aggregation and increases nerve growth factor in the aged brain.
Nicergoline is a nootropic (and requires one week off per month) Caution must be used when the dog has potential to suffer acute bleeding, myocardial infarction (heart conditions), hypertension, bradycardia or using alpha or beta receptor agonists.
Recommended dose rate in dogs is 5 μg/kg given orally once daily.
While this drug is often prescribed there are studies suggesting that it has very little efficacy compared with cabergoline or adrafinil (Adrafinil is also a Nootropic that gives wakefulness-promoting agent used to relieve excessive sleepiness and inattention). It has been a favourite of shift workers. It also causes increased concentrations of modafinil in the body.
2. Selegeline - (Anipryl brand in USA) is a reversible Monoamine Oxidase-B inhibitor (MAOI-B). In humans selegiline has been used in the treatment of Parkinson’s disease as well as an antidepressant. In the USA and Australia the main behavioural use of selegiline is for Canine cognitive dysfunction syndrome in old dogs.
It is also useful in some anxiety problems. It may take up to three months to see the full behavioural benefits of selegiline although often owners have reported improvement in their dogs within 7-10 days.
" Selegiline increases 2-phenylethylamine (PEA) in the dog brain (Milgram et al., 1993), which is a neuromodulator that enhances dopamine and catecholamine function and may itself enhance cognitive function (Paterson et al., 1990). Catecholamine enhancement may lead to improved neuronal impulse transmission.
Selegiline may also contribute to a decrease in free radical load in the brain by directly scavenging free radicals and enhancing scavenging enzymes such as catalase and superoxide dismutase (SOD), the latter of which is increased in dogs on selegiline therapy (Carillo et al., 1994). In addition, because MAOB is inhibited, fewer toxic free radicals may be produced.
Selegiline may also have neuro-protective effects on dopaminergic, noradrenergic, and cholinergic neurons (Heinonen and Lammintausta, 1991). For CDS, selegiline is dosed at 0.5–1 mg/kg each morning and, if there is not significant improvement in 30 days, the dose can be adjusted up to the next tablet size for another month. Toxicity has been reported on rare occasions in humans when selegiline is used concurrently with antidepressants, ephedrine, narcotics, phenylpropanolamine, or other MAO inhibitors." (REF 1)
3. Propentofylline - " Propentofylline is licensed for the treatment of dullness and lethargy in old dogs in a number of European countries. It is purported to inhibit platelet aggregation and thrombus formation, make the red cell more pliable and increase blood flow. (REF 1)
" Propentofylline is a xanthine derivative that has proved effective in clinical trials in patients with vascular dementia and those with dementia of the Alzheimer type. Some of the pathological process of Alzheimer’s including glial cell activation and increased production of cytokines, free radicals and glutamate have been shown to be modulated by propentofylline. Propentofylline has been demonstrated to improve learning and memory deficits induced by beta-amyloid protein deposition. In clinical studies in humans it improved cognitive functions and improved the ability of patients suffering from Alzheimer's disease and vascular dementia to cope with the routine tasks of daily life. " REF 2
"One recent study has compared changes in activity produced by adrafanil, nicergoline and propentofylline. While adrafanil led to a significant increase in locomotion, there was no effect of nicergoline or propentofylline (Siwak et al., 2000b). " REF 1
NOTE Adrafinil(used to be branded as Olmifon) is used in America mainly as a wakefulness-promoting agent (or eugeroic) used to relieve excessive sleepiness and inattention.
OTHER MAIN anti senility dog PRODUCTS
1. S-adenosyl methionine - (SAMe) is an amino acid metabolite that has been linked to several important body processes, one of which seems to be a cognitive function. The reason it is given to humans and dogs is that people with Alzheimer's have been found to have a reduced amount of SAMe in their bodies.
Giving SAMe to dogs has found to reduce cognitive decline and increase activeness.
2. Neutricks contains apoaequorin, a substance derived from jellyfish. Studies indicated that dogs taking it performed better at learning and attention tasks.
3. Senilife (USA) and Aktivait (UK)
Both products contain phosphatidylserine,
which is part of a cell membrane that has been used to treat humans with Alzheimer’s disease.
Some owners prefer this nonprescription drug as an alternative to pharmaceuticals,
It is said to be a synergistic combination of nutrients, antioxidants and mitochondrial co-factors which has been demonstrated to be of reducing canine cognitive dysfunction
I have included the full description of "How AKTIVAIT Works" from the reference source, because as you will find in the next blog - it seems to contain the majority of the nonprescription chemicals recommended to stop cognitive dysfunction IN ONE BOTTLE!
" AKTIVAIT® contains a number of ingredients which act together synergistically to alleviate CCD. Ingredients include:
Docosahexaenoic Acid (DHA) – Reduces neuronal inflammation and apoptosis. DHA is also responsible for increasing neuronal levels of phosphatidylserine
N-Acetyl Cysteine (NAC) - A primary precursor to glutathione a crucial endogenous antioxidant which protects neurons from oxidative damage. NAC levels decrease significantly with age
L-Carnitine & Acetyl L-Carnitine - Essential in the transport of long chain fatty acids. L-Carnitine enhances mitochondrial function whilst Acetyl L-Carnitine acts synergistically with α-lipoic acid to improve brain function, memory and activity levels by helping to reduce mitochondrial damage and increase mitochondrial numbers
Phosphatidylserine – Regulates the fluidity of neuronal membranes. It enhances transmembrane transport, ion channel function and enhances neurotransmitter release. Phosphatidylserine also protects cholinergic neurons and pyramid cells of the hippocampus from apoptosis and loss of dendritic spine. It also increases nerve growth factor synthesis and release, thus stimulating neuron sprouting and growth. Phosphatidylserine stands out as an essential brain nutrient (Osella, MC 2008).
Coenzyme Q10 – A lipid soluble antioxidant which helps to maintain antioxidant defences by regenerating vitamin E. Coenzyme Q10 is essential for electron transport in the mitochondria, while deficiency impairs ATP production and leads to oxidative stress. Supplementation with Coenzyme Q10 has been shown to delay brain atrophy and to protect against cognitive decline.
Selenium – An antioxidant which can help prevent cognitive decline and oxidative damage
Vitamin E & Vitamin C – Antioxidants which have a synergistic benefit in protecting mitochondria from age-associated oxidative damage and it has been shown that in cases of CCD, vitamin E levels in the brain are significantly reduced.
α-Lipoic Acid – A powerful mitochondrial antioxidant capable of regenerating most other antioxidants. α-lipoic acid protects cortical neurons from β-amyloid and hydrogen peroxide induced cytotoxicity and reduces lipofuscin levels. Synergistic antioxidant effects have been demonstrated with vitamin E, Coenzyme Q10 and Acetyl L-Carnitine. α-lipoic acid has been reported as toxic in cats and as such, is not included in AKTIVAIT® Cat.
In clinical trials, it was indicated that AKTIVAIT® has a clear, beneficial effect on aspects of behaviour associated with CCD (Heath, Sarah 2007)." REF 4
Ref 1 Review article Therapeutic agents for the treatment of cognitive dysfunction syndrome in senior dogs
REF 2 NOW WHY DID I COME HERE? CANINE COGNITIVE DYSFUNCTION Dr Kersti Seksel BVSc (Hons), MRCVS, MA (Hons), FACVSc, DACVB DECVBM-CA CMAVA Registered Veterinary Specialist in Behavioural Medicine
REF 3 http://dogdementia.com
REF 4 http://vetsci.co.uk/ (2011/10/04/canine-cognitive-dysfunction/)
REF 5 Comparison of the effects of adrafinil, propentofylline, and nicergoline on behavior in aged dogs. (nov 2000) xxx Muggenburg BA, Murphey, Milgram NW.
To compare the efficacy of adrafinil, propentofylline, and nicergoline for enhancing behavior of aged dogs.
36 Beagles between 9 and 16 years old.
PROCEDURE: Dogs were randomly assigned to receive adrafinil (20 mg/kg of body weight, PO, q 24 h; n = 12), propentofylline (5 mg/kg, PO, q 12 h; 12), or nicergoline (0.5 mg/kg, PO, q 24 h; 12) for 33 days. Baseline behaviors in an open field and in kennels (home cage) were recorded before treatment. After treatment, behaviors in the open field were recorded 2 hours after drug administration on days 2, 15, and 28, and 10 hours after administration on days 7, 20, and 33. Behaviors in the home cage were recorded 2 and 7 hours after drug administration on days 4, 17, and 30.
Treatment with adrafinil resulted in a significant increase in locomotion in each of the open-field tests and an increase in locomotion in the home cage. This latter increase was smaller and more variable than that in the open field. Locomotion was not affected by treatment with propentofylline or nicergoline. In the open field, sniffing decreased over time in all 3 groups, but the largest decline was observed in the propentofylline group.
CONCLUSIONS AND CLINICAL RELEVANCE:
Treatment with adrafinil may improve the quality of life of aged dogs by increasing exploratory behavior and alertness.
ALWAYS CONSULT YOUR VET BEFORE BEGINNING A DOG ON ANY MEDICATION TREATMENT !!!