CPD ACCREDITED ARTICLE
In a marketing study by Hills Pet Nutrition, 75% of
owners of dogs aged 7 years and older reported at
least one change in behaviour consistent with cog-
nitive dysfunction but only 12% of these owners had
reported the change to their veterinarian of their own
accord.
Brain Function and Ageing
With increasing age there is a reduction in brain mass,
increased ventricular size, meningeal calcification, de-
myelination and glial changes, neuro-axonal degen-
eration and a reduction in neurons. In dogs, cats and
human beings with cognitive dysfunction there is also
an increased accumulation of diffuse beta-amyloid
plaques and perivascular infiltrates. In humans neu-
rofibrillar tangle formation is an important component
of the disease. This is not seen in dogs but is seen
in cats. Cerebral arteriorsclerosis may also be seen in
older dogs and cats resulting in compromised blood
flow. Changes are irreversible but clinical signs can be
managed and improved.
The brain is highly metabolically active, accounting for
2-3% of body weight yet consuming 25% of available
glucose. Normally glucose is the main energy source
of the brain. Cerebral glucose metabolism is reduced
in healthy ageing people and dogs. Cerebral glucose
metabolism correlates strongly with cognitive func-
tion and reduced metabolism occurs years before
clinical signs are evident.
With ageing there is an increase in reactive oxygen
species leading to oxidative damage. The brain may
be particularly susceptible of the effects of free radi-
cals because of its high lipid content, high rate of oxi-
dative metabolism and limited ability for regeneration.
Functional changes in the ageing brain include deple-
tion of monoamine oxidase inhibitors (MAOIs) and a
decline in cholinergic activity. Increases in MAO activ-
ity increases dopamine catabolism and also increases
free radicals. Widespread oxidative damages, free rad-
ical production and lowered Vitamin E levels have all
been demonstrated in dogs with dementia.
Ketone bodies (KB) can be used as an alternative en-
ergy source for the brain when available;–prolonged
starvation, and high fat- low carbohydrate diets. KB
can supply up to 60% of the energy requirements of
the brain during starvation in humans. Collectively
these ageing changes cause working memory dys-
function as well as alterations in motor function and
REM sleep.
CLINICAL PRESENTATION
The most central diagnostic tool for detecting Cog-
nitive Dysfunction is owner-based questionnaires or
assesments. (Tables 1 and 2)
Many of the behavioural complaints of older pets are
related to anxiety, including an increased prevalence
of separation anxiety, phobias, excessive vocalisation,
aggression and waking at nights. Not all such changes
in the older dog are however due to cognitive dys-
function. Other disease process which may cause or
contribute to these signs must be excluded. (Table 3)
TREATMENT
Because neurophsychological testing procedures of
dogs and cats are now standardised, therapeutic in-
terventions can now also be evaluated and in some
cases approved, for use in clinical cases. Drugs, die-
tary changes and environmental enrichment and ad-
justment are the three mainstays of treatment.
Drugs (See table 4)
Selegiline
Selegiline is a selective irreversible monoamine oxi-
dase B inhibitor (MAOB). The mechanism by which it
causes its effect in dogs is not clear but three concur-
rent actions are proposed:
• increases 2-phenyl ethylamine (PEA) in the dog brain,
a neuromodulater which enhances dopamine and
catecholamine function and itself enhances cong-
nitive function. Catecholamine enhancements may
lead to enhance neuronal transmission.
• contributes to decreasing the free radical load in
the brain by scavenging free radicals and enhancing
scavenging enzymes such as superoxide dismutase
(SOD) and catalase.
• is neuroprotective effect on dopaminergic, noradr-
energic and adrenergic neurons
Dose: 0.5 – 1 mg /kg oid in am. If there is not signifi-
cant improvement in 30 days the dose can be adjust-
ed upwards for another month. Toxicity can occur if
used concurrently with other MOAIs.
Drugs for Enhancing Cerebral Perfusion
Propentophylline (Karsivan®) is licensed for the
treatment of dullness and lethargy in older dogs.
Propentophylline is a phosphodiesterase inhibitor and
also acts as an adenosine reuptake inhibitor. Both
these actions cause vasodilation and increased blood
flow especially to the heart, skeletal muscles and the
brain. It thus decreases ischaemic damage to the brain
and also stimulates the synthesis and release of nerve
grow factor. Tablets are administered at 5mg/kg, bid.
The drug is contraindic=ated in dogs weighing less
than 2,5 kg and those with advanced heart disease.
Drugs Enhancing the Noradrenergic System
Nicergoline: alpha 1 and alpha 2 adrenergic antag-
onist. Adrafanil, modafinil: enhance noradrenergic
system –improve alertness and help maintain normal
sleep-wake cycle by increasing daytime exploration
and activity. The noradrenergic system helps to main-
tain alertness, wakefulness, attention, memory and
learning and also functions in neuroprotection. Treat-
ment with these drugs causes improved learning but
Issue 06 | DECEMBER 2017 | 35