SENILITY:
As we and our pets age, there is a natural reduction in many biological processes and a
lost of tissue structure. This includes the CNS and the cerebral tissues. Neurochemicals change
with a general reduction in certain chemical reactions. Neurons are gradually lost from the wear
and tear of daily life. Researchers believe Cognitive Dysfunction Syndrome (CDS) is caused by
physical and chemical changes that affect the brain function in older dogs; however, in dogs with
CDS the signs of confusion or various other behavioral changes are greater than the normal
alterations of aging. Most dogs age without the accentuated signs seen in CDS, yet the changes
that lead to CDS take place in all dogs to some extent. In one study at the University of
California-Davis, 62% of 11- to 16-year-old dogs showed signs in at least one category of CDS.
In a pet owner survey, nearly half of dogs age 8 and older showed at least one sign associated
with CDS.
Pathophysiology:
Monoamine oxidase (MAO)s are widely distributed throughout the body and are subclassified
into 2 types, A and B, which differ in their substrate specificity and tissue distribution.
MAO plays a role in the catabolism of catecholamines, (dopamine, and, to a lesser extent,
norepinephrine and epinephrine) and serotonin. CDS is thought to result in part from reduced
catecholaminergic nerve function and decreased dopamine levels in the CNS. The pathogenesis
of the development of clinical signs associated with cognitive decline is considered to be partly a
result of a decrease in the level of catecholamines in the CNS and deficiencies in
neurotransmission. There is also evidence which points to hypothalamic dopamine deficiency
playing a role in the pathogenesis of pituitary dependent hyperadrenocorticism in the dog.
In people, numerous studies have indicated that senility and Alzheimer’s disease are
related to similar changes as occur in CDS. In those human conditions, oxidative free-radicals
have been shown to play a key role in causing the pathologic changes seen. Anything which
improves cerebral blood flow and enhances cerebral oxygen (cosmic Qi) delivery to the CNS
will reduce the rate of progression and improve cognitive function. While people suffer more
from cerebral vascular insufficiency than dogs and cats (people get atherosclerosis), animals still
respond to the same treatments used in human beings. Recently, it has been suggested that
glutamate levels increase in Alzheimer’s disease which results in stimulation of specific neural
receptors that result in cytotoxic reactions. This glutamate-dependent receptor’s effects are
blocked by antioxidants.
Diagnosis:
The diagnosis of CDS is based upon the presentation of the clinical signs in a older
patient and ruling out other causes to explain the presence of the condition. A work-up should
include a thorough physical and neurological examination. A CBC, chemistry profile and UA may be helpful in recognizing any additional systemic factors which need therapy or which
might contribute to the symptoms. Remember that CDS is a chronic and slowly progressive
problem, not one that occurs over-night. Chest and abdominal radiographs and abdominal
ultrasound may help look for other complication and diseases which might result in similar
symptoms. Perineoplastic signs could mimic signs of CDS and the minimum database helps
provide evidence which precludes systemic neoplasia as part of the process. A CSF tap is usually
normal with the exception of a possible mild increase in CSF protein. An MRI can be helpful
since many of these patients show signs of de novo hydrocephalus from cortical atrophy. If no
other signs, except for behavior and the MRI changes are seen, then the tentative diagnosis of
CDS is made.
Treatment:
Anipryl is the first and only drug approved by the FDA for the control of clinical signs
associated with canine Cognitive Dysfunction Syndrome. Most dogs are prescribed one tablet
each day, preferably in the morning. (Anipryl can be given with food.) It's important to
administer every tablet as directed since interruption of therapy could lead to the reappearance of
signs.
In studies, pet owners reported that 69 to 75% of dogs improved in at least one clinical
sign after one month of Anipryl therapy. Because CDS is a syndrome (a collection of signs), no
two dogs will show exactly the same signs. Response to Anipryl may vary from dog to dog.
In the blinded, placebo-controlled study, owners reported that 69% of dogs improved in
at least one clinical sign after one month of Anipryl therapy, compared to 52% of placebo-treated
dogs. A second open label clinical study revealed that 75% of dogs improved in at least one
clinical sign after one month of Anipryl therapy. Some dogs in both studies showed increased
improvement for up to three months, indicating that some increased improvement may be seen
with continued use. However, onset, duration and magnitude of response varied with individual
dogs. In studies, the most common side effects were vomiting, diarrhea or changes in behavior
such as hyperactivity and restlessness. Most side effects were mild to moderate.
Based upon IV administration of selegiline to 4 mixed breed female dogs, the plasma
elimination half-life was estimated to be 60 ± 10 minutes (mean ± SD) and the volume of
distribution at steady-state (Vss) was estimated to be 9.4 ± 1.6 L/kg (mean ± SD). The relatively
large Vss suggests that the selegiline is extensively distributed to body tissues. The absolute
bioavailability, F, of an oral solution was less than10%.
Alternative Therapy. Although Anipryl is recommended for treatment of CDS, I prefer
to try other measures before resorting to it for the control of the condition. Aerobic exercise has
been shown to improve cognitive function and should not be overlooked as a simple way to
improve the pets cerebral functions. Antioxidants can be very useful including vitamin E,
vitamin C, Vitamin A (or beta carotene) and selenium should be given. Vitamin E, however,
should be given at therapeutic levels which are 50-100 IU/kg. Grape seed extract can be helpful
as an antioxidant as well. Ginkgo biloba extract (2-4 mg/kg every 8-12 hours) can be very
helpful and has been shown to provide long-lasting and effective help in human Alzheimer’s
patients. Another antioxidant that has been demonstrated in studies to help in senile dementia
and Alzheimer’s disease is acetylcysteine (25 mg/kg every 8 hours). Compared with vitamin E and C, acetylcysteine is even more potent as an antioxidant. In addition, coenzyme Q-10, soy
lecithin, omega-3-fatty acids, gammalinolenic acid and vitamin B complex can be very useful in
helping support CNS function, oxygen utilization, membrane stabilization and neurochemical
production. If these measures do not help (and the diagnosis is correct), then Anipryl can be
tried.
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