Definition

Syndrome associated with brain aging. Leads to alterations in awareness, decreased responsiveness to stimuli, deficits in learning and memory and agitation and anxiety. Subtle signs seen in early stages, referred to as cognitive decline may include alterations in activity and play and increasing anxiety.

Pathophysiology

• Unclear which changes are associated with the clinical signs.
• Decline in neurons, decrease in frontal lobe volume, increase in ventricular volume and neurotoxic deposits including lipofuscin, ubiquitin, and beta-amyloid.
• Toxic free radicals (reactive oxygen species) increase with age because of chronic illness and stressors, age-related decline in mitochondrial efficiency, and decreased clearance mechanisms.
• Possible correlation between cognitive decline and amount of beta-amyloid in the cerebral cortex and with increases in toxic free radicals.
• Compromised cerebral vascular blood flow and infarcts may be contributory.
• Neurotransmission is compromised. May be a decline in catecholamine and cholinergic transmission.

Systems Affected

• Behavioral
• Nervous

Genetics

May be genetic correlation with respect to the distribution of beta-amyloid and the age at which it begins to accumulate.

Incidence/Prevalence

• Clinical signs of cognitive dysfunction have been reported to arise in 41% of dogs over 14.
• Prevalence in dogs over 10 estimated at 14.2%.
• Clinical signs reported to arise in 50% of cat over 15.
• Prevalence in cats over 10 estimated at 35%.
• Progressive-pets with existing signs more likely to develop additional signs over next 12 months.

Signalment

Signs

Causes

• Exact cause is unknown and animals are variably affected.
• Environmental factors may contribute to age related degeneration
• May also be predisposing genetic factors
• Diet, enrichment, and stress management may be in part preventive.
• See “Pathophysiology.”

Risk Factors

• Chronic or recurrent illness or stress might lead to increased accumulation of reactive oxygen species.
• Conditions that affect the cerebral vascular blood supply (e.g., systemic hypertension, anemia).

Differential Diagnosis

• Any medical condition or disease process that affects the pet's mental attitude or behavior must be ruled out.
• Pain (e.g., arthritis, dental disease) can lead to increased irritability, anxiety, and altered response to stimuli
• If mobility is affected, the pet may become increasingly aggressive rather than retreat and may be less able to access its elimination area.
• Impaired sight or hearing might lead to a decreased responsiveness or increased reactivity to stimuli.
• Diseases of the urinary tract can cause inappropriate urination.
• Organ failure, tumors, and immune diseases can also affect behavior.
• Endocrinopathies such as hypothyroidism can lead to behavior changes ranging from lethargy to aggression, while hyperadrenocorticism may be associated with altered sleep-wake cycles, housesoiling, panting, and polyphagia. Hyperthyroidism in cats can lead to increased irritability and increased activity.
• Diseases that affect the central nervous system or its circulation can affect behavior.

CBC/Biochemical/Urinalysis

Normal with CDS but concurrent disease processes common in aged dogs.

Other Laboratory Tests

Normal with CDS

Imaging

• Used to rule out primary organic/structural cause.
• Most important when there are abnormalities on the neurologic examination or when the onset is sudden; less likely to be of diagnostic value if signs are slowly progressive in the absence of other neurologic findings.
• Pets with cognitive dysfunction may have increased ventricular volume and an overall decline in brain mass, but these findings alone are not diagnostic.

Diagnostic Procedures

• Endoscopy, radiography, ultrasound, and other specialized diagnostic procedures may be necessary to rule out other causes of the clinical signs.
• BAER testing or ophthalmologic referral might be indicated if sensory dysfunction is a suspected cause of the signs.
• A therapeutic trial might be a useful diagnostic aid, for example, to determine the effects of pain management on the resolution of clinical signs.

Pathologic Findings

Evaluation for brain pathology and staining for -amyloid deposition might be indicative of the degree of cognitive dysfunction. This type of assessment is available only on postmortem samples.

Appropriate Health Care

Outpatient care

Nursing Care

Depends on the type and severity of the clinical signs of cognitive dysfunction.

Activity and Training

• Maintain as much exercise, play, training, work, and other daily routines as is practical for the pet's age and health.
• Maintaining mental and physical stimulation has been shown to reduce or slow progression of cognitive decline.

Diet and Neutraceuticals

• Selected based on the pet's health assessment.
• If the pet's health does not require the need for a special therapeutic diet, then a senior diet that has demonstrated efficacy in improving cognitive function should be used.
• Hill's Prescription Diet b/d has been shown to improve memory, learning ability, and clinical signs of cognitive dysfunction syndrome. The diet is supplemented with antioxidants such as vitamins E and C, selenium, beta carotene, and flavonoids and carotenoids, omega-3 fatty acids EPA and DHA, and carnitine and alpha lipoic acid, which may improve mitochondrial health.
• A canine diet (Purina ProPlan Bright Minds 7+), which is supplemented with medium-chain triglycerides to provide ketones to aging neurons as an alternative energy source has also been shown to improve signs of cognitive function in older dogs.
• Some natural supplements may help to improve the signs or slow the decline of cognitive dysfunction.
  • Supplements containing phosphatidylserine (Senilife, CEVA Animal Health and Activait, VetPlus), apoaequorin (Neutricks, LLC), and SAMe (Novifit, Virbac Animal Health) have demonstrated some evidence of efficacy.
  • For cats, SAMe and a diet containing fish oil, arginine, and antioxidants (not presently available commercially) has demonstrated a beneficial effect.

Client Education

• Lifelong therapy is required, and concurrent medications may be necessary if the pet has multiple problems.
• Any changes in the pet's health or behavior should be reported immediately, as this may be due to cognitive dysfunction or new health problems.
• Considering the pet's health and cognitive status, the owner must be advised on any limitations on what might be achieved.
• Signs are generally progressive; treatment is aimed at slowing the progression of the disease, not cure.

Drug(s) Of Choice

Contraindications

• Selegiline should not be used concurrently with MAO inhibitors such as amitraz, narcotics, alpha-adrenergic agents such as phenylpropanolamine or ephedrine, or selective serotonin reuptake inhibitors (e.g., fluoxetine) or tricyclic antidepressants (e.g., clomipramine).
• A 2-week washout is suggested following most tricyclic antidepressants and up to 5 weeks following fluoxetine before starting selegiline.

Precautions

• Choose medications that are least sedating and least anticholinergic.
• Potential drug interactions must be considered with concurrent use of drugs and over-the-counter medications.

Possible Interactions

See “Contraindications.”

Alternative Drug(s)

• Enhancement of the noradrenergic system with drugs such as adrafanil and modafinil to improve alertness and exploration.
• Anti-inflammatory medication, and natural supplements such as gingko biloba and curcurmin might be considered based on preliminary work in other species.
• Medication used in humans for Alzheimer's disease to enhance cholinergic transmission might be useful, but doses and pharmacokinetics in dogs have not been determined. Potential side effects include nausea, vomiting, diarrhea, and sleep-wake disturbances.
• Anxiolytics such as buspirone, drugs to help induce sleep such as benzodiazepines, or antidepressants such as fluoxetine (not in conjunction with selegiline) might be considered to treat anxiety and apathy.
• Natural supplements might help to normalize sleep-wake cycles or reduce anxiety (e.g. melatonin, valerian, l-theanine, alpha-casozepine, Harmonease [VPL], Adaptil and Feliway [CEVA]).

Patient Monitoring

• If a drug or diet is dispensed, then therapeutic response should be evaluated after 30–60 days and the dose adjusted or treatment changed if there is insufficient improvement.
• If the pet is stable, twice-yearly checkups are recommended for senior pets unless new problems arise before a reassessment is due.

Prevention/Avoidance

• Providing an enriched environment and as much physical activity as is practical for the pet's age and health may help to prevent or delay the onset of cognitive decline.
• Early intervention is the best way to slow the progress or prevent complications.

Expected Course and Prognosis

• Diet and medication should control the clinical signs and slow progression in a majority of cases.
• Because of the pet's increasing age, cognitive decline may advance and other concurrent health problems are likely to arise.

Synonyms

• Age-related cognitive and affective disorders, involutive depression, dysthymia
• Dementia
• Senility

Abbreviations

• BAER = brainstem auditory evoked response
• CDS = cognitive dysfunction syndrome
• CNS = central nervous system
• MAO = monoamine oxidase
• SAMe = S-adenosyl-L-methionine-tosylate disulfate

Client Education Handout Available Online