Canine Cognitive Dysfunction (CCD)

By Michele James, DVM, DACVIM (Neurology)
angell.org/neurology
neurology@angell.org
617-541-5140

July 2025

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Introduction

Canine cognitive dysfunction (CCD) is a common neurodegenerative disease in geriatric dogs (i.e., older than 8 years old), with an estimated prevalence of 14% to 35% in the pet canine population. The risk of CCD exponentially increases with age, such that the odds of developing CCD increase by 52% with each additional year of age. CCD has no known breed disposition, although it is more commonly recognized in smaller breed dogs due to their generally longer life expectancy. CCD shares both a similar clinical course and pathological findings to Alzheimer’s disease (AD) in humans, making CCD an ideal model for AD research. Clinical signs of CCD include changes in sleep-wake cycles, disorientation, decreased interaction with owners, anxiety, and loss of house training/learned behaviors. Despite the pervasiveness of CCD in the canine population, treatment options remain limited. Like AD, there is unfortunately no cure for CCD at this time.

Pathophysiology of Disease

The pathophysiology of both CCD and AD is multi-faceted and complex, involving cerebrovascular disease, neuritic plaques in the brain parenchyma, and protein aggregation. Beta-amyloid (Aβ) plays a central role in the pathogenesis of CCD. Aβ is a neurotoxic and insoluble protein that forms aggregates or extracellular plaques (neuritic plaques) in the brain around neurons and blood vessels. These plaques affect neuronal signaling and activate glial cells, which, in turn, lead to neuroinflammation and subsequent cell loss and dysfunction. In addition to Aβ aggregates, intraneuronal accumulation of tau protein also occurs, which may contribute to axonal transport dysfunction and neuronal death. Other contributing processes for cognitive impairment observed in CCD include cholinergic dysfunction, neuronal mitochondrial dysfunction, impaired neuronal glucose metabolism, and neuronal hyperexcitability.

Clinical Signs and Diagnosis

Dogs with CCD typically present with a chronic progressive history of forebrain dysfunction, characterized by confusion, anxiety, a change in sleep/wake cycle, and decreased interaction with owners. Owners may report observing pacing at night, hearing loss, and excessive vocalization. Upon examination, abnormal/inappropriate mentation and compulsive circling are commonly observed. Transient vestibular episodes and/or a new history of seizure activity may also be noted. Diagnosis of CCD is a diagnosis of exclusion, typically based on signalment, history, and clinical signs. Other medical conditions that may exacerbate clinical signs should be excluded, namely, hypertension, metabolic disease, pain, and brain tumors. To further aid in CCD diagnosis, veterinarians may use questionnaires for screening and evaluating the severity of the disease. These questionnaires include the Canine Dementia Scale (CADES) and Canine Cognitive Dysfunction Rating Scale (CCDR).

MRI may be used for the diagnosis of CCD; however, it is infrequently performed due to concerns from owners regarding general anesthesia, the cost of the procedure, and the low likelihood that an MRI diagnosis will significantly impact the treatment plan. MRI findings in dogs with CCD are consistent with brain atrophy and include ventricular enlargement, widening of the cerebral sulci, and an interthalamic adhesion thickness of 5 mm or less. Other MRI findings in CCD include cerebral microhemorrhages and leukoaraiosis. Leukoaraiosis is a term used to describe abnormal changes in the white matter of the brain, particularly near the lateral ventricles, and is thought to be secondary to vascular abnormalities. Despite the described MRI findings for CCD, a definitive diagnosis can only be obtained postmortem on histopathology.

Treatment

Though there is no cure for CCD, there are treatment options available to improve the quality of life for the pet and owner by slowing cognitive decline.

Diet and Supplements

1. Exogenous antioxidants (i.e., Vitamin B, Vitamin C, Vitamin E) have been used to mitigate oxidative damage. Together with mitochondrial cofactors (i.e., L-carnitine, DL-α-lipoic acid), they have been shown to increase cognitive function in aged dogs, though they are unable to reverse neuron loss.
2. Docosahexaenoic acid (DHA) is an omega-3 fatty acid in the brain that plays a role in neuroinflammation, neuroprotection, and synaptic health and is vital for brain function.
3. Medium chain triglycerides (MCTs) offer an alternative energy source for the brain in CCD patients that suffer from impaired neuronal glucose metabolism via ketone bodies. They have been shown to improve cognitive function in aged dogs. To obtain the highest dose of MCTs, MCT oil made from coconut oil may be a suitable option.
4. Commercially available diet options for CCD include Hill’s b/d and Purina Neurocare.

Pharmaceuticals and Nutraceuticals

1. L-deprenyl (Selegiline) is the only FDA-approved treatment for CCD. It is an irreversible monoamine oxidase B inhibitor (MAOI) that is believed to improve cognitive function by restoring dopamine balance, decreasing free radicals, and increasing catecholamine levels. It may take a month to see positive results.
2. Nicergoline is an α-adrenergic antagonist that increases blood flow to the brain and has been used to treat cognitive and behavioral disorders in humans, and is used in dogs with CCD.
3. Levetiracetam (Keppra) is an anti-seizure medication that has been shown to improve cognitive function in AD by decreasing neuronal hyperexcitability.
4. Apoaequorin is a calcium buffering protein from jellyfish that has demonstrated improvement in cognitive function in dogs by decreasing intracellular calcium dysregulation.
5. Antidepressants (i.e., Fluoxetine, Clomipramine) and anxiolytics (i.e., Gabapentin, Pregabalin) may also be used to address clinical signs of anxiety and aggression that may occur as sequelae of CCD. The use of Selegiline with antidepressants should be avoided due to concern for serotonin syndrome.

Cognitive Enrichment

1. Exercise and social interactions can improve cognitive function by improving neuronal plasticity and hippocampal atrophy. This may include regular walks, new toys, and even physical rehabilitation.

Chinese Herbs and Acupuncture

1. Single Chinese herbs and herbal formulas have been shown to improve cognitive function via several processes, including antioxidant activity, anti-inflammatory activity, improved blood flow to the brain, and decreasing Aβ in the brain. These include Ginkgo biloba (Bai Guo), Ginseng (Ren Shen), Crocus sativus (Zang Hong Hua), among others.
2. Acupuncture may be a therapeutic option for CCD based on promising findings in AD. Acupuncture is believed to enhance neuroplasticity and enhance hippocampal activity.

Conclusion

Canine cognitive dysfunction (CCD) is a common disease in veterinary medicine and is likely to become increasingly prevalent as the life expectancy of our pet dogs continues to increase.  Further research is warranted to improve early detection and therapeutic intervention. CCD’s similarities to AD make it an ideal model for AD. Hopefully, the future will hold more targeted therapies and preventative strategies for both conditions.

References

1. Dewey et al. Canine cognitive dysfunction: pathophysiology, diagnosis, and treatment. Vet Clin Small Anim. 49: 477-499.
2. Kim et al. Recent advances in diagnostic and therapeutic strategies for canine cognitive dysfunction. AJVR. 2025. Doi.org/10.2460/ajvr.25.02.0053.
3. Mihevc et al. Canine cognitive dysfunction and Alzheimer’s disease – two facets of the same disease?. Neurosci. 2019. 13:604. Doi:10.3389/fnins.2019.00604.
4. Yarbrough et al. Evaluation of cognitive function in the dog aging project: associations with baseline canine characteristics. Scientific reports. 2022. 12:13316. Doi.org/10.1038/s41598-022-15837-9.