Does My Dog Have Alzheimer’s Disease?

As dogs age, many owners report changes in their behavior that are strikingly similar to humans suffering from dementia, including  progressive cognitive decline, disrupted sleep patterns, increased anxiety, and aimless wandering. These owners will often ask their veterinarian if their dog is suffering from Alzheimer's Disease (AD), and the answer may be yes. In dogs the condition is referred to as Canine Cognitive Disorder (CCD) and it does share many characteristics with AD, though there are some important differences.

Some degree of cognitive decline is normal for aging humans and dogs. In people, this may include briefly forgetting a name but remembering it later, taking longer to learn new information, or misplacing items such as keys or a phone. In dogs, normal aging can include a shorter attention span, reduced trainability, slower adaptation to new rules, and less responsiveness to familiar commands. People and dogs with typical age-related cognitive changes, however, can still manage everyday life.

Dementia, by contrast, causes memory and behavioral changes that make it difficult to accomplish normal daily tasks and routines. A person with dementia may forget a name permanently or misplace keys or a phone only to later find them somewhere inappropriate such as the refrigerator or trash. As the disease progresses, they may show impaired judgment and decision-making and become unable to care for themselves. Dogs suffering from dementia may become “stuck” in corners, stare at walls, or seem lost in familiar places. The dog’s interactions with people or other pets may also change, with some becoming clingier and others withdrawing. For many owners, changes in their dog’s sleep pattern may be the most difficult to manage, as dogs with CCD are often awake at night, wandering and pacing aimlessly, only to sleep soundly during the day.

In addition to some common clinical signs, the prevalence of both AD and CCD increases with age. For example, according to the Alzheimer's Association, roughly 5.2% of people between the ages of 65 and 74 suffer from AD, but in individuals over 85 years of age the incidence is 35.8%.  Although estimates of the prevalence of CCD vary widely, studies consistently find an increasing incidence with age. For example, one study found that 8.1% of dogs 8–11 years of age suffer from CCD, but almost 80% of dogs over the age of 17 have signs of moderate to severe dementia.

The pathological processes associated with dementia in humans and dogs are also similar, though there are significant differences. AD, the most common cause of dementia in humans, is marked by two hallmark protein abnormalities: amyloid-beta plaques that accumulate between neurons and neurofibrillary tangles (NFTs) which are hyperphosphorylated tau proteins that form inside neurons. AD is also associated with neuroinflammation and neuron loss. Dogs with CCD also show a progressive accumulation of amyloid-beta peptides in the brain parenchyma and associated vasculature. However, canine amyloid plaques are diffuse, lacking the dense core seen in human AD. In addition, well-defined NFTs are either absent or extremely rare, even in very old dogs with severe cognitive decline and a heavy burden of amyloid-beta plaques. While some studies have found evidence of phosphorylated tau epitopes, they do not appear to progress beyond the initial stages of the pathological tau cascade. It may be that dogs don’t live long enough to develop NFTs or there may be intrinsic differences in the canine tau protein or its associated kinases and phosphatases that render it less prone to aggregation. In humans the severity of clinical signs of AD correlates with tau burden, but even dogs with severe dementia exhibit very little in the way of tau-associated NFTs. This suggests that in dogs the development of dementia may follow different pathological processes than those associated with AD. In addition to amyloid-beta plaques, these processes may include early-stage tau phosphorylation, neuroinflammation, oxidative stress, vascular injury, and generalized atrophy. CCD has been proposed as a model for AD, though the differences in the pathological processes associated with its development may limit its ultimate value for that purpose. Alternatively, exploration of these alternative pathways in the dog may yield new insights into disease processes yet to be fully appreciated in humans.

Diagnosis of AD and CCG
Until recently a diagnosis of AD was based on symptoms and the elimination of other causes, with a definitive diagnosis being made only postmortem. Advances in imaging and detection of specific biomarkers, however, now allow for an earlier definitive diagnosis in individuals presenting with symptoms of dementia. For example, amyloid-beta plaques and NFTs in the brain can now be imaged using positive electron tomography (PET) and the concentrations of these proteins can be determined in the cerebral spinal fluid and blood using advanced mass spectrometry and digital immunoassays. Unfortunately, these tests are not readily available for dogs, and therefore most canine diagnoses are based on owner reported declines in cognition, the elimination of other possible causes, such as losses in hearing or vision, and veterinary assessments.

Therapy for AG and CCG
There are several approaches to the treatment of AD. Symptomatic (Cognitive Enhancing) Drug Therapy is an older approach that still remains standard of care for managing the symptoms of AD. Cholinesterase inhibitors, including donepezil, rivastigmine, galantamine are approved for mild-to-moderate AD, while memantine, an NMDA receptor antagonist, is typically added for moderate-to-severe disease. These drugs enhance cholinergic pathways and moderate excess glutamatergic transmission to stabilize cognition, but they don't alter the underlying disease course.

In contrast, the aim of more recently approved monoclonal antibody therapies is to slow progression of the disease. Lecanemab, for example, preferentially targets amyloid protofibrils, which are intermediate, still-soluble aggregates that appear to be particularly toxic to neurons. In contrast, Donanemab is plaque-selective, targeting a modified form of amyloid found specifically within already-formed plaques. Both are appropriate only for patients with confirmed amyloid pathology and mild cognitive impairment, which is a small subset of AD patients. The clinical effects of both treatments are significant, but modest. For example, lecanemab showed a 27% slowing of clinical decline over 18 months, while donanemab slowed decline by 35% in patients with low-to-medium tau burden and 22% in the full trial population. These agents only remove beta-amyloid accumulations and do not address the tau-associated NFT burden.  This may explain in part their limited efficacy, because tau appears to be more important than beta-amyloid for the development of severe dementia in humans suffering from AD.  There are also significant safety concerns with both drugs, primarily the development of brain swelling or microbleeds, referred to as amyloid-related imaging abnormalities or ARIA. Both treatments are also expensive, in the range of $30,000 a year for the drug alone.

Selegiline, a selective irreversible monoamine oxidase B inhibitor (MOA-I), is the only drug approved to treat CCD in dogs. Decreased levels of catecholamines neurotransmitters, such as norepinephrine, serotonin, and dopamine, have been shown to be associated with AD and with dementia in animal models. MOA-I drugs, like selegiline, slow the degradation of these neurotransmitters which may enhance cognitive function.  Selegiline may also enhance enzymes that neutralize toxic free radicals, reducing oxidative damage within neurons. Its benefits are measurable but modest, and it appears most useful when therapy is initiated early in the disease course.

Non-Pharmacological Interventions
Although there is a paucity of drugs available to treat CCD, there are other interventions that may help stabilize the condition or slow its progression. In humans suffering from AD, diets high in whole grains, fruits, vegetables, olive oil and fish and low in saturated fats, salt, and refined sugar have been shown to have positive effects on the rate of cognitive decline. Although the specific nutrients responsible for this positive effect have not been well defined, these diets are high in nutrients that address multiple pathological processes important in AD, including but not limited to neuroinflammation, insulin resistance, and oxidative stress. Based on the success of dietary modulation in humans, attempts have been made to enrich canine diets in nutrients hypothesized to enhance cognitive function. For example, supplementation of omega-3 fatty acid (O3-FA) was shown in one trial to improve learning, but they did not affect memory, while in a second study combining sphingolipids and O3-FA showed benefits for learning and executive functions while slowing memory decline. In a similar manner, a diet containing 5.5% medium chain triglycerides also significantly improved executive and visuospatial functions in laboratory dogs. Other ingredients that have been shown to have positive effects on cognition in dogs include S-adenosyl methionine, homotaurine, and apoaequorin though more research is needed.

Exercise may also have beneficial effects on the clinical signs of CCD. For example, in an observational, cross-sectional study of 287 dogs, physical activity was robustly associated with better cognitive outcomes as reported by the owners. A different study found that dogs that participated with their owners in regular exercise including running, walking, and playing fetch, were substantially less likely to suffer from CCD as they aged. While the results of studies on the benefits of exercise on cognitive decline in dogs are not universally positive, none of them found any negative effects on cognition. In addition, a recent review found that regular aerobic and resistance training helped to mitigate cognitive decline and enhance the overall well-being of older humans. Just one more reason to get up, pick up a leash, and get out there!

– Cindy Cole, DVM, PhD, DACVCP





First Five
First Five is our curated list of articles, studies, and publications.

1/ Cat behavior linked to breed
The domestication and selective breeding of cats has resulted in almost a dozen breeds with major morphological differences. Many of these breeds also demonstrate very different behaviors.  A 2019 Finnish study of over 2,500 cats determined that many of the behavioral traits associated with specific breeds are moderately- to highly-inheritable. For example, Burmese and Oriental cats had the highest probability for excessive grooming, while British and Persian cats were least likely to exhibit the behavior. Oriental and Persian cars were the most likely to exhibit behavior problems, whereas European and British Shorthairs were the least likely. The authors concluded that breeding programs using personality as a main selection criterion could lead to less unwanted behaviors and thus improve cat welfare.

2/ Dogs can tell our emotions? Well duh!
Researchers tracked the brain activity of 14 family dogs, which included Border Collies and Golden Retrievers, that had been trained to lay still inside an MRI scanner. When the dogs were shown images of unfamiliar human faces with happy or neutral expressions, the reward region of their brains lit up more strongly than when they were shown neutral faces. When the dogs were shown pictures of angry, sad , or fearful human faces, different brain regions were activated. Researchers indicated that this is the first evidence that dogs can differentiate between positive and negative emotions on people’s faces, though this is likely no surprise to most dog owners.

3/ Horseracing like it used to be?
During the summer, a rocky, uninhabited spit off the coast of Connemara, Ireland becomes a haven for horse racing fans with horse and pony races conducted on the sand. For more than a century, races have been held on the island which is only accessible during low tide. Ireland hosts a circuit of amateur horse and pony contests every summer, with jockeys as young as 11 years old. However, the Omey Races, named for the island, are unique as the contestants race against each other and the rising tide.

4/ A whale of a rescue
In early 2023, an aquarium in Canada announced that it was for sale, closing to the public in the summer 2024. The closure left 30 Beluga whales stranded and in danger because the facility was bankrupt. An unprecedented rescue effort was organized by zoos, aquariums, and public and private organizations across the globe. Transported in special slings in chartered Boeing 777s, the whales have been rehomed across the U.S. as well as an aquarium in Valencia, Spain. The latter also received two Beluga’s from Kharkiv, refugees from the war in Ukraine.

5/ The Worst Aquarium Ever
In 2020, the New Bedford Whaling Museum in Massachusetts took advantage of a one-star Google rating to create a brilliant marketing campaign. The reviewer, disappointed because the museum had whale skeletons and art, but no living marine animals, labeled the museum as the “Worst Aquarium Ever.” The museum took advantage of the visitor’s confusion and created a line of merchandise, including T-shirts, sweatshirts, and tote bags emblazoned with a whale skeleton and the now famous motto.

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