Inside the brains of aging dogs

Numerous domestic dogs are contributing to a citizen science study that aims to better understand how memory and cognition change as we age.

Hana did well on her memory exam. The three-year-old Cavalier King Charles spaniel had to recall which of three identical boxes housed a reward after examining the contents of each one; a job she swiftly mastered after just a few tries.

Scientists are learning something else thanks to Hana and her human partner Masami Shimizu-Albergine of Bainbridge Island, Washington: when dog intelligence peaks and how it decreases with age.

Hana is a member of the Dog Aging Project, a citizen science project started in 2014 that already includes close to 40,000 domestic dogs. One of the project's two major objectives is to comprehend the biology of aging in companion dogs, according to cofounder and codirector Matt Kaeberlein, a pathologist at the University of Washington in Seattle who specializes in aging. The alternative is to take action.

The University of Washington and Texas A&M University effort will monitor several facets of dogs' life over time through veterinarian records, DNA samples, health surveys, and cognitive assessments like Hana's treat-finding task. Hana will take part in fewer, more narrowly focused research and thorough assessments than the other canines. From all of information, researchers seek to identify trends and establish connections between lifestyle choices and health from early development to old age.

The Family Dog Project was started in the 1990s at Eötvös Loránd University (ELTE) in Budapest to investigate "the behavioral and cognitive elements of the dog-human interaction," and tens of thousands of dogs took part during the course of the project's existence. The scientists anticipate that working with such a sizable combined group of dogs would enable them to elucidate the genetic and environmental variables that influence how long dogs live and how much of that time is spent in good health. The two teams have started working together across continents.

Hana, a three-year-old companion dog, is one of the hundreds of canines taking part in the Dog Aging Project. She is shown here with her owner Masami Shimizu-Albergine.

Given that there are probably hundreds of millions of dogs kept as pets worldwide, it is crucial to understand how they age in order to enhance both their quality of life and the care they get. Following the lives of some of these canine partners, however, may offer insights into how to age more healthfully as well as information about our own aging brains.

Studying the biology of human aging is difficult since the process lasts for many decades. It entails keeping track on individuals for 50, 60, 70, or even longer, which may be time-consuming and costly. Dogs, on the other hand, age fast. For those who adore their pets, this is terrible, says dog lover Kaeberlein. However, it makes dogs a great model system for research on aging. (Though Bernese mountain dogs have an average lifetime of seven years and Chihuahuas nearly double that at 13 years, it may be said that a 70-year study of humans is about similar to one dog decade.)

There are additional benefits to studying dogs as well. They are superior animal models to the inbred mouse strains that are generally employed in aging studies due to their genetic variability. And while though researchers prefer to examine their subjects in the controlled setting of a lab, the fact that humans and their pets share homes with a wide range of conditions is really helpful when trying to draw conclusions about human aging. A complicated human world cannot be duplicated in a lab setting. However, according to Kaeberlein, there is no need to if you study pet dogs.

Wrapping up

According to ELTE ethologist Enik Kubinyi, who has spent over 30 years researching canine cognition, scientists had long seen dogs as "manufactured creatures" with abnormal behavior. In fact, Kubinyi claims that when the Family Dog Project—to which she contributes—was developed in 1994 by a group of Hungarian ethologists, many people believed the concept was absurd. However, opinions are beginning to shift. Numerous research have examined dog behavior, genetics, and neurobiology so far, across breeds and throughout time.

The Dog Aging Project, on the other hand, looked into the effects of the medication rapamycin in a small-scale clinical study including 24 companion dogs. The drug has been found to lengthen longevity in yeast, roundworms, fruit flies, and mice. It is also used to treat cancer and prevent organ rejection in humans. When compared to dogs that received a placebo in that 2017 trial, pups who had taken rapamycin exhibited enhanced cardiac function, according to heart scan results. The Dog Aging Project has since started a larger, longer-term rapamycin experiment as part of its objective to learn more about the biology of how dogs age.

That includes having a healthy brain. According to comparative psychologist Evan MacLean, director of the Arizona Canine Cognition Center at the University of Arizona in Tucson and a partner in the Canine Aging Project, "there's a lot we really don't know about how dog cognition evolves with age." What does typical cognitive aging entail? Do early memory problems indicate dementia later on? The longer-term objective, according to MacLean, is to find early therapies that could stop the decline.

A battery of canine cognitive tests based on research on rodent cognition is being developed by MacLean's collaborator Emily Bray, a psychologist at the University of Arizona and the service-dog organization Canine Companions, in order to achieve this goal (it includes the "1-2-3-treat" test that Hana completed). For some of these tests, the canines must learn how to communicate with touch displays, another pervasive object in the human world.

Dogs are trained to link three vividly colored, aggressively patterned squares with a particular area on the screen in one memory and learning test, for instance. Dogs are placed in front of a screen within a wooden box for the test, and they are instructed to contact the square with their noses only when it is at the proper location. However, they also focus on abilities that may deteriorate with age and are reliant on brain areas impacted by Alzheimer's disease in humans and its canine counterpart, canine cognitive impairment. Dogs' memory and learning skills will be evaluated on a regular basis to examine how they hold up over time. Based on the waving of their tails, dogs learn to adore screen time.

As part of a research at the Arizona Canine Cognition Center, Kai the dog selects a symbol from a touch screen. The goal of the study is to examine changes in canine memory and cognition throughout time.

In a different study, the two citizen science initiatives collaborated and discovered, using pet dogs donated post-mortem, that older dogs and those who displayed dementia-like behaviors had higher levels of amyloid-beta, a misfolded protein that is also linked to Alzheimer's disease in humans, in their brains. Mice that have been genetically manipulated to develop dementia have been utilized in the majority of animal investigations of Alzheimer's disease. But because canine cognitive failure appears to develop spontaneously in dogs, just as it does in people with Alzheimer's, the researchers are hoping that their continued study of dog brains may also provide insights that help comprehend the human condition.

Life of a dog

One benefit of following so many dogs over their careers is that researchers will have access to enough information to begin establishing links between the way that dogs live and age and their settings, habitats, and behaviors. Physical exercise, which has been demonstrated to be protective against brain aging in humans and several other species, is one aspect they are paying special attention to. Emerging findings from a survey of Dog Aging Project participants imply that the same could apply to canines. Some of the participating canines will wear a gadget "like a Fitbit, but for a dog," according to Bray, to test the connection.

Calorie restriction is also a popular issue in aging research since studies on lab mice have shown that eating less and regulating when one eats can lengthen life. The situation is more complicated outside of a lab's well regulated environment. Bray is in charge of a research that compares the feeding behaviors of over 10,000 dogs of various ages, sizes, and breeds in an effort to shed some light on the situation.

According to the findings, 8 percent of the dogs that were fed just once per day on average had better health. Compared to dogs fed twice a day or more, these single-meal pups had less gastrointestinal, dental, orthopedic, renal, and other diseases. Additionally, they marginally outperformed them on cognitive tests. According to Bray, it's unclear how eating less frequently enhances cognition, but the impact was notable: it was about the same magnitude as the difference in the average cognitive scores of 7- and 11-year-old dogs.

So what changes do dogs' brains undergo as they age? Scientists in Hungary working on the Family Dog Project are monitoring that. EEG scans of dogs' brains and even training them to remain still within fMRI machines have shown that, like humans, the size of dogs' brains decreases with advancing age.

In a related imaging research, Colorado State University veterinary neurologist Stephanie McGrath conducts MRI scans on participants in the Dog Aging Project in search of characteristics that may link brain shrinkage and other physical changes to dementia in senior dogs. She finds it most fascinating because her research implies MRI might someday be utilized as a tool for early detection.

New tricks

Ageism and a dismissive attitude have long been present in society toward the elderly. Older dogs are not any different, according to veterinarian Patrizia Piotti of the University of Milan and former team member of the Family Dog Project. While it may be more difficult to teach an old dog a new skill, it may enhance their cognition to keep trying, according to a body of studies on problem-solving, memory, and attention in dogs as they age.

In reality, according to experts from the Clever Dog Lab at the Messerli Research Institute in Vienna, not all new skills are more difficult for senior dogs. Zsofia Virányi, an expert in comparative cognition, and Durga Chapagain, a former student, administered 119 pets canines a battery of 11 cognitive tests that involved activities including playing, viewing photos, finding concealed food, and manipulating toys. They discovered that characteristics including the capacity for problem-solving, boldness, and fun decreased consistently with age. However, older dogs fared as well in a challenge that required them to make eye contact with the trainer after discovering and eating a piece of sausage that had been placed on the floor.

According to Chapagain, this proves that we shouldn't undervalue elderly dogs' mental capabilities. Older dogs may have the same drive to continue learning as younger pups, but "humans are less willing to play with them," she adds (at least when sausage is involved). They are considerably more powerful than we realize. Throughout their lifetimes, owners should continue to provide their canine friends with cerebral stimulation such as trick training and nose work such as concealing goodies for a game of "sniff and seek," says Piotti. "Anything that causes the dog to pause for a moment."