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When old dogs forget old tricks

New drug offers hope

Tuesday, January 05, 1999

By Sharon Voas, Post-Gazette Staff Writer

Mickey just loves his people.

  Lynn Ramage with her dog Mickey, who has a disease that veterinarians are calling a canine

equivalent of Alzheimer's disease. (Tony Tye, Post-Gazette)

A fuzzy poodle-terrier mutt with bangs hanging in his eyes, he follows Dr. James Ramage and his wife, Lynn, everywhere around their home and fields in Ford Cliff, Armstrong County. When he can't be right next to them, he's so excited when they come back that he tears mad joyous circles around the dining room table.

Two years ago, something went awry with Mickey. The dog, who was 14 at the time, started getting lost in his own back yard. He lost his enthusiasm and stopped greeting his owners when they came home. He walked up to walls or the bathtub and just stood and stared at them. He didn't seem to be all there anymore.

"He wasn't our old Mickey," said James Ramage, a veterinarian. "His actions were almost like that of an aging person with Alzheimer's."

In fact, that is basically what Mickey has.

Veterinarians recently learned that geriatric canines - and maybe geriatric felines - can get something like Alzheimer's disease when they age, just as humans do. Cognitive dysfunction syndrome, as it is called in dogs, produces a cluster of symptoms similar to those of Alzheimer's patients, including disorientation and confusion, memory loss and personality changes.

In addition to getting lost in their own yards, dogs with cognitive dysfunction syndrome may cower in the corners of familiar rooms unable to remember how to get out past the sofa and chair. They forget the distinction between indoors and outdoors and soil the carpets and floors.

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The addled Fidos can't figure out how to navigate stairs. They stop greeting their owners. They sleep more during the day and keep their owners awake at night pacing. As they worsen, they may lose their ability to even recognize their owners, as people with advanced Alzheimer's may stop recognizing friends and family members.

The syndrome may also afflict older cats, although research on cognitive dysfunction in felines has just begun. Dr. Gary Landsberg, an Ontario veterinarian who has studied cognitive dysfunction in dogs and just started the research in cats, took an informal survey of the owners of about 50 feline old-timers and found they had noticed symptoms akin to what dog owners had seen.

The disease is heartbreaking for the many pet owners who form a special bond with their dogs and cats, taking daily pleasure in snuggling with them in bed or simply enjoying their company.

As the behaviors of these animals deteriorate, many pet owners are left with little choice but to euthanize their animals, Landsberg said.

Now there may be hope for these decrepit dogs.

Many veterinarians didn't know the cluster of symptoms was a disease that could be treated until about seven months ago when the pharmaceutical company Pfizer Animal Health described it in a journal, said Dr. Amy Hinton, president of the Pennsylvania Veterinary Medical Association.

"We all used to just feel they were going into senility, and we really didn't have any answer except behavior modification, such as crating them [to keep them from pacing at night and going to the bathroom on the floors]," Hinton said.

But a drug used to treat Parkinson's disease in humans and Cushing's disease in dogs has been found to also reverse many of the symptoms of the canine equivalent of Alzheimer's disease, she said. The drug, Anipryl, has been used in Canada for two years to treat canine cognitive dysfunction. Pfizer has applied to the U.S. Food and Drug Administration to approve Anipryl for the treatment of cognitive dysfunction here.

The drug is in the later stages of the FDA review process, said William Ruehl, a vice president of Deprenyl Animal Health, the Kansas animal pharmaceutical research company that developed the drug. In the meantime, American vets are increasingly using Anipryl to treat cognitive dysfunction even though that is not the condition for which its use is approved - an "off-label" practice that is common and legal in the medical and veterinarian worlds.

The Ramages put Mickey on Anipryl after the Pfizer announcement. To their delight, Mickey has returned to his old self. He improved in about a week. He has suffered no ill side effects except that, with his renewed vigor, he tries to become physically amorous with the Ramage's male pit bull, Sluggo.

Pets living longer

Vets expect to see more of the heartrending, Alzheimer's-like condition in cats and dogs because medical advances are keeping pets alive longer. The older dogs get, the more common cognitive dysfunction becomes. Large dogs typically live 8 to 10 years; smaller dogs, 12 to 14 years. But some dogs are living to 18 or 19 years old.

Researchers at the University of California at Davis who studied 139 elder dogs found 62 percent of dogs between the ages of 11 and 16 have at least one major symptom of cognitive dysfunction. The prevalence rose from 32 percent among the dogs in the study that were 11 years old, to all of the dogs in the study that were 16 years old.

With an estimated 7.3 million dogs in the United States that are 11 or older, this disease may affect the lives of millions of dog-loving Americans.

Although the cause of cognitive dysfunction is unknown, autopsies reveal that the brains of old dogs are often clogged with globs of nerve-damaging beta-amyloid plaques similar to those found in the brains of people with Alzheimer's disease.

"The more amyloid plaques a dog has in his brain, the more severe his cognitive impairment was when he was alive," said Brian Cummings, a researcher at the Institute for Brain Aging and Dementia at the University of California at Irvine. The amyloid seems to alter how nerve cells function so it messes up the messages sent between nerve cells, he said.

Dogs do not develop the knots of dead nerve cells in their brains called neurofibrillary tangles that are the other brain characteristic of Alzheimer's disease.

Cummings also found the plaques in the brains of three cats during autopsies.

"The owners reported [that before the cat's deaths] their cats were behaving weird, getting lost in their own houses, howling at night for no reason," he said. "One was going in a closet and couldn't find its way out. One cat would no longer go up and down stairs and seems to have forgotten how."

Some researchers suspect that dogs with cognitive dysfunction also suffer from inefficient use of dopamine, a brain chemical that transmits messages among nerves. Anipryl is a version of a drug called L-deprenyl that is used to treat people with Parkinson's disease, who suffer from a shortage of dopamine.

There is no blood test or CAT scan to test for cognitive dysfunction; the physical evidence can be found only in autopsies. Veterinarians make the diagnosis by ruling out other problems that cause similar symptoms.

Drug reverses symptoms

In the clinical trials, Anipryl basically reversed most of the symptoms of cognitive dysfunction, said Landsberg, the Ontario veterinarian who conducted some of the trials. About 20 to 25 percent of the dogs on Anipryl in the trials vomited or had diarrhea, compared with 10 to 20 percent of those who got placebos, Ruehl said. Some dogs also exhibited behavior changes. Most dogs that experienced side effects had only mild side effects that went away quickly, Ruehl said.

Landsberg has used Anipryl in about 20 cats and found it helpful.

"But that is very experimental," he said. "The company hasn't tested it on cats. The toxicity hasn't been tested in cats. It's not something we can recommend right now."

For dogs, Anipryl is a one-a-day pill that costs 80 cents to $2 per pill depending on the pet's weight, Hinton said. Because the FDA has approved Anipryl only to treat Cushing's disease, it is not likely to be covered by animal health insurance if dispensed for other uses.

Hinton said the vets in her group, Best Friends Animal Hospital in Chambersburg, Franklin County have used Anipryl in about two dozen dogs and saw them improve about 75 percent. About two weeks after starting on the drug, the dogs stopped soiling the floors, getting lost and keeping their owners awake nights.

"A lot of these animals [on Anipryl] ultimately live longer lives because their owners wouldn't have dealt with their behavior otherwise," Landsberg said.

The Ramages are thrilled to have their exuberant old Mickey back, padding after them everywhere.

"A lot of older dogs are just written off, as older people are," James Ramage said. Anipryl "might help. It helped Mickey."

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