Brain Stormer

This specialist in brain diseases cares, in both senses of that word

by Mark Pendergrast

memcent0312William Pendlebury, MD, co-founded The Memory Center at Fletcher Allen Health Care in 1991. He is also director of the UVM Center on Aging and medical director, elder care services, at Fletcher Allen.

When asked how old he is, Dr. William Pendlebury says, “I have celebrated the 22nd anniversary of my 39th birthday.” He then explains his joke. “Age-related memory loss begins at 40.”

Pendlebury is medical director of The Memory Center at Fletcher Allen Health Care. As a neurologist and neuropathologist who specializes in brain diseases, he is acutely aware of how memory can become more untrustworthy for all of us as we age. “You might forget someone’s last name, or you don’t remember that you left your car keys in the coat you wore last night,” he explains.

Such memory lapses are normal, have little impact on day-to-day living, and do not get much worse with time. That’s not true of the patients he sees at The Memory Center, most of whom suffer from Alzheimer’s, a fatal, progressive brain disorder that gradually robs people of their most cherished memories.

One might think that working with such patients and their caregivers would be overwhelming and depressing, but Pendlebury and his staff are remarkably upbeat. Janis Peyser, a neuropsychologist who co-founded The Memory Center with Pendlebury in 1991, still works with him.

“I’m just fascinated by working with these patients,” she says. “They are a rewarding group of people. It doesn’t get me down. On the other hand, I could never be a veterinarian, working with injured animals.”

Pendlebury and Peyser started The Memory Center to provide a one-stop location for patients and their families, so they wouldn’t have to shuttle back and forth between their primary care physicians and specialists. The two have worked well together for over 20 years.

“Bill and I have the same work ethic,” Peyser says. “We’re both deeply committed to these patients. Bill is calm, unruffled by difficult situations, and responsive to people.” They keep in mind that this is the care they would want their own parents to have.

The small staff includes two nurse practitioners, a second neuropsychologist, a social worker, and an administrator. All have similar praise for Pendlebury, the medical director.

Pendlebury grew up in Rhode Island, earning an undergraduate degree in biology from Brown University in 1972. He studied medicine at the University of Vermont, did his internship at Presbyterian St. Luke’s in Denver, and then served two years in the Public Health Service as payback for his med school scholarship.

“I worked with John Straub, an elderly solo practitioner in Limon, Colo.” Pendlebury credits Straub, a prototypical small-town doc complete with suspenders and stethoscope, with teaching him the art of medicine. “He taught me how to interact with people.”

In 1979, Pendlebury returned to what was then called the Medical Center Hospital of Vermont for a two-year residency in neurology, followed by a three-year fellowship in neuropathology. By the time he joined the UVM College of Medicine faculty in 1984 as assistant professor in the department of pathology with a secondary appointment in neurology, his hair had begun to turn an early silvery white.

He became a tenured professor in 1990 and a full professor in 1995. Nowadays, Pendlebury spends about half his time in clinical work at The Memory Center. The remainder of his time is divided between his work as a pathologist — examining the brains and spinal cords of the recently deceased, and tissues from living patients, including nerve and muscle biopsies and brain tumor biopsies — and his teaching and administration duties.

Beyond this, he is well respected on the national scene. He serves as an external reviewer for numerous journals and granting agencies and is a reviewer of the 27 Alzheimer’s research centers around the country funded by the National Institute on Aging, for which he is an ad hoc consultant.

In his office, he discusses his life and work, as well as the disappointing performance of his beloved Patriots in the recent Super Bowl. He is a devout fan of New England teams in all four sports.

He and his wife, Dr. Mary Cushman (a UVM professor of medicine and pathology and director of the thrombosis and hemostasis program at Fletcher Allen), live in Shelburne with their 15-year-old daughter, and he has two older children from a prior marriage.

He owns a condo at Jay Peak, where he skis in the winter. He used to run marathons but now, to keep down his weight, Pendlebury takes long walks with George Langdon, his neighbor. “Yes, he talks about cases, but no names,” Langdon says. “Bill talks about how important it is to spend enough time with patients, which few doctors can do.”

The Memory Center sees about 500 new patients a year and follows a cohort of established patients on a regular basis. As part of the initial three-hour examination, Peyser administers a battery of psychological tests designed to test long-term and short-term verbal and spatial memory, language function, attention, and problem-solving.

Pendlebury does the medical intake, conducting a physical exam, making sure blood tests and a CT scan are ordered, and studying the results. “I am a synthesizer, putting together the tests and arriving at a diagnosis.”

A minority of people turn out to be the “worried well” with only normal, non-degenerative memory issues. Others do, indeed, have memory problems, but they may stem from alcohol abuse, depression, stress, or medications. These are reversible and correctable causes, and such patients are referred back to primary care providers or to appropriate treatment resources.

The remainder suffer from age-related memory disorders, mostly Alzheimer’s disease, and become long-term patients, seen every six months or so.

Pendlebury explains the latest research, theories, and treatment of Alzheimer’s, which affects 5.5 million Americans, but as baby boomers age with increasing longevity, that number is likely to triple by mid-century, he says.

There is evidence that the disease may be caused by an accumulation in the brain of A Beta 42 (Aß42), a peptide that is part of a protein we all make. In Alzheimer’s patients, he says, there is an overabundance of Aß42, either because of overproduction or decreased clearance. “We think that Aß42 kills neurons and synapses, leading to the clinical features of Alzheimer’s.”

Clinicians can now spot abnormal levels of Aß42, before the onset of symptoms, through PET scans or by analyzing spinal fluid through lumbar punctures. “If we can develop pharmaceuticals to remove the Aß42 from the brain before too many neurons are destroyed, we might be able to prevent the disease,” says Pendlebury.

A new drug called bapineuzumab forms a complex with Aß42 and the complex is removed from the brain via the bloodstream. Some of his patients are enrolled in a large international double-blind study of the drug. Several similar drugs are under development.

“We know that the drug is biologically active, but we don’t at this point know if it is clinically effective” he cautions. “It might be too late by the time one already has symptoms,” he says. “There is no evidence that it stops the progression of the disease.”

It remains to be seen whether it could prevent the onset of Alzheimer’s if administered early enough. In the meantime, patients take a variety of FDA-approved drugs that cannot cure but may slow the disease progression.

Would Pendlebury perform a test for Aß42 on an asymptomatic 55-year-old? “No, that would be unethical. I would essentially be giving a diagnosis that might be wrong — there is no certainty that they would get Alzheimer’s, and we don’t yet have a treatment intervention that has been shown to work.”

Pendlebury also feels strongly that it would be unethical not to tell patients when he has arrived at a new Alzheimer’s diagnosis. “Some family members are opposed to telling them,” he says, “but patients have a right to know. An early diagnosis gives them the opportunity to plan for the rest of their life. How do they want to be cared for? Who will be in charge of finances? Do they have a living will? It gives them a new set-point for their life. It might not be the way they want to live it, but at least they can adjust to going forward.”

Art and Maureen Loeffler of Essex Junction can testify to that. Four years ago, Maureen, then the director of medical education at Fletcher Allen, began to show signs of memory loss. At 60, she was diagnosed with early-onset Alzheimer’s.

Today, she still lives at home and takes vigorous daily walks with Art. She takes Aricept and Namenda, and since she took part in the bapineuzumab study, she can take that drug also.

The couple see Pendlebury every 13 weeks for a checkup and chat. “There is no magic bullet,” says Art, “but Dr. Pendlebury is extremely caring, down-to-earth, laid-back, calm. My wife thinks the world of him. He has a great bedside manner.”

Pendlebury stresses the rewards of his jobs, even when he is cutting into brains at autopsy. “I go into the morgue on a regular basis. It has given me a higher feeling of comfort with my own mortality. I have more respect for death.”

He isn’t sure about the soul or an afterlife, though he sometimes attends Trinity Episcopal in Shelburne. “I’m still working on that — from dust to dust.”

As a pathologist, Pendlebury has sometimes autopsied the brains of former patients. He sees it as “the ultimate final service” he can provide for them and their families.

“There is always a level of uncertainty about a clinical diagnosis. You could be wrong. So when I see the brain of one of my patients who has died, I provide that final confirmation.” •