SACREMENTO, California - Gasps were audible as the images flashed before a gathering of scientists at a recent UC Davis Alzheimer's Disease Center pathology conference. On the screen before them were photos of a brain severely wasted with age, with what looked like silver rivers of atrophy cutting deeply through the tissue. Even for the experts, it can be shocking to see the damage that Alzheimer's disease inflicts on the aging brain.
What can stop the devastation of Alzheimer's? Without better answers from researchers, the degenerative brain disease -- already the nation's sixth leading cause of death -- will be diagnosed in as many as 16 million aging baby boomers by 2050. Unchecked, it could rob millions of their memories and lives, their past and future, even as it threatens to overwhelm the health care system.
Against the setting of this looming public health crisis, scientists devote themselves to diagnosis and research along the third-floor hallways of the Lawrence J. Ellison Ambulatory Care Center on the leafy UC Davis Medical Center campus. They are unlikely warriors on the front lines: the neurologists and neuropsychologists, the project scientists and brain-imaging whiz kids and dedicated clinic staff who are fascinated by the science of the aging brain but frustrated by how little public recognition there seems to be that a crisis is at hand.
Led by neurologist Charles DeCarli, the disease center's researchers test patients for Alzheimer's and other dementias. They counsel patients and their families _ the caregivers _ on how to cope with the disease. Searching for breakthroughs, they run clinical trials of medications that might help slow the progress of Alzheimer's disease. And they perform research on the aging brain using cutting-edge imaging technology, as well as extensive neuropsychological testing of a core of volunteers.
But progress is slow: Prevention and cure are probably many years away. Miracles are in short supply; so is funding.
And for every answer, it seems, there's another question.
"Do I find it discouraging that we're no closer to an answer?" asked DeCarli, 58, who has been the center's director for the past decade. "No, no, no. Sure, I'd like us to get an answer, but who's going to do the work?
"We can lick this thing. It's just finding the path."
The process of searching for answers begins in the Alzheimer's Disease Center's quiet third-floor clinic, a place of hope and fear. Here, patients and research participants are tested and diagnosed. The staff members offer visitors a cup of coffee and candy from a plentifully stocked bowl. Newcomers, fearful of the news that could await them, are often too nervous to accept.
"They're scared when they first come through that door," said patient-care coordinator Rebekha Alfaro.
Referred by concerned primary-care physicians or family members, about five patients visit the clinic each Wednesday for testing or follow-up diagnosis. They huddle with their family members in the conference room, and they listen to the words they don't want to hear. Sometimes, it's DeCarli who breaks the news; sometimes, it's the center's associate director, Sarah Farias.
It's never an easy conversation.
Treatment remains limited. DeCarli prescribes only Aricept and Nemenda to people with Alzheimer's. Those medications can help slow memory loss in patients in the early stages of the disease but not always, and not with other forms of dementia.
To give people diagnosed with mild cognitive impairment, or MCI, some sense of hope, the Alzheimer's center recent launched Brain Fitness 101, a series of classes led by an earnest post-doctoral fellow, Tim Davis, to promote lifestyle changes that can keep aging brains healthy.
One of the center's new grants, pending funding, will study the aging brain and vascular illness: As people routinely survive stroke and heart attack, how is brain health affected? Are these people more likely to develop Alzheimer's, too?
For now, the basic equation for dementia researchers is that heart health equals brain health, because of the brain's rich blood supply network. A good diet won't prevent Alzheimer's, but researchers suspect it can help older adults forestall the development of memory loss by a few years.
It won't be long enough to find a cure.
Don Reynolds referred himself to the clinic for testing four years ago, concerned about his memory.
Now, at 81, the retired social worker comes to his monthly counseling appointments with the center's clinical social worker, Esther Lara, armed with a file folder of information and a big spiral notebook filled with questions and observations on his illness. He is remarkably analytical and self-aware despite his diagnosis, which worsened over the past year from MCI into possible Alzheimer's disease. He'll describe entering a room at home and not remembering why he is there -- but unlike simple forgetfulness, the reason never comes back to him.
"I'm the person who likes to be equipped for things," said Reynolds, who lives with his wife, Ruth, 79, in Carmichael.
"How do I prepare for that and do some understanding of what's coming? When I have the quality of half a brain, how do I function? How do I make day-today decisions?"
He isn't happy to have a dementia diagnosis, but he accepts it. But the unknown and unknowable hang over his life.
Research is the heart of the Alzheimer's Disease Center operation: Through longitudinal studies --following more than 500 research participants over a period of years _ the center's scientists work to determine the differences between the normal aging of the healthy brain and, on the other hand, the aging of brains that have deteriorated because of dementia.
As part of a federal research grant on how brains age, research volunteers visit the center every year for extensive neuropsychological testing and physical exams. Some of the volunteers have been participating for 15 years; as they've grown older, some have remained healthy.
But others have experienced gradual declines in reasoning, judgment and memory. By 85, almost half of people will develop dementia, studies show. The greatest risk factor for Alzheimer's is age.
Past testing has shown research participant Joseph Giel to be in good cognitive shape.
For Giel, a 90-year-old retired McClellan manager who lives in Loomis, coming to the center is his way to give back. A widower and stroke survivor, he has participated in the center's cognitive functioning research since 2011. His daughter, Kathleen, drives him to the annual appointment, which typically takes all morning.
He takes all the same standard diagnostic tools that are used to evaluate patients for memory loss.
The basic mini-mental status exam measures recall, logic and problem-solving ability. Widely available on the Internet, the mini-mental generally includes questions about the date and place, asks test-takers to remember a series of words, and checks their ability to follow written instructions and copy a geometric design.
Alzheimer's first affects the areas of the brain that control memory, planning and spatial relationships. The point of testing is to differentiate between normal aging -- occasionally losing track of dates or names, for example, and occasionally misplacing items -- and the steadfast march toward severe memory loss that characterizes Alzheimer's.
"What state are we in?" asked April Medina, a young researcher.
She and Giel were seated at a table in a tiny testing room, underneath a framed photograph of yellow and orange flowers.
"California," replied Giel. "I live in Placer County, but this is Sacramento."
"You're trying to get extra credit there," she said, smiling.
She marked his answers on a thick pad of test sheets. There were flashcards with drawings of objects to identify, flip books of words to name, pages to fill in by copying geometric figures and sheets of connect-the-dots tests. There were stories with details to remember, and several series of words and numbers to repeat.
Down a hall from the clinic, stacks of thick medical charts filled the middle of a long table in the neurology department's meeting room.
The monthly case conferences led by DeCarli evaluate the brain health of research participants: Are they still cognitively normal? Have they developed MCI, a kind of age-related forgetfulness? It can sometimes lead to an eventual diagnosis of Alzheimer's -- but it can also be reversible if it's the result of medication, dehydration, vitamin deficiency or depression. Have vascular problems such as stroke caused participants' memory to deteriorate? Has an existing diagnosis of Alzheimer's deepened?
When volunteers' brain health is found to have deteriorated, the center doctors notify them and their primary-care physicians and make recommendations for treatment, if appropriate.
Armed with coffee and a breakfast sandwich, DeCarli listened as center geriatrician Will Seavey along with Farias and
Lara discussed participants' annual testing. With his laptop open, he checked the most recent brain imaging of a woman in her 70s already diagnosed with MCI. The new scan showed changes in her white matter, the brain's superhighway of nerve tissue that connects the parts of the brain to each other and to the spinal cord.
"Oh, wow," he said.
"It's not what you want to hear from your neurologist when he's looking at your brain scan," Farias said.
"I'm worried about her," DeCarli said. "It looks like she has progressive disease."
"There's not too much we understand about how to change or stop white-matter disease," Seavey said.
Solving the riddle of the aging brain takes money. And that's a problem.
The disparity in disease research funding is striking. While cancer research garners more than $5 billion in federal funds each year, Alzheimer's research across the country receives about $560 million. That includes a new infusion of $122 million from the recently enacted National Plan to Address Alzheimer's Disease.
The disparity partly reflects the newness of Alzheimer's: It was identified as a disease a century ago, but it wasn't until 1976 that scientists discovered that it's the most common cause of dementia. Research has evolved slowly from there. Even the breakthroughs, such as the discovery in the 1980s of the beta amyloid protein plaques and tau protein tangles suspected to trigger the Alzheimer's brain degeneration, are still considered hypotheses.
As a result of the money crunch, the center lost four staff members and four faculty members in recent years. And young researchers like Farias -- whose early research received a decade of federal funding _ struggle to renew the grants that will help them unlock the mysteries of Alzheimer's. In short, the slow process of finding answers has become even slower.
"Funding is an issue of research in general, but it impacts Alzheimer's and dementia more because this is a health crisis," DeCarli said. "There's an impact on funding for cancer and cardiovascular disease and other areas, too, but they've made advances already."