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Client: UCI Magazine

Date: May 15, 2016

Online: bit.ly/2cMCWla

Alzheimer’s: It’s Not What You Think


Claudia Kawas turns the study of the disease on its head, leading other researchers to change their assumptions


Mindful Art

The painting on this page was created by individuals with Alzheimer’s dementia who took part in Memories in the Making. The program, sponsored by the Alzheimer’s Association, enables patients to share what’s going on inside long after they’ve lost the ability to communicate with words. These pieces were bought at a charitable auction and donated to UCI MIND, where they hang in tribute to the artists’ determination to maintain their independence and dignity through varying stages of the disease.

The comment is a startling one, and she repeats it: “If you give me a choice, give me Alzheimer’s disease.” Dr. Claudia Kawas, a professor in UCI’s Department of Neurology, knows exactly what she’s saying. It’s the rest of us who don’t understand.

Her point is that Alzheimer’s isn’t what we think it is. Kawas’ groundbreaking 90+ Study, which was the subject of two lengthy “60 Minutes” episodes and exhaustive press coverage, has forever changed what we thought we knew about Alzheimer’s disease.

Her vast library of brain tissue samples from study participants who died shows that many people can have the amyloid plaques and tangles associated with Alzheimer’s without the cognitive symptoms, while others can have dementia without the brain changes.

Alzheimer’s ranks relatively low for increasing the risk of dementia compared to other conditions found in the brain samples, including white matter disease and microinfarcts (both considered forms of vascular disease), Lewy bodies (associated with Parkinson’s) and hippocampal sclerosis.

“If you have Alzheimer’s pathology, your risk of dementia is perhaps twice as likely,” says Kawas, also a professor in the Department of Neurobiology & Behavior. “But if you have microinfarcts, your likelihood of having dementia is four times greater; if you have hippocampal sclerosis, your likelihood is 10 times greater.

“That’s why I always say: Give me Alzheimer’s; it only doubles your risk of dementia. I don’t care what’s in my brain; I only care if I can still think.”

Findings from The 90+ Study are causing practitioners and researchers across the country to rethink their assumptions and look for new explanations for dementia – such as the one recently advanced by UCI’s Mathew Blurton-Jones: that the immune system may be in play.

As we age, our immune system deteriorates, making fewer B and T cells, he says, and “our mouse data would predict that this aging of the immune system would impair the ability to clear amyloid from the brain.” People who age successfully are often more healthy in multiple ways, including their immune health. “Many of the beneficial lifestyle factors that Claudia studies are also associated with improved immune health,” says Blurton-Jones, an assistant professor at the UCI Institute for Memory Impairments and Neurological Disorders.

UCI MIND, where Kawas serves as clinical core director, is internationally recognized for its research accomplishments in disorders of the brain, particularly those that are age-related. It is also home to one of 29 Alzheimer’s Disease Research Centers across the country funded by the National Institute on Aging.

The lifestyle factors referenced by Blurton-Jones are among the reasons that The 90+ Study rocketed into the limelight. The headlines are intriguing: “Secrets From the Oldest-Old,” “Do You Want to Live Past 90?”and “90 and Beyond.”

Studying Nonagenarians

The landmark study that sparked the headlines got its start in the early 1980s, when 14,000 members of the Orange County retirement community Leisure World – now renamed Laguna Woods Village – were surveyed about their habits and lifestyles.

Flash forward to 2003, as Kawas and her co-principal investigator, Maria Corrada, an epidemiologist in the Department of Neurology, conceived the idea of The 90+ Study and obtained a $6 million grant from the National Institutes of Health to launch it. The goal was to gather data about the oldest-old – the fastest-growing age group in the U.S. – utilizing information from the original survey and updates on the remaining Laguna Woods Village participants.

Kawas and Corrada reasoned that because little was known about people over 90 – they were traditionally ignored in research studies – the impending “silver tsunami” of aging baby boomers presented a public health priority to promote the quality as well as the quantity of life.

Surprisingly, the 90+ team was able to round up nearly 1,700 subjects out of the original 14,000, making the study one of the largest ever done on this group.

“We wanted to know how long and how well they lived,” Kawas says. Many members of the original group still live in Laguna Woods Village. Others are spread throughout the U.S. and abroad. Each is examined physically and cognitively every six months. Recently, brain scans were added to the tests, opening up new avenues for research.

“The mean age is 96; almost one-third live at home with minimal or no support,” Kawas says. A third of the group show no signs of dementia, while another third have dementia, and the final third are “somewhere in between.” Most of those in the study have agreed to donate their brains after death.

In the past dozen years, Kawas has spent a great deal of time getting to know Laguna Woods Village and its nonagenarian residents. “They’ve had 90-year-old mayors on more than one occasion. They have clubs, their own TV station. They make me feel tired and old,” she says, laughing.

They’ve also taught her a lot about aging.

“People who exercised definitely lived longer than people who didn’t exercise,” Kawas says. As little as 15 minutes a day, on average, made a difference in promoting longevity. “Forty-five minutes a day is best. And it doesn’t help to do a lot more. Three hours a day is no better than 45 minutes.”

Keeping active mentally and socially – such as playing board games and attending book clubs – also helped.

National Outlook

Kawas’ pioneering research at UCI has set the stage for others.

“When I started, everyone asked me what I could possibly find interesting in studying the oldest-old,” she says. “Now every place in the world has these studies.”

Meanwhile, the number of nonagenarians is exploding, making the research even more relevant. Over the past century, the U.S. has added 27 years to life expectancy, with about 2 million people currently over age 90. It’s estimated that by 2050 there will be more than 10 million. One out of every 50 people will be 90-plus.

“I can remember when there were so few centenarians that the president wrote a birthday card for each one,” Kawas says. “There’s no way that could happen today.”

Of course, one of the major downsides to increased life expectancy is dementia.

“Age is far and away the biggest risk factor for dementia, no matter what you’ve heard about head trauma or other factors,” Kawas says. “And right now dementia costs the nation more than cancer and heart disease put together. We need to know how to lower the risk.”

Her sobering conclusion if we don’t: “I’m pretty convinced that the risk of dementia after age 65 doubles with every five years of life through and past age 100. It doesn’t mean you can’t get past 100 without it, but your odds aren’t good.”

Among other findings:

  • Taking vitamins E, A or C made no difference in longevity.
  • Drinking green or black tea made no difference.
  • People who drank moderate amounts of alcohol or coffee lived longer than those who abstained.
  • People who were overweight in their 80s and 90s lived longer than normal-weight or underweight people did. Those who were overweight in their youth did not live as long.
  • Almost 80 percent of people 90 and older are disabled. Dementia and disabilities are more common in women than men.
  • About half of people over 90 with dementia do not have sufficient brain neuropathology to explain their cognitive loss.

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