Brain Pathology in Centenarians

Robert W. Griffith, MD
May 19, 2004

Professor Thomas Perls of Harvard Medical School is the founder of the New England Centenarian Study (NECS); this study reports on the heath of some of the United States' oldest citizens. He has distilled the most interesting results in his book "Living to 100". Here are some further extracts. Robert Griffith, Editor.

Alzheimer's disease and other dementias

Only 30 years ago, mental decline was considered an inevitable consequence of old age. In fact, the common term for dementia was "senility," a word derived from the Latin word for "old". When older patients complained about memory loss, their doctors often replied, "What do you expect at your age?" Both doctors and patients were resigned to the idea that, with or without disease, the brain would disintegrate as time went on.

In 1906, German neurologist Alois Alzheimer examined the brain of Auguste D., a 56-year-old woman who died after several years of mental degeneration. For many years Alzheimer's disease [the condition he described] was thought to be extremely rare. In the early 1980s, however, awareness of dementia began to rise. When former screen actress Rita Hayworth was diagnosed with Alzheimer's disease in the mid-1980s, the news made headlines.

In the early 1990s, determining the true rate of Alzheimer's disease in the general population became an important goal for researchers. The 1994 Canadian Study of health and aging, for example, suggested that dementia was a virtual certainty in anyone over age 100.

The health of centenarians

We were becoming convinced that the phenomenon of demographic selection -- by which some people were selected to live to extreme old age -- dictated that centenarians would be a group of people who were relatively resistant to cancer, heart disease, and, as our study indicated, Alzheimer's disease. There were other hints that this was the case. Our patient's families reported that most of our centenarians were seldom sick; 95% of them had been free of major diseases into their nineties.

We got another hint of this overall resistance to disease when we used a computer program, called Clinquiry, to informally look at patient data from the Beth Israel Deaconess Medical Center. Among 145 centenarians involved in the 220 patient admissions over a 10-year period, there were only 10 cases of cancer. In the general population, cancer rates rise exponentially as the population ages, just like Alzheimer's disease. But our survey of the health status of NECS centenarians revealed a similar low cancer rate. Out of 169 centenarians seen thus far, only three have had a history of life-threatening cancer (that is, cancers other than relatively benign skin cancer or slow-growing prostate cancer).

The implication was clear that centenarians had the potential to completely escape some of the diseases associated with aging, like Alzheimer's disease, and perhaps escape dementia altogether. But we still couldn't be sure without results from the brain autopsies, and we were anxious to hear from our collaborators at Massachusetts General Hospital. This upcoming part of the study might begin to tell us how centenarians avoided or delayed Alzheimer's disease for so long. About 20% of the subjects agreed to brain autopsies. We retested these people frequently so we would know how well their brains were functioning near the time of their deaths.

Mrs. Morgan

In early 1995, we met a woman who would prove to be one of our most fascinating subjects: Mrs. Morgan. In accordance with the study design, we asked Mrs. Morgan if she would be willing to donate her brain so that we could look for the plaques and tangles that indicate Alzheimer's disease.

"But I'm still using it," replied Mrs. Morgan with a smile.

Indeed she was. From the time we met her at the age of 100 until she died almost two years later, Anna Morgan was one of our most remarkable and mentally vigorous centenarians. When we first met her, she was still deeply aware of current events in politics. Despite cataracts, glaucoma, and macular degeneration, she read a newspaper each day with the aid of bright lights and a magnifying glass. She placed telephone calls and stuffed envelopes for local groups. She also worked on efforts for a postage stamp to commemorate the black singer, actor and political figure Paul Robeson. Even on her hundredth birthday, when most of us would be content with being surrounded by family members, she was testifying at the Massachusetts State House on healthcare matters.

Mrs. Morgan, at the age of 101, was one of the first of our centenarian brain donors to die. At a memorial service held in the First Congregational Church in Cambridge, people arrive from all over the country to attest to her great strength, courage and humor. Several friends have composed songs about her life and sang them at the service. We were asked to speak about Mrs. Morgan's contribution to the study. It was a true celebration of life -- just the way Mrs. Morgan would have wanted it.

Mrs. Morgan's brain

A few months before her death, Mrs. Morgan's testing had shown that her mind was still very clear. We were particularly curious about the physical state of her brain. Would it show signs of Alzheimer's pathology? If so, we would have to conclude that the physical changes of Alzheimer's were probably inevitable, no matter how well one ages. At the same time, we would have to begin looking for explanations of how Mrs. Morgan might have compensated for the damage Alzheimer's disease did to her brain, so that she was able to remain so thoroughly functional.

But lack of Alzheimer's disease lesions would tell us that we had been correct all along; that centenarians were special in that they delay the disease, and in some cases avoid it. That finding would make them a new model for the study of Alzheimer's disease that no one could ignore all. But until the autopsies were performed we would not know whether centenarians somehow compensated for Alzheimer's disease, or whether they were able in some cases to live their entire lives without it.

One spring morning, we received a call from Kathy Newall, the neuropathologist working on our project. She had just finished staining key areas of Mrs. Morgan's brain with a pink die that would reveal whether they had the telltale neurofibrillary tangles of Alzheimer's disease. "What a beautiful brain!" Kathy cried. "There are very few tangles in any parts of the brain where we would expect to see them. It's like the brain of a healthy 50-year-old."

This was just the first of our extraordinary autopsy findings. Thirteen centenarians have undergone brain autopsies so far, and only four have shown signs of Alzheimer's disease.

Is it nature or life-long nurture?

While these findings inspired us, we also began to realize that there was something very important and mysterious about the people we had decided to study. Living to 100, we realized, was like a very fine filter. Our centenarians had arrived at this stage of life for very good reasons. Either they had lived a particularly healthy lifestyle and taken superior care of themselves, or they were endowed with excellent genes for aging. Something has allowed them to escape many of the diseases that normally kill people at much younger ages. Exactly what that "something" was, we would spend the coming months trying to determine.

The next extracts from Professor Perls' book look at the influence of lifestyle in getting to be a centenarian. You can buy his book "Living to 100" at Amazon, click here.

Source

• Living to 100: Lessons in Living To Your Maximum Potential at Any Age. TT Perls, MH Silver, 1st edition, Basic Books, New York, NY, 1999

Related Links
The Centenarians Study
Antioxidants Against Alzheimer's, Redux
The New England Centenarian Study
Raised Homocysteine Levels: an Alzheimer Risk Factor

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