Herman Reedy, 81, a retired fireman, sat in a Johns Hopkins Hospital clinic answering questions from nurse Mary Jane Lucas.
"What day of the week is it?" Lucas asked.
"Monday, I'd say," he answered quickly.
"What month is it?"
"May, that's my birthday," he responded confidently.
"What year is it?"
A pause, and then, "1981."
"What city are we in?"
"I don't know."
Actually, Reedy was in Baltimore, his home town, and the day was July 1, 1982, a Thursday. While he did get some other answers right -- he knew the season was summer -- he flunked the "Mini-Mental State" test developed by Hopkins psychiatrist Marshal F. Folstein to measure recall, language and writing abilities.
The test is used worldwide to help screen patients for one of the worst afflictions of old age: senility, or senile dementia. The word senile is derived from the Latin root "to grow old." Dementia means "deprived of mind."
Outwardly, Reedy couldn't appear healthier. His tanned, trim body made him look at least 10 years younger. But inside his head in recent years thoughts slowly had become more tangled. He often failed to recognize his daughter.
Slowly losing one's mind was once considered an inevitable part of growing old. "It was thought that if people lived long enough they became senile," said Dr. Robert N. Butler, former director of the National Institute on Aging.
But the rapid recent growth of neuroscience and geriatric research has begun to create a newer, and more optimistic, view of the aging brain.
"We believe that people remain much more intellectually active and capable longer than previously thought. When intellectual disabilities do occur you better think about disease and not just write it off as old age," said Butler, who recently left the government to start a geriatrics department at New York's Mt. Sinai School of Medicine, the first such program in the country.
While most elderly people in good health will remain mentally alert, aging experts now estimate that 3 million to 4 million Americans have some type of senile dementia.
About 10 percent of those over 65 show mild "senility," including classic forgetfulness, some confusion and personality and behavioral changes. Another 5 percent suffer from more severe forms of dementia.
Senility once was commonly considered to be the result of "hardening of the arteries of the brain," but it is now believed that only about 20 percent of senility results from such narrowing of blood vessels, which can lead to a series of minor strokes.
More than half of the severe cases instead are thought to be victims of Alzheimer's disease, a progressive and irreversible destruction of the brain striking about 1.5 million people in this country, including Reedy.
The number of Alzheimer's disease victims will increase in coming decades as the number of aged Americans increases, leading Stanford University physician Leo E. Hollister to warn that a "quiet epidemic" soon may be under way, with a costly emotional and financial toll, particularly in long-term nursing-home care.
While there is no practical way to prevent or cure this devastating disease, a recent series of basic research findings has excited the scientific community about the prospects of doing so.
Three government health research agencies, the National Institute on Aging (NIA), the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the National Institute of Mental Health (NIMH), have stepped up funding to aid in the search.
It has long been known that the brains of Alzheimer victims undergo severe changes. A German physician, Alois Alzheimer, first discovered the disease in 1906, while doing an autopsy on the brain of a demented 51-year-old woman. He found twisted nerve fibers -- "neurofibrillary tangles" -- and senile "plaques" -- degenerating nerve terminals.
Similiar changes were found later in elderly senile patients. The greater the number of plaques and tangles, the more severe the destructive effects on the mind appear to be.
A major advance in the search for a specific chemical abnormality came in 1976, when researchers found that the brains of Alzheimer's disease patients showed a dramatic decrease in chemical markers for the compound acetylcholine, particularly in centers thought to be involved in memory.
Acetylcholine is a neurotransmitter that is crucial in sending messages between nerve cells in the higher learning centers of the cerebral cortex, the brain's outer covering.
A new clue came when Johns Hopkins University scientists discovered that, in animals, destruction of an area deep in the brain reduced acetylcholine production. In humans, this region is called the nucleus basalis of Meynart, and consists of a cluster of large nerve cells in the forebrain, below the cortex.
Armed with this new clue of where to look, another Hopkins team did autopsies of several Alzheimer victims and found that in each case the nucleus basalis had degenerated, losing as many as 80 percent of the acetylcholine-producing nerve cells there.
Further work suggested that the nerve cells' projections into the cortex had shriveled up and had died, creating the "plaques" Alzheimer had found.
Scientists still don't know what caused the destruction, but Hopkins' Dr. Donald Price says the recent discoveries represent the first documentation linking dementia with the loss of a specific group of nerve cells.
Several experimental research projects are under way to see if the symptoms of Alzheimer's disease might be arrested by replenishing the supply of acetylcholine. So far the results generally have been disappointing.
Other researchers have turned to drugs that slow the breakdown of acetylcholine. Drs. Kenneth Davis and Richard Mohs of the Bronx Veterans Administration Medical Center, for example, have found that a chemical called physostigmine, which can improve recall in healthy young subjects, also may enhance memory temporarily in some Alzheimer's disease patients. Unfortunately, physostigmine is short-acting and potentially toxic, so researchers are looking for other drugs that may act the same way.
Albert Einstein College of Medicine scientists are getting some promising results using a combination of physostigmine and the dietary ingredient lecithin. A New York University group is teaming up a drug called piracetam, which boosts brain metabolism, and physostigmine, with some improvement in at least a sub-group of patients.
"It seems only a matter of time before some drug or combination is found that will be clinically useful and give patients more years of productive life, so they don't have to be placed in nursing homes under custodial care," Mohs said.
Other theories suggest that environmental chemicals, viruses, heredity or immune system reactions may be involved in the development of Alzheimer's disease.
Canadian researchers, for example, have found higher concentrations of aluminum in the brains of Alzheimer's disease patients, and the University of Vermont's Daniel Perl found the common metal to be concentrated in nerve cells containing "tangles."
Although the relationship to dementia is not known, a new study by Perl suggests an environmental link between aluminum and certain degenerative nervous system diseases.
One major problem at the heart of Alzheimer's disease studies is accurately defining the victims of the disease. Early signs include inability to remember recent events, failing attention and declining mathematical ability. Poor orientation, errors of judgment, personality changes and physical deterioration may appear slowly, and in the worst cases the patient, like an infant, can no longer be trusted to take care of himself.
The only way to know for sure that Alzheimer's disease is present is to take a sample of living tissue, a risky procedure, or to examine the brain after a person has died. But researchers are making progress in other diagnostic tests.
New findings suggest that some 100 physical and mental conditions may mimic the dementia of Alzheimer's disease, and many are treatable if discovered soon enough. A National Institute on Aging task force projected that 10 to 20 percent of the dementias in the elderly are reversible.
The most common cause of dementia-like symptoms is an adverse drug reaction. Older people, who are frequently prescribed several medications, are far more sensitive to drugs than are younger people.
Depression is also more frequent with advancing age, and may carry with it signs of forgetfulness and confusion that could be treatable. Any major illness or stressful event also can cause mental loss.
The best preventative for dementia resulting from a series of tiny strokes, which appears in sudden rather than gradual losses, is keeping high blood pressure down.
A number of specialized centers around the country, including outpatient clinics like that at Johns Hopkins as well as one at the NIH clinical center in Bethesda, are working on better ways to diagnose the different dementias and helping patients and their families cope with their emotional burden.
While scientific attention has been directed largely at the disease end of the spectrum, other researchers are looking at the normal human aging process and the cutoff point between health and disease.
Earlier studies suggested that brain tissue simply deteriorates over time. Total brain weight may fall gradually by as much as 10 to 20 percent, starting at the age of 20. The loss of nerve cells, or neurons, is estimated to be greater than 25 percent in some parts of the brain. Certain brain chemicals also decrease with age.
But such changes do not necessarily affect function, unless they are associated with disease. Many researchers now believe that the healthy brain is able to compensate for known age-related losses by rerouting information along alternative pathways.
Recent studies of the brain's metabolism, through blood flow, use of oxygen and energy consumption, have found that the activity doesn't change much with age in healthy subjects.
In a recent National Institute on Aging animal experiment, rat metabolic activity fell between 3 and 12 months of age, but remained relatively constant from then on. This suggests that the greater loss occurs in the first third to half of the life span, rather than later in life.
PET (positron emission tomography) scans, which provide a new view of the functioning human brain, also have shown that energy use need not decline sharply in the elderly.
In another NIA study headed by Dr. Stanley Rapoport, regional energy consumption was not linked significantly with age. A joint effort by New York University and Brookhaven National Laboratory scientists found the same thing, NYU's Dr. Steven H. Ferris said.
A UCLA PET scan study of healthy volunteers from 17 to 80 did find a gradual average decline in brain metabolism of about 25 percent. But there was a wide range of brain metabolic activity at all ages.
"I was surprised that there was so little change in the brain of an elderly person who is healthy compared to the healthy young adult," noted UCLA's Dr. David Kuhl.
Another challenge to the conventional wisdom that it is all downhill with age comes from a recent study by University of Rochester researcher Paul Coleman. In the absence of disease, he found that portions of nerve cells in the cortex not only stay healthy but may continue to grow in old age.
Again, Coleman speculated, the aged brain may be compensating for the loss of some cells by boosting growth in others.
Much of the earlier research suggesting a gradual decline in intelligence was based on comparisons of young and old adults at the same point in time. Critics point out that this may be a generational change, not one related to age: the young people generally had more education that their grandparents had.
Long-term studies of a single aging population have been more promising.
An NIMH study that followed healthy elderly individuals over time generally found no major intellectual losses, but did find a slowing in response time. It just may take longer for the elderly brain to make its complex and circuitous connections.
More recently, a 21-year study of intellectual performance in several thousand healthy, aging adults in Washington state concluded that, "At all ages the majority of people studied maintained their levels of intellectual competence -- or actually improved -- as they aged," a new NIA report says.
Fewer than 30 percent of those between 60 and 67 in the University of Southern California study showed a decline in mental and psychological performance. Those who moved from their 70s to 80s in the course of the study showed a slightly greater decline of 35 to 44 percent.
More intriguing, however, was the group in each age range that continued to improve. Of those tested between 74 and 81 nearly 10 percent showed better performance than they had at earlier ages.
The reasons remain elusive. K. Warner Schaie, who directed the project, suggests that those in higher socio-economic groups are more likely to keep up high levels of intellectual functioning because they live in more stimulating environments. And those whose life styles and attitudes are most flexible in middle age fare better in keeping their mental faculties as they age.
Other researchers warn of the danger of a self-fulfilling prophecy if a person and his family believe that mental loss is an unavoidable part of aging.
"In fact, older people are often accused or accuse themselves of memory changes that are not really taking place. If a person in his 30s misplaces keys or a wallet, forgets the name of a neighbor or calls one sibling by another's name, nobody gives it a second thought. But the same forgetfulness for people in their 70s may raise unjustifiable concern," said NIMH's Dr. Gene D. Cohen.
Maintaining activity also seems to be important in keeping the brain in shape. There are famous examples, like Pablo Picasso, but everyone knows an elderly relative, friend or neighbor who stays active and doesn't miss a thing.
Hopkins brain researcher Donald Price said his 103-year-old grandfather, who was once a financial analyst, stills asks to have The Wall Street Journal read aloud to him each day, since he can't see well enough to read it himself. He chides his grandson to hurry and find a cure for aging before it's too late for him.
No one expects such a cure in the near future for the mental losses that are feared by young and old alike. But the younger Price, 47, expresses "a feeling of optimism that was not there a few years ago."