How Aging Affects Your Memory

If a young or middle-aged man, when leaving company, does not recollect where he laid his hat, it is nothing; but if the same inattention is discovered in an old man, people will shrug up their shoulders and say, "His memory is going."

—samuel johnson

Age-related memory loss occurs in all mammals, from mice to humans. Research has narrowed down the myriad biological theories of aging into a few that are backed by scientific evidence: genetically programmed cell death, disruption of biological clocks, and free radical toxicity.

Programmed Death of Cells

The theory of programmed cell death states that every cell in the body is genetically programmed to die at a certain point in time, and that this time frame is specific for each type of cell. Many cells in the body regularly die, but other reproducing cells make up the deficit. Erythrocytes, or red blood cells, that carry hemoglobin have an average life span of only 120 days, but stem cells in the bone marrow continually develop into new erythrocytes and enter the bloodstream to make up for this loss. But in cells that do not reproduce and are meant to last a lifetime, especially those in the brain, programmed cell death may play a major role. Just as there are genes that tell each cell to synthesize the right kinds of proteins to maintain life, other genes are programmed to turn off protein synthesis and destroy the cell. Currently, we do not know what triggers these "suicide '' genes to come alive as we grow older. If the genes that trigger programmed cell death are successfully blocked, the human life span can be greatly prolonged. But what will society be like if new genetic therapies make people live to the age of 150 or 200 years? If in addition to increased longevity there is a corresponding improvement in quality of life, then the ensuing problems won't be as overwhelming as we now imagine.

Biological Clocks

Programmed cell death is like the entire assembly line going on permanent strike, leading to factory closure. Disruption of biological clocks is the entire managerial staff, including the chairman and board of directors, calling it quits. Many of the natural ebbs and flows in the body—including sleep, body temperature, and hormone secretion—are under the control of biological clocks that are genetically programmed to react according to set time sequences, such as the twenty-four-hour day, based on environmental inputs. As our DNA decays with aging, these natural rhythms become erratic and begin to desynchronize, weakening our natural defenses against disease. Gradually, over time, the disruption of biological clocks becomes a central feature of the aging process.

By itself, this theory does not explain why we age the way we do. Many bodily functions do not have natural biological clocks, and only a few of the brain's functions, particularly sleep, are under this type of rhythmic control. Even the heart, a structure that requires near-perfect rhythmic performance to ensure survival, is not affected very much by circadian (twenty-four-hour) rhythms.

Free Radicals Are Toxic

That's what some people said in the 1960s and 1970s. But jokes aside, what exactly are free radicals? Free radicals are formed when an atom or molecule carries an unpaired electron. This extra negative electrical charge launches a cascade of chemical reactions that eventually lead to cell death. Free radicals are constantly produced by chemical reactions throughout the body, and both stress and a diet high in saturated fats increase free radical formation. The most common free radicals are hydrogen peroxide, which is formed when a molecule of water gets an extra oxygen atom, as well as oxygen itself.

Oxygen is essential for life, but the addition of an unpaired electron makes it toxic to cells in the body. Dr. Jekyll turns into Mr. Hyde, and life-giving oxygen metamorphoses into a merciless killer.

If toxic free radicals are continually being formed in our bodies, how do we survive? As with everything else, nature has provided a counterbalance to deal with this threat. Enzymes called free radical scavengers, notably superoxide dismutase, routinely destroy the free radicals that are formed. These enzymes decline with age, and a gradual imbalance develops, with free radicals gaining the upper hand. Many therapies are based on the idea that decreasing free radical toxicity will slow down the aging process. For example, vitamin E is the most widely used antioxidant, and it destroys the bad oxygen when it appears in the body. Melatonin also possesses some antioxidant properties, as does the prescription medication selegiline (Deprenyl). These substances can help prevent the ravages of the aging process, and memory loss in particular.

Genes versus Environment

Some people have an excellent memory for words, others for numbers, and still others for music. But are there genes that regulate how the brain ages? Do genes give us our memory power during our youth? And as we age, to what extent do genes control or program the time when nerve cells degenerate in the hippocampus and frontal lobes? We are waiting for the answers to these questions, because only then will it become possible to translate this genetic knowledge into practical, therapeutic interventions.

George Burns drank like a fish, smoked like a chimney, and did a few more exciting things on the side. Nevertheless, he lived to be over a hundred; obviously he had good longevity genes. Inherent genetic variability influences not only longevity but also intellectual functions and memory, so that a fifty-year-old may have the brain of an eighty-five-year-old, and vice versa. But in addition to genetic influences, environmental factors can magnify, and sometimes directly cause, memory loss as you grow older. These effects can be directly altered, unlike your genes. I will focus on these environmental, usually reversible, factors in a later section in this book.

Aging Weakens Recent Memory

Do you remember what you ate for lunch today? How about yesterday? And how about a week ago? For most of you, whatever happened today is still in active memory, yesterday is hovering above the "memory trash," and the meal from a week ago is already in the trash and likely gone for good. The time factor is crucial; as you go further back in time, memories begin to vanish. The paradox is that as you grow older, it is not the old memories that disappear but more often the recent ones. Most recent memories—even if they are closer to consciousness and hence more "active"—are not hardwired in your brain as firmly as old memories, so you can understand why lapses in recent memory occur during the aging process.

The Power of Learning

When infant mice are made to learn a complex task like traversing a maze to reach a source of food, the process leads to increased branching and connectivity among nerve cells in the brain. Learning literally leads to a structural change in nerve cells in the mouse brain, and these changes can become permanent, resulting in superior memory and intelligence. In children, we call this education. In the mice experiments, the branching of dendrites slows down and then stops as age advances, so that new learning becomes more limited. Similarly, in people, the ability to learn new information is greatest during childhood and decreases in later life when nerve cells lose their capacity to grow and branch out to form new contacts with other nerve cells. This topic reminds me of an incident that taught me a great deal about our capacity to learn, and how this changes as we grow older.

Back when I was at Yale, I met Anil Deolalikar, an economist who was then a junior faculty member. Later, he got married and settled down in Seattle. When I visited him there, his daughter was barely three years old. One morning, he played a game in which he showed her several large cards filled with red polka dots closely packed across the white surface. One card had sixty-seven dots, another sixty-nine, a third seventy-one, and so on. Each time he flashed the card in front of her, she would immediately blurt out the right number of dots. For the life of me, I couldn't make out the differences between the number of red dots on these cards, and neither could Anil. I was impressed, because clearly his three-year-old daughter wasn't familiar with the concept of numbers, let alone the meaning of sixty-nine or seventy-one. Anil explained to me that his daughter wasn't really unique—very young children normally possess a nearly perfect visual photographic memory. This ability is lost when they grow older, perhaps because it is displaced by the development of language.

This experience increased my awareness of the fact that there are many untapped resources within each one of us. Cultivating these skills is essential to developing and maintaining our intellectual faculties, including memory. Even though prime time for learning is when you are young, learning and memory can still be enhanced in middle age and beyond, provided you undertake the right steps.

What Is Senility?: Esther's Story

Esther Erickson, an eighty-three-year-old retired bookkeeper living alone, came with a long-standing friend and neighbor who had persuaded Esther that her memory needed to be checked. Esther had begun to forget names, locked herself out of her apartment a couple of times, and had accidentally left the stove on once. Other than a slight slowness in walking, there wasn't anything unusual in her neurological examination, and her psychiatric assessment was completely normal. The rest of my diagnostic workup was notable for only two findings. Her memory was slightly below par, but otherwise she scored in the normal range for someone her age on the neuropsychological tests. Her MRI scan revealed a very small stroke in the basal ganglia, which is a brain center that controls motor movements. This helped explain her slowness in walking but not her memory lapses.

Before I complete her story, put on your diagnostic hat for a moment. Is this normal aging? Is this mild memory loss? Or is this early Alzheimer's disease? And where does "senility'' fit into the picture?

Esther Erickson does not fit well into any diagnostic category. She is precisely the kind of patient who would have been rated as being on the way to "senility" if she had come to see a doctor fifty years ago. Nowadays, we don't like to use the term senility because it blurs the distinctions between mild memory loss and dementia. Also, the old concept of senility implied that it was caused by hardening or blocking of arteries and their smaller branches. However, recent research has shown that age-related memory loss is usually not caused by diseases of arteries or other blood vessels in the brain.

A year later, Esther died suddenly of a heart attack. The brain autopsy showed no evidence of stroke other than in the basal ganglia, consistent with the clinical and MRI results. The only other abnormality was an occasional amyloid plaque without any neurofibrillary tangles. Amyloid plaques and neurofibrillary tangles, both of which are visible only under a microscope, are the pathologic features of Alzheimer's disease. But with aging, an occasional amyloid plaque can appear even in the absence of any symptoms of memory loss. So while her autopsy told us that she did not have Alzheimer's disease, we couldn't rule out the possibility that it would have developed if she had lived for another five to ten years.

I think it is best to drop the term senility because it doesn't tell us anything beyond the fact that the person is old and has memory loss.

What Aging Is and Isn't

Dr. Robert Butler, formerly the head of the department of geriatric medicine at Mount Sinai School of Medicine in New York, cautioned against "ageism," which is a tendency to think of every problem of the elderly as being a natural consequence of aging and hence doing nothing to solve it. Ageism also underlies the widespread prejudice against older people and is sometimes used to prevent them from working, or forcing them to retire early.

Aging does not mean you have to:

Lose interest in doing things.

Lose your memories permanently.

Get depressed.

Focus on death more than on life.

Think that it is no longer possible to change.

Be satisfied with being bored.

View the rest of your life as a downhill course.

Successful aging involves:

A positive outlook.

Continuing to maintain interests and hobbies.

Looking forward to change and having a willingness to adapt. Maintaining strong relationships and social bonds. Maintaining high self-esteem. Bouncing back from adversity.

Young Learning, Old Learning

Aging has a gradual, steadily progressive impact on memory processes. Compared to young people, older people are less skilled in associating unrelated items presented to them. This decline is greatest when older subjects have to associate different stimuli to produce a complex memory, and is probably due to loss of nerve cells in the association areas (brain regions responsible for associating different events and stimuli) in the parahippocampus and the frontal lobes. However, in these same experiments, older people were much better than their young counterparts at tasks requiring planning, organization, and the manipulation of information. In other words, even though young adults are much better at learning new information than middle-aged and older people, they fall short when it comes to tasks that require careful planning and judgment. You should recognize this organizational capacity as an important strength in yourself when you evaluate your intellectual capabilities.

Aging Changes Your Mental Abilities

Reaction time to an event slows

Dealing with multiple stimuli and tasks becomes difficult Thinking slows

Learning new information becomes difficult Remembering names becomes more difficult Short-term memory slowly deteriorates

Intelligence and long-term memory are preserved, including memory for music and other artistic memories

Common sense, planning, organizational skills, and judgment improve. You develop wisdom. Creativity and Associative Thinking

The flip side of cognitive decline is cognitive improvement, and further along the spectrum lies the phenomenon of creativity. Some creative abilities are innate or genetic, like musical skills, but learning and practice are necessary to develop such talents. Associative thinking, which is controlled by the parahippocampus and parts of the frontal lobe, involves taking a new piece of information and linking it to another piece of data that lies stored in memory. We all do this from time to time, but the creative person tends to do it more often and can sometimes take big leaps by connecting ideas that many would consider to be quite distinct and separate. The creative individual recognizes the importance of this new connection, builds on it, and is off and running.

Einstein's Brain

Therefore, from a theoretical perspective, the association areas in the parahippocampus and the frontal lobes should be better developed in highly creative people. The initial autopsy evaluation of Albert Einstein's brain revealed that it was a normal size, and the association areas in his cerebral cortex were not large. But a recent reexamination showed that his brain lacked the Sylvian fissure, which borders the temporal lobe, and had a slight enlargement in the lower part of the temporal lobe near the association areas. These results were given big play in the media, but they don't really resolve any issues. Maybe Einstein wasn't the best prototype to study, because he made quantum leaps to develop entirely new fields virtually from scratch, leaving bread-and-butter associative thinkers behind in the dust. Maybe the unique connections within his brain were simply beyond the detection capability of standard neuropathologic methods.

The Nobel Prize: Old Winners, Young Winners

In general, aging does have a negative impact on creativity, and this is probably due to the decay in association cortex nerve cells over time. Nobel Prize winners invariably complete their groundbreaking work in their thirties and forties, although the rest of the world may take a few decades to catch on and give them their just reward. But creativity does not disappear as you grow older. Rather, it gets modified by a lifetime of experience that results in your balancing new ideas with common sense and judgment, leading to what is commonly called wisdom. As a matter of fact, some people continue to be creative even after developing severe memory loss. After Willem de

Kooning developed Alzheimer's disease, he remained a productive painter into his eighties and nineties. The quality of his paintings changed, and the precise line of his brush strokes became blurry. The art critics, who were unaware of his brain disorder, announced a new creative phase in the painter's career.


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