Not in Love With AAMI

Might as well begin with the latest one: This morning, walking the beagle and thinking how to start this article, I began to pass the springhouse (a little shed over a cinderblock tank at the top of our hill), which I rebuilt last year in preparation for piping water to the outbuilding where I have my office. Sparky, deep in his world of smells, was having his usual good time but—just back from a quick trip to San Diego and a long beach stroll that compared favorably with dog walking in the chill of a January morning in upstate New York—I was not. I owed my stepson, Ricky, for his good care of my cats while Ann and I were away, but was wishing that my voluntary repayment had not taken the form of walking his dog for him. Hurrying as I was, I had already passed the springhouse before I stopped, recalling Ann’s comment of the night before that it would be good to check the water level, now that the water project was nearing completion in a time of relative drought in our area. Maybe we’d get all through with the work, only to discover that the source was dry.

Hopping cautiously over the ice crust on the drainage ditch, I entered the woods, removed the access panel on the north side of the springhouse, lifted and set aside the screen that is supposed to keep mice and other small creatures from drowning in the water beneath, then found a pole, poked it through the surface ice, and ascertained that a recent heavy snow and subsequent thaw had indeed helped to raise the level of the water. Pleased with the information I had obtained, I put down the pole, replaced the panel, twisted the four pieces of hardware into place to hold it, recovered the dog’s leash, and started down the hill.

Then I stopped, decided I had to go back to recheck, renegotiated the frozen ditch, reopened the panel, and, sure enough, found that I had not repositioned the varmint screen over the top of the holding tank. As I closed up the shed, I asked myself if I had now got everything right, and I wondered whether, in a few years, I might instead be asking questions like, “Now tell me, are you Ricky or Sparky?” And would I be addressing my question to my stepson or his dog? Or perhaps to a shed? I wasn’t really ready to think about that, but I couldn’t help it. I had a more general question on my mind that was shaping my thinking and is the subject of this essay: Does my age-associated memory impairment (AAMI) represent the insidious onset of Alzheimer’s disease (AD), or is it something I can continue to live and function with? It is a question that many people ask in an aging America.

As a neurologist, I have tried in the past to answer that question for some of my patients from the physician’s side of the desk. The case of “Mort” is one example. (Circumstances alter cases, and in this and other descriptions of persons in this essay, I have had to change names and occupations, but I have not otherwise created fiction.) Until his retirement, which had taken place a couple of years before he came to see me, Mort was an administrator at the hospital where I also worked. We knew each other casually, and I thought he always looked harried. This time, though, he admitted it. He wanted to know if he was becoming demented and, from experience, I knew that I could not just pat him on the head. Like medical students who must undergo a complete neurological examination before they can begin to believe that the muscle twitches that prevent them from concentrating on their studies are benign, and not the first sign of amyotrophic lateral sclerosis, people who come for reassurance about their subjective mental decline must also be put through their paces. This is the rule of thumb: If the patient is the one who made the appointment to complain about his memory, he is fine; if a family member made the appointment and brought the patient in, and the patient says he is fine, he isn’t. But you can’t reach either conclusion without examining the patient. Moreover, the rule works best when things have moved along. At the onset of dementia, insight may be retained. This poignant line appeared in a British medical journal, The Lancet, in an anonymous woman’s essay on her father’s progressive dementia: “In that moment he knew for certain that he was losing his mind, and I think he knew as well as I did that he was losing it for ever.”

He was 70, Mort said, and his mother had become demented in the 10-year course of Parkinson’s disease. He was concerned about his tendency to lose a thought, especially when he was distracted. And he would often go somewhere in the house to get something, then stand there wondering what he had come for. Usually—not always—he could retrace his steps mentally and recover the lost plan. Sometimes, he woke up too late to the fact that he should be in a meeting or picking up a friend at the airport.

I did examine Mort, but it was his history that answered his question. From one full-time job he had gone to so many part-time jobs it was no wonder he was forgetting to keep appointments. He volunteered at the library, at the synagogue, at the town office, at the local newspaper. There were projects in various stages of completion. The list was so long I stopped writing (and now, of course, I can no longer remember what the items all were).

After my neurological examination, which showed none of the stigmata of parkinsonism or those that may accompany AD, multi-infarct dementia and other forms of cerebral vascular disease, or normal-pressure hydrocephalus, I gave Mort the Folstein/McHugh Mini-Mental State Examination (MMSE), the best known of the screening tests for dementia, which has been in use for nearly a quarter of a century. Neurologists like it for its brevity. Mort liked it because his score was perfect. He got 30 out of 30. It is rare for an elderly person who has AD to be able to score 24 or higher. One of his tasks was to write a sentence. The sentence has to have a subject and verb, and be sensible. The patient can still get credit despite faulty grammar and punctuation, but must produce it spontaneously rather than to dictation. Mort wrote, “The quick brown cow jumped over the mooning dog.” I gave him credit for that.

I sent Mort my office note, which I dictated in the form of a letter to him with a copy to his doctor. My diagnosis at the time of our goodbyes in the office was, “Mort, you are one of the ‘worried well.’” Time has proved me right: When I see him in the hall—we both return often to our place of previous employment—he has the same sagging shoulders and drooping mouth, but by mutual unspoken agreement, we let sleeping dogs lie. It had been embarrassing for him to have to tell a colleague that he thought he was becoming demented—whether he was or not.

That was really what was happening to “Sal,” a neurologist in practice on the north side of the city at that same time. Sal was skilled and kindly, but he had to close his office at once on the day he was diagnosed as having early AD. His daughter kept me posted on his rapid decline. It was not long from the time he stopped seeing patients until he no longer knew his family. No amount of magical thinking can protect us from feeling vulnerable when those who succumb to disease (not just dementia, of course, but any serious medical condition) are cut from the same cloth as ourselves. I took it hard when my favorite teacher—among the many good teachers I knew during my residency in neurology at the Neurological Institute of Columbia-Presbyterian Medical Center in New York City—succumbed to AD. How, I asked, could that dapper man, so talented, so enthusiastic about his profession, so dedicated to excellence, slip away like that? I did not set out in this article to address that question or questions such as What causes AD? and How can I prevent it? (clearly, “Use it or lose it” is fatuous advice) but, rather, to look for ways of answering the question Mort asked me: “Am I really losing my mind?”

AAMI. It has also been called such things as benign senescent forget-fulness. For clinical and research purposes, it is a diagnosis applied to persons 50 years old or older. That isn’t to say that healthy young people may not be forgetful in similar ways (although not to the same extent): We seniors face the daily difficulty of learning the names of people we meet, recalling phone numbers and zip codes, remembering where we put our keys and our glasses. I deliberately did not mention the car. The reason, I suspect, is that, in an article entitled “Is it Alzheimer’s?” in a recent issue of Hospital Practice I read this: “A common initial symptom [of AD] is to return to the parking lot and not remember where the car is parked or to forget the way home.” Not fair! Who doesn’t have trouble finding the car? Now, if you left the grandchild in the back seat, that might be a different story. “Taken individually,” the article continued, “most of the memory lapses that occur in early Alzheimer’s disease are hard to distinguish from normal patterns of behavior. But eventually they aggregate, and at a certain threshold the spouse or someone else will seek medical attention for the patient.” That, I concede, is true.

We who have AAMI have trouble shopping successfully without a list (a list that may have only three items on it; a list that is still on the kitchen table when we are frozen in front of a freezer in the supermarket). We do not do well at retrieving a piece of information right now, when it is still useful, instead of the next morning, when it has been passively presented to memory like a polished shell washed in on the high tide or, perhaps more aptly, like the bloated intestine of a mouse deposited on the doormat during the nocturnal predations of the family cat. It is often just a word that we (all right—that I) want. Because I have a large vocabulary, I can usually produce a synonym, and usually so adroitly that I hardly know I’m doing it; but if the word is one I rarely use, really want, and have relatively recently acquired, it may be a bear to bring to mind. Example: ataxithymia. It translates as “not touching the mind.” It is not in my medical dictionary, but Ann and I read it somewhere (where?), and it means not being in touch with one’s feelings. It is a word I wanted because it applies to the way I (neurologist/essayist; senior citizen/possible pre-clinical AD patient) was trying to approach this discussion, which could so easily touch a raw nerve. After scrabbling through my mental lexicon for days, I called a good friend who is a neuropsychologist, gave him the definition, asked if he knew the word (he didn’t), and, before you know it, was making tentative arrangements to be tested formally for dementia! I think that word search had pushed me further than I wanted to admit. The more I wanted to remember it, the less successful I was. I was nixing memory with desire. Then, at 2:30 a.m., in the bathroom, I found it—“illuminated,” Ann said next morning, “by the night light.” It had taken four days. What’s more, I had only begun to savor the honey of having shoved that bear of a word through a tight place in my memory when I thought, naturally enough, of Winnie-the-Pooh and how he was stuck in a hole at a friend’s house after eating too much “Hunny,” and how he had to stay stuck until he lost weight—and now I can’t remember if he was at Piglets or somewhere else, and I realize that it is not just recent memory that is vulnerable. Kurt Vonnegut summed it up: “And so it goes.”

I am not alone in complaining about my memory. I don’t mean that my family is complaining. They are really too nice about it, and my wife is forever creating specious excuses for my lapses, in order to assuage my concerns. I mean that most older people have the same complaint. Among the numerous epidemiologic studies from which the Mayo Clinic derives a part of its fame is a group of investigations that goes by the lugubrious and presumably crafty acronym MOANS (Mayo Older Americans Normative Studies). One such study was an assessment of subjective memory complaints that provided these findings: Only one in eight older persons living in the community reports having no memory problems. Fewer than 3 percent of such people, however, consider their problems “major,” and only a small proportion believe that their memory has changed substantially for the worse in the past five years.

On the objective side, these reports proved to be of little value. Although those persons who thought poorly of their memory were sometimes right, they were sometimes wrong, and the overlap was too great to make their opinion a substitute for testing. Of the 281 participants who provided the “longitudinal sample” in the five-year study, who were 55 years of age or older and “normal” to start with, only 11 were diagnosed as being cognitively impaired when the study ended. What did correlate best with subjectively poor memory? Psychological distress. As the Mayo investigators put it, “level of psychological distress was far more predictive of subjective memory complaint than absolute level of learning performance” on the memory tests. They caution against concluding that being depressed makes a person feel that he is losing his memory. It could be that people who hold a generally low opinion of themselves and their ability to control their lives would rate both memory and mood as being impaired, without providing support for a cause-and-effect relationship.

To illustrate the everyday problems we all face in recognizing dementia and deciding what to do about it, not only as potential patients but as friends and relatives, I will tell you briefly about two octogenarian women who came to have a meal with us just this past week. Both are Ann’s long-time friends. Each lives alone. They were invited separately, on different days. Each of them has been to our house several times. Each one arrived to say that she had driven past the house, realized she had gone too far, and then turned around and found us.

“Lola,” who is nearly 87, is an insomniac, subject to bouts of depression, but usually interested in her hobbies: genealogy and astrology. She comes from a long line of people who lived long lives and kept their wits about them. She herself has outlived two husbands. Although she lives alone, a son lives nearby and she keeps in close touch with all of her children, who help her to rally when she is feeling low.

Lola is confident of her own continuing capacities, and we agree. She is sharp, and good company. Just after I typed this paragraph, she called to ask me a question: What five U.S. presidents are not buried on U.S. soil? When I said I didn’t know, she told me Ford, Carter, Reagan, Bush and Clinton. She got the question from a book on “brain building.”

“Lily” is also in her 80s, but nobody has more exact information than that. She never married, and the companion who lived with her died three years ago of breast cancer. Lily is a former librarian, a voracious reader and, until perhaps a year ago, she was always ready to discuss her reading. Now the mainstay of her conversation has become questioning, and she asks each of her questions over and over: Is Ricky doing well in school? Is he in high school now? Is this a new car? (N0, you have ridden in it before. Here, I’ll help you with the seat belt.) Have you redecorated this room? (N0, we have done some remodeling, but this room looks the way it has for the past three years.) When we ask her about her own life, she is dismissive: “Boring.” No details. At the time of this last encounter, she had a hard time hearing Ann, who has a small voice, and Ann asked her why she was not wearing her hearing aids. “I don’t have any,” she replied. I called her on that one, but she insisted she had never owned aids. Then she corrected herself. “They are at home,” she said. We suspect she has mislaid them.

We are confident about Lola: Despite the loneliness and depression, we think she will make it through life cognitively intact. Lily, we fear, is doomed. She has no relatives. She lives in a big house with a difficult dog she would not part with. (The dog is also showing signs of senility and has become a hazard. It has bitten her, and it is one of the things she manages to trip over.) She smokes (another hazard). When she came down with the flu, some weeks ago, and we stopped by to check on her, we found her sitting at the kitchen table with a bottle of whiskey—drunk, surly and despondent. Her housekeeper, who does not live there and, like us, had just come by to see how she was managing, was trying to get her to bed. We did not stay, and I will not keep you with her, either. It is really too sad.

Because we are not all doomed to dementia in old age and because we do not expect perfect performance from others (with the exception of concert pianists and bank tellers), we should try to keep a lid on the anxiety generated by our quotidian glitches, but it’s hard: Yesterday, while I was putting up a towel rack, I spent as long finding and refinding one of the screws as I did in any other phase of the procedure. That example, like the one with which I led off this essay (don’t look: it was the “varmint-screen caper,”) is mundane, but that is exactly the reason it is so galling. We need to both admit our limits and affirm our capabilities, like Tennyson’s Ulysses: “Tho’ much is taken, much abides; and tho’/We are not now that strength which in old days / Moved earth and heaven, that which we are, we are.” But, without thinking of ourselves as heroes, we also need to keep striving, as did Ulysses: It is the tension between the wished-for and the feasible that produces the frustration of aging.

The way to confirm the presence of AAMI, if confirmation is required (because worry over the situation is beginning to depress and disable the individual, as it did Mort or because things are getting so bad that the family are worried, too) is to be interviewed and tested. This may require the collaboration of a neurologist and a neuropsychologist, ultimately but it should start with one’s personal physician, because such things as depression and hypothyroidism, to cite single examples of emotional and physical disorders that can masquerade as dementia, need to be exposed by the approach of a generalist before the specialists get involved. The criteria for diagnosis of AAMI (as described by Dr. Thomas Crook, a memory-clinic director) include these: memory problems that have come on gradually, not suddenly; scores below the cut-off on standardized memory tests, such as the Benton Visual Retention Test or the Logical Memory and Associate Learning subtests of the Wechsler Memory Scale; adequately functioning intelligence as determined by, for example, the Vocabulary subtest of the Wechsler Adult Intelligence Scale; and absence of dementia as indicated by the score achieved on the MMSE. I don’t believe that Dr. Crook would maintain that vocabulary is not vulnerable to the aging process: There is difficulty in assimilating new words. (In my case, words such as hermeneutics and epistemology, which I have only recently decided I wanted to learn, have driven me back to the dictionary too many times to make my decision worth the bother.) Besides that, there are the words we think we have filed somewhere that won’t come back. I started this essay by describing as “pieces of hardware” the gizmos I now know to call turnbuttons. I had to ask a friend who owns a hardware store. I knew they were not wingnuts or turnbuckles. But why would I look up the similar word turnbuckle, just, to be sure it was not the right word, if the right word (which isn’t in my unabridged dictionary) had not been lurking in the shadows of my memory? And didn’t I already discuss vocabulary?

If a physician is consulted, the investigation must be thorough. Physical ailments such as low thyroid function, kidney failure and liver disease must be sought. Problems attributable to substance abuse—nice old ladies like Lily may be secret alcoholics, and she is—and to the drugs prescribed to treat physical and emotional disorders (especially tranquilizers, sedatives, antidepressants and other psycho tropic agents) must be looked for. Alcohol is more likely to compound the memory problems than to cause them but, occasionally, the Wernicke-Korsakoff syndrome, brought on by severe nutritional deficiency and usually secondary to alcoholism, can wipe out recent memory. Special attention must be paid to the special senses, audition and vision. It is not possible to remove AD plaques from the brain, but it may help a lot to remove wax from the ears. Someone who does not hear well is likely to seem much less “with it” than he really is.

After all the other investigations have been completed, the neurologist may come to the conclusion that there is a familial or sporadic brain disease in progress—a primary dementia. Among those disorders, the most common and, today, the best known to the public is Alzheimer’s.

In the dry language of a scientific journal, “a grossly impaired ability to acquire and retain temporally and spatially bound information is a hallmark of AD that occurs early in the pathogenesis.” That kind of remembering is called episodic memory. It is what gives me the ability to recall that it was on the boulder near the big oak at the southeast boundary of her property that I first photographed Ann, who is now my wife. She was wearing the blue jacket she has finally given up wearing, jeans, and that Indian-design shirt she will never give up, on the first warm day of the spring of 1996. Again in psychologese, “in many instances, the degree to which an individual is able to utilize cognitive support in episodic memory tasks is related to successful use of semantic memory aids.” Semantic—general—knowledge, such as how to speak English or perform an arithmetical operation or categorize, can in various ways come to the assistance of learners, young or old, who are not demented: If we can call on what we already know, we may be better able to commit new information to memory. We can follow instructions on how to organize the material, and we can also perceive a pattern for ourselves. We can take more time to learn, “enrich” the task by creating mental images (one of the well-known mnemonic “tricks”), and profit from hints (“cues”) when we learn and when we try to retrieve what we have learned.

A person who has full-blown AD can do none of that well. “AD is associated with a reduced ability to use cognitive support for improving memory: a reduction in cognitive reserve capacity.” It takes maximum effort to make AD patients do better (not well, but better): Support strategies have to be used both when they try to learn something (encoding) and when they try to bring it to mind (retrieval). Even then, AD patients “typically require more support than their healthy older counterparts to exhibit memory improvement.” An explanation for “the reduced effects of cognitive support on memory in AD may be that the semantic network that guides the encoding and retrieval of episodic information functions less efficiently in AD.” If you have heard the incoherent babbling of an AD patient in a far-advanced state of mental dilapidation you will find that to be a believable hunch about what is in progress. Our focus, though, is not on full-blown AD. It is incipient AD that is the concern. OK, my focus, my concern.

We have only to remember the jokes about Ronald Reagan when he was in office to recognize the shift in attitude we undergo when someone moves along the continuum. Only in retrospect can we be suspicious that what seemed laughable at the time was really ominous and not just the innocent absentmindedness we might have overlooked in somebody who did not have such an important job. But is AD only quantitatively different from AAMI? Is it correct to think of a slippery slope along which all of us with the wrong footwear will slide into mental oblivion? Observations to date are too limited to be reassuring.

The investigators at Stockholm’s Karolinska Institute whose words appear above looked at a group of physically healthy elderly people (aged 75 or older). Some of them remained cognitively intact throughout the three years of the study (the normals). Some of them, although not demented by clinical criteria when initially tested, had become Alzheimer victims when they were retested three years later. The investigators called this subgroup “incident” AD patients, using the word incident in an epidemiological sense, to suggest that they “came down with the disease,” if you will, during the time that the study was going forward. (It turned out that, collectively, the incident AD patients had not done quite as well as the normals when they took the MMSE the first time, but their scores had been above the formal cutoff for dementia.) The two subgroups also differed at baseline with specific regard to their episodic memory function, the incident AD patients again not doing as well as the normals. Both subgroups could make use of cognitive support—organizing, working slowly, using cues—but this support was not enough to make up for the deficits of the incident AD patients as compared with the normals. The graph showed parallel lines: The two groups, the normals and the incident AD patients, both improved with support, and to the same extent. This meant that there was still the same gap between them. If cued retrieval had proved capable of bringing the performance level of the incident AD patients up to normal, it would have suggested that retrieval was the predominant problem. But that did not happen. The problem had to be more than retrieval. The Swedish research workers and others think it is a problem with encoding—of moving information from primary (immediate or short-term) memory, which suffers little in mild to moderate AD, to secondary Gong-term) storage. This is consistent with the finding on neuroimaging studies that the hippocampus and related parts of the temporal lobes atrophy early in AD. Those parts of the brain, neuroscientists believe, function in encoding, rather than in retrieval.

There was, in the Swedish study, a third subgroup, comprising 106 patients, whom they called “prevalent” AD patients because, although free from other diseases, they already had AD when they entered the study. Of course, they still had it three years later when they were retested, if they could be retested; 46 of them had died! Whether that was bad or good is not for me to say. I know what I would want for myself.

One group of people who have subjected themselves to scrutiny for the possible emergence of AD are healthy members of certain families in which genetically determined AD has appeared both early and often, as compared with the general population. The unnerving finding is that even in those persons who later develop aggressive (rapidly progressive) illness, there is a lengthy period during which, although there are no symptoms of dementia, there are selective deficits in verbal memory and in performance IQ. This can be looked upon as hopeful in the long run: A good protection for vulnerable neurons or a good treatment of early disease, when it becomes available, should obviously be started as soon as possible, and a leisurely onset of disease may permit treatment to be started when the signs are subtle and thus make it more effective.

Clinicians admit that they cannot confidently distinguish someone who shows “normal” age-associated cognitive change from someone on the cusp of AD, although I have detailed some of the ways that they are trying to do so. Neuropathologists, too, are unable to identify any feature of “age-related” neurodegeneration (the presumed neuroanatomical substrate of at least some AAMI) that absolutely sets it apart from the microscopic plaques and tangles that are the hallmark of AD. Plaques and tangles are numerous in AD, but they are present to some extent in aging normal brains as well. Because of those limitations, and because neuropathologists enter the picture after the subject’s death, there is increasing interest in special laboratory tests that may help to predict the rate of an individuals progression into the seventh age of man. Authorities agree, though, that it is not a good idea for someone who does not have a strong family history of AD and who has no evidence of early dementia to be genetically tested or undergo MR scanning, since the findings will be hard to interpret and, at present, the therapeutic benefit of any treatment strategy is debatable at best. (Only one in 20 persons who go on to develop AD has an identifiable single genemutation that reliably predicts the disease.) And even if there have been numerous cases in the family, it is the individual’s right to choose not to know. We can all plan for the worst and hope for the best.

As I conclude this account, I think I have decided what to do about checking out my own memory bank. I want to undergo formal testing. My neuropsychologist friend is prepared to help. Maybe I have moved much of my savings to an account for which I have forgotten the number. Or maybe I have withdrawn and squandered a substantial amount and mislaid the withdrawal slips. Is there gold dust or just dust in my cranial vault? I’m not sure, but Ann can let you know, if you’re interested. Give it some time, then get in touch with her. Probably it’s best if you don’t try to get in touch with me.

About the Author

David Goldblatt

David Goldblatt, M.D., is Professor Emeritus of Neurology and the Medical Humanities at the University of Rochester School of Medicine and Dentistry. He has retired from the practice of neurology but is active as a member of the Ethics, Law and Humanities Committee of the American Academy of Neurology.

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