EIGHT

NEW YORK CITY

Spring 2013

Not long after we got B.’s diagnosis, we went back to Mount Sinai to meet Dr. Sam Gandy, the hospital’s top dog in Alzheimer’s research—a neurologist and a psychiatrist. He was the guy who, along with Dr. Martin Goldstein, would be following B.’s case.

I’ll say this about Alzheimer’s: it sure is a bonding experience. Start telling people Alzheimer’s has hit your family, and damned if almost everyone you meet doesn’t have a story of how it hit theirs. Dr. Gandy was no exception. He told us about growing up in rural South Carolina with a grandmother whose Alzheimer’s grew quite extreme by the time Sam was ten years old. Sam’s grandmother didn’t get forgetful or withdrawn. Instead, she got hostile and agitated, and just took off down the road, to be picked up, sooner or later, by the police—and then reclaimed by the family at the police station.

Sam’s grandmother was institutionalized sooner than she would have been today. Families didn’t try to keep their addled grandparents at home if their behavior became difficult to control, or if, as often happened, they became incontinent. Sam’s grandmother was increasingly psychotic, which is a not-unusual symptom of Alzheimer’s in its later stages. Eventually her family had to put her in the state-run Hall Psychiatric Institute, in Columbia, South Carolina. Sam and his parents would visit her weekly. She wouldn’t recognize them. She knew she had family; she just didn’t know who they were.

As a kid of ten or eleven, Dr. Gandy told us, he would get fidgety on these visits, and so would wander off around the hospital to see what he could see. Virtually everyone in that hospital had late-stage Alzheimer’s. Some were tied to their wheelchairs, others tied to their beds. Almost all had vacant stares, or were babbling to themselves. The hospital staff got to know Sam, and the doctors would explain each patient’s condition to him.

In most other ways, Sam’s grandmother was healthy as a horse. She lived fifteen years with Alzheimer’s, and Sam kept visiting, right up through medical school. He didn’t know at first that he wanted to be a neurologist and study the disease that took his grandmother. For a while he just knew he loved research. But he found himself fascinated by the mystery of why and how the brain began to destroy itself. He went on to earn both an MD and PhD, and to devote his life to unlocking that mystery.

“I still find it thrilling, all the more so now that we’re getting so close—not to a cure, but to stopping this dreadful disease from progressing,” Dr. Gandy told us. “I think there’s a more than even chance we’ll get there by 2020, and I think it’s entirely feasible that B. will still be a mild-stage patient, with a decent quality of life, when we do.”

Dr. Gandy told us there was new excitement about the success of vitamin E in slowing the progress of Alzheimer’s, especially in mild-to-moderate-stage patients. “It’s not great, but it’s real,” he told us. “That’s what progress usually looks like with a tough disease like Alzheimer’s: small steps that add up. Until now we had lots of conflicting research about Vitamin E. No longer.” Now a consensus had formed: Vitamin E did seem to help.

Another small but significant step was the development of new drugs to stimulate the formation of nerve cells in the brain. The drugs didn’t prevent amyloid plaques, or the protein “tangles,” called tau, that actually seem to kill cells. “But they help restore or maintain function in the face of the disease,” Dr. Gandy told us. Not a treatment, not a cure, just a bit of help for the brain—I was getting the picture.

There were new drug trials, and B. would qualify for one or more of those, Dr. Gandy assured us. The one he had in mind was for an insulin-based drug called T-817MA. There was evidence that people with type 2 diabetes and a resistance to processing insulin were at high risk for developing Alzheimer’s. A particular gene seemed to cause both insulin resistance and Alzheimer’s. “So there’s been a small trial for patients who have some related symptoms, with insulin given intranasally,” Dr. Gandy explained. “It improves their memory by getting insulin to the brain.” Again, it wasn’t a cure, or even a treatment. And for B., who had neither diabetes nor high blood sugar, it was a bit of a stretch. But it might help. All B. had to do in order to qualify was take Aricept for three months. It would alleviate a little of the fog of Alzheimer’s, enough that the researchers could more accurately measure the effect of the new insulin drug on her.

Dr. Gandy cautioned us that one new drug was almost certainly not the answer to Alzheimer’s. Other drugs were needed. Unfortunately, the funding for Alzheimer’s research was shockingly minimal. Heart disease, cancer, and AIDS got billions of research dollars each year from the National Institutes of Health, and more from national nonprofits like the American Cancer Society. The NIH’s annual budget for Alzheimer’s was, by comparison, minuscule: $400 million. There were plenty of good ideas to try, he said. The problem was resources. “People spend years raising the money, then five years to get the trial done. A decade here, a decade there, pretty soon your life’s over!”

Meanwhile, the problem continued to grow. “Almost half of Americans over eighty-five years old have Alzheimer’s,” Dr. Gandy said, his frustration all too clear. “The disease will cost every one of those patients an average of one million dollars: about fifty to one hundred thousand dollars a year for home care, not to mention drugs, over the ten-year average that a patient lives with the disease.” Multiply that by 5.2 million people with Alzheimer’s and what do you get? A trillion dollars and change. “We have this expensive common problem,” Dr. Gandy said soberly. “It’s been there for a while and we weren’t paying attention to it. Now the aging of the baby boomers means the numbers keep going up.”

It was like some secret club we hadn’t even known existed. And now we, too, were members. The dues? Up to a hundred thousand dollars a year. Length of membership? Eight to ten years on average. The emotional cost of it all to us as a family?

Priceless.

LESSONS LEARNED

BASIC PERSONALITY CHANGES

Early-onset Alzheimer’s patients tend to fall into one of four common personality types. I was relieved to know that B. in her mild stage, at the start of summer 2013, was a perfect example of the best of the bunch. She was—and still is—good-natured and open to suggestion most of the time. She knows she has Alzheimer’s, and sometimes gets depressed about it, but more often than not her spirits are up. That is a blessing.

The other three personality types are far more challenging:

Apathetic

As a mild-stage patient begins to struggle with tasks or thoughts or sentences that are in some way complex, so grows the inclination to abandon the effort. The patient is losing the part of his brain that governs what’s called executive function. Antidepressant medicine may help; physical exercise is certainly helpful, as are small household tasks that the loved one can feel some pride in mastering, like organizing kitchen cabinets or vacuuming. I do see some apathy in B., but having a task, or a plan of any kind, tends to bring her spirits back up.

Depressed

Often the awareness of one’s worsening condition, and the helplessness one feels to affect it, can increase tensions and antisocial behavior, which in turn feed depression and anxiety. I see that in B. maybe more now than I used to, but so far exercise and satisfying tasks like cooking help.

Paranoid and Frightened

As Alzheimer’s loosens a patient’s perceptions and sense of reality, she may create new realities to fill what’s missing. A handyman who’s come to fix the stove may suddenly seem an intruder; a spouse may seem a stranger. Thankfully, B. hasn’t had any interludes like that.

These personality changes are hard to accept—believe me, I know—but as a caregiver you learn to react with gentleness, to sympathize but not to correct, and, when possible, to take the loved one to a new environment—an ice-cream parlor, say—to dispel the paranoia.

THE POWER OF LOVE

In a San Diego suburb in the early 1980s, a pioneer in Alzheimer’s research, George Glenner, together with his wife, Joy, started the country’s first private home-care facility for Alzheimer’s patients. The Glenners were doing cutting-edge lab research to understand what the disease was, and what caused it, in the hope of finding a cure. But they saw the need for immediate, hands-on help for Alzheimer’s patients, and turned a Hillcrest cottage into the Alzheimer’s Family Center. As the Glenners began tending their first guests, they let instinct guide them. The best thing they could do, they saw, was to alleviate their patients’ stress, however they could: to be soothing, supportive—and loving. Joy Glenner came to believe that a treatment for Alzheimer’s lay right at hand. “It’s a glue called love. You can have a very disoriented or combative person, and love can help calm them.”

THE DAILY INTAKE OF PILLS

There are no drugs that cure a patient of Alzheimer’s; there are not even any drugs that keep it in check. All we have are four drugs that help treat Alzheimer’s symptoms.

Three of those drugs take the same approach, boosting the brain’s supply of acetylcholine, a neurotransmitter that communicates signals from neuron to neuron. Alzheimer’s damages those neurotransmitters. With more acetylcholine coursing through their brains, many patients find they can think more clearly and maintain better memories. B. was prescribed the one called Aricept (donepezil). Others are Razadyne (galantamine) and Exelon (rivastigmine). All work best in patients with early-stage Alzheimer’s.

A fourth drug, Namenda (memantine), regulates the action of another neurotransmitter called glutamate, which is central to learning and memory. In another context glutamate is a common food ingredient, conferring flavor, and helps the process of metabolism; in moderate amounts, it’s essential to health. In the brain, glutamate plays a key role. It attaches to cell surface “docking sites” called NMDA receptors, allowing for the transmission of calcium, which enables learning and spurs memory. Alzheimer’s gums up the process, leading to excess glutamate and calcium, which can damage the cells. Namenda helps control this runaway process by partially blocking the NMDA receptors so that not too much calcium goes from cell to cell. The good news is that the U.S. Food and Drug Administration has allowed it to be prescribed for patients with moderate to severe Alzheimer’s. The bad news is that it works for just a few months, if at all.

With all four drugs, only about half the patients who take them see improvement. And as they say in all those drug commercials on TV, some patients experience serious side effects.

ALTERNATIVE MEDICATIONS

For some years, natural substances thought to enhance memory have offered hope for Alzheimer’s patients. One that we’ve tried is ginkgo biloba, derived from the leaves of the plant. Ginkgo has been used for centuries in Chinese traditional medicine as an antioxidant and anti-inflammatory agent, and is thought to keep brain cells healthy and functioning. Early clinical studies showed mild improvement in cognitive function for older patients with Alzheimer’s and other kinds of dementia. Unfortunately, a recent large-scale trial conducted by branches of the National Institutes of Health has disappointed all of us who thought it might be a magic bullet. Some three thousand participants aged seventy-five or older, some with no signs of dementia, others with mild impairment, took either ginkgo extract or a placebo regularly for six years. The bottom line: just as many members in the ginkgo group got Alzheimer’s over those six years as in the placebo group.

I’m sorry to say that it’s more of the same with a moss extract called huperzine A, another ancient Chinese medicine. Huperzine A appeared to have the same effect as those three drugs that boosted acetylcholine. Unfortunately, in its first large-scale US trial, run by the Alzheimer’s Disease Cooperative Study (ADCS), it performed no better than a placebo in slowing the progress of the disease in mild to moderate cases. The Alzheimer’s Association now actually warns against its usage. Available over the counter as a dietary supplement, it may have harmful side effects, especially if taken in addition to FDA-approved Alzheimer’s drugs.

The word on omega-3 fatty acids, mentioned earlier, is more promising. Omega-3s, a kind of polyunsaturated fatty acid, are thought to help prevent heart disease and stroke, and are included in various over-the-counter food supplements. Some studies have shown that omega-3s can help counteract Alzheimer’s and other forms of dementia: healthy brain cells contain the omega-3 called DHA, and omega-3 supplements may boost their ability to fight the inflammation associated with Alzheimer’s. (As amyloid forms plaques, it causes inflammation, and that, as Rudy Tanzi notes in his Foreword, becomes a vicious circle: more amyloid, more inflammation, more amyloid. Inflammation is also associated with the tau tangles found in brain cells under siege.) Again, large-scale clinical trials have tempered expectations. One found that DHA offered no more help to individuals with mild to moderate Alzheimer’s than a placebo. But a second trial using only healthy older adults showed that those who took DHA scored better on memory tests over time than those given placebos.

So maybe it’s a matter of taking the omega-3s earlier—like maybe years earlier, as a preventive measure. Or perhaps the omega-3s found in foods work in tandem with antioxidants or other substances to sharpen memory. No study has yet proved exactly how omega-3s work in the body, and whether they actively work against Alzheimer’s, as either a treatment or preventive measure. All I know is that unlike huperzine A, omega-3s appear to have no downside. Until that downside is found, B. and I will stick by our omega-3–rich Mediterranean diet and hope for the best.

THE PROBLEM WITH ALTERNATIVES

All drugs are subjected to three phases of federally monitored tests. In Phase I, a drug is given to a small group of patients. If results are promising and if the drug is deemed safe—then it’s on to the larger Phase II, and finally Phase III, usually with thousands of trial participants. The larger the group, of course, the more likely that some dangerous side effect may appear. All it takes is a bad side effect in one or two of those thousands of participants to imperil a new drug’s chances. When it comes to alternative or natural medicines for Alzheimer’s, most fall short when put through three-phase trials. Most, for that matter, turn out to have no efficacy at all.

Often, when makers of those alternatives get bad news from clinical trials, they bail out of the process and call their products “supplements,” not drugs. In natural supplements stores, for example, you can buy a “medical food” called Axona. Its chief ingredient is caprylic acid, which in the body breaks down into substances that may act like a glucose supplement, strengthening brain cell capacity after Alzheimer’s has reduced natural glucose levels. A Phase II study with a limited number of volunteers appeared to show that Axona at least worked better than a placebo. But according to the Alzheimer’s Association, the manufacturer of Axona has declined to conduct large-scale Phase III studies. Instead, by claiming that it is merely a supplement, it has been able to market Axona without performing those tests. The Alzheimer’s Association has, as a result, expressed concern about Axona. Coconut oil, another source of caprylic acid, has had anecdotal success, but it has not been put to any formal tests.

Another kind of “medical food,” called VIVImind, uses an amino acid called tramiprosate, found in seaweed. Unlike Axona, VIVImind was subjected to Phase III trials as a possible Alzheimer’s drug treatment. When results proved inconclusive, the manufacturer withdrew it and chose instead to market VIVImind as a “medical food” like Axona. Neither the FDA nor the Alzheimer’s Association has recommended its use.

Coenzyme Q10 is an antioxidant that B. and I take every day, because it, like Axona, has had anecdotal success in slowing the progression of Alzheimer’s. It’s a natural substance in the body, essential for normal cell reactions; synthesized and sold as a natural supplement, CoQ10, or ubiquinone, has been tested for Alzheimer’s and found to have no discernible benefit. The Alzheimer’s Association warns that in excess amounts, it could have harmful effects, but B. and I just take the recommended dosage, and hope that it does have some healthful effects on our energy and memory.

Coral calcium is another over-the-counter supplement that needs no FDA approval because it’s not marketed as a drug. Its manufacturers claim that it’s derived from the shells of dead coral reef organisms, and that its calcium has various health benefits, among them promoting the production of calcium in the brain, which in turn staves off Alzheimer’s. The Federal Trade Commission has filed a formal complaint against the makers and distributors of coral calcium, noting that there’s no proof it has any benefits at all.

Phosphatidylserine is a lipid that surrounds nerve cells. The theory here is that phosphatidylserine extracted from various sources may keep those cells from breaking down. Supplements based on lipids from soy extracts have not been tested, and the FDA declares that no evidence of their efficacy yet exists. The Alzheimer’s Association recommends not using it.

Doctors tend to feel the same. Along with one of the four symptom-treating drugs, a doctor will usually prescribe simple vitamins and, depending on the patient’s frame of mind, perhaps an antidepressant, as ours did for B.—but not any of those alternative approaches.

Lest all this sound even more discouraging than it is, let me end this section of alternative therapies on a high note: BDNF, or, if you want the whole tongue-twister, brain-derived neurotrophic factor. It’s not a supplement sold over the counter but a protein found in our brains. More BDNF in the brain appears to mean better brain health—better enough to reduce Alzheimer’s in 50 percent of a group of older adults followed for ten years in a study by researchers from Boston University. But I’ll let the doctor who’s doing the most to get BDNF to market explain his hopes for it in a later chapter.

PREVENTING BURNOUT

At the top of the list of specific tips for caregivers is not to burn out, since that of course helps neither party. How to do it? Don’t forget to give care to yourself.

• Get enough rest.

• Take enough time off to recharge.

• Get family members and friends to help.

• When the need arises for a home health-care worker, don’t ignore it.

OTHER IDEAS THAT HAVE HELPED US

• Read the literature; learn as much as you can about the disease; get in touch with your local branch of the Alzheimer’s Association.

• In conversational groups of three or more, don’t treat your loved one as if she doesn’t exist, and don’t refer to her in the third person.

• Don’t try to finish a loved one’s sentences. Give her time to respond. If she can’t retrieve her thought after a long pause, gently prompt her with what you think she’s trying to say.

• Avoid being condescending or critical, at all costs. It’s debilitating, and simply doesn’t work. Try to ask questions that can be answered with a yes or no. Instead of “What shall we wear today?” try “How about these black pants?”

Above all, never lose sight of the dignity within the human being who has the disease.

SEX AND SEXUAL BEHAVIORS

Nothing is the same with Alzheimer’s—including sex. So far, we have managed to maintain a semblance of the sexual relations we shared before our lives changed. Not all couples are so lucky. A wife may slip into the covers beside her husband and ask why he’s there in bed with her: a buzzkill for even an ardent partner. She may, instead, engage in sex with her husband, only to lose all memory, a few minutes later, of having done so: another dampener, for sure. B. has not acted in those ways—not yet—though I’ve certainly learned that sex with Alzheimer’s means more cuddling and touching than intercourse.

As the disease progresses, a patient’s interest in sex will likely diminish, increasing a partner’s stress and frustration as a caregiver. Unfortunately, there’s no easy answer for that. Other patients may show a heightened interest in sex, creating problems of a different kind. In Living with Alzheimer’s, from the Chicken Soup for the Soul series, a support group counselor recalls a new member raising her hand to say she had an odd issue to report. “The problem is that we will have sex in the morning and by lunchtime he forgets that we had sex. He will approach me longingly and say, ‘Honey, c’mon, we haven’t had sex for days. He’s insatiable.’ ” There was, as the counselor recalls, a moment of grave silence before someone else cried, “I wish I had that problem!” and the whole group collapsed in laughter.

Occasionally, a patient will exhibit inappropriate behavior, such as touching himself or herself, even masturbating. Alarming and embarrassing as this behavior may be, family and friends need to recognize that the patient hasn’t lost his sense of decorum or become some sort of sex maniac. This is the disease in action, not the patient. I’m relieved to say that hasn’t been our issue, but what the experts say to do makes complete sense to me. Gently advise the patient that that’s not what we do, and quickly suggest a more constructive activity! Preparing a meal together, perhaps, or taking a walk.