He smiled at her. It was a kind smile, and it dulled the edges of her apprehension.
“Okay, how about your memory? Are there any additional concerns or changes since the last time you were here?”
“Well, I’d say I’m having a harder time keeping track of my schedule. I have to refer to my BlackBerry and to-do lists all day long. And I hate talking on the phone now. If I can’t see the person I’m talking to, I have a really hard time understanding the entire conversation. I usually lose track of what the person is saying while I’m chasing down words in my head.”
“How about disorientation, any more episodes of feeling lost or confused?”
“No. Well, sometimes I get confused as to what time of day it is, even looking at my watch, but I eventually figure it out. I did go to my office once thinking it was morning and didn’t realize until I got back home that it was the middle of the night.”
“You did?” asked John. “When was this?”
“I don’t know, last month, I think.”
“Where was I?”
“Asleep.”
“Why am I just finding out about this now, Ali?”
“I don’t know, I forgot to tell you?”
She smiled, but it didn’t seem to change him. If anything, the edges of his apprehension got a little sharper.
“This type of confusion and night wandering is very common, and it’s likely to happen again. You might want to consider attaching a jingle bell to the front door or something that would wake John up if it opened in the middle of the night. And you should probably register with the Alzheimer’s Association’s Safe Return program. I think it’s something like forty dollars, and you wear an ID bracelet with a personal code on it.”
“I have ‘John’ programmed into my cell phone, and I carry it with me in this bag at all times.”
“Okay, that’s good, but what if the battery goes dead or John’s phone is off and you’re lost?”
“How about a piece of paper in my bag that has my name, John’s, our address and phone numbers?”
“That’ll work, as long as you always have it on you. You might forget to bring your bag. The bracelet, you wouldn’t have to think about.”
“It’s a good idea,” said John. “She’ll get one.”
“How are you doing with the medications, are you taking all of your doses?”
“Yes.”
“Any problems with side effects, nausea, dizziness?”
“No.”
“Aside from your night at the office, are you having any trouble sleeping?”
“No.”
“Are you still getting regular exercise?”
“Yes, I’m still running, about five miles, usually every day.”
“John, do you run?”
“No, I walk to work and home, that’s about it for me.”
“I think it’d be a good idea for you to take up running with her. There’s convincing data in animal models that suggest exercise alone can slow the accumulation of amyloid-beta and cognitive decline.”
“I’ve seen those studies,” said Alice.
“Right, so keep up with the running. But I’d like it if you could pair up with a running partner; that way we don’t have to worry about you getting lost or skipping your run because you forgot about it.”
“I’ll start running with her.”
John hated running. He played squash and tennis and an occasional game of golf, but he never ran. He could certainly outpace her mentally now, but physically, she was still miles ahead of him. She loved the idea of running with him but doubted that he could commit to it.
“How’s your mood been, are you feeling okay?”
“Generally good. I’m definitely frustrated a lot and exhausted from trying to keep up with everything. And I’m anxious about what lies ahead for us. But otherwise, I feel the same, better actually, in some ways, since telling John and the kids.”
“Have you told anyone at Harvard?”
“No, not yet.”
“Were you able to teach your classes and meet all your professional responsibilities this semester?”
“Yes, it took a lot more out of me than it did last semester, but yes.”
“Have you been traveling alone to meetings and lectures?”
“I’ve pretty much stopped. I canceled two university lectures, and I skipped a big conference in April, and I’m missing the one in France this month. I normally travel a lot in the summer, we both do, but this year we’re spending the whole summer at our house in Chatham. We’re heading down there next month.”
“Good, that sounds wonderful. Okay, it sounds like you’ll be well taken care of for the summer. I do think you should come up with a plan for the fall that involves telling the people at Harvard, maybe coming up with a way of transitioning out of your job that makes sense, and I think traveling alone should be out of the question at that point.”
She nodded. She dreaded September.
“There are some legal things to plan now as well, advance directives like power of attorney and a living will. Have you thought about whether or not you’d like to donate your brain to research?”
She had thought about it. She imagined her brain, bloodless, formalin-perfused, and Silly Putty–colored, sitting in the cupped hands of a medical student. The instructor would point to various sulci and gyri, indicating the locations of the somatosensory cortex, the auditory cortex, and the visual cortex. The smell of the ocean, the sounds of her children’s voices, John’s hands and face. Or she imagined it cut into thin, coronal slices, like a deli ham, and adhered to glass slides. In such a preparation, the enlarged ventricles would be striking. The empty spaces where she once resided.
“Yes, I’d like to.”
John cringed.
“Okay, I’ll have you fill out the paperwork before you leave. John, can I have that questionnaire you’re holding?”
What did he say about me in there? They would never talk about it.
“When did Alice tell you about her diagnosis?”
“Just after you told her.”
“Okay, how would you say she’s been doing since then?”
“Very well, I think. It’s true about the phone. She won’t answer it at all anymore. Either I get it or she lets the machine pick it up. She’s become glued to her BlackBerry, almost like a compulsion. She sometimes checks it every couple of minutes in the morning before she leaves the house. That’s a little difficult to watch.”
More and more, it seemed he couldn’t bear to look at her. When he did, it was with a clinical eye, like she was one of his lab rats.
“Anything else, anything that Alice may not have mentioned?”
“Nothing I can think of.”
“How’s her mood and personality, any changes you’ve noticed there?”
“No, she’s the same. A little defensive, maybe. And quieter, she doesn’t initiate conversation as much.”
“And how are you doing?”
“Me? I’m fine.”
“I have some information for you to take with you about our caregivers’ support group. Denise Daddario is the social worker here. You should make an appointment with her and just let her know what’s going on.”
“This is an appointment for me?”
“Yes.”
“Really, I don’t need one, I’m fine.”
“Okay, well, these resources are here if you find you come to need them. Now, I have some questions for Alice.”
“Actually, I want to talk about some additional therapies and clinical trials.”
“Okay, let’s do that, but first, let’s finish up her exam. Alice, what day of the week is it?”
“Monday.”
“And when were you born?”
“October eleventh, 1953.”
“Who is the vice president of the United States?”
“Dick Cheney.”
“Okay, now I’m going to tell you a name and address, and you’re going to repeat it back to me. Then, I??
?m going to ask you to repeat it again later. Ready? John Black, 42 West Street, Brighton.”
“The same as last time.”
“Yes, it is, very good. Can you repeat it back to me now?”
“John Black, 42 West Street, Brighton.”
John Black, 42 West Street, Brighton.
John never wears black, Lydia lives out west, Tom lives in Brighton, eight years ago I was forty-two.
John Black, 42 West Street, Brighton.
“Okay, can you count to twenty forwards and then backwards?”
She did.
“Now, I want you to raise the number of fingers on your left hand which corresponds to the place in the alphabet of the first letter of the city you’re in.”
She repeated what he said in her head and then made the peace sign with her left index and middle fingers.
“Good. Now, what is this thing called on my watch?”
“A clasp.”
“Okay, now write a sentence about today’s weather on this piece of paper.”
It is hazy, hot, and humid.
“On the other side of that paper, draw a clock showing the time as forty-five minutes past three.”
She drew a big circle and filled in the numbers starting at the top with twelve.
“Oops, I made the circle too big.”
She scribbled it out.
3:45
“No, not digital. I’m looking for an analog clock,” said Dr. Davis.
“Well, are you looking to see if I can draw or if I can still tell time? If you draw me a clock face, I can show you 3:45. I’ve never been any good at drawing.”
When Anna was three, she’d loved horses and used to beg Alice to draw pictures of them for her. Alice’s renditions had looked, at best, like postmodern dragon-dogs and always failed to satisfy even the wild and generously accepting imagination of her preschooler. No, Mom, not that, draw me a horse.
“I’m actually looking for both, Alice. Alzheimer’s affects the parietal lobes pretty early on, and that’s where we keep our internal representations of extrapersonal space. John, this is why I want you to go running with her.”
John nodded. They were ganging up on her.
“John, you know I can’t draw.”
“Alice, it’s a clock, not a horse.”
Stunned that he didn’t defend her, she glared at him and raised her eyebrows, giving him a second chance to verify her perfectly valid position. He just stared back at her and spun his ring.
“If you draw me a clock, I’ll show you three forty-five.”
Dr. Davis drew a clock face on a new sheet of paper, and Alice drew the hands pointing to the correct time.
“Okay, now I’d like you to tell me that name and address I asked you to remember earlier.”
“John Black, something West Street, Brighton.”
“Okay, was it forty-two, forty-four, forty-six, or forty-eight?”
“Forty-eight.”
Dr. Davis wrote something lengthy on the piece of paper with the clock.
“John, please stop shaking my chair.”
“Okay, now we can talk about clinical trial options. There are several ongoing studies here and at the Brigham. The one I like the most for you starts enrolling patients this month. It’s a phase three study, and it’s a drug called Amylix. It appears to bind soluble amyloid-beta and prevent its aggregation, so unlike the drugs you’re on now, there’s the hope that this could prevent the disease from progressing further. The phase two study was very encouraging. It was well tolerated, and after a year on the medication, the patients’ cognitive functioning seemed to have stopped declining or even improved.”
“I assume it’s placebo-controlled?” asked John.
“Yes, it’s double-blind and randomized to placebo or one of two doses.”
So I might get only sugar pills. She suspected that amyloid-beta didn’t give a shit about placebo effects or the power of wishful thinking.
“What do you think of the secretase inhibitors?” asked John.
John liked these best. Secretases were the naturally occurring enzymes that released normal, unharmful levels of amyloid-beta. The mutation in Alice’s presenilin-1 secretase rendered it insensitive to proper regulation, and it produced too much amyloid-beta. Too much was harmful. Like turning on a faucet that couldn’t be turned off, her sink was rapidly overflowing.
“Right now, the secretase inhibitors are either too toxic for clinical use or—”
“What about Flurizan?”
Flurizan was an anti-inflammatory drug like Advil. Myriad Pharmaceuticals claimed it decreased the production of amyloid-beta 42. Less water into the sink.
“Yes, there’s a lot of attention on that one. There’s an ongoing phase two study, but only in Canada and the UK.”
“How do you feel about Alice taking flurbiprofen?”
“We don’t have the data yet to say whether or not it’s effective for treating Alzheimer’s. If she decides not to enroll in a clinical trial, I would say that it probably couldn’t hurt. But if she wants to be in a study, flurbiprofen would be considered an investigational treatment for Alzheimer’s, and taking it would exclude her from the study.”
“All right, what about Elan’s monoclonal antibody?” asked John.
“I like it, but it’s only in phase one and enrollment is currently closed. Assuming it passes safety, they won’t likely initiate phase two until spring of next year at the earliest, and I’d like to get Alice in a trial sooner if we can.”
“Have you ever put anyone on IVIg therapy?” asked John.
John also liked the idea of this one. Derived from donated blood plasma, intravenous immunoglobulin was already approved safe and effective for treating primary immune deficiencies and a number of autoimmune neuromuscular disorders. It would be expensive and not reimbursable by their insurance company because of its off-label use but worth any price if it worked.
“I’ve never had a patient go on it. I’m not against it, but we don’t know the proper dosing, and it’s a very untargeted and crude method. I wouldn’t expect its effects to be anything more than modest.”
“We’ll take modest,” said John.
“Okay, but you need to understand what you’d be trading off. If you decide to go ahead with IVIg therapy, Alice wouldn’t be eligible for any of these clinical trials with treatments that are potentially more specific and disease modifying.”
“But she’d be guaranteed not to be in a placebo group.”
“That’s true. There are risks with either decision.”
“Would I have to go off the Aricept and Namenda to participate in the clinical trial?”
“No, you’d keep taking them.”
“Could I go on estrogen replacement therapy?”
“Yes. There’s enough anecdotal evidence to suggest that it’s at least to some degree protective, so I’d be willing to write you a prescription for CombiPatch. But again, it would be considered an investigational drug, and you wouldn’t be able to participate in the Amylix trial.”
“How long would I be in the trial for?”
“It’s a fifteen-month study.”
“What’s your wife’s name?” asked Alice.
“Lucy.”
“What would you want Lucy to do if she had this?”
“I’d want her to enroll in the Amylix trial.”
“So Amylix is the only option you can recommend?” asked John.
“Yes.”
“I think we should do the IVIg along with flurbiprofen and the CombiPatch,” said John.
The room became still and quiet. An enormous amount of information had just been passed back and forth. Alice pressed her fingers on her eyes and tried to think analytically about her treatment options. She did her best to set up columns and rows in her head to compare the drugs, but the imaginary chart didn’t help, and she tossed it into the imaginary trash. She thought conceptually instead and arrived at a single, crisp image that made sense. A shotgun or a single b
ullet.
“You don’t need to make a decision on this today. You can go home and think about it some more and get back to me.”
No, she didn’t need to think about it any further. She was a scientist. She knew how to risk everything with no guarantees in search of the unknown truth. As she’d done so many times over the years with her own research, she chose the bullet.
“I want to do the trial.”
“Ali, I think you should trust me here,” said John.
“I can still draw my own conclusions, John. I want to do the trial.”
“Okay, I’ll get you the forms to sign.”
(Interior of Doctor’s Office. The neurologist left the room. The husband spun his ring. The woman hoped for a cure.)
JULY 2004
John? John? Are you home?”
She was sure that he wasn’t, but being sure of anything these days was tattered with too many holes to contain the meaning that it used to. He had left to go somewhere, but she couldn’t remember when he left or where he was going. Did he run to the store for milk or coffee? Did he go out to rent a movie? If either were the case, he’d be back any minute. Or did he drive back up to Cambridge, in which case he’d be gone for at least several hours and possibly the night? Or did he decide, at last, that he couldn’t face what lay ahead for them, and he just plain left, never to return? No, he wouldn’t do that. She was sure of it.
Their Chatham Cape, built in 1990, felt bigger, more open, and less compartmentalized than their house in Cambridge. She walked into the kitchen. It was nothing like their kitchen at home. The bleached effect of the white painted walls and cabinets, white appliances, white barstools, and white tile floor was broken up only slightly by the soapstone countertops and splashes of cobalt blue in various white ceramic and clear glass containers. It looked like a coloring book page that had been only tentatively filled in with a single blue crayon.
The two plates and used paper napkins on the island counter displayed evidence of salad and a spaghetti and red sauce dinner. One of the glasses still held a gulp of white wine. With the detached curiosity of a forensic scientist, she picked up the glass and tested the temperature of the wine against her lips. It was still a little cold. She felt full. She looked at the time. It was just after nine o’clock.