“She’s not a neurologist, John. I get plenty of sleep. And that was in November. It’s been a couple of months, and it’s not getting any better. It’s getting worse.”

She was asking him to believe in a single conversation what she had denied for months. She started with an example he already knew.

“Remember I didn’t go to Chicago?”

“That could happen to me or anyone we know. We have insane schedules.”

“We’ve always had insane schedules, but I’ve never forgotten to get on a plane. It’s not like I just missed my flight, I completely forgot about the conference altogether, and I’d been preparing for it all day.”

He waited. There were giant secrets he didn’t know about.

“I forget words. I completely forgot the topic of the lecture I was supposed to give in the time it took to walk from my office to class, I can’t decipher the intention behind words I write in the morning on my to-do list by the middle of the afternoon.”

She could read his unconvinced mind. Overtired, stress, anxiety. Normal, normal, normal.

“I didn’t make the pudding on Christmas Eve because I couldn’t. I couldn’t remember a single step of the recipe. It was just gone, and I’ve made that dessert from memory every year since I was a kid.”

She presented a surprisingly solid case against herself. A jury of her peers might’ve heard enough. But John loved her.

“I was standing in front of Nini’s in Harvard Square and had absolutely no idea how to get home. I couldn’t figure out where I was.”

“When was this?”

“September.”

She broke his silence, but not his determination to defend the integrity of her mental health.

“That’s only some of it. I’m terrified to think about what I’m forgetting that I’m not even aware of.”

His expression shifted, as if he identified something potentially meaningful in the Rorschach-like smudges on one of his RNA films.

“Dan’s wife.” He said it more to himself than to her.

“What?” she asked.

Something cracked. She saw it. The possibility of it seeped in, diluting his conviction.

“I need to do some reading, and then I want to talk to your neurologist.”

Without looking at her, he got up and went straight into the study, leaving her alone on the couch, hugging her knees, feeling like she needed to throw up.

FEBRUARY 2004

Friday:

Take your morning medications

Department meeting, 9:00, room 545

Return emails

Teach Motivation & Emotion Class, 1:00, Science Center,

Auditorium B (“Homeostasis and Drives” lecture)

Genetic counselor appointment (John has info)

Take your evening medications

Stephanie Aaron was the genetic counselor affiliated with Mass General Hospital’s Memory Disorders Unit. She had shoulder-length black hair and arched eyebrows that suggested a curious openness. She greeted them with a warm smile.

“So, tell me why you’re here today,” Stephanie said.

“My wife was recently told she has Alzheimer’s disease, and we want her screened for the APP, PS1, and PS2 mutations.”

John had done his homework. He’d spent the last several weeks buried in literature on the molecular etiology of Alzheimer’s. Errant proteins born from any of these three mutated genes were the known villains for the early-onset cases.

“Alice, tell me, what are you hoping to learn from the testing?” Stephanie asked.

“Well, it seems like a reasonable way to try to confirm my diagnosis. Certainly more so than a brain biopsy or an autopsy.”

“Are you concerned that your diagnosis might be inaccurate?”

“We think it’s a real possibility,” said John.

“Okay, first, let’s walk through what a positive versus a negative mutation screen would mean for you. These mutations are fully penetrant. If you’re mutation positive for APP, PS1, or PS2, I would say that’s a solid confirmation of your diagnosis. Things get a bit tricky, though, if your results come back negative. We can’t really interpret with any certainty what that would mean. About fifty percent of people with early-onset Alzheimer’s don’t show a mutation in any of these three genes. This isn’t to say that they don’t actually have Alzheimer’s or that their disease isn’t genetically based, it’s just that we don’t yet know the gene in which their mutation resides.”

“Isn’t that number more like ten percent for someone her age?” asked John.

“The numbers are a bit more skewed for someone her age, that’s true. But if Alice’s screen comes back negative, we unfortunately can’t say for sure that she doesn’t have the disease. She may just happen to fall in the smaller percent of people that age with Alzheimer’s who have a mutation in a gene not yet identified.”

It was just as plausible, if not more so when coupled with Dr. Davis’s medical opinion. Alice knew that John understood this, but his interpretation fit the null hypothesis of “Alice does not have Alzheimer’s disease, our lives aren’t ruined,” whereas Stephanie’s did not.

“Alice, does this all make sense to you?” Stephanie asked.

Although the context made the question legitimate, Alice resented it and glimpsed the subtext of conversations in her future. Was she competent enough to understand what was being said? Was she too brain-damaged and confused to consent to this? She’d always been addressed with great respect. If her mental prowess became increasingly replaced with mental illness, what would replace that great respect? Pity? Condescension? Embarrassment?

“Yes,” said Alice.

“I also want to make it clear that if your screening comes back with a positive mutation, a genetic diagnosis isn’t going to change anything about your treatment or prognosis.”

“I understand.”

“Good. Let’s get some information on your family, then. Alice, are your parents living?”

“No. My mother died in a car accident when she was forty-one, and my father died last year at seventy-one of liver failure.”

“How were their memories while they were alive? Did either of them show signs of dementia or personality changes?”

“My mother was perfectly fine. My father was a lifelong alcoholic. He’d always been a calm man, but he got extremely volatile as he got older, and it became impossible to have a coherent conversation with him. I don’t think he recognized me at all for the last several years.”

“Was he ever brought in to see a neurologist?”

“No. I’d assumed it was the drinking.”

“When would you say these changes began?”

“Around his early fifties.”

“He was blind drunk, every day. He died of cirrhosis, not Alzheimer’s,” said John.