In a 1996 letter to their children, Joanna Moore, a retired teacher who thought it important to record their family history, described the disease's progress. Her husband could still drive well, with her help as navigator, but could not do simple arithmetic. He still enjoyed reading and going to movies. He had trouble with time and was unable to follow through on plans. In conversation, he failed at finding even ordinary words. He could no longer compare two thoughts or visualize something.

"He wants to open his own mail, answer the phone, continue the routines he has followed for many years," Joanna wrote. "Bob does the dishes and usually does the laundry. I'm grateful. He washes the kitchen floor and vacuums the rugs. He locks the house at night and turns out the lights and pulls the blinds... .

"Normal life consists of a hundred small responsibilities, and I hope we can continue our normal life for a long, long time."

Physical signs of Alzheimer's

From autopsies of people who died in different stages of Alzheimer's, scientists know that its first physical signs usually appear in the medial temporal lobes. These reception areas for sensory input near the temples help produce memories.

Particularly hard hit is the hippocampus, a three-inch-long portion shaped like a sea horse that records new memories. Trojanowski calls it "the epicenter of disaster."

From there, the protein hallmarks of Alzheimer's - plaques, or clumps of protein fragments that form outside nerve cells, and tangles, twisted strands of a different protein that form inside cells - move up, forward and back through the brain. Scientists do not know how or why.

The amygdala, which is beside the hippocampus, is an early casualty. Damage there may cause emotional changes. As the disease moves along the sides of the brain, it affects language skills. In the frontal lobe near the top of the brain, executive function - the ability to make rational decisions - is disrupted. As this section erodes, people find it harder to plan and understand time. At roughly the same time, the parietal lobe, which helps people orient themselves in space, is damaged, making it harder for people to find their way around.

The path and its connection to behavior grow hazier after that because the disease destroys not only brain cells but also the connections between them, isolating regions that may still look fine. "It just sits there and rips the brain apart," Trojanowski said.

There's no clear physical explanation for the incessant walking, agitation and violent behavior that some patients exhibit.

Some agitation likely stems from the fear that constant surprises breed. As memories fade, people do not know how to react.

"Their frame of reference is disappearing," said Christopher Clark, director of Penn's Memory Disorders Clinic and Bob Moore's doctor after his diagnosis. "You know who you are based on your past. You use that to project what's going to happen in the future. As your past disappears, your ability to project into the future essentially disappears, too."

Ultimately, Alzheimer's destroys enough of the brain that patients can't walk. By the time they can't swallow, the brain may be so far gone that it's hard to pinpoint why.

"At one point," Trojanowski said, "this is a train wreck, and there's so much damage it's hard to say what killed the passengers."

Increased dependency and anger

As the '90s waned, Bob Moore became increasingly dependent on Joanna and increasingly angry.

For one who had taken such pride in his verbal abilities, being incapable of finding the right words was humiliating, Alison Moore said. Unable to marshal an argument, he'd exclaim: "Damn it! I am... I am..." Finally, he'd remember. "I'm a man," he'd say emphatically.

As the dementia worsened, his frustration grew. "I am...," he'd stammer. "I am..."

The sentence would hang unfinished, a reminder of what he'd lost.

By 2000, an exhausted Joanna Moore was keeping a journal. Pages and pages are devoted to the vagaries of her husband's behavior. Like the mother of a difficult toddler, she focused on his bowels and his tantrums, and was grateful for the good days when he was pliable and she could get a full night's sleep.