In March 2008, we returned to the Johnnie Byrd Alzheimer’s Institute in Tampa to have Steve evaluated and to find out if there were any new studies on the horizon that he could participate in. At that time, there were no drug studies. However, we enrolled him in a study that included an annual evaluation with extensive memory testing, an assessment of activities of daily living, an evaluation for depression, and a physical examination, blood work, and an MRI scan—all part of an Alzheimer’s Disease Research Center study funded by the National Institutes of Health (NIH). While there, we were also approached about donating Steve’s brain, which would be beneficial from a scientific point of view, since they could correlate his clinical condition with the condition of his brain at the time of his death. Steve told them he wasn’t ready to give it to them yet, but agreed to think about it.
We left somewhat dismayed, since once again it looked like the future was grim and there was little hope that a drug would come along in time for Steve. The results of his MRI from the evaluation were even more depressing. His previous MRI several years earlier was normal, but this time he had considerable shrinkage of the brain in the areas (hippocampus and amygdala) associated with Alzheimer’s disease. These two areas were moderately affected on one side and severely affected on the other. He also had atrophy (shrinkage) of the cerebral cortex (portions of the brain related to higher functions), and the ventricles (areas that contain cerebrospinal fluid deep inside the brain) were enlarged, in this case replacing areas previously occupied by normal brain tissue that had now atrophied. Atrophy can occur in any organ of the body when areas of cells die due to lack of circulation, lack of energy to the cells, or lack of use.
It was clear that Steve was “going down the tubes,” as we often say in the medical world. He seemed less and less like the Steve I had married and more like a cross between a frail elderly man and a two-year-old, but without the energy. I had to constantly worry about where he was and what he was doing. If he disappeared from the room for too long, I looked for him, and more often than not, found him rummaging through his closet, the garage, or the drawers of his vanity, looking for what he did not know. This poem by Lois Walsh describes “trying to live with ambiguity” that accompanies Alzheimer’s.
ALZHEIMER’S DISEASE
I have found an unwanted guest inhabiting our home.
Oh, at first she was sly like a fox,
Showing up briefly but with slow determination.
Then little by little snatching away what was ours.
Now I find myself alone with you beside me And this uninvited guest.
You are with me, but I miss you, alive but not here.
Here but gone at the same time.
Such an ambiguous loss.
There is no closure like in death.
Each day I grieve over another loss and your former self.
Then feel guilty because it is not all about me.
I am letting go, hanging on,
And at the same time, trying to live with ambiguity.
A couple of months later I saw an ad in the paper for a clinical trial for the ICARA (Investigational Clinical Amyloid Research in Alzheimer’s) study of a new vaccine called bapineuzumab by Elan Pharmaceuticals and learned that the Johnnie Byrd Alzheimer’s Institute would be participating. I looked it up on www.clinicaltrials.gov (a registry of federally and privately supported clinical trials conducted in the United States and around the world) and found out that Steve should meet all the criteria. In contrast to the previous trials I had seen, this one did not have an exclusion criteria for a history of depression or use of antidepressants. On May 9, 2008, with hopeful anticipation, we made the hour drive to the University of South Florida for the screening.
We were met by a research assistant named Laura, and she made us feel very comfortable with the screening process. We were told all about the new medication, a vaccine that would be given intravenously at various intervals. A previous vaccine drug trial was discontinued because some of the subjects developed inflammation in the brain. This was a different type of vaccine that also removes beta-amyloid from the brain but by a different mechanism. Beta-amyloid is a protein normally made in the body whose function is not completely understood. When it accumulates in excess in brain tissue, it forms dense plaques, a hallmark of Alzheimer’s disease. These plaques appear to be toxic to nearby brain cells and to interfere with communication between brain cells. We also learned that about 40 percent of the people in the study would receive a placebo instead of the vaccine, which is typical of drug studies, so that researchers will be able to determine if the drug is effective and safe. We were given consent forms for the screening process. Steve needed to initial and date each page, but could not remember what he was supposed to do and where to sign from page to page, much less remember the date. He needed to be shown exactly what to do each time and talked through each entry.
Some basics were done to determine if he qualified, such as taking a medical history and checking a list of his medications. Steve was taken to another room for the Mini-Mental Status Exam, or MMSE, and when he returned, we received the shocking news that his score was quite a bit lower than on his previous visit two months earlier. He needed at least a score of 16 to qualify for the study, since they wanted to investigate the drug using people with mild to moderate Alzheimer’s. Steve only scored a 12, indicative of a more advanced stage of Alzheimer’s, and he was not accepted. This was a serious blow to both of us. The physician came to speak with us and advised us that we could schedule another visit to try for a better score, since he appeared to qualify in every other respect. We left quite devastated, back to square one. It seemed that this disease was going to take Steve from me after all.
A few days after I discovered the ICARA study, I read about another new drug trial, this one at the Comprehensive Neuro-Science Center (CNS) in St. Petersburg, Florida, for a drug semagacestat by Eli Lilly & Company. Once again, it appeared that Steve should qualify for the study. Semagacestat is an oral medication, a gamma-secretase inhibitor that is intended to decrease substances in the bloodstream that become beta-amyloid plaque in the brain. It was not known if this drug would actually decrease the beta-amyloid in the brain, but it would hopefully keep more from accumulating. One exciting aspect of this study was that, after a year, people who were given the placebo during the study would be switched to the actual medication. I had two days off coming up and had scheduled screenings for the ICARA study vaccine and the Eli Lilly drug on back-to-back days.
A few days before the discovery discussed in Chapter 4, Steve came out to the kitchen for breakfast in a fog, as usual, barely talking. I put a bowl of cereal at his place at the table, and he sat down and said, “Oh, I need a spoon.” He turned around to the buffet behind him, opened the drawer, looked and looked, and picked up a small knife. He turned around to the cereal and said once again, “Oh, I need a spoon.” He repeated this process four more times, finally coming back with a spoon on the final attempt. I offered to help him find it, but he said, “No, I need to do this.” It is so much easier to do these things for him, but whenever possible, painful as it is to watch, I try to respect his wishes and just let him try to figure it out, no matter how long it takes. That particular episode of “slow motion” stuck in my mind because just a few days later, life was about to change so that such episodes would become a thing of the past.