Neurologist Faces His Alzheimer Diagnosis Determined to Lessen Stigma Surrounding the Disease

JAMA. Published online April 28, 2021. doi:10.1001/jama.2021.5333

Case reports are a mainstay of medical journal publishing, but a recent  in a dementia journal came with an unusual twist. The 66-year-old patient had received a  experimental monoclonal antibody for Alzheimer disease in an open-label extension of a clinical trial. Suddenly, his blood pressure soared, he had explosive headaches, and he could no longer read.

Lois Seed

Although the phenomenon was a known consequence of the treatment, the authors noted that clinical details hadn’t been widely reported. However, only careful readers would have noticed another unusual, if not unprecedented, characteristic of the article: One coauthor, neurologist Daniel Gibbs, MD, PhD, was the 66-year-old man with Alzheimer disease described in the report. Following a stint in the intensive care unit (ICU), Gibbs eventually recovered from the adverse effects, enabling him to coauthor the case report about his experience.

Now 69 years old—5 years out from his diagnosis—Gibbs, who retired from practice at the Oregon Health & Science University in Portland, wants to clear the air about Alzheimer disease. By avoiding discussions about the “A” word, he says, high-risk individuals could miss out on potential opportunities to delay a diagnosis or slow the progression of Alzheimer disease.

Gibbs recently spoke with JAMA about life with early-stage Alzheimer disease. The following is an edited version of that conversation.

JAMA:How is your health right now?

Dr Gibbs:My health is great. Actually, I've never felt better except for, you know, a few aches and pains after getting the second COVID virus vaccination.

JAMA:Are you still reading 2 books a week and attending neurology meetings?

Dr Gibbs:I still read as much as ever, and I still attend, virtually, the neurology grand rounds at the medical school. I get something out of it, but I can't remember the details anymore. It's more of a gestalt from the meeting, if you will, rather than being able to remember the fine details of new neurological things.

JAMA:What were the earliest clues that you might have Alzheimer disease?

Dr Gibbs:The first clue, although I didn't recognize it at the time, was when I started to lose my sense of smell about 15 years ago. About a year after that, I started to have these olfactory hallucinations that were like a combination of baking bread mixed with perfume. Quite pleasant, actually. They would last a couple of minutes to up to an hour, and there was no external olfactory stimulus. These were coming out of the blue. And they were just kind of a curiosity.

But after a year or so, as my sense of smell got worse and worse, I began to wonder if it might be a harbinger of Parkinson disease, because about 80% of people with Parkinson disease will have problems with their ability to smell many years before the onset of any of the typical Parkinson symptoms, like tremor or trouble walking. At that time, I didn't know there was an association with loss of smell and Alzheimer, but it turns out that virtually everybody with Alzheimer, when tested, has at least some degree of loss of sense of smell.

JAMA:And then you inadvertently learned that you had a higher risk of Alzheimer disease?

Dr Gibbs:It was 2012. My wife, who is an amateur genealogist, wanted us to get our DNA tested for genealogical purposes. At the time, it came with a lockbox you could unlock to see the results of 2 genes of neurological consequence. One was the , which is the most common cause for hereditary Parkinson disease. I thought it would be interesting to see if I'm more at risk for getting Parkinson disease.

The other gene was the , which is the most common genetic risk factor for Alzheimer disease. Alzheimer was not on my radar screen. Both of my parents died early from cancer, and I wasn't thinking of a family history of Alzheimer. I was shocked when I opened the lockbox and the LRRK2 gene wasn't there. But I had 2 copies of the APOE4 allele, which put me at substantial risk for developing Alzheimer.

JAMA:Why do you think early diagnosis is important?

Dr Gibbs:That's the banner I'm carrying right now. When I started practicing neurology in 1989, there was absolutely nothing that we could do for Alzheimer disease. There were no medications. It was before  (donepezil), and neurologists didn't even see patients with Alzheimer until they were quite advanced in their disease. At that time, when I saw patients with possible Alzheimer disease, my whole attitude was to avoid making a diagnosis until as late as possible, because there was just nothing that we could do to help them. At least I didn't think there was anything I could do to help them.

There are things that might be done early in the disease, even before there are cognitive symptoms, to slow the progression. There is some science to support a number of lifestyle modifications that could slow the progression of the disease. I've become a zealot about trying to move the conversation of Alzheimer from the late-stage demented person who is in a nursing home to the earliest stages before there are any cognitive symptoms, because that's when intervention could help.

JAMA:What would you say to people who would rather not know that they're likely to develop Alzheimer disease?

Dr Gibbs:Well, that's a choice. I was interviewed for an  in The New York Times a year ago or so, and the whole point of the article was: Is there a reason to make an early diagnosis of Alzheimer disease, and do people really want to know? It's a very controversial issue. I think nobody would object to having a definitive diagnosis through  PET (positron emission tomography) scans for people who are interested in being research subjects, because you need those to define whether the person has the neuropathology of Alzheimer disease before they go into a study to see if that drug, lifestyle change, or whatever can improve the outcome.

Testing is going to get easier and easier in the next few years because a number of blood tests look like they will be quite usable to detect both  and  in the brain and will be much less expensive than PET scans. So it’s going to become an issue of even more debate. What should people do if they're at risk? My answer to that would be, well, you don't need to be tested. I mean if you have significant risk factors—and the most significant risk factor is a family history of Alzheimer disease—then you need to start those lifestyle changes as early as possible. They're probably most effective when started in the 40s or 50s, and it's hard, because those are the busiest times of our lives.

But it’s really, really important to get that message if you have risk factors. Some of the things just are common sense, like good control of cardiovascular risk factors, hypertension, and diabetes. The diet and exercise aspect of it—the data are best for them—are not that hard to follow: Get adequate aerobic exercise and move to more of a plant-based Mediterranean-style diet.

JAMA:What lifestyle changes did you make when you began to suspect you might have Alzheimer disease?

Dr Gibbs:I retired in 2013 before I had any cognitive impairment, but I was worried it was imminent. I didn't want to be in the position where I had cognitive issues that suddenly impaired my ability to safely treat patients. I've had all the time in the world to make some of these modifications. There are data to support increasing the amount of aerobic exercise. There is not total agreement on how much is enough, but I've been aiming for 10 000 steps a day. I walk my dog in the hills. I'm not a runner, but running would be fine. Strength exercise doesn't seem to be quite as important. You've got to get the heart beating faster.

The evidence for diet is almost as good as for exercise. There just isn't as much of it. There are mixed studies about the Mediterranean diet, but they  a benefit in slowing progression or decreasing the risk of Alzheimer. There's one diet in particular that was developed several years ago called the , and it's a variation of the Mediterranean diet that leans a little more heavily on foods that are particularly high in flavanols, including berries and nuts.

There's pretty good evidence for staying socially active, and that can be a problem, particularly as the disease progresses, because there is an apathy that is almost universal in people with Alzheimer disease, even early on. It's just hard to get too enthusiastic about talking to other people or meeting people. I really have to make an effort to overcome that. Particularly with this year of pandemic isolation, it's been hard to get together with people, and I'm so happy that I've had my 2 vaccinations.

There's been a lot of information, some of it conflicting, about staying intellectually active, but the sorts of activities that seem to be most helpful are those involving new learning. You know, developing new synapses, new connections in the brain rather than just recall. People make the comment that doing a lot of crossword puzzles makes you good at doing crossword puzzles, but it may not help your memory much. While I'm having my lunch, my daily activity is to do the New York Times puzzle online. But I try to stretch my mental activity, particularly toward the end of the week when the crossword puzzles are tougher. If there's a new word, I look it up and try to learn something new about that rather than just plug in, you know, the same old words like on a Monday puzzle.

The last thing is sleep. It's a fairly new area of research, but it looks like sleep is really important. During sleep, there's this very interesting process that seems to go on around the brain where fluid is transferred through what's called the glymphatic circulation in the brain. There actually are these little vessels in the brain that carry fluid, and then fluid goes over the various lobes of the brain and kind of washes the brain. And when this research came out a few years ago, the newspapers and magazines almost always had the headline that said brainwashing, as a joke. This happens during non-REM, slow-wave sleep, that there is this flushing of fluid through the brain that gets rid of toxins including amyloid. It's recommended that you get at least 7½ hours of sleep. I get 8 hours of sleep every night unless I have problems with my sleep; in people with Alzheimer, sleep disturbances are quite common.

JAMA:It's been said that physicians make the worst patients. So, switching that up a bit, do you think your experience treating Alzheimer patients makes it more difficult for you to be a patient? After all, you know better than most what lies ahead.

Dr Gibbs:Being a neurologist, I'm able to study my own disease, and that has been a coping mechanism. I've been able to intellectualize the changes that are going on in my brain. You know, I've seen all my scans, and that provides a way of stepping back and having another view of myself that's not particularly frightening. I mean, for example, after my first amyloid PET scan back in 2015, it was done as part of a research study, and we all gathered around in this room at UC San Francisco in the Memory and Aging Center.

There were probably 20 or 30 people in the room—visiting fellows who were coming from other countries, residents, and other researchers. Dr Gil Rabinovici, who was the neurologist leading the study, asked me before the scans were shown, what would I think if the scan was normal? I said I didn't expect that to be the case, but if it were, then I'd have to look for another cause of my cognitive impairment at that time. Then we went to look at the scans, and there was amyloid, and I was almost immediately struck by the fact that there was amyloid in the olfactory parts of my brain. And I thought that was really cool, and everyone else did too, because that really hadn't been discussed in PET scans before. So, I was actually very much wearing the hat of a scientist at that time, which was quite therapeutic in helping me ignore the fact that I was due to have major problems in the future from Alzheimer disease.

JAMA:You've participated in several clinical trials. What motivated you to enroll in them?

Dr Gibbs:The main motivation was to do everything I could to get to a cure of Alzheimer sooner. I realized that there was very little chance that any of these studies would benefit me directly, but, you know, I wanted to do whatever I could to hurry along the discoveries of possible treatments and cures. I've been in 5 studies up to this point, and they've all been fun. I've really enjoyed them. I did have fairly serious side effects in 1 that put me in an ICU for a few days, but I fully recovered, and it was quite an experience.

JAMA:Are you hopeful that a treatment might become available that will give you more years than would be expected at this point?

Dr Gibbs:I'm always hopeful. Over the last 2 years, I've been very engaged intellectually in writing and reading research in the literature. I think that probably is slowing the progression of my disease. There is this concept of cognitive reserve. People who have more schooling tend to have less cognitive problems for the same degree of neuropathology in the brain.

But at a certain point, in their disease, they fall off the cliff. So, someone with high cognitive reserve does pretty well for a number of years, and then all of a sudden, they don't. And they can go into the later stages of Alzheimer disease very rapidly. Whereas somebody with less cognitive reserve has a more constant slope of their deterioration over many, many years.

I probably have a fair amount of cognitive reserve that I'm running off of right now. But I'm not doing this to help myself. I'm really trying to help my children's generation, because I think there's a real chance that we'll have something that will make a major impact on their disease.

JAMA:You mentioned that you attend grand rounds virtually. What advice do you give physicians about how to treat patients with mild cognitive impairment or dementia?

Dr Gibbs:I tell them I think it's important to identify and then manage Alzheimer disease in the earliest stages. Even though we don't have a drug that works really at any stage, there are hints that these drugs work best in the earliest stages. That's one of the exciting things about the , which looks like it is most effective before there's much tau apparent on the PET scan.

For people with more severe Alzheimer disease, the horses are out of the barn, but the earliest stage, probably even before there are significant cognitive impairments, looks like the sweet spot for management.

JAMA:You've written a  of your experience as someone who went from treating Alzheimer disease to living with it. What does the title, A Tattoo on My Brain, refer to?

Dr Gibbs:I actually came up with the title before I started writing the book. There are 2 aspects of the tattoo on my brain. In the study in which I ended up in the ICU, I had bleeding into the brain, little, tiny bleeds that weren't really of any consequence in terms of damage, but the remnants of that blood, the iron pigment called hemosiderin, are still in my brain. All the other things that happened during that episode, the areas of swelling in my brain, they've all resolved, but I still have this little tattoo on my brain. In fact, that hemosiderin is not all that different from the ink that is used in a tattoo parlor.

The other aspect of a tattoo is more figurative. I've not had a real tattoo, but to me, a tattoo is a coming out. It's an expression of who you are, and you hold it out for people to see or maybe you hide it someplace. For me, it represents kind of coming out of the closet, and that's something that I hope we can do in general for Alzheimer disease: Get rid of the stigma and the avoidance of conversations about it and accept it and deal with it openly.

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