When chatting with Daniel Gibbs, MD, PhD, it's easy to forget that he has Alzheimer disease. For example, ask him whether he saw the northern lights on his recent trip to northern Norway, and he'll gently point out that it doesn't get dark there this time of year, so No.
But Gibbs, who turns 73 years old in July, does have Alzheimer disease, and in hindsight believes that his first symptom occurred back in 2006, when he began to lose his sense of smell. At the time, he chalked it up to normal aging.
Six years later, though, he took a DNA test to inform his wife's genealogy research. The results would be life-changing. Besides learning where his ancestors had lived and whether his face is likely to flush after drinking alcohol, Gibbs discovered he had 2 copies of the apolipoprotein E (APOE) ε4 allele. As a practicing neurologist, he knew that homozygosity for APOE4 meant he had a greatly increased risk of developing Alzheimer disease.
It has now been 8 years since Gibbs was diagnosed with the condition. Although he retired from the faculty at the Oregon Health & Science University (OHSU) a year after he received the diagnosis, Gibbs continues to teach about Alzheimer disease through his writing and speaking engagements.
He first spoke with JAMA Medical News 3 years ago, when his book about living with Alzheimer disease, A Tattoo on My Brain, was published. A short documentary based on it is now available for streaming, and he recently published a collection of essays entitled Dispatches From the Land of Alzheimer's.
His cognitive ability has continued to decline, he says, but at a very slow pace. As the documentary shows, Gibbs can't remember the 5 words his neurologist told him just a few minutes earlier, and he has had to relinquish balancing the family checkbook to his wife, Lois Seed, who sometimes retraces his steps around their house to make sure he remembered to turn off lights and water.
Gibbs recently spoke with JAMA Medical News about his health, misconceptions about Alzheimer disease, and what he is doing in the hope of staving off the condition. To help him prepare for the interview, which has been edited for clarity and length, some questions were provided in advance.
JAMA:How have you been since we last talked?
Dr Gibbs:Well, generally speaking, I really can't complain. My MoCA score yesterday at my biannual visit with my neurologist was 22 out of 30 [the average score for mild cognitive impairment], which is where it's been for the last couple of years, plus or minus a couple points.
JAMA:What is MoCA?
Dr Gibbs:MoCA stands for Montreal Cognitive Assessment, one of several popular screening tests. It was my favorite when I was giving it to people because it comes in 3 iterations. One of the problems with the screening tests is that after you've given them a couple of times to a patient, they learn the answers. And I can still tell you that the 3 things you have to remember for the MMSE [Mini-Mental State Examination] are apple, table, and penny, even though I haven't given or taken the MMSE forever. But with the MoCA, there are 3 totally separate versions of it.
My short-term memory is getting a little worse, but not alarmingly so. I misplace things a little more often, but in general, I'm getting by. I'm reading fewer books because my reading speed has slowed, and I have to go back to reread pages from before. But I still enjoy reading. A couple of days ago I finished Hampton Sides' new book, The Wide Wide Sea, about Captain James Cook's last voyage to Hawaiʻi. Today, I started some light reading, PG Wodehouse's Uneasy Money. His books are fun, easy to read, and short. Also, they have fewer characters. I'm not very good with fiction that has a lot of characters I have to remember. I love mysteries, but I don't do well with ones where there are 10 or 12 potential suspects. I've got to have only 4 main people to remember.
JAMA:To what do you attribute your fairly steady MoCA score?
Dr Gibbs:I think we have a misconception of Alzheimer disease being this rapidly progressive disorder. It used to be thought that 8 years after diagnosis you'd be dead. The reason that's just not true is that we've broadened our definition of Alzheimer disease and Alzheimer dementia. Researchers have found that the pathology in the brain of Alzheimer disease begins about 20 years before there's any cognitive impairment. The first noticeable stage, mild cognitive impairment, didn't even used to be called Alzheimer disease.
For me, finding out I had 2 copies of the APOE4 allele was eye-opening and made me focus on things I could do to slow the progression of the disease.
The intervention that has the most complete data is aerobic exercise. Running is great, but most of us, when we get to our 70s, may not be running anymore, so just walking.
I follow a variant of the Mediterranean diet called the MIND diet, which has some additional nuts and berries compared with the Mediterranean diet.
The next lifestyle change that is important, although the data are not quite as robust, is staying intellectually and socially active. And it seems like getting less than 7 and a half hours of sleep per night increases Alzheimer risk. Not a lot, but enough that it's worth paying attention to. And then there are all the cardiovascular risk factors, because what's bad for the heart is bad for the brain. People with APOE4 are much more likely to have cardiovascular disease. I found out I have hyperlipidemia back when I was in medical school. Now I'm on 2 medications and a plant-based diet to keep my lipids down.
Alcohol is a new controversy because the pendulum is swinging back toward recommending no alcohol. And I'll have to say that I do not follow that recommendation because having a glass of wine with dinner is, frankly, one of my few pleasures in life, so I'm going to continue that, recognizing that it might not be good for the progression of my Alzheimer.
JAMA:What do you think about the recent study that concluded that APOE4 homozygosity is a distinct genetic form of Alzheimer disease?
Dr Gibbs:It's not unreasonable. We've known for several years that having 2 copies of APOE4 is not good. On the other hand, plenty of people die of other things before they die of their Alzheimer. So, I guess my response to that is, well, look at me, I have 2 copies of APOE4, and I've had something that's symptomatic for Alzheimer for nearly 20 years.
JAMA:You mentioned the importance of staying intellectually and socially active. How do you do that?
Dr Gibbs:I enjoy speaking to groups. The groups that I most enjoy speaking to are the elderly, and they've got great questions. I've screened the film [A Tattoo on My Brain] 3 or 4 times now, with Q&As afterward. And sometimes the Q&A session has gone on for another hour, and I really, really get something out of that. It makes me feel like I'm making a difference. There's an event coming up at OHSU, where I did my residency and where I get my care now. They're going to do a screening as part of alumni day, and then I'm going to do a Q&A afterwards, with Lois, my wife, and with Joe Quinn, my neurologist.
I think I'm done writing books. Blog writing has become much more difficult. If I see a journal paper and don't make a note of it, I will never remember that I read that. I've got a few more blog posts percolating in the back of my mind and I need to get busy on that because, at the very least, I want to have 1, hopefully, 2 posts per month. I started out doing them every week, but I just don't have enough to say at this point.
JAMA:Based on your experience, what would you tell someone who's newly diagnosed with Alzheimer disease?
Dr Gibbs:To watch out for the apathy. I do not do well in group settings anymore. I can handle a family dinner, or even a birthday party for grandchildren, but I will not go to a cocktail party unless I have to, because I can't unhook the multiple conversations. It all blends together into cacophony. That's not really a form of apathy, but it's a reason to be antisocial. That may seem at odds with my just having said that I love talking to big groups. But only one of them is talking back to me at a time, and so that works out fine.
With apathy, part of it is being uncomfortable with social situations and part of it is just a change in the brain. It's not exactly the same, but it certainly is a close relative of depression. Some years ago, I started taking an antidepressant, and it's made quite a difference. I don't think I would stop it. Every once in a while I go through and see this ever-expanding number of medications I'm taking, and think, well, what could we dispense with? Most of these drugs I'm taking are for my hyperlipidemia. It would just be my luck that I would stop all my medications and have a hemiplegic aphasic stroke and not die.
JAMA:Do you miss anything that you've had to stop doing because of your illness?
Dr Gibbs:I don't really mourn for the things I don't have anymore, maybe because I don't remember them. I don't have intrusive memories of, boy, that used to be so great when we would do such and such. So, I think that's one of the good things of losing some memory. We don't have bacon very often, but when I see bacon in the frying pan, it reminds me of how that used to be my favorite smell, and now I can't smell it at all. But now it's a shrug of the shoulders; I'm not pining for it. Smell certainly enhances enjoyment of food, so all food pretty much tastes the same to me now. But I've just adjusted to that, and I put a lot of spice on my food because that activates the taste sensors, which can fool your brain into thinking that you're getting some smell. I think people who lose their sense of smell when it's sudden -- for example, with COVID-19 -- are much more troubled by it. Mine was a very gradual change.
JAMA:You've written that the best chance of success in stopping the progression of Alzheimer disease likely lies in treating people before they have symptoms. But you experienced amyloid-related imaging abnormalities, or ARIA, a potentially lethal adverse event, when enrolled in a phase 3 trial for aducanumab [Aduhelm]. Is it wise to treat asymptomatic individuals for a condition that might never manifest clinically?
Dr Gibbs:Everything new in medicine involves a balance between risk and benefit. We're facing that now with the Alzheimer drugs. The risk may be acceptable. But the drugs are still not very good at doing what we want. Sure, they get rid of amyloid, they're great at that, but that's not translating so far into more than a 35% slowing of the progression of Alzheimer. I think we need to explore the presymptomatic stages of Alzheimer with treatment, and we've got to assess what the risk is. And what I hope, and I think it's a reasonable guess, is that the side effects of these medications will be less onerous in presymptomatic disease.
For example, the thing that makes one susceptible to ARIA is having cerebral amyloid angiopathy [CAA], which is amyloid deposits in the smooth muscle of the small blood vessels in the brain. And it's certainly related to Alzheimer disease, but it's not exactly the same thing. And we don't know much about it, particularly in younger people, because almost all the data on CAA have been collected by autopsy.
I gave part of a grand rounds at the NIH [National Institutes of Health] a couple of months ago, where I presented my case of ARIA for about 20 minutes. And then [Harvard physician and scientist] Steve Greenberg spoke eloquently for the next 90 minutes about the relationship between ARIA and CAA and Alzheimer disease. I wish I could remember 10% of what he said, but again, my hope is that we'll find in these presymptomatic studies that [the drugs are] safer, and perhaps we'll have more success at blocking the subsequent progression. But it is a minefield of possible things that could happen.
JAMA:What about the concept of cognitive reserve? Hasn't that likely slowed the progression of your Alzheimer disease?
Dr Gibbs:Unfortunately, we can't do as much about cognitive reserve. That's something that I have because of my education and maybe my genes. Having a higher cognitive reserve is protective of the brain. However, there is a suggestion that once your cognitive reserve runs out, then you have a very rapid progression of disease and end up at the same place as somebody of low cognitive reserve. At least that's one model of how cognitive reserve may work. But right now, I'm just taking it a day at a time, and still enjoying life.