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I'm a Neurologist With Alzheimer's

— How knowledge helps the uncertainty

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This story is from the Anamnesis episode called Heal Thyself and starts at 15:52 in the podcast. It's from Daniel Gibbs, MD, PhD, a retired neurologist.

I'm a 70-year-old retired neurologist. I also have early-stage Alzheimer's disease. In retrospect, my first symptom of Alzheimer's probably occurred over 15 years ago when I started to lose my sense of smell. Within 3 or 4 years, I had no ability to detect odors, although I did have occasional stereotypic phantosmias that seemed to be connected to two odors.

Early on they consisted of a smell like baking bread, mixed with perfume. They would last a few minutes, up to an hour. My most recent one smelled a little bit more like Lemon Pledge. In the beginning, I was unaware of the association of anosmia with Alzheimer's, but it turns out that virtually all people living with Alzheimer's have some degree of olfactory impairment when tested, but most are not aware of it.

The Beginning

About 10 years ago, I started to have some very mild problems with memory. I had recently moved to a new office and I was never able to learn my new office's phone number or address. I also started to have trouble occasionally forgetting names of colleagues and even neighbors.

When I was attending on the wards, I couldn't find my way around the large academic hospital without guidance from my residents. I found that my fund of knowledge was still intact, I could hold forth on rounds, and give lectures. I had no trouble remembering the names and doses of medications. I really didn't worry very much. I thought that these mild memory issues were probably due to normal aging.

About this time, I accidentally learned that I have two copies of the APOE4 allele. My wife had suggested that we get our DNA tested for genealogical purposes. At that time a number of health-related genetic risk factors were listed, along with potential DNA relatives. There was also a locked box containing genes of neurological interest -- the LRRK2 gene for Parkinson's disease and APOE4, the most significant risk gene for Alzheimer's.

At that time, Alzheimer's disease was not on my radar. Both of my parents had died early from cancer. I opened the box to see if I might have a genetic risk for Parkinson's disease, because I knew that 80% of people with idiopathic Parkinson's have trouble with olfaction. Half of those with Parkinson's due to a mutation in the LRRK2 gene also have olfactory loss.

But I didn't have the LRRK2 mutation. But I was shocked to see my two copies of APOE4. That gave me a virtual certainty of having moderate to severe Alzheimer's by age 80 and a 50% chance by age 70.

I retired 8 years ago and I got involved with research studies as a volunteer subject 2 years later in 2015. At this time, I was still in the mild cognitive impairment range by testing.

The first study was a longitudinal mirror-imaging investigation of a then-new PET ligand for detecting abnormal tau protein. This study involved a high-resolution MRI, an amyloid PET scan, and the tau PET scan, as well as 2 days of cognitive testing.

I was able to look at all the scans. The amyloid test showed a moderate amount of beta-amyloid, particularly in the prefrontal cortex and precuneus, but also in the orbitofrontal cortex and piriform cortex -- both important centers for processing olfactory information.

The tau PET showed a small amount of tau in the mesial temporal lobes adjacent to the hippocampus, more on the left side. Interestingly, when the PET scans were repeated 3 years later, the tau had spread on both sides throughout the temporal lobes.

I have also been in the phase III clinical trial of aducanumab, the . I have mixed feelings about the recent FDA approval of aducanumab. During the trial, I had serious side effects, including widespread areas of brain edema, multiple microhemorrhages, and malignant hypertension -- all after just four doses of aducanumab. I had severe encephalopathy and headache, and I lost the ability to read. I was treated in an ICU for 2 days for blood pressure control and eventually needed high-dose IV steroids.

However, I fully recovered over the next few months and may possibly have benefited. I think these rare severe reactions have been minimized in the discussions around the controversial approval of aducanumab. It can be successfully treated, but should in my opinion be managed only by those with considerable experience.

It's Not That Bad

I am going to make a couple of points. Early-stage Alzheimer's is not that bad. I can't work as a physician anymore, but I'm still able to be intellectually active. I participate in virtual neurology meetings. I've given a couple of grand rounds. I have published a book about my experience of Alzheimer's. I read a couple of books a day. I volunteer for the Alzheimer's Association. I can still take care of myself, and I am reasonably happy.

It's likely that our first successes in the treatment of Alzheimer's will be won in this early stage of the disease before too many neurons have been destroyed. At first, success may be measured by simply prolonging the early stage, but I think that's a worthy goal.

However, I think that early diagnosis, even before symptoms readily appear, will be essential for more effective treatment, at least with the first generation of disease-altering medications.

Remember that amyloid plaque starts to form up to 20 years before the onset of cognitive impairment. Evidence of the tau-containing neurofibrillary tangles can be found at least several years before the beginning of cognitive decline. I think the pre-symptomatic stage of Alzheimer's disease will likely be where we see our first unequivocal treatment successes. Dare we say "dementia prevention?"

As we come to understand the disease better, it's possible that therapies will emerge that may mitigate the more advanced stages of disease as well. But we don't have to wait for these new drugs. There are important lifestyle modifications that can reduce the risk and slow the progression of Alzheimer's if started early.

The strongest data are for aerobic exercise. In all but the late stages of Alzheimer's, virtually all studies of exercise show a slowing of progression of Alzheimer's by up to 50%.

Getting Rid of the Uncertainty

Mediterranean-style diets, good control of cardiovascular risk factors such as hypertension, diabetes, and hyperlipidemia, staying mentally and socially active, and getting at least 7 hours of sleep nightly have all been shown to be beneficial in reducing risk and slowing disease progression, especially when started before the onset of cognitive decline.

People sometimes ask me what it's like to be a neurologist with Alzheimer's disease. Doesn't it terrify you, they want to know, to know so much about what's coming down the road?

Honestly, being able to examine my case from the outside looking in as a neurologist, has been an important coping mechanism. Oddly, being able to see my first amyloid and tau PET scans was a relief.

It took away the uncertainty of the diagnosis and allowed me to focus on doing everything possible to slow progression.

Other stories from the Heal Thyself "Researcher Turned COVID Long-Hauler" and "Prayer's Place in Treatment."

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