Thinking about Alzheimer’s
I have a marked family history of age-related neurodegenerative disease. Relatives in the two generations above me have suffered from Alzheimer’s and Lewie Body disease.
These conditions are heritable, so of course they concern me. I live my life profoundly between my ears — I enjoy learning and thinking and reading and writing and making things. The prospect of losing those abilities, and losing the memories that they have created, frightens me.
I know that we live on the cusp of all kinds of new discoveries. I have been rooting for neuroscientists who study ways to diagnose and treat those diseases. And real progress is happening! Experimental treatments have shown some promise in animal models, and all kinds of people are trying to figure out how to translate those results to human subjects.
I figure I have a couple of decades, based on family history, for a breakthrough in treating Alzheimer’s in people. Of course, even if that breakthrough happens, it might not help me. If treatments have to start in your 30s or 40s to preclude symptomatic onset in your 70s or 80s, then I’m already too late to the party.
So I have this grinding, low-grade worry that my grasp on the world might start to slip. To cope, I spend time reading articles about scientific advances in the field. I keep an eye out for people doing interesting work and connect with them when I can.
Early this year, that habit led me to Dr. Christin Glorioso, an MD/PhD with degrees from the University of Pittsburgh School of Medicine and MIT. She’s the founding CEO of NeuroAge Therapeutics.
NeuroAge is working on both diagnostics and treatments for Alzheimer’s. The company uses a battery of tests to assess your “brain age” — how your brain compares to the population generally, and to folks who are the same chronological age as you. Neurodegenerative disease is marked by shrinkage in well-defined regions of the brain, so fine-grained measure of those structures is a useful indicator of susceptibility to, and progress of, Alzheimer’s. And cognitive function, like the ability to recall names or memorize lists of numbers, also changes with age and illness, so cognitive tests are a good way to complement brain imagery for a more accurate measure of brain age.
Finally, the company uses blood analysis to track “biomarkers” related to Alzheimer’s — proteins in the blood whose levels correlate with disease presence and progress. They also look for specific mutations in the genome associated with the disease.
All of that is useful for diagnostic purposes. Are you suffering from Alzheimer’s now? How is your disease progressing over time? But of course the company is called NeuroAge Therapeutics, so aims also to identify and deliver treatments to manage or reverse the disease. This last is, so far, partially aspirational. There are no magical molecules yet. But there’s good evidence that sleep, social engagement, managing stress, a good diet and regular exercise can all be helpful. Depending on your susceptibility, NeuroAge is able to recommend lifestyle changes that can help delay onset and slow progress.
I don’t have any stake in the company and they’ve never paid me any money. When I explained my family history and interest to Dr. Glorioso, she offered to let me participate in the early testing of their commercial offering. Basically, I was one of the beta testers for their brain age measurement service. I didn’t have to pay anything for that.
I think I was a useful guinea pig. They identified issues with partners and providers during the process, and I gave them feedback on the web dashboard they built for customers.
That’s the limit of my pecuniary relationship with the company. I expect to become a paying customer after they launch their commercial service because I found the information I got useful and I want to track it over time. I never promised to provide any public endorsement. They may well use this post in their publicity, but I’m writing it because I found the whole experience interesting and helpful and I want to let others know about it.
So: Here’s what I learned as a NeuroAge beta tester.
Brain imaging
NeuroAge contracts with specialists that perform various tests for them. The first thing they did was put me in touch with a facility that has an magnetic-resonance imaging, or MRI, machine, so that they could take a 3D picture of my brain. That image got processed by another NeuroAge partner, brainkey.ai, to assess fine-grained structure.
I’ve had MRIs before to check for a shoulder injury and so on, so this wasn’t a brand-new experience for me. If you’ve ever done it, you know that getting an MRI is a moderate hassle. You can’t have any metal anywhere on or near you, because the machine uses magnetic fields to direct the beam that actually captures the image of your insides. You have to lie perfectly still for a pretty long time — mine took nearly an hour — and the machine is loud.
But all that is a small price to pay to get a high-resolution picture of your actual brain. Here’s mine:
It’s fun to play with. You can use the mouse to grab your brain and spin it around, so you can look at it from different angles:
We know a fair amount about brain structure and what different regions of the brain do. The brainkey.ai interface lets you look at some of those structures in your own brain, and tells you how they compare to other people your age. Here’s my frontal grey matter and hippocampus:
On the right side of those two images, you can see that brainkey.ai has compared my brain’s structures with those of other men of my age (sixty-two years old as I write this, but sixty-one when I was in the MRI scanner). The analysis combines all of those metrics, for each of the structures and for the whole brain, to produce an overall “brain age” based on the population at large.
So far, I’m feeling pretty good. My brain age, based solely on structure, is four years younger than my chronological age. (Friends tell me that makes sense — there was a period in my twenties when I wasn’t using it much). That suggests that age-related conditions like Alzheimer’s may show signs later for me than they would if my brain age were older.
I own a 3D printer, and I thought it would be fun to 3D print my brain as a sort of souvenir. I contacted the folks at brainkey.ai. They shared my brain image with me in a file format suitable for 3D printing. You can also just buy a 3D printed copy of your brain from the company, though! So now I’ve got a life-sized back-up brain in my nerd cave down in the basement.
Cognitive tests
The MRI gives you a structural assessment of your brain, but doesn’t say anything about how well it’s working. For that purpose, NeuroAge has a battery of cognitive tests that you can take on-line. You memorize word pairs and lists of numbers, associate names with faces, react to real-time events and so on. You can do the tests multiple times. The dashboard tracks your performance across the various tests and computes an age based on that measure.
The games are actually kind of fun. Here’s my dashboard for this part of the assessment.
Positive numbers are better, negative numbers are worse. These results don’t surprise me much. I’m good with words and numbers and terrible at names and faces. What I’ve long known about myself was borne out by the games.
My performance produced an assessment of my brain age based just on cognitive test performance:
Once again, I’m feeling good!
Blood biomarkers
The last piece of the NeuroAge assessment is to draw blood and test it for specific proteins associated with neurodegenerative diseases. There are more than forty biomarkers that the company looks for. In addition, they look for specific genes in your genome that are Alzheimer’s-linked.
You can think of these biomarkers sort of like cholesterol. Everyone has cholesterol in their blood. What matters is how much you have and what kinds. Likewise, everyone has these biomarker proteins. NeuroAge knows what levels are normal and how values outside the normal ranges correlate with neurodegenerative disease onset and progress.
I didn’t go to a lab for this test. During my beta testing of the service, the company contracted with a service that sent a trained assistant to draw my blood at my dining room table. Drive-by phlebotomy!
The company calculates a third NeuroAge based levels of these proteins in your blood. Overall, my results were good:
Research has shown that if your blood biomarker NeuroAge is five years younger than your chronological age, then you’re six times less likely to develop Parkinson’s or Alzheimer’s. My levels are what they’d expect in a 47-year-old, fifteen years younger than my chronological age.
This was one place where I got some bad news, though.
In addition to measuring biomarker levels, NeuroAge looks for genes specifically associated with Alzheimer’s and other diseases. My sequence includes the APOE4 allele of the APOE gene. That specific allele is the strongest risk factor gene for Alzheimer’s disease. Simply having the gene doesn’t mean that you’ll develop the disease, and knowing it’s there is an inducement to the kind of diet, exercise and lifestyle habits that reduce risk.
I wasn’t really surprised to learn that I have the APOE4 allele. Family history and heritability suggested strongly that my ancestors had the gene and passed it down. The certainty gives me motivation to embrace those lifestyle habits.
Overall results
The different tests that NeuroAge performs produce distinct NeuroAges based on cognitive games, blood biomarkers and the brain MRI. The company combines all of those to compute an overall NeuroAge:
I’m a 62-year-old man with a 51-year-old brain. That’s a great result. The biomarker indicators in particular are encouraging to me. But the genetic risk is absolutely there. That red bar at the bottom of my overall dashboard says I’m 17% “resilient” to Alzheimer’s. The number for the population at large is 50%. That’s due to my inheritance of APOE4.
What’s next?
NeuroAge Therapeutics plans to launch their commercial offering in early December, 2024. When they do, people will be able to buy the testing and assessment service through concierge medical clinics or directly from the company.
If you have a family history like mine, this assessment can help you better understand your risk of Alzheimer’s and how you’re doing so far. It can give you the incentive you need to manage your risk more thoughtfully.
My assessment, shown in the preceding sections, is a snapshot in time. I took all the tests this year, so I have a this-year picture of my status and risk. As we age, so do our brains, and my scores will change as that happens. As a result, I plan to sign up for the NeuroAge service and to re-run the assessment yearly or so. I’ll take guidance from Dr. Glorioso and her team on how often is often enough.
And I’ll continue to do what I can to manage my risk while I wait for researchers to come up with a cure, or at least an effective treatment. I hope they hurry up!
