Few, if any, concepts in longevity medicine are more powerful than biological age. As I wrote in my previous blog post, if we can identify a valid biomarker of aging for a particular organ system, we can track it over time, uncovering vulnerabilities that need to be shored up before disease strikes and gauging the effectiveness of any lifestyle changes or supplements/drugs.
OK, you may ask, what about the brain? Adequately measuring the changes that occur in the brain over time is, to put it mildly, tough. But there’s been exciting progress on that front. First, let me set the table.
In some respects, brain aging is a straight-forward proposition. Every year that we push beyond our late twenties, we’re losing neurons, as well as the neuronal structures (“dendritic spines”) that allow us to create and maintain the connections between neurons – synapses – that make thinking and reacting and remembering possible. By late middle age, most of us are aware that we’re more liable to misplace the car keys or struggle to remember the name of that actor whose films we know so well. In other words, “normal” brain aging. But for about 10% of us, by the time we’ve reached Medicare age and beyond, the neuronal and synaptic die-off will rise above a certain functional threshold and we’ll be saddled with dementia, Alzheimer’s disease being the most common diagnosis.
This is the main reason why some people have mixed feelings about living longer – why keep your body in shape if this is what your brain has in store for you?
But what if we had reliable and actionable biomarkers of brain aging? If you found out that your brain was aging slower than your same-age peers, that would be a great relief. If it was aging faster, that would be a call to action to do everything in your power to get regular exercise, hew to a high-fiber, lower-carb, whole-and-plant food-oriented diet, and manage your sleep and stress wisely. Because we do know that the best way to take care of the brain is to take care of the rest of your body. (Dean Ornish, the well-known preventive health researcher, just published a study showing that a small group of Alzheimer patients following his diet/exercise/stress management/support group protocol slowed the progression of their dementia by 18%, not a mind-blowing number, but not nothing either.)
The big problem with the brain aging field is that for the past three decades it’s been mired in the “amyloid hypothesis.” This holds that Alzheimer’s is caused by the progressive build-up in the brain of clumps of toxic protein – amyloid plaque. Billions of dollars of research have yielded, to date, a handful of amyloid-lowering drugs that are relatively ineffective or freighted with serious side-effects, or both, and almost no progress on other biomarkers of brain aging that might steer us to safer and more efficacious therapies. The research indicates that amyloid likely is a risk factor for Alzheimer’s, as cholesterol is for atherosclerosis, but it's far, far from the whole story.
Into the void stepped M.I.T.-trained neuroscientist Dr. Christin Glorioso whose Global Longevity Summit I recently presented at. NeuroAge Therapeutics, the Bay Area start-up she co-founded and leads, has developed a package of biomarker tests, measuring brain aging, and consequently Alzheimer’s risk, that’s available through a small but growing number of longevity clinics, including Raffaele Medical, as well as direct-to-consumer.
The company takes a “multi-omics” approach. To measure cognitive performance, it uses a battery of standard and well-studied computer tests (or “games”), very similar to what I offer in my practice’s biomarker testing to assess CognoAge. Then, using a new technology developed by Glorioso and her team, it identifies levels of messenger RNA (which “translates” DNA instructions into the actual production of proteins) in the blood plasma that predict brain aging. To which is added “whole genome DNA testing,” to screen for known biomarkers of neurodegenerative disease. Finally, there is an MRI test, which conventional medicine typically reserves for patients showing dementia symptoms. It shows brain volume shrinkage, more-than-average shrinkage for one’s age being suggestive of increased Alzheimer’s risk or Alzheimer’s itself. The NeuroAge version is ultra high-tech, the images interpreted by an AI-driven algorithm to give a more precise read-out, in essence, the brain version of the Cleerly CT angiogram which I’ve written about.
The end result is a brain “age” which NeuroAge derives from weighting all this data according to an AI-driven “Superpredictor,” trained on data derived from, to date, half-a-million brains. Glorioso calculates that people who score a brain age five years younger than their chronological age have a six-fold less chance of developing Alzheimer’s than the average person, more than enough protection to override the increased risk they face if they have a single copy of the much-feared APOE4 gene variant.
What’s the take-away here? To have a window onto your brain’s aging process is to be given more time to reduce, as much as possible, any risks that may reveal themselves. Especially if NeuroAge’s research into brain biomarkers yields better targets for Alzheimer’s drugs (the company is in the hunt), old age becomes a less daunting proposition.
Ornish, D., Madison, C., Kivipelto, M. et al. Effects of intensive lifestyle changes on the progression of mild cognitive impairment or early dementia due to Alzheimer’s disease: a randomized, controlled clinical trial. Alz Res Therapy 16, 122 (2024). https://doi.org/10.1186/s13195-024-01482-z
Christin A Glorioso et al. Rate of brain aging and APOE ε4 are synergistic risk factors for Alzheimer's disease. Life Sci Alliance. 2019 May 27;2(3):e201900303. doi: 10.26508/lsa.201900303.
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