Physiology Friday #245: Fitness Protects against Neurodegenerative Diseases—Even in Those at the Greatest Risk
Dementia and Alzheimer’s are no match for a high VO2 max.
Greetings!
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"The mind and the body are like a pilot in his ship; although they are distinct, they are closely interconnected." — René Descartes
As I’ve outlined in my book on VO2 max, aerobic fitness isn’t just a number—it represents the coordinated ability of your heart, lungs, blood vessels, skeletal muscles, and mitochondria to transport oxygen and utilize it to produce energy—it’s a measure of how well the body (and its systems) work and synchronize.
Because the body and the brain are interconnected, it’s no surprise that when we exercise to elevate physical fitness, “cognitive fitness” follows in lockstep.
Having a high aerobic fitness necessitates better blood vessel function, and that means more blood flow to the brain. This increased blood flow delivers more oxygen and nutrients to brain cells, helping to maintain their health and function. Improved cerebral blood flow also helps clear away metabolic waste products that could contribute to neurodegeneration, including beta-amyloid proteins. Angiogenesis—an enhancement in the brain's vascular network—also improves its resilience and ability to compensate for age-related declines or damage. A richer vascular network ensures a more robust delivery of essential nutrients to brain tissues.
High cardiorespiratory fitness is also linked to better metabolic health, including improved insulin sensitivity. Insulin resistance and impaired glucose metabolism are risk factors for Alzheimer's disease, hence why the disease is sometimes referred to as ‘type 3 diabetes.’
These mechanisms certainly explain why having a higher VO2 max is one of the most potent predictors of how long you’ll live.
But could fitness also influence our risk for common diseases of aging like dementia and Alzheimer’s? These neurodegenerative conditions run rampant in modern society and there are very few (effective) ways to thwart them. Lifestyle appears to be the most robust intervention, with physical activity topping the list of remedies.
And while lifestyle factors play a crucial role in mitigating the risk of dementia, our genetic makeup also plays a part. One’s risk of certain diseases (i.e., dementia and Alzheimer’s) can be assessed using polygenic risk scores, which aggregate the effects of numerous genetic variants to estimate genetic predisposition. While we can’t control our genes (yet), we can control modifiable lifestyle factors that interact with genes to influence our disease risk.
This leads us to several important questions. Physical activity helps reduce neurodegenerative disease risk, but does physical fitness (e.g., VO2 max) show a similar protective effect? And if so, do these protective effects extend to people at a high genetic risk of dementia and Alzheimer’s disease?
These questions were addressed in a new study published in the British Medical Journal that included 61,214 adults aged between 39 and 70 (52% of whom were women).1
Each participant had their cardiorespiratory fitness measured—not using the conventional method of a maximal exercise test but with a 6-minute submaximal exercise test. Data from this test were then used to estimate their maximal aerobic capacity. The participants were split into three groups based on their fitness level:
Women
Low: 19.1–23.5
Moderate: 24.1–31.1
High: 31.9–41.6
Men
Low: 23.7–30.8
Moderate: 31.7–39.8
High: 41.6–50.9
Using this valid measure of cardiorespiratory fitness along with a polygenic risk score (PRS) for each participant, the researchers then studied the incidence of dementia and Alzheimer’s during a 12-year follow-up period. Cognitive assessments were performed once during the study, providing valuable additional information on the association of fitness with brain function and disease risk.
Their findings?
Cardiorespiratory fitness was dose-dependently associated with better global cognitive function and improved prospective memory, verbal/numeric memory, and processing speed. This was true when fitness was assessed on a continuous scale or when the low, moderate, and high fitness groups were compared and across participants with different levels of genetic risk. Moderate and high levels of fitness were related to better brain function across the board.
During the 12-year follow-up period, having higher cardiorespiratory fitness was associated with a lower risk of developing dementia and Alzheimer’s disease.
Specifically, compared to participants with a low cardiorespiratory fitness (estimated VO2 max of ~19–24 for women and ~23–31 for men), those with a high cardiorespiratory fitness (estimated VO2 max of ~32–42 for women and ~42–51 for men) had a 40% lower risk of dementia and a 38% lower risk for Alzheimer’s disease. A moderate fitness level was associated with a 24% and 25% lower risk of dementia and Alzheimer’s disease, respectively, but this association was not significant.
The onset of dementia and Alzheimer’s disease was delayed by 1.5–1.8 years in the high-fitness group. Moderate fitness, on the other hand, wasn’t associated with a delay in either condition.
Among the participants at a moderate or high genetic risk of dementia and Alzheimer’s, only high fitness was protective—mitigating the impact of dementia by 35% among these participants compared to those with low fitness and the same genetic risk. However, moderate fitness was not protective against dementia and Alzheimer’s in high-risk participants.
For the participants at a low genetic risk of neurodegenerative conditions, the benefits of high(er) fitness were even more pronounced, at least when compared to the people at high risk.
For example, the low-risk participants with low to moderate fitness levels experienced a 47% risk reduction for dementia, while those with low risk and high fitness experienced an incredible 65% risk mitigation. Win the genetic lottery and be fit—that seems to be the best combination for living disease-free.
Achieving high cardiorespiratory fitness might be one of the most effective strategies to reduce the risk of dementia.
The levels of fitness that are linked to a significant decrease in dementia risk are within reach for anyone. Generally speaking, the lower end of the fitness range in the “high fitness” groups in this study falls near the 50th percentile for VO2 max values in the general population. You do not have to have the fitness (or fortunate genetics) of an elite athlete to reap the benefits of fitness on brain health. However, given that only high levels of fitness were significantly associated with a lower disease risk in this study, it does appear that a VO2 max of 50 or above (if you’re a man) and 42 or above (if you’re a woman) represent a worthy target.
What I do find interesting is that if you have a family history of neurodegenerative conditions, making sure you work to increase your aerobic fitness is prudent—only a high fitness level mitigated disease risk in high-risk individuals. Offsetting a high genetic predisposition might require a bit more focus and attention to optimizing your cardiorespiratory fitness.
And the good news is that fitness is a modifiable risk factor. Of course, there’s some genetic component to VO2 max, but it’s highly amenable to training. The authors of the study even note that—although the data weren’t presented—frequent physical activity was associated with having a higher cardiorespiratory fitness.
In the next version of my book, I’m planning to devote an entire section to the relationship between VO2 max and brain health. This study is just one of many that have strengthened the relationship between brain health and fitness. It’s so apparent that what benefits the body benefits the mind.
Thanks for reading. See you next Friday.
~Brady~
The VO2 Max Essentials eBook is your comprehensive guide to aerobic fitness, how to improve it, and its importance for health, performance, and longevity. Get your copy today and use code SUBSTACK20 at checkout for a 20% discount. You can also grab the Kindle eBook, paperback, or hardcover version on Amazon.
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Having a healthy social life along with consistent training and healthy eating are key factors to prevent dementia. People don’t talk enough about this stuff, so thank you for this article!
Increasing your cardio fitness will improve your VO2 but so will lowering your weight since VO2 max is a function of body weight. It would be good to know which one matters more.
A google tells me VO2 is calculated as absolute without factoring in weight and normalized by weight so it might be important to clearly define which is used.