Did you know an estimated 6.7 million Americans aged 65 and older are living with Alzheimer's disease? Alzheimer’s disease is the most common form of dementia, contributing to 60–70% of dementia cases. Being that aging is the primary risk factor for developing dementia, the Longevity By Design team has been eager to discuss dementia on the show.
In this episode, Dr. Blander and Ashley Reaver, MS, RD, CSSD interview Dr. Joseph Maroon. Dr. Maroon is a professor of Neurosurgery at the University of Pittsburgh Medical Center and longtime team neurosurgeon to the Pittsburgh Steelers.
Dr. Maroon shares a ton of interesting science related to Alzheimer's disease. He discusses findings from his recently published research on how oxidative stress is a primary cause of Alzheimer’s disease. He explains why sleep can help prevent Alzheimer’s, and gives other lifestyle advice for how to promote brain health as we age.
Dr. Maroon also talks about his experience in the NFL, how concussions impact the brain, new concussion-detection technology, why VO2max is a great biomarker of fitness, and how triathlons saved his life.
- Introduction: (0:00–2:50)
- Why Dr. Maroon became a physician: (2:50–6:20)
- Most common diseases seen by a neurosurgeon: (6:20-7:38)
- Most common neurological conditions associated with aging: (7:38-10:40)
- Lifestyle interventions to decrease oxidative stress: (10:40-12:13)
- Cigarettes and marijuana impact brain connectivity: (12:13–16:00)
- What is a concussion?: (16:00–19:00)
- NFL guidelines for concussions: (19:00–22:04)
- Dangers of returning to play too soon after a head injury: (22:04–23:30)
- Do football players age faster than the general public?: (23:30–29:16)
- New technology for detecting concussions in athletes: (29:16–32:10)
- Neuroprotective supplements: (32:10–34:00)
- Hyperbaric oxygen therapy for severe concussion treatment: (34:00–38:50)
- “Triathlons saved my life”: (38:50–45:55)
- Free radicals and exercise: (45:55–48:40)
- What happens to the brain when we sleep: (48:40–50:52)
- The ketogenic diet and cancer: (50:52–58:00)
- VO2 max and aging: (58:00–1:04:10)
- VO2 max is correlated with other biomarkers of health: (1:04:10–1:10:47)
- Top tip for healthspan: (1:10:48–end)
About Dr. Joseph Maroon
Joseph Maroon is a Professor of Neurosurgery at the University of Pittsburgh Medical Center (UPMC), a longtime team neurosurgeon to the Pittsburgh Steelers, and the Medical Director of World Wrestling Entertainment (WWE).
Dr. Maroon received his education at Indiana University, Georgetown, University of Vermont, and Oxford University, England. Academically, he has authored more than 300 scientific peer-reviewed papers, seven books, and 60 book chapters. He is Senior Vice President of the American Academy of Anti-aging Medicine.
Please note: These are the opinions of Dr. Joseph Maroon and not those of UPMC, the Pittsburgh Steelers, or the NFL. Dr. Maroon’s comments are for general educational purposes, and should not be used as a medical opinion. Any comments or treatments that are discussed by Dr. Maroon should be discussed with your healthcare provider before starting them.
Most common conditions treated by neurosurgery
The discussion with Dr. Maroon begins by detailing common conditions treated by neurosurgeons.
Traumatic brain and spinal cord injuries are the most frequently encountered surgeries in neurosurgery. Additionally, neurosurgeons often address a spectrum of spinal conditions, including quadriplegia, paraplegia, cervical spondylosis, spinal arthritis, and herniated discs.
Dr. Maroon notes that the field of pediatric neurosurgery focuses on congenital brain and spinal cord diseases. In essence, neurosurgeons have a diverse landscape of expertise.
How prevalent is dementia in the US population?
Aging is the primary risk factor for most neurological conditions, including dementia.  Alzheimer’s disease is the most common form of dementia, contributing to 60–70% of dementia cases.  Alzheimer’s disease is characterized by the loss of memory and other cognitive functions, as well as the buildup of certain proteins in the brain—like beta-amyloid and tau. As of 2023 data, an estimated 6.7 million Americans aged 65 and older are living with Alzheimer's disease. About 10% of people aged 65 and older have Alzheimer's, and almost two-thirds of Americans with Alzheimer's are women. 
Other forms of dementia include vascular dementia, dementia with Lewy bodies (abnormal deposits of protein inside nerve cells), and a group of diseases that contribute to frontotemporal dementia (degeneration of the frontal lobe of the brain).
Oxidative stress contributes to the development of Alzheimer’s disease
Oxidative stress occurs when there is an imbalance between the production of harmful molecules called free radicals and the body's ability to neutralize them with antioxidants. Excess free radicals can damage cells, proteins, and DNA. Oxidative stress contributes to the development of various chronic diseases—one of which is Alzheimer’s disease.
Dr. Maroon shares his perspective on the etiology of Alzheimer’s disease, sharing that the primary cause is still being debated amongst the scientific community. The most prominent hypotheses are a buildup of amyloid beta (Aβ) in the brain and excessive phosphorylation of tau protein. Oxidative stress is linked to amyloid beta and tau protein—however was thought to be a result of the abnormalities of Alzheimer’s rather than a causal factor.
Dr. Maroon shares his findings from new research published in September 2023, showing that oxidative stress might be the primary cause of Alzheimer’s. He argues that oxidative stress is the precursor that leads to subsequent amyloid beta deposits and abnormal tau protein in the brain. This oxidative stress theory suggests new ways to develop treatments, like using antioxidants to boost a brain molecule called glutathione which neutralizes free radicals. To read Dr. Maroon’s study, click here.
The brain is susceptible to oxidative stress which can lead to Alzheimer’s disease development
The brain is a high-energy organ. It relies on certain chemical reactions—called redox reactions—to generate this energy. This high energy demand makes the brain susceptible to oxidative stress because free radicals are a byproduct of redox reactions. Some of the free radicals generated in redox reactions can also be classified as reactive oxygen species (ROS) if they involve oxygen molecules in their structure. While some free radicals and ROS are necessary for normal cell function, excess of these molecules can harm cells by causing damage to lipids, proteins, DNA, and other important molecules. For this reason, oxidative stress is thought to be an early event in Alzheimer's disease development, not just a result of it. It can affect various processes in the brain, including signaling pathways and the production of harmful substances like amyloid beta.
Lifestyle interventions can help decrease oxidative stress
Reducing oxidative stress involves addressing five key lifestyle factors:
- Following a healthy dietary pattern can provide essential antioxidants to neutralize reactive oxygen species. Fruits and vegetables are particularly high in antioxidants.
- Exercise increases the production of endogenous antioxidants in the body, such as superoxide dismutase and glutathione peroxidase. Exercise also enhances the body's ability to repair oxidative damage to cells and tissues. 
- Avoiding environmental toxins, such as smoking, reduces oxidative stress in the body.
- Controlling mental and emotional stress is crucial, as stress is neurotoxic to the brain and contributes to oxidative stress.
- Getting adequate sleep supports the body's restorative processes.
Sleep is a preventative mechanism for Alzheimer’s disease
The glymphatic system is a waste removal system in the central nervous system that clears out soluble proteins and metabolites from the brain. The glymphatic system mainly works during sleep and isn't as active when we're awake. Interestingly, the glymphatic system was not discovered until 2013.  Scientists now believe that the biological need for sleep may reflect the brain's need to activate the glymphatic system to enable the elimination of neurotoxic waste products. 
One of the waste products the glymphatic system clears from the brain is beta-amyloid—a main substance associated with Alzheimer's disease. Dr. Maroon explains that when we sleep, our glymphatic system drains beta-amyloid, which prevents it from accumulating in the brain. Moreover, a growing body of evidence suggests that people who get more deep sleep are less likely to develop Alzheimer's. [6, 7]
What is a concussion?
A concussion is a mild traumatic brain injury (TBI) that occurs when a blow to the head or body causes the brain to briefly and temporarily malfunction. Concussions can result in a range of cognitive, physical, and emotional symptoms. Common symptoms of a concussion include fogginess, headache, mood swings, photophobia, and slow information processing. Dr. Maroon shares that only 10% of concussions result in unconsciousness.
Why is returning to play too early dangerous for someone who has a concussion?
In a healthy brain, blood vessels constrict and expand to maintain proper cerebral blood flow. When an individual has a concussion, their brain experiences a loss of its ability to regulate blood flow.
This lack of auto-regulation makes the brain more vulnerable to second impact syndrome. Second impact syndrome can occur when an individual sustains a second concussion or head injury before fully recovering from a previous concussion. The brain swells rapidly, and increased intracranial pressure can result in loss of consciousness, respiratory failure, and even death in a matter of minutes. While second impact syndrome is relatively rare, it is still dangerous for athletes to return to play without proper concussion recovery.
Hyperbaric oxygen therapy for severe concussions
Between 1.7 and 3.8 million sports and recreation-related concussions happen each year in the United States.  The majority of concussion cases resolve on their own when patients properly rest and allow the brain to recover. However, some severe concussions do not resolve on their own. Dr. Maroon has seen some of these patients who don't get better, and he refers them to hyperbaric oxygen therapy HBOT. “It’s amazing how the families react to the therapy. After 20 or 30 uses in HBOT, the parents come back and say, ‘You've given me my son back, you've given me my daughter back,’ ” he shares.
To learn more about hyperbaric oxygen therapy, listen to this episode with Dr. Shai Efrati.
What is VO2max?
VO2max, or maximal oxygen uptake, is a crucial measurement in assessing an individual's aerobic fitness. It quantifies the maximum amount of oxygen a person can use during exercise. This measurement is typically conducted using a stress test, where the individual wears a mask delivering oxygen, and the volume of oxygen consumption is measured over a specific period.
VO2max scores provide insights into an individual's respiratory and cardiovascular health. When you inhale oxygen, it travels through your bronchial tubes into your alveoli, which should ideally be healthy and efficient for oxygen exchange. From there, oxygen enters the microvascular circulation, binds to hemoglobin, and gets transported to the body's tissues, where it plays a crucial role in cellular energy production through processes like the Krebs cycle and ATP generation. VO2 max serves as a valuable indicator of one's overall fitness and aerobic capacity.
VO2max is correlated with aging
VO2max is highly correlated with age. As a person gets older, their VO2max will naturally decline. This decline results from multiple factors, including a decrease in the heart's ability to beat rapidly, less effective blood circulation in the muscles, and stiffening of the heart and arteries. Additionally, older muscles may not extract oxygen from the blood as efficiently with age, leading to a reduced ability to utilize oxygen during exercise. 
VO2max is also indicative of functional capacity. As VO2max decreases with age, so does an individual's ability to complete tasks of daily living. Dr. Maroon explains this is one of the reasons it’s crucial to measure VO2max and take action to maintain it with age—so that we are able to do the things we love for longer.
How to maintain VO2max with age
“In order to maintain VO2 max with age, we must stress the body,” says Dr. Maroon. He describes a graph in which, on one side, there is eustress—healthy stress—and on the other, there is distress—which leads to burnout. He says finding the middle ground where you are engaging in regular exercise and stressing the body is crucial for maintaining VO2max, as long as it doesn't get to a point where you dip into distress, and the body is not adequately recovering.
Dr. Maroon recommends High Intensity Interval Training (HIIT) to obtain optimal VO2max.
Top tip for healthspan
Dr. Maroon’s top tip for healthspan is to live a balanced life.
His recent book Square One outlines the four pillars to living a balanced life. “Picture a square with four equal sides. One side represents work, one family and social life, one spirituality, and the last one physical health,” he says. “You should be putting an equal amount of effort into these four areas of your life.”
Reflecting on his own experience, he says he reached a point of burnout in neurosurgery when his lines were dominated by work, leaving little room for family, spirituality, or physical well-being. The key takeaway here is the significance of achieving equilibrium among these four pillars of life.
Similar Longevity By Design episodes we think you would love:
- How Hyperbaric Oxygen Therapy Improves Cognition with Dr. Shai Efrati
- How Exercise Improves Healthspan with Dr. Rachele Pojednic
- Dr. Marco Altini—Heart Rate Variability and the Stress Response