HORSEMAN #4: ALZHEIMER’S—PREVENTION

As promised, this week we will look at some strategies for preventing Alzheimer’s and Other Neurodegenerative Diseases.? Let me be clear, the work and literature on preventing Alzheimer’s is relatively new.? However, Dr. Attia believes that today we know more about preventing it than we know about preventing cancer.? As he notes:

“With Alzheimer’s disease, we have a much larger preventive tool kit at our disposal, and much better diagnostic methods. ?It’s relatively easy to spot cognitive decline in its early stages, if we’re looking carefully. ?And we’re learning more about genetic factors, including those that at least partially offset high-risk genes like APOE e4.”

He also notes that:

“If there were ever a disease that called for a Medicine 3.0 approach—where prevention is not only important but our only option—Alzheimer’s disease and related neurodegenerative diseases are it.”

It is our only option because:

“Once dementia is diagnosed, it is extremely difficult to slow and maybe impossible to reverse (though we’re not certain of that). ?So we are forced to leave the familiar territory of the medicine that we know, with its promise of certainty, and embrace the Medicine 3.0 concepts of prevention and risk reduction.”

Dr. Attia starts by checking for a few things when he suspects Alzheimer’s:

• Level of Lp(a), the high-risk lipoprotein
• Apolipoprotein B (or apoB) concentration because every single lipoprotein that contributes to atherosclerosis carries this apoB protein signature.
• Apolipoprotein E (or APOE) genotype—the gene related to Alzheimer’s disease risk.? This gene, which is involved in cholesterol transport and processing, has three variants: e2, e3, and e4. ?Of these, e3 is the most common by far, but having one or two copies of the e4 variant seems to multiply one’s risk of developing Alzheimer’s disease by a factor of between two and twelve.

?You should also note that Alzheimer’s disease is almost twice as common in women than in men and that people of African descent are at an overall increased risk of developing Alzheimer’s disease.? Also, women have a greater age-adjusted risk of Alzheimer’s, as well as faster rates of disease progression overall, regardless of age and educational level.

He also advises that:

“… while female Alzheimer’s patients outnumber men by two to one, the reverse holds true for Lewy body dementia and Parkinson’s, both of which are twice as prevalent in men. ?Yet Parkinson’s also appears to progress more rapidly in women than in men, for reasons that are not clear.”

Based on his research, supported by controlled trials, Dr. Attia suggests that interventions around nutrition, physical activity, and cognitive training can help maintain cognitive function and prevent cognitive decline.

METABOLIC ISSUES

This first step recommended by Dr. Attia is to address any metabolic issues.? The first goal is to improve glucose metabolism, inflammation, and oxidative stress by:

• Switching to a Mediterranean-style diet: a way of eating that emphasizes minimally processed, plant-based foods, such as fruits, vegetables, nuts, beans, whole grains, olive oil, and fish, which also includes moderate amounts of dairy, poultry, eggs, and red wine, and limits red meat, added sugars, and processed foods.? It is rich in antioxidants, fibre, omega-3 fatty acids, and other nutrients.
• Cutting out added sugar, highly refined carbohydrates, and alcohol.
• Supplementation with the omega-3 fatty acid DHA, found in fish oil, may help maintain brain health, especially in APOE e4/e4 carriers.
• Diversifying the brain’s fuel source from only glucose to both glucose and ketones (compounds produced when your body breaks down fats for energy) since studies in Alzheimer’s patients find that while their brains become less able to utilize glucose, their ability to metabolize ketones to produce fuel does not decline.

EXERCISE

OUR MOST POWERFUL TOOL FOR PREVENTING COGNITIVE DECLINE IS EXERCISE

However, Dr. Attia believes that:

?The single most powerful item in our preventive tool kit is exercise, which has a two-pronged impact on Alzheimer’s disease risk: it helps maintain glucose homeostasis, and it improves the health of our vasculature.

He focuses on regular exercise, steady endurance exercises to improve mitochondrial efficiency and produces factors that directly target regions of the brain responsible for cognition and memory while helping to lower inflammation and oxidative stress.

The greater someone’s grip strength, the lower their risk of dementia!

He also believes that strength training is very important.

“A study looking at nearly half a million patients in the United Kingdom found that GRIP STRENGTH, an excellent proxy for overall strength, was strongly and inversely associated with the incidence of dementia.? People in the lowest quartile of grip strength (i.e., the weakest) had a 72% higher incidence of dementia, compared to those in the top quartile.? The authors found that this association held up even after adjusting for the usual confounders such as age, sex, socioeconomic status, diseases such as diabetes and cancer, smoking, and lifestyle factors such as sleep patterns, walking pace, and time spent watching TV.? And there appeared to be no upper limit or “plateau” to this relationship; the greater someone’s grip strength, the lower their risk of dementia.

SLEEP

While we are in deep sleep our brains are essentially “cleaning house,” sweeping away intracellular waste that can build up between our neurons.

Dr. Attia notes that:

“Sleep is also a very powerful tool against Alzheimer’s disease.? Sleep is when our brain heals itself; while we are in deep sleep our brains are essentially “cleaning house,” sweeping away intracellular waste that can build up between our neurons. ?Sleep disruptions and poor sleep are potential drivers of increased risk of dementia. ?If poor sleep is accompanied by high stress and elevated cortisol levels … that acts almost as a multiplier of risk, as it contributes to insulin resistance and damaging the hippocampus at the same time. ?Furthermore, hypercortisolemia (excess cortisol due to stress) impairs the release of melatonin, the hormone that normally signals to our brains that it is time to go to sleep (and that may also help prevent neuronal loss and cognitive impairment).”

So please ensure that you are getting enough sleep, on average 7 hours every night.

OTHER INTERVENTIONS

In addition to these Dr. Attia suggests that the following may reduce the risk of Alzheimer’s disease:

• BRUSHING AND FLOSSING ONE’S TEETH may help reduce systemic inflammation, and possibly risk.? I use interdental brushes as well which gets between the teeth.? There is a growing body of research linking oral health, particularly the state of one’s gum tissue, with overall health.
• Although he is not quite as confident that REGULAR SAUNA USE will reduce your risk of Alzheimer’s disease as he is that exercise will do so, he believes that at least four dry sauna sessions per week, of at least 20 minutes per session, at 82 degrees Celsius or hotter seems to be the sweet spot to reduce the risk of Alzheimer’s by about 65% (and the risk of heart disease and stroke by 50%).”
• Using B VITAMINS to lower homocysteine, while optimizing omega-3 fatty acids.
• Supplementing with VITAMIN D since higher vitamin D levels have been correlated with better memory in APOE e4/e4 patients.
• HORMONE REPLACEMENT THERAPY for women during the transition from perimenopause to menopause?

The longer we can go without developing dementia, the better our odds of living longer, and living in better health.? But until science comes up with more effective treatments, prevention is our only option.?

As Dr. Attia advises:

“Alzheimer’s disease is the last of the Horsemen that we must bypass on our way to becoming centenarians; it’s the last obstacle we face.? Typically, it is diagnosed later in life—and centenarians develop it much later in life, if at all.? The longer we can go without developing dementia, the better our odds of living longer, and living in better health.? But until science comes up with more effective treatments, prevention is our only option.? Therefore, we need to adopt a very early and comprehensive approach to preventing Alzheimer’s and other forms of neurodegenerative disease based on the following principles:

1. WHAT’S GOOD FOR THE HEART IS GOOD FOR THE BRAIN.? That is, vascular health (meaning low apoB, low inflammation, and low oxidative stress) is crucial to brain health.?
2. WHAT’S GOOD FOR THE LIVER (AND PANCREAS) IS GOOD FOR THE BRAIN.? Metabolic health is crucial to brain health.
3. TIME IS KEY. ?We need to think about prevention early, and the more the deck is stacked against you genetically, the harder you need to work and the sooner you need to start.? As with cardiovascular disease, we need to play a very long game.
4. OUR MOST POWERFUL TOOL FOR PREVENTING COGNITIVE DECLINE IS EXERCISE.? We’ve talked a lot about diet and metabolism, but exercise appears to act in multiple ways (vascular, metabolic) to preserve brain health; we’ll get into more detail in Part III, but exercise—lots of it—is a foundation of our Alzheimer’s-prevention program.”

Next week we will look at the five tactical domains that we can address to improve our health: exercise, diet or nutrition, sleep, emotional health, various drugs, supplements, and hormones.? Again, I strongly urge you to read Outlive and I hope that these excerpts will help convince you to do so.

Please accept my very best wishes for robust good health, peace, joy, and fulfilment in 2024 for you and your loved ones.? If you find this advice helpful, please share with your friends and colleagues.? As usual, I look forward to your questions and comments.? Be safe.? Take good care, and if you can, help someone in need.?

Cheers, Nigel

Nigel Romano, Senior Director, Moore Trinidad & Tobago, Chartered Accountants