A poll from the Marist Center for Public Opinion shows that Alzheimer’s disease (AD) is the most feared health condition, outranking cancer, heart disease and other killers. It’s not hard to understand why. In Alzheimer’s (and other forms of dementia), you don’t just lose your health. You lose your self, as memory, mental clarity, and language fade away.

One in nine Americans ages 65 and older—6.7 million people—have Alzheimer’s disease. By the age of 85, one in three have it. And many die from it, with deaths from AD more than doubling between 2009 and 2019. Alzheimer’s disease now kills more people annually than breast cancer and prostate cancer combined.

But these tragic statistics mask a much more positive reality. After decades of diligent research, neuroscientists, neurologists, and other brain experts have begun to understand the cause and progression of Alzheimer’s disease, and they are finding new ways to predict, detect, and treat it. Those breakthroughs include science-­supported lifestyle changes that can prevent, slow, stop, or even reverse the brain-based progression of AD.

The proven cause of AD

Alzheimer’s disease is triggered by an abnormal accumulation of amyloid beta protein in the brain, the infamous “plaques” that collect between neurons (brain cells). Think of amyloid as the match that starts the fire of Alzheimer’s disease.

In turn, amyloid plaques trigger the abnormal accumulation of a protein called tau inside the neuron. Tau grows in sticky threads that become tangles. It quickly spreads from cell to cell, causing widespread destruction and death of neurons. Think of the tangles as the brushfire started by the match.

With increasing cell death, there is neuroinflammation—the same type of chronic, low-grade inflammation that drives heart disease and diabetes. Neuroinflammation causes more cell death. It also destroys synapses, a microscopic gap between neurons where they connect and communicate. With the death of neurons and the loss of synapses, the symptoms of Alzheimer’s disease begin—sometimes 20, 30, and even 40 years after the initial appearance of amyloid.

Early prediction

The first step in preventing or treating Alzheimer’s disease is early prediction. Genetic testing can play a role.

One to two percent of people with AD have early-onset Alzheimer’s disease, which typically starts in a person’s 40s or 50s, but it can start as early as the 20s. These people have a mutation of the beta-amyloid precursor protein, which is cleaved twice to release the amyloid beta protein, driving up toxic beta amyloid deposition in the brain. Or they have a mutation of a presenilin gene, which produces gamma-secretase, an enzyme that helps control the production of the beta amyloid protein. If you have a family history of early-onset Alzheimer’s, you are at greater risk for the same form of AD.

If you have a family history of late-onset AD—which typically begins in the mid-60s—you also may be at greater risk. There are approximately 100 genes that can drive susceptibility to the disease. The most well-known is APOE e4, which is found in 25 percent of people with late-onset Alzheimer’s disease. If one parent has APOE e4, you have a three- to four-fold higher risk of the disease. If both parents have APOE e4, you have a 25-fold higher risk. APOE controls the clearance of beta-amyloid.

If you have a family history of either early-onset or late-onset Alzheimer’s disease, consider genetic testing to better determine your risk. The more informed you are about risk, the more accurately you can evaluate and decide on detection and treatment.

Early detection

If you and your doctor determine that you’re at a higher-than-average risk for Alzheimer’s disease (or even if you haven’t had genetic testing, but you and your doctor want to determine if you have amyloid), the best two tests for early detection are a blood test or a PET scan for amyloid in the brain. The best blood tests are the PrecivityAD and PrecivityAD2 tests from C2N. These tests have been compared to a PET scan, and research shows they are as accurate as a PET scan in detecting amyloid in the brain.

Alzheimer’s disease pathology begins to develop up to three decades before symptoms of cognitive decline. So, the best time to take these tests is well before you develop cognitive decline or dementia—because at that point, controlling or reversing the disease is much more difficult.

Early intervention

We are on the cusp of a new era of effective Alzheimer’s disease treatments that target amyloid. The drug lecanemab (Leqembi) targets and reduces amyloid. In an 18-month clinical trial involving 1,800 people with the earliest, mildest symptoms of Alzheimer’s disease, Leqembi slowed and reversed symptoms. However, the drug has significant safety issues and is very expensive.

But, after 20 years of research and development, new drugs are in the pipeline that target gamma-secretase, the enzyme that cleaves the amyloid precursor protein, triggering the formation of amyloid. In other words, the drug prevents the formation of amyloid. The first gamma secretase modulators were invented over 20 years ago, and versions of these original drugs are currently being developed by pharmaceutical and biotech companies.

Roche is currently conducting a phase 1 trial to verify the safety of a gamma-secretase modulator, and Acta Pharmaceuticals is awaiting approval to start a phase 1 trial. If these drugs are proven safe and effective, they will become the gold standard of early intervention, stopping amyloid before it builds up in the brain and triggers the deadly cascade leading to dementia.

SHIELD your brain

Several lifestyle habits target amyloid, tau, neuroinflammation, and other forms of harm to the brain, helping to prevent cognitive decline and Alzheimer’s disease. They are summarized by the acronym SHIELD:

Sleep. During sleep, the brain’s glial cells—which are like scrubbing bubbles—remove debris, including amyloid. To get enough cleaning, you need seven to eight hours of sleep, including dream sleep (REM) and deep sleep. The best tip for a good night’s sleep: Maintain a regular sleep cycle, going to bed and getting up at approximately the same time each day and night. For example, go to bed at 11 p.m. and get up in the morning at 7 a.m.

Handle stress. Stress hurts the brain in several ways. It triggers the release of the hormone cortisol, which is neurotoxic, and dying neurons create neuroinflammation, which, in turn, kills more brain cells. Stress can also trigger the “default mode network” of the brain, in which Alzheimer’s pathology propagates. Whenever you’re not engaged in a goal-oriented task, but idly judging others around you or worrying about the past or future, this pathway is activated. The solution: When you’re stressed or anxious, do something else to engage your mind, like meditating, taking a walk in nature, gardening, or engaging in a hobby you love.

Interact with others. Persistent loneliness—being alone and not liking it—doubles your risk of Alzheimer’s disease. In contrast, human interaction stimulates the brain to make new synapses and is neuroprotective. But research shows that not every interaction is equally neuroprotective. Besides the family you see every day, at least once a month try to see one or two relatives or close friends—people who you feel close to and can confide in.

Exercise. Aerobic exercise, like brisk walking, stimulates the birth of new neurons, particularly in the hippocampus, the location of short-term memory. Aerobic exercise also generates brain-derived neurotropic factor, which is needed to keep neurons alive—especially the neurons in an aging brain. In addition, exercise increases the production of muscle-­derived hormones that stimulate brain enzymes capable of breaking down beta amyloid. Aim for at least 150 minutes of exercise every week, or 22 minutes per day. Start with a few minutes a day and build up gradually. Heavy aerobic exercise is not necessary. Just get your blood flowing.

Learn new things. As with social interaction, learning stimulates the brain to make new synapses. This increases what is called your “cognitive reserve.” You’re building up synapses like savings in the bank, for the inevitable loss of synapses that accompanies aging. Learn a new language or a new musical instrument. Watch a documentary or listen to a nonfiction audiobook. Try a new recipe.

Diet. Recent research shows that balancing the bacteria in the gut microbiome, the trillions of bacteria that live in your gastrointestinal tract, triggers the brain to activate the glial cells that eat beta amyloid. The diet the gut microbiome likes best is rich in vegetables, fruits, whole grains, legumes, nuts, and seeds—a diet rich in prebiotics, the fibers that make friendly gut bacteria healthier.

The Amyloid Hypothesis From Theory to Fact

The landmark scientific paper that ended most of the resistance to the “amyloid hypothesis” was published in the prestigious journal Nature in 2014. Mice genetically bred to develop Alzheimer’s developed amyloid plaques outside the cell, but not tau tangles inside. If amyloid wasn’t triggering tau, how could amyloid be the root-cause of the disease? The paper in Nature showed that mice can’t make tau. You need a human neuron to produce tau tangles. This production was achieved by creating mini human brain organoid models of Alzheimer’s disease in petri dishes with gene mutations that drive amyloid deposition.

Another objection was that clinical trials showed that getting rid of amyloid in Alzheimer’s patients didn’t improve their symptoms. How could amyloid be the cause if getting rid of it wasn’t the cure? Amyloid starts developing 10, 20, and even 30 years before the onset of Alzheimer’s symptoms. Expecting an amyloid drug to reverse Alzheimer’s is akin to expecting a cholesterol-lowering drug to reverse the heart symptoms of someone who needs coronary bypass surgery. That’s not going to happen.

In 2024, the “amyloid hypothesis” is now a science-supported and widely accepted paradigm: Amyloid triggers Alzheimer’s disease, and amyloid should and must be the focus of preventing and treating it, prior to the onset of cognitive symptoms.

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