summarize this "Sleep is also a very powerful tool against Alzheimer’s disease, as we’ll see
in chapter 16. 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, as in Stephanie’s case, 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). Addressing
Stephanie’s difficulties with sleep was therefore urgent. Her divorce and her
work situation were making it almost impossible for her to get more than four
hours of uninterrupted sleep on any given night.
Another somewhat surprising risk factor that has emerged is hearing loss.
Studies have found that hearing loss is clearly associated with Alzheimer’s
disease, but it’s not a direct symptom. Rather, it seems hearing loss may be
causally linked to cognitive decline, because folks with hearing loss tend to
pull back and withdraw from interactions with others. When the brain is
deprived of inputs—in this case auditory inputs—it withers. Patients with
hearing loss miss out on socializing, intellectual stimulation, and feeling
connected; prescribing them hearing aids may help relieve some symptoms.
This is just a hypothesis for the moment, but it is being tested right now in a
clinical trial called ACHIEVE (Aging and Cognitive Health Evaluation in
Elders) that is currently ongoing.
While depression is also associated with Alzheimer’s disease, it appears to
be more of a symptom than a risk factor or driver of the disease.
Nevertheless, treating depression in patients with MCI or early Alzheimer’s
disease does appear to help reduce some other symptoms of cognitive
decline.
Another surprising intervention that may help reduce systemic
inflammation, and possibly Alzheimer’s disease risk, is brushing and flossing
one’s teeth. (You heard me: Floss.) There is a growing body of research
linking oral health, particularly the state of one’s gum tissue, with overall
health. Researchers have found that one pathogen in particular, a microbe
called P. gingivalis that commonly causes gum disease, is responsible for large
increases in levels of inflammatory markers such as IL-6. Even stranger, P.
gingivalis has also shown up inside the brains of patients with Alzheimer’s
disease, although scientists are not certain that this bacterium is directly
causing dementia, notes Dr. Patricia Corby, a professor of dental health at
New York University. Nevertheless, the association is too strong to be
ignored. (Also, better oral health correlates strongly with better overall health,
particularly in terms of cardiovascular disease risk, so I pay much more
attention to flossing and gum health than I used to.)
One other somewhat recent addition to my thinking on dementia (and
ASCVD while we’re at it) prevention is the use of dry saunas. Until about
2019 I was very skeptical of the data linking sauna use to brain and heart
health. However, the more time I spend buried in this literature, the more I
become convinced by the magnitude of the benefit, the uniformity of the
studies, and the mechanisms providing plausibility. I’m not quite as confident
that regular sauna use will reduce your risk of Alzheimer’s disease as I am
that exercise will do so, but I am much more confident than I was at the
outset of my journey. The best interpretation I can draw from the literature
suggests that at least four sessions per week, of at least twenty minutes per
session, at 179 degrees Fahrenheit (82 degrees Celsius) or hotter seems to be
the sweet spot to reduce the risk of Alzheimer’s by about 65 percent (and the
risk of ASCVD by 50 percent).
Other potential interventions that have shown some promise in studies
include lowering homocysteine with B vitamins, while optimizing omega-3
fatty acids. Higher vitamin D levels have been correlated with better memory
in e4/e4 patients but it’s difficult to know from the current literature if this
means supplementing with vitamin D will reduce risk of AD. And as
mentioned earlier, hormone replacement therapy for women during the
transition from perimenopause to menopause seems promising, especially for
women with at least one copy of e4.
—
The scariest aspect of Alzheimer’s disease boils down to this: Medicine 2.0
cannot help us. At all. The point at which Medicine 2.0 steps in, the point of
diagnosis, is also likely near the point of no return for most Alzheimer’s
patients, beyond which little or nothing can be done. 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.
As it stands now, 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. (Remember,
cognition is one of the three key vectors of healthspan.) 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.
Broadly, our strategy should be 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.
I have great hope that in the future we will learn much more about how to
prevent and treat all forms of dementia. But it’s going to take hard work and
creative thinking from scientists researching the disease, a significant
investment in new theories and approaches, much more attention to strategies
of prevention, and courage on the part of patients such as Stephanie who
must face down this most feared and least understood of all the Horsemen."