My nervous system is the basis of everything I think, do, and feel. To me, it is of utmost priority that it stays in the best possible shape. However, just as any other cell, tissue, or organ, the brain deteriorates over time.
Humans usually peak around 20-25 years in terms of mental capabilities. From then on, it goes downhill for everybody. This includes gradually progressing compromised blood flow, reduced neurogenesis, and lower neuron health. There is no way to completely prevent this.
Furthermore, as I age, I will progressively and stochastically lose neurons (in addition, to a decline in neuron function), which is likely part of the reason people’s cognitive abilities progressively decline as they age. For the most part, neurons in the CNS are postmitotic cells (i.e., they cannot divide) and neurogenesis is limited to a few select sites.
Even if we could replace neurons, newborn neurons are mostly incapable of replicating the functional connectivity of a dying neuron, particularly the sometimes macroscopic length of the axon. Thus, in contrast to other cells of most organ systems, neurons cannot be replaced. I discuss this in more detail here: Intelligence Enhancement
Dementia 101
While some form of neurodegeneration (e.g., loss of neuron number and function) happens to everyone, not everyone will get diagnosed with dementia.
It is only called “dementia” when neurodegeneration has progressed to the point that mental capabilities become so bad that they severely impair daily living. However, by that point, mental function has usually already been declining for a couple of decades.
“Dementia” is a catch-all term that includes a couple of neurodegenerative diseases that often present in a mix & match form. Most of these diseases are characterized by the aggregation of one or more faulty proteins. For example:
- Alzheimer’s dementia: The brains of people with Alzheimer’s disease are full of extracellular plaques of beta-amyloid and intracellular aggregates of tau protein, though it is still unsure whether these protein aggregates are a cause or a consequence of the disease. There are probably multiple different paths that lead to Alzheimer’s. These include vascular, metabolic, inflammatory, metabolic, toxic, and genetic “versions” of the disease – and it is not even clear whether different “kinds” of Alzheimer’s represent the same “disease”. About 80% of all dementia forms are Alzheimer’s dementia.
- Frontotemporal dementia: Frontotemporal dementia is associated with aggregates of another set of proteins (tau, TDP-43, FUS), particularly in frontal and temporal regions.
- Others: Faulty proteins also accumulate in Lewy body dementia, and Parkinson’s disease.
While we have identified a handful of clear-cut risk factors, nobody exactly knows why in certain people a certain subset of neurons degenerates. Furthermore, nobody knows whether the protein aggregates are a cause, byproduct, or both.
Tactics I follow to preserve brain health
- Having no ApoE4 allele
- Putting a prime on exercise
- Optimizing metabolic health
- Preventing atherosclerosis
- Optimizing hormones
- Lowering inflammation
- Fish oil
- Preventing nutrient deficiencies
- Senolytics
- MAO-B inhibition
- Optimizing sleep
- “Brain stimulation”
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Genetics
By far the biggest aspect of avoiding dementia is choosing the right parents. My grandfather recently died at 96 years old. He died with no discernible dementia and his memory was as sharp as ever despite having been strongly hearing-impaired for over a decade – hearing impairment is highly associated with developing dementia. Furthermore, he had been using lorazepam for sleep for many years. Lorazepam is a strong benzodiazepine, which is strongly associated with cognitive decline.
Having no ApoE4 allele
ApoE4 is a protein found on lipoproteins, and the ApoE4 version is associated with an increased risk for dementia, in particular Alzheimer’s, and cardiovascular disease. ApoE is the principal cholesterol carrier in the brain and seems to be involved in cholesterol transportation from astrocytes to neurons.
About 25% of the population has one ApoE4 allele. Having one ApoE4 allele roughly triples one’s risk for developing AD. One’s ApoE genotype is strongly correlated with the lifetime risk of Alzheimer’s dementia.
For example, carriers of the E4/E4 genotype, about 2% of the population, have a lifetime risk of about 70%, whereas carriers of the E2/E2 genotype are pretty much protected from developing AD. Nonetheless, these genes are not deterministic and about 1/3 of people with the E4/E4 genotype do not seem to develop AD. Likewise, a very small fraction of people with the E2/E2 genotype do develop AD.
I personally carry the E3/E3 genotype, which 60% of the population have.
Putting a prime on exercise
I do about 1 hour of exercise per day.
As of yet, exercise is probably the most potent way I have for staving off neurocognitive decline. After all, next to regulating homeostasis, the brain is all about movement (behavior) anyway.
For me, the primary reason I do lots of exercise is not related to metabolic health or looks, but rather to elevate brain function (e.g., executive functions) and to promote long-term brain health.
I discuss the benefits of exercise on vitality and brain health in more detail here.
All three kinds of exercise have (partially) independent benefits.
- Low-intensity cardio (zone II): it particularly increases mitochondrial and metabolic health.
- High-intensity cardio: It particularly boosts the release of a host of growth factors such as VEGF and BDNF, and increases the genetic expression of antioxidant systems.
- Resistance exercise: It particularly improves insulin sensitivity, IGF-1, and myokine signaling.
Optimizing metabolic health
Optimizing metabolic health is crucial to preserve brain function, presumably through a plethora of interconnected mechanisms. Furthermore, it counteracts the development of cardiovascular disease (discussed next).
I discuss metabolic health here: The Seven Pillars of Metabolic Health
Preventing atherosclerosis
There is a saying among doctors that “Everything that is good for the heart, is good for the brain.” In fact, there is a linear relationship between the media thickness of the internal carotid artery and the decline in cognitive function or said in another way, there is a strong relationship between atherosclerosis and neurodegeneration.
Furthermore, next to dementias associated with the accumulation of faulty proteins, there are so-called “vascular dementias”, which are caused by insufficient blood supply (oxygen, glucose, nutrients, hormones) and micro-strokes (the latter of which often go unnoticed), both of which lead to neuron death.
The tactics I follow to prevent or delay atherosclerosis are discussed here: My Most Likely Cause Of Death – My Protocol for Fighting Atherosclerosis
Optimizing hormones
I keep an eye on my hormones. Multiple hormones have beneficial effects on the brain as they also function as growth factors and metabolic modulators. These include T3, IGF1, GH, estradiol, and leptin. Neurosteroids (converted in part from other steroids) may also play a role however, their clinical importance is currently uncertain.
Conversely, if one of the major hormones is deficient, this will accelerate brain aging. At the time of this writing, I supplement with a low dose of leptin and I am on my TRT Lite protocol.
I am specifically pleased that my IGF-1 levels are naturally slightly above the reference range. IGF-1 is one of the major systemic growth factors. While it slightly increased the risk of cancer, it reduces the risk of cardiovascular disease, metabolic disease, and specifically neurodegenerative disease. In fact, low levels of IGF-1 are strongly associated with brain atrophy and dementia.
Furthermore, higher GH & IGF-1 are associated with more vitality as they improve energy levels, mood, overall health, and muscle mass, all of which are essential to living a brain-health-conducive lifestyle.
Growth hormone and leptin in particular increase REM sleep, which is crucial for brain plasticity.
Lowering inflammation
Low-level inflammation is toxic to brain integrity through a variety of mechanisms. Tactics aimed at reducing inflammation are discussed here: Burning to Death – My Protocol for Lowering Inflammation
Fish oil
I take 2g of EPA/DHA per day. Simplistically speaking, EPA is a structural building block of neurons, while DHA is a precursor to anti-inflammatory prostaglandins. We do not really know which of these is more important so it is probably best to include both.
40%-50% of the brain is composed of PUFA. DHA is the main building block and most common in the brain. EPA is less abundant but may have more anti-inflammatory properties compared to DHA. Therefore, elevating O3-fatty acid intake may be somewhat protective against dementia.
Preventing nutrient deficiencies
I make sure I have no mineral or nutrient deficiencies by occasionally measuring some of these in my blood.
I take a load of supplements – discussed here: Supplements I Take
Senolytics
It was found that senolytics reduce senescent oligodendrocyte progenitor cells, reduce beta-amyloid plaque in the hippocampus, reduce neuroinflammation, and improve memory and learning in mice. In animal models, rapamycin acted on the early stage of dementia but senolytics were found to act on the later stages, ameliorating already established disease. Unfortunately, there is currently no human data. I discuss my experience with the senolytics dasatinib, quercetin, and roxithromycin in detail here: Eliminating Zombie Cells – My Protocol for Fighting Senescent Cells
MAO-B inhibition
The catecholaminergic neurons (dopaminergic & noradrenergic neurons) are among the most rapidly dying neurons in the human brain. In fact, it is thought that we lose about 10% of the originally half a million or so dopaminergic neurons per decade.
The ongoing loss of catecholaminergic activity not just progressively diminishes drive, energy, and zest for life, but also sets a limit to the upper human lifespan as these neurons are required to keep many parts of the nervous system functioning.
If more than 80% of these neurons are dead, it is called Parkinson’s disease, which is often prefigured by depression. Inhibition of MAO-B is known to drastically slow the loss of dopaminergic neurons, as DA neuron death is in part a consequence of reactive molecules produced by MAO-B. In the past, I was taking low doses (0.05mg per day) of rasagiline. Unfortunately, the increase in dopamine levels turned me into an asshole, so I reduced my dosage to 0.02mg per day (I make microdoses myself using a morter, methylcellulose, and a capsule machine).
Optimizing sleep
Obviously, sleep is crucial to many aspects of brain health, ranging from housekeeping functions that cannot be carried out during wakefulness, to glymphatic outflow of waste products, to neuroplasticity.
I usually go to bed at the same time, make sure my room is dark and quiet, take a couple of supplements (magnesium, taurine, glycine), and expose myself to blue light in the morning.
In the past, I have taken sleeping pills for some time, which though was presumably a bad idea because a variety of CNS depressants (anticholinergics, antihistamines, GABAergics) are associated with dementia progression in ways that seem not accounted for by residual confounding.
I discuss my sleep optimization routine in more detail here. I discuss hypnotics in more detail here.
“Brain stimulation”
Keeping the brain active and engaged is probably the most important of all. I keep my brain active by exercising, continuously learning and doing new things, having meaningful social relationships, and creating purpose for myself. I wish I could travel more (“environmental enrichment”). The anti-neurodegenerative effects of these “interventions” are just a nice add-on.
Whether psychedelic drugs are more hype than hope, or worse, whether they do more harm than good remains to be seen.
I discuss these and other matters in more detail here: Intelligence Enhancement
Sources & further information:
- Podcast: Peter Attia & Richard Isaacson: Alzheimer’s prevention
- Scientific article: Rapamycin and Alzheimer’s disease: Time for a clinical trial?
- Scientific article: Major Neurocognitive Disorder (Dementia)
Disclaimer
The content on this website represents the opinion and personal experience of the author and does not constitute medical advice. The author does not endorse the use of supplements, pharmaceutical drugs, or hormones without a doctor’s supervision. The content presented is exclusively for informational and entertainment purposes. Never disregard professional medical advice or delay in seeking it because of something you have read on the internet.