Establishing Your Brain Health Baseline
In my article, “Your Genes Are Not Your Fate,” published in the February 2024 English Rose newsletter, I shared the good news that you can lower your risk of getting Alzheimer’s disease, even if you have genetic predisposition for the disease.
The first step to lowering your risk of cognitive decline is to establish a brain health baseline. This accomplishes two objectives:
- It identifies which factors, unique to you, are most likely to compromise your future cognition.
- It establishes initial comparison metrics so you can track progress as you embark on your brain health journey.
“I may not be able to ward off dementia completely, but research makes a strong case that I can act now to potentially slow the speed, and lower the severity, of future cognitive decline.”
I’m a relatively healthy man in my 50s with a higher-than-normal risk of Alzheimer’s, as both my parents had it. Naturally, I have a little anxiety about the role dementia may play in my future. I am choosing, however, to use my uneasiness as motivation. I am being proactive by fighting for my brain health now, rather than waiting for symptoms to appear. I may not be able to ward off dementia completely, but research makes a strong case that I can act now to potentially slow the speed, and lower the severity, of future cognitive decline.
In this article, I will walk you through the process I used to establish my Brain Health Baseline, which is made up of four components: [1] Genetic Screening, [2] Brain Health Blood Markers, [3] Cognitive Testing, and [4] Modifiable Risk Factors. I hope that what I share will make it easier for you to better understand how you can assess the current health of your brain as a first step toward strengthening it.
1. Genetic Screening
Genes that positively correlate with Alzheimer’s are classified into two aptly named categories: risk genes and deterministic genes. Risk genes increase the probability, compared to the general population, that a person will develop Alzheimer’s. Deterministic genes guarantee that a person will develop Alzheimer’s, typically before the age of 65.
There are several Alzheimer’s risk genes (e.g., ABCA7, CLU, CR1, PICALM, PLD3, TREM2, and SORL1), all of which can be identified in a full battery of genetic testing, but the most well-established risk gene is called apolipoprotein E (APOE). This gene has three forms, or alleles. The least common allele is e2, which if present, reduces the risk of developing Alzheimer’s. The most common allele is e3, which does not seem to affect Alzheimer’s risk at all. The final allele is e4. This is the variant that is linked to an increased risk of developing Alzheimer’s disease.
Every person has two APOE genes, one copy from each biological parent. The presence of one e4 allele doubles or triples the risk of developing Alzheimer’s disease compared to the general population. The presence of two e4 alleles increases the risk by eight to twelvefold.
To be clear, having an e4 allele, or even two e4 alleles, does not mean you will develop Alzheimer’s disease. In fact, for people who age normally into their 70s without developing Alzheimer’s, approximately 25% of them have at least one copy of e4. Conversely, the absence of e4 alleles doesn’t mean you are fully protected from developing the disease. Approximately 35% of people with Alzheimer’s do not have an e4 gene. The presence of an e4 allele simply means a person is at an increased risk of developing Alzheimer’s.
Compared to APOE e4, present in about 25% of the general population, deterministic genes are extremely rare, present in less than 1% of all Alzheimer’s cases—so far less than 1% of the general population. The three deterministic genes are amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2). All three are related to young-onset Alzheimer’s, a variant of the disease with symptoms that begin to exhibit when a person is in their 40s to mid-50s. Young-onset Alzheimer’s is hereditary, which means high-risk individuals are usually aware of their genetic risk, even before testing for these genes.
2. Brain Health Blood Markers
Many of us visit a doctor once a year for an annual physical. As a part of the exam and assuming you are healthy, your doctor probably checks your blood pressure and orders a few blood tests to get a high-level assessment of your overall health. You need more than the typical tests, however, to understand the health of your brain.
Generally, brain health blood tests assess two physiological factors: inflammation and blood flow. A comprehensive set of blood tests can help assess your current state in these areas and might include the blood tests listed below. You can learn more about these tests in the endnotes.
“It took 16 vials of my blood to conduct these tests, but the information I gained was enlightening and empowering.”
- C-Reactive Protein, Cardiac
- Complete Blood Count (CBC) with Differential/Platelet
- Complete Metabolic Panel (CMP)
- Copper
- Cortisol
- DHEA-Sulfate
- Estradiol and Progesterone
- Folate (Folic Acid)
- Glutathione
- Hemoglobin A1c
- Homocysteine
- Insulin
- Lipid Panel
- Magnesium
- MTHFR (methylenetetrahydrofolate reductase)
- OmegaCheckä (EPA+DPA+DHA)
- Pregnenolone
- Selenium
- Sex Hormone Binding Globulin (SHBG)
- Testosterone
- Thyroid Antibodies
- Thyroxine (T4) Free and Direct
- Triiodothyronine (T3)
- TSH
- Uric Acid
- Vitamin B12
- Vitamin D, 25-Hydroxy
- Vitamin E
- Zinc
It took 16 vials of my blood to conduct these tests, but the information I gained was enlightening and empowering. I identified specific actions I could take to decrease my risk of cognitive decline. Some of the markers related to brain inflammation and blood flow are also linked to other health risks that extend beyond brain health. These risks may have remained undetected for years had I not had these tests. Only after getting a full picture of where I stood along key blood marker continuums could I chart a path forward that optimized my future brain health.[1]
[1] In Part IV of this essay series, I will share some of my test results and the corrective actions I’ve taken to move the needle on these metrics.
3. Cognitive Testing
Cognitive testing is an important part of any plan that aims to develop a baseline for cognitive health. It may also identify subtle shortfalls that people don’t even realize existed. These tests are designed to measure a person’s cognition in the following areas:
| Looks at how well you perceive and respond to social cues and interactions |
Behavioral neurologists and neuropsychologists specialize in cognitive issues and, with the help of these sorts of tests, are adept at detecting subtle compromises in brain performance. There are also many online resources that make these tests incredibly accessible and convenient to complete. Like the blood markers, the goal of cognition testing is to establish a baseline so you can identify issues that need attention and easily monitor improvements and deterioration over time.
4. Modifiable Risk Factors
There is a wonderful report from the Lancet Commission on dementia prevention, intervention, and care[1] that identifies 12 potentially modifiable risk factors for dementia. While the Lancet Commission’s primary objective is to influence health policy and improve dementia practices across the world, the list of these 12 risk factors is a useful tool when developing a personalized cognitive health baseline. Assessing ourselves along these 12 dimensions is especially powerful because they are, in fact, modifiable. A person can make choices associated with these risk factors that can impact their future risk of developing dementia.
The image below is from the Lancet Commission report, setting forth the 12 mechanisms for reducing dementia risk.
[1] Volume 396, Issue 10248, pp. 413-446, August 08, 2020.
Possible Brain Mechanisms for Enhancing or Maintaining Cognitive Reserve and Risk Reduction of Potentially Modifiable Risk Factors in Dementia
These risk factors will be familiar to people already interested in their general health and wellbeing because what’s good for the body is usually good for the brain. That’s not just convenient, but also motivating. For example, someone whose A1C score or blood pressure has been slowly increasing for a few years may not feel the urgency to do something about it. For many, the future threat of diabetes or hypertension just isn’t that scary. The realization that these trends are also increasing the chance that they develop Alzheimer’s may be just what they needed to start to make positive changes that improve both their physical and brain health.
To establish a modifiable risk factor baseline, go through this list and score your performance on each risk factor. Give yourself a score of 1 if you are weak in an area, 2-4 if you’re doing OK but could do better, and 5 if you are doing great. Although each factor doesn’t impact your dementia risk equally, this simple scoring approach helps you chart a path forward to strive toward higher numbers.
Using a five-point scale helps you remember that these risk factors are not simply on/off switches, too. A single risk factor is not either working for you or against you. Each one is on a continuum. Your goal is to try and optimize each by taking steps that move your score in a positive direction.
Conclusion
The first step to reduce your risk of developing dementia is to establish your brain health baseline. It shows where you lie on the cognition continuum and what levers, if any, you need to pull to improve future outcomes. A comprehensive brain health baseline includes genetic testing for Alzheimer’s-related genes, a blood panel of key brain health markers, cognitive testing, and an evaluation of your status along 12 modifiable risk factors. Establishing your brain health baseline will leave you with a sense of empowerment on a topic that is often associated with fear and helplessness. It will also help you chart a clear path forward toward long-term health and wellbeing.
It may surprise you that it’s possible (even likely) that your doctor may be taken aback by your request for these tests, especially if you’re not experiencing any cognitive decline. This is because our medical ecosystem is designed primarily to react to “signs and symptoms”—what your doctor can objectively observe plus your subjective description of what you are feeling or experiencing. “React” is the key word. Without symptoms, your doctor may resist your desire to search for signs of risk. In my next article, I’m going to share the reasoning behind this and how to overcome what I have coined as the “healthcare headwinds.”
Endnotes: Brain Health Blood Markers
Beyond genetics, medical experts widely acknowledged that low inflammation and increased blood flow are critical components for a healthy brain. A comprehensive set of blood tests can help assess your current state in these areas.
An extensive analysis might include the blood tests listed below:
- Complete Blood Count (CBC) with Differential/Platelet: A CBC helps identify signs of infection, inflammation, and blood disorders that can impact the brain. For example, a high white blood cells count might indicate inflammation or infection. Abnormal platelet levels can be related to issues with blood clotting, and this can impact blood flow to the brain.
- Complete Metabolic Panel (CMP): The CMP provides an overview of the body’s chemical balance and metabolism. Abnormal results could indicate diabetes, liver disease, or kidney issues, all of which can impact the health of your brain.
- Lipid Panel: Most people know what this refers to—total cholesterol, triglycerides, HDL cholesterol, and LDL cholesterol. High levels of LDL and low levels of HDL can lead to atherosclerosis, or narrowing of the arteries. This can lead to less blood flow going to the brain.
- Hemoglobin A1c: This measures your average blood sugar level over the past few months by looking at the percentage of hemoglobin coated with sugar. High levels of sugar leads to vascular damage and reduced blood flow to the brain.
- Insulin: Insulin regulates blood sugar by making it easier for glucose to enter cells. In addition to its role with metabolism, insulin also impacts cognitive functions. High insulin levels have also been linked to Alzheimer’s disease. Alzheimer’s disease is often referred to as diabetes of the brain, and insulin resistance is a precursor to type 2 diabetes.
- OmegaCheckä (EPA+DPA+DHA): This measures your level of omega-3 fatty acids in the blood. Having adequate levels is critical for brain health because omega-3s are involved in anti-inflammatory processes. Proper levels of omega-3 are associated with reduced risk of cognitive decline and better brain function overall.
- Homocysteine: Our body uses homocysteine, an amino acid in the blood, to make protein and build and maintain tissue. High levels, however, can damage the lining of the arteries and potentially lead to blood clots. That’s why high homocysteine is a marker for potential heart and brain health issues.
- MTHFR (methylenetetrahydrofolate reductase): MTHFR is involved in changing homocysteine, a potentially harmful amino acid, into methionine, a useful and necessary amino acid. A common genetic mutation of MTHFR reduces your body’s ability to absorb folate, or Vitamin B9, and B vitamins, in general. That’s why MTHFR is a genetic risk factor for a condition tied to high levels of homocysteine in the blood.
- Folate (Folic Acid): Folate is basically the same nutrient as Vitamin B9. It supports neurotransmitter function and cognitive processes. It also helps manage levels of homocysteine, an amino acid linked to cardiovascular disease and cognitive decline when it’s elevated.
- Vitamin B12: Vitamin B12 is critical in maintaining nerve cells and producing DNA and RNA. DNA contains genetic instructions and RNA converts those instructions into proteins to carry out cellular functions. Lower levels of Vitamin B12 can lead to memory loss, cognitive decline, and mood issues.
- Vitamin D, 25-Hydroxy: Vitamin D is crucial for bone health, the function of your immune system, and overall health. For the brain, sufficient Vitamin D levels are associated with a lower risk of cognitive decline and dementia.
- Vitamin E: Vitamin E protects cells from harmful molecules, called free radicals. Oxidative stress occurs when there are too many harmful molecules compared to the level of antioxidants. This imbalance leads to cell and tissue damage. This is critical for the brain because oxidative stress contributes to the development of Alzheimer’s disease.
- Glutathione: Glutathione is an antioxidant that protects cells, including brain cells, from oxidative stress and damage. Adequate levels help maintain cognitive function, prevent neurodegenerative diseases, and support overall brain health.
- Selenium: This mineral acts as another antioxidant that helps protect the brain from oxidative stress and inflammation.
- DHEA-Sulfate: Dehydroepiandrosterone Sulfate (and that’s why you usually see it as DHEA-Sulfate!) is a hormone that helps create male and female sex hormones. It’s also linked to cognitive function, mood regulation, and stress response. High or low levels can impact memory, learning, depression, and anxiety.
- Sex Hormone Binding Globulin (SHBG): SHBG helps make sure you have proper levels of sex hormones, like estrogen and testosterone, in your body. Estrogen and testosterone play roles in brain function, mood regulation, and neuroprotection.
- Testosterone: This hormone isn’t just important for reproduction and libido purposes. Testosterone influences cognitive functions, too. In fact, men in the lowest quintile of testosterone levels have a higher risk for Alzheimer’s disease. This is likely because testosterone may help protect the brain from Amyloid, the protein that is closely associated with Alzheimer’s disease.
- Estradiol and Progesterone: Like testosterone for men, these hormones are involved in mood regulation, cognitive functions, and neuroprotection for women. They may also protect against dementia.
- Cortisol: Cortisol is the “stress hormone.” It is critical for managing stress, metabolism, and immune response (think being attacked by a lion). A chronically high level of cortisol, however, can impair cognitive function, contribute to anxiety and depression, and increase the risk of neurodegenerative diseases.
- Pregnenolone: We measure this steroid hormone to assess the body’s production of other hormones, like cortisol, testosterone, and estrogen. High or low levels of pregnenolone can impact mental clarity and overall brain function.
- Thyroid Antibodies: Thyroid antibodies can signal thyroid disorders, and thyroid disorders can lead to mood changes, anxiety, depression, and difficulties with concentration and memory.
- TSH: TSH stands for Thyroid-Stimulating Hormone. It helps regulate the production of thyroid hormones. Imbalances in THS levels can indicate thyroid disorders and those can lead to neurological problems and cognitive impairments.
- Triiodothyronine (T3): This thyroid hormone influences neuron growth, brain development, and cognitive functions. Proper levels are crucial for maintaining your memory, mood, and focus.
- Thyroxine (T4) Free and Direct: The T4 hormone is a critical component for metabolism and energy regulation. For adults, abnormal levels can affect mood, memory, and cognitive abilities.
- C-Reactive Protein, Cardiac: This is usually used to assess the risk of cardiovascular disease, but there’s a saying: What’s good for the heart is good for the brain. Elevated CRP levels indicate inflammation in the body, including the brain.
- Uric Acid: This one is complicated. It’s well-established that high uric acid can result in gout and kidney stones. Regarding the brain, however, the picture is less clear. Some research suggests that elevated uric acid levels might have antioxidant properties, which can protect the brain. If levels are too high, however, you may have an increased risk of cognitive decline.
- Copper: Copper is involved in neurotransmission, antioxidant defense, and energy production (Did you know that the brain represents about 2% of the body’s weight and uses approximately 20% of the body’s energy?). Copper imbalances can contribute to Alzheimer’s disease.
- Zinc: Like copper, zinc is critical for brain health. It plays a role in neuron growth and neurotransmission, influencing learning and memory. It also plays a role in the body’s defense against neurodegenerative diseases.
- Magnesium: Magnesium supports cognitive functions like learning and memory. It also helps regulate neurotransmitters, which send messages throughout your brain and body.
These blood tests are so powerful. For example, you can easily measure your Vitamin D or
Omega-3 levels and if they are not optimized for brain health, you can adjust your diet or take supplements. Not every suboptimal blood test result is so simply addressed, but many are. The fact is, too, that if you don’t know a problem exists or the risk of a problem occurring is higher than it needs to be, you can’t take any action to address it.
About the Author: Hal Kaufman is the person who meticulously collected and analyzed data about indoor air purifiers, masks, and outdoor heat lamps during COVID to make sure his family had what they needed. His friends are the people who know the diligence that goes into Hal’s analyses and then skip all the work and just buy what Hal buys. Joking aside (that’s not really a joke though), Hal is passionate about his long-term health and continues to do the research to define his personal objectives and methods for achieving his goal, which is to increase his years of healthy living. Given his family history, he has spent considerable time researching brain health and is incredibly appreciative of English Rose’s leadership in caring for people with dementia and their willingness to share what Hal knows with others. If you wish to contact Hal, please email him at kaufmanhal@gmail.com.
