The 14 Modifiable Risk Factors of Dementia
Disclaimer: Not Medical Advice. Opinions are my own.
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I will be speaking in Nashville, Tennessee, in two weeks, on September 12th. I'm joining my friends Dr. Vonda Wright, Dr. Louisa Nicola, and Dr. Darshan Shah at the Next Health Longevity Summit.
Only 500 seats were allocated to ensure the event is personalized for each participant.
Seats are selling out, and I would love to see you there!
Today's Newsletter at a Glance:
- Understanding Dementia
- The Uncontrollable Factors: Age, Sex, & Genetics
- The 14 Modifiable Risk Factors
Roughly 57 million people worldwide currently live with dementia, and approximately 153 million are projected by 2050.
Dementia consistently hovers around the 7th leading cause of death worldwide.
"What exactly is dementia?
You may be familiar with the diagnosis, but I want to ensure everyone is on the same page.
Dementia is not a single disease.
Dementia is a clinical syndrome of chronic, acquired loss of cognitive ability. Decline in domains such as memory, language, executive function, and visuospatial ability.
It can be severe enough to interfere with independence in everyday activities, caused by underlying brain disease or injury.
There are many different forms of dementia: Alzheimer's (AD accounts for 60-80% of cases), vascular (stroke), Lewy body (Parkinson's), and frontotemporal (typical early onset) dementia.
The disease process for dementia happens decades before symptoms appear.
In today's newsletter, we will cover the non-modifiable and modifiable risk factors for dementia. I will leave you with evidence-based levers to reduce your risk of dementia.
The Uncontrollable Factors: Age, Sex, and Genetics
Let's start with the factors we can't control.
Not to induce anxiety, but to help you understand where your risk profile stands.
The most dominant factor is age.
That's right, age is the single strongest risk factor for all-cause dementia and AD. Prevalence rises exponentially after 65: AD affects 5–10% of people over 65 and up to ~33% of those aged 85+.
Next, women account for roughly two-thirds of AD cases. This is partly because women, on average, outlive men. Another major factor is that women are more affected by the APOE ε4 gene.
The third risk factor is genetics.
You can't run from your genes, especially the APOE gene.
The APOE gene plays a crucial role in lipid transport and regulates the clearance and aggregation of amyloid-β— a mechanistic link to Alzheimer's disease.
APOE comes in three variants (ε2, ε3, ε4) that differ by only one or two amino acids, yet these tiny differences make APOE the single strongest genetic risk factor for late-onset Alzheimer's disease.
Function Health (long-time newsletter sponsor) offers APOE gene testing as an add-on.
You carry two copies. ε2/ε2 is the lowest risk, and ε4/ε4 the highest.
APOE ε2 is the protective allele. You hit the genetic lottery, reducing AD risk by roughly 40% and delaying onset.
APOE ε3 is the most common allele worldwide and is considered neutral for Alzheimer's risk.
APOE ε4 increases Alzheimer's risk in a dose-dependent way — roughly 3–4× with one copy and ~10–15× with two copies.
Now that we have discussed the most prominent non-modifiable components of dementia, let's cover the modifiable risk factors.
The 14 Modifiable Risk Factors
I recognize the section above can be daunting, but I want you to understand the full risk landscape when discussing dementia.
The good news is that we have many levers we can pull to reduce your risk of dementia. We often discuss many of these levers on the platform.
Why? There are many overlapping risk factors when we look at heart disease and dementia. The common theme is that these risk factors damage the inner lining of blood vessels.
- Hypertension (high blood pressure) is one of the most prominent risk factors for dementia. High blood pressure damages vascular function throughout the body, and your brain is no exception. Controlling your blood pressure is paramount.
- Smoking. Avoid smoking anything: cigarettes, THC, or vaping. All carry toxic metabolites that can directly damage the vascular lining.
- Elevated Apolipoprotein B (ApoB) refers to the dangerous cholesterol particles that can penetrate the blood vessel lining and start the atherosclerotic cascade. Continuing the theme of vascular injury in the brain and amyloid processing.
I do want to make one note about cholesterol and the brain, given the confusion on social media.
The brain holds about 20-25% of the body's total cholesterol. The brain produces its own cholesterol supply and doesn't rely on serum or dietary cholesterol.
Statins and other cholesterol-lowering medications do not cause dementia. In fact, observational studies have shown they can help protect the brain's blood-vessel highway, reducing the risk of vascular dementia.
- Diabetes, visceral fat, and physical inactivity each damage the vascular lining and leave it more vulnerable.
Addressing the risk factors above will also reduce your risk for cardiovascular disease.
A good rule of thumb: what's good for the heart is typically good for the brain.
"What about risk factors that are more specific to dementia?
- Early-life education — builds cognitive reserve and delays clinical expression of dementia pathology.
- Hearing loss — If you don't use it, you lose it. Hypothesized to act via sensory deprivation, impacts cognitive load, and downstream social isolation, largely independent of vascular disease.
- Untreated vision loss — the newest sensory factor, analogous to hearing loss
- Traumatic brain injury — a direct neurodegenerative/mechanical insult.
- Depression — an independent risk factor for dementia
- Social isolation — independently associated with dementia, though the mechanism may partly overlap with cardiovascular and depression pathways.
- Excessive alcohol and air pollution — environmental/toxic exposures.
The goal is to address each risk factor before problems arise, not after.
The window of greatest opportunity is midlife — the same decades in which the pathology is already accumulating silently, and the same decades in which most people assume they have time.
Take action today.
A one-paragraph summary of take-home tactics:
Get your blood pressure under 130/80 and start now, not at 70. Get your hearing tested and wear the hearing aids if you need them. Exercise regularly — both cardio and resistance training. Manage your ApoB, blood sugar, and weight. Correct your vision. Don't smoke. Keep alcohol intake low. Wear a helmet and don't shrug off head injuries. Treat depression. Stay socially and mentally engaged. Sleep properly.
That's the list.
Do these like your life depends on it, because it does.
Stay Hydrated. Replace What You Lose.
Hydration isn’t just about drinking more water — it’s about replacing what you lose.
When you sweat (from workouts, sauna sessions, or just daily life activities), you’re not just losing water — you’re losing electrolytes like sodium, potassium, and magnesium.
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Only the best,
Jeremy London, MD
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* Disclaimer: This blog is for general informational purposes only and does not constitute the practice of medicine, nursing, or other professional health care services, including the giving of medical advice, and no doctor/patient relationship is formed. The use of information on this blog or materials linked from this blog is at the user’s own risk. The content of this blog is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard or delay seeking medical advice for any medical condition they may have and should consult their healthcare professionals for any such conditions.
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