Causes & Risk Factors

The causes of Alzheimer’s disease are not yet fully understood, but probably include a combination of various factors. Normally there are two type of risk factors which may case Alzheimer’s diseases.

  • Non-modifiable: age, gender, genetics, family history, ethnicity, etc.
  • Modifiable: high blood pressure, high cholesterol, diabetes, obesity, smoking, head trauma, exercise, nutrition, education, etc.

There are 14 most well-known risk factors of Alzheimer’s disease:

  1. Advanced age
  2. Genetic predisposition and family history
  3. Chronic diseases associated with vascular injury
  4. Inflammatory diet
  5. Heavy metal toxicity
  6. Chronic stress
  7. Sleep issues
  8. Sedentary lifestyle
  9. Hormone imbalances
  10. Head injury
  11. Dysbiotic gut microbiome
  12. Gum disease
  13. Female gender
  14. Cellular function problems

Age

One of the great mysteries of Alzheimer’s disease is why it largely affects older adults. Research on normal brain aging is exploring this question. With increasing age, there is a greater incidence of cognitive decline. For example, scientists are learning how age-related changes in the brain may harm neurons and affect other types of brain cells to contribute to Alzheimer’s damage. These age-related changes include atrophy (shrinking) of certain parts of the brain, inflammation, blood vessel damage, production of unstable molecules called free radicals, and mitochondrial dysfunction (a breakdown of energy production within a cell).

Patients over 65 are at increased risk for dementia compared to the younger generation. While advanced age is undoubtedly a risk factor for Alzheimer’s and dementia, that doesn’t mean that this debilitating disease is a natural part of your golden years. Less than 5% of all patients have early-onset Alzheimers, which is usually linked to a genetic predisposition. In other words, 95% of Alzheimer’s patients are senior citizens, and their risk increases even more as they continue to age.

Though Alzheimer’s may be one of the leading causes of death, both in the USA and across the world, it may be possible to slow its spread or practice prevention. Below is the distribution of Alzheimer’s disease among adults in the United States as of 2021, by age group.

Source:

Genetics

Most people with Alzheimer’s have the late-onset form of the disease in which symptoms become apparent in their mid-60s or later. Researchers have not found a specific gene that directly causes late-onset Alzheimer’s, but having a form of the apolipoprotein E (APOE) gene increases a person’s risk. This gene has several forms, and one of those, APOE ε4, increases a person’s risk of developing Alzheimer’s and is also associated with an earlier age of disease onset. However, carrying the APOE ε4 form of the gene does not mean that a person will definitely develop the disease, and some people with no APOE ε4 may also develop Alzheimer’s.

Scientists also have identified several regions of interest in the genome (an organism’s complete set of DNA) that may increase or decrease a person’s risk for late-onset Alzheimer’s to varying degrees.

Early-onset Alzheimer’s occurs between a person’s 30s and mid-60s and represents less than 10% of all people with Alzheimer’s. Some cases are caused by an inherited change in one of three genes. For others, research shows that other genetic components are involved.

Most people with Down syndrome develop Alzheimer’s. This may be because people with Down syndrome have an extra copy of chromosome 21, which contains the gene that generates harmful amyloid.

Family history

If someone’s first-degree relative (mother, father, or sibling) has Alzheimer’s, the chances are up to seven times greater that they may develop the disease.

Chronic Diseases Associated with Vascular Injury

Chronic diseases associated with vascular injury can link into subtype 4, or vascular Alzheimer’s. These may include:

Heart disease (cardiovascular disease)

  • Diabetes
  • Stroke
  • High blood pressure (hypertension)
  • High cholesterol

The National Institutes of Health point out that having cardiovascular risk factors like blood pressure and cholesterol levels in midlife may lead to an increased risk of dementia down the road.

Inflammatory Diet

Research continues to point toward inflammation as an underlying cause of Alzheimer’s, particularly subtype 1. An inflammatory diet has the following traits:

  • High in simple carbohydrates/sugars. The brain loses the ability to burn sugars as the disease progresses, and they’re known to feed inflammation. A high sugar diet may also lead to insulin resistance and prediabetes, seen in subtype 2.
  • Constant eating and snacking. A fasting window of 12 hours allows your cells to enter autophagy, the body’s routine “cleaning” process for cells. Without this break, your body is literally not “taking out the trash” that is created by cell turnover, contributing to inflammation.
  • Deficiencies in vitamin B12, D3, and zinc. These help the body function properly and fight off inflammation. Additionally, a vitamin B12 deficiency causes high homocysteine levels, which are associated with Alzheimer’s.
  • Limited antioxidant intake. Antioxidants can help remove free radicals and fight inflammation in the body.

What is the Bredesen diet? The Bredesen diet is an anti-Alzheimer’s way of eating that emphasizes whole foods, healthy fats and lean proteins, fasting, and mild ketosis to reduce inflammation. It’s also known as the KetoFLEX 12/3 diet.

Heavy Metal Toxicity

This risk factor of heavy metal toxicity often plays into subtype 3 of AD. Heavy metals like lead, cadmium, and manganese can be stored and transported throughout the body, accumulating over time. These can come in the form of food, medicines, containers and cookware, and more.

As these environmental toxins build up, these neurotoxicants are associated with cognitive decline and impaired cognitive function in adults. People with regular exposure to these metals are at a higher risk for dementia like Alzheimer’s.

Chronic Stress

Chronic stress and depression are known to contribute toward the buildup of amyloid-beta proteins in the brain, playing a potential role in the pathogenesis of Alzheimer’s.

People with high-stress lifestyles or jobs may run a greater chance of developing Alzheimer’s down the road, particularly subtype 1 or 3.

Sleep Issues

Sleep issues earlier on in life may create problems with mild cognitive impairment later down the road. Regularly getting poor sleep, which many Americans admit to, can trigger the beginnings of Alzheimer’s.

Poor sleep means not getting 7-8 hours a night or getting poor quality sleep (limited deep sleep and REM). The most common causes of this are sleep-disordered breathing, a high-stress lifestyle, sleep apnea, and a poor diet (especially too much alcohol or caffeine late at night).

Sedentary Lifestyle

A sedentary lifestyle is a major risk factor for Alzheimer’s, including a lack of stimulation for both mind and body. 

People who don’t get enough physical activity (at least 30 minutes daily) are more likely to develop the disease. Even a 30-minute walk can be effective in getting active.

Additionally, a sedentary mind can contribute to the issue. Not getting enough social engagement and no longer learning new skills or solving new problems can spell trouble. Be a lifelong friend and learner; keep the mind active as well as the body!

Interestingly, sedentary behavior may also contribute to inflammation, which is all the more reason to get moving.

Hormone Imbalances

Unbalanced hormones can create havoc within the body in many systemic ways, and the risk of Alzheimer’s and dementia is no exception. Changes to estrogen levels, in particular, seem to affect cognition, as estrogen both protects the brain and helps it to grow.

Insulin, another hormone, can influence inflammation as well as other hormones, often playing a part in subtypes 1, 2, and 1.5.

Head Injury

A head injury can usually be directly linked to subtype 5, with a moderate or severe head injury doubling the chances of developing Alzheimer’s or other forms of dementia later on in life. 

Children who play contact sports and those who have been in car accidents are especially susceptible. 

Dysbiotic Gut Microbiome

A dysbiotic gut microbiome may play tricks on bacterial balances in other areas of the body, including the brain. This can happen in the absence of probiotics, after a course of antibiotics, and an inflammatory diet.

When pathogenic bacteria run rampant, they are a risk factor for Alzheimer’s on their own and contribute to issues like obesity, type 2 diabetes, and inflammation.

Gum Disease

Your oral microbiome has a lot more to do with your brain health than you might expect. For years, scientists have understood that periodontal disease (periodontitis or gum disease) increases the risk of developing Alzheimer’s disease.

The bacterial culprit for gum disease, P. gingivalis, can make its way to the brain. There, it builds up over time, inducing inflammation and causing amyloid-beta deposits on the brain.

In a 2019 study, researchers found evidence that P. gingivalis in the brains causes the development of compounds called gingipains. This groundbreaking discovery strongly suggests a rare causal link, not just a correlation, between P. gingivalis bacteria and Alzheimer’s disease.

Translation: The study postulates that gum disease may literally cause Alzheimer’s disease in certain patients.

Female Gender

Sadly, being a woman is a risk factor that puts you at a greater likelihood of developing this disease.

Female patients make up approximately ⅔ of those diagnosed with Alzheimer’s disease.

However, it’s important to remember another statistic: Roughly 30% of people will develop Alzheimer’s by age 90. Considering that aging is the most well-known risk factor and that women live longer, there may be some overlap to account for here.

Cellular Function Problems

Specific cellular function problems may raise the odds of developing Alzheimer’s, particularly:

Limited mitochondrial function

Limited SirT1 gene function

Low nerve growth factor (NGF) levels

These issues with the inner workings of your cells can affect your body’s functioning and impact long-term neurological health.