What Causes Alzheimer’s Disease?

Dementia, which includes memory loss, thinking difficulties, and the inability to reason logically, is the end result of Alzheimer’s disease, a degenerative neurological (brain) disorder. Most cases occur in those over the age of 65, and age itself is the greatest risk factor associated with Alzheimer’s disease.

Alzheimer’s disease is not brought on by aging. It may take years, or even decades, before you experience any symptoms because of complex brain changes. Scientists think that predisposing variables include both heredity and environmental/lifestyle choices.

Alzheimer’s disease can manifest in either an early or a late onset form. The beginning of symptoms for a late-onset illness often occurs in people aged 65 and over. It accounts for the vast majority of cases of Alzheimer’s disease. Fewer than 10 percent of Alzheimer’s patients experience early onset, with symptoms appearing between the ages of 30 and 65.

Predicting who may get Alzheimer’s disease remains a major challenge. Scientists are continuously investigating potential risk factors, and have proposed several ideas as to the nature of the brain alterations that trigger the illness. This is the current state of their proposals:

Hypotheses

Alzheimer’s disease causes extensive degeneration of neurons and the synapses between them, first affecting the regions of the brain responsible for memory. Cognitive and physical impairments worsen as damage to the brain progresses. Because of this, brain size decreases physically.

Both cholinergic and amyloid explanations have been proposed to explain the disease’s onset and progression.

The Cholinergic Postulate

The cholinergic hypothesis has been around longer than any other theory to explain Alzheimer’s. Cognitive processes (including learning and comprehension) rely heavily on the brain’s cholinergic neurons. Alzheimer’s patients have a significant deficit in acetylcholine (ACh), a chemical messenger in the brain critical for learning, memory, and other cognitive processes.

The only FDA-approved Alzheimer’s drugs work by keeping the brain’s supply of ACh from depleting. These medications may alleviate cognitive problems in the short term, but they do nothing to prevent permanent brain damage.

The Amyloid Theory

Amyloid plaques were once thought to be generated in the brain due to excessively high amounts of beta-amyloid (a protein that surrounds the nerve cells). These plaques are suspected to have a role in the dementia that characterizes Alzheimer’s disease. The beta-amyloid theory originated from a seminal publication that appeared in Nature in 2006.

However, beta-amyloid medicines did not alleviate Alzheimer’s symptoms. Scientists have discovered that age-related amyloid plaques appear in persons who do not get Alzheimer’s disease.

Then, in July of 2022, a research published in Science threw serious doubt on this central concept. According to the findings of one neuroscientist, the photos used in the 2006 study were doctored. Since then, scientists have taken a more cautious approach to the beta-amyloid theory.

New evidence regarding beta-amyloid’s function in Alzheimer’s disease was shown in a November 2022 clinical study of a drug named Leqembi (lecanemab). After 18 months, patients who used lecanemab reported a modest improvement in their symptoms.

To definitively prove the idea, more tests and studies are required. New potential causes of neuron death are also being investigated.

Is Alzheimer’s Disease Hereditary?

Children may inherit specific mutations that cause early-onset Alzheimer’s disease from their parents in some situations. When this occurs, illness is due to a mutated gene. If there is a history of Alzheimer’s disease in your family, you may want to talk to a doctor about getting genetic testing.

It is estimated that genetics have a role in about 70% of Alzheimer’s cases. However, there is less certainty about the genetics of late-onset Alzheimer’s disease.

When it comes to late-onset Alzheimer’s disease, apolipoprotein E (APOE) is the most influential gene. The APOE gene exists in at least one form (or variation) in every human being. Inheriting the 4 variations, however, increases your risk of developing the condition. However, carrying the uncommon APOE 2 mutation can protect you from developing Alzheimer’s disease.

Who Typically Develops Alzheimer’s?

The risk of developing Alzheimer’s disease varies from person to person. Some examples of potential risk factors are:

• Age: Age is the most significant risk factor for Alzheimer’s, with symptoms typically starting after the age of 65. The percentage of people affected by Alzheimer’s increases with age, and around 40% of individuals over the age of 85 have the disease.
  
• Biological sex and gender: Nearly two-thirds of Alzheimer’s cases occur in individuals assigned female at birth. However, this may be attributed to the fact that women tend to live longer than men on average. In the United States, the rates of Alzheimer’s development at each age are similar between women and men. Recent studies have also revealed biases in older research regarding sex and gender.
  
• Ethnicity: Black and Hispanic populations were previously considered to be at a higher risk of Alzheimer’s. However, newer studies have challenged this idea, suggesting that socioeconomic factors and health conditions such as heart disease and diabetes, which are more prevalent in these populations, may contribute to the differences in risk. Structural racism can also impact other social and environmental risk factors for Alzheimer’s.

It’s important to note that these factors contribute to the overall risk but do not guarantee the development of Alzheimer’s. Ongoing research aims to further understand the complex interplay of these factors and develop strategies for prevention and treatment.

Risk Factors

There are various conditions, injuries, and circumstances that have been identified as potential contributors to the development of Alzheimer’s disease:

• Vascular (Blood Vessel) Conditions: High blood pressure (hypertension), heart disease, and stroke are examples of vascular conditions that can impact the blood supply to the brain. These issues can lead to brain inflammation and eventually increase the risk of Alzheimer’s.
  
• Metabolic Conditions: Conditions such as type 2 diabetes, high LDL cholesterol levels, and obesity, particularly when experienced during midlife, have been associated with an increased risk of Alzheimer’s disease.
  
• Depression: Depression has been linked to an elevated risk of Alzheimer’s. Although there is limited evidence, treatment with antidepressants may potentially reduce this risk. It is worth noting that depression can also serve as an early indicator of Alzheimer’s, as both conditions can exhibit similar mood symptoms.
  
• Social Isolation and Loneliness: Both social isolation, which refers to a lack of social interaction, and loneliness, the feeling of being alone or disconnected even in the presence of others, have been identified as risk factors for Alzheimer’s disease. Engaging in social activities, conversing with others, or volunteering can help mitigate these risks and enhance overall well-being and cognition.
  
• Traumatic Brain Injury (TBI): A history of traumatic brain injury, ranging from mild concussions to severe head injuries, can increase the likelihood of developing Alzheimer’s. Even minor TBIs can have long-term effects on cognitive health, underscoring the importance of preventing and managing head injuries.
  
• Heavy Alcohol Use: While heavy alcohol use has been associated with changes in the brain and cognitive decline, the direct causal relationship with Alzheimer’s is still unclear. However, it is worth noting that light to moderate alcohol consumption in middle to late adulthood has shown a decrease in the risk of cognitive decline and dementia.
  
• Smoking: Individuals who have never smoked or have quit smoking long-term may have a lower risk of Alzheimer’s disease. Reducing smoking habits, even if complete cessation is not achieved, can still lower the risk. Secondhand smoke exposure, particularly at home, can also increase the likelihood of developing Alzheimer’s.
  
• Hearing Loss: Alzheimer’s has been linked to hearing loss, although the exact relationship remains unclear. One hypothesis suggests that hearing impairment may contribute to social isolation, which is itself a risk factor for Alzheimer’s. Another hypothesis suggests that the increased cognitive resources required to process sounds in individuals with hearing loss may leave fewer resources available for other cognitive functions.
  
• Air Pollution: Elevated levels of tiny particulate matter, known as PM 2.5, which stem from sources like power plants, construction sites, and fires, have been associated with higher rates of Alzheimer’s. Other forms of pollution, including nitrogen oxides emitted from burning fuel in cars and power plants, as well as sulfur dioxide emitted from burning fossil fuels in industrial facilities, can also cause brain damage similar to that observed in individuals with Alzheimer’s.
  
• Physical Inactivity: Regular physical activity has been shown to reduce the risk of Alzheimer’s and other forms of dementia. Long-term studies have indicated that engaging in physical activity can provide protection against Alzheimer’s over time.
  
• Low Mental Engagement: Maintaining mental stimulation, especially earlier in life, can help safeguard against Alzheimer’s. Higher education has been linked to a reduced risk of dementia, and engaging in cognitively stimulating activities such as reading, learning a second language, playing music, and pursuing mentally challenging jobs can also contribute to lower risk levels.

A Brief Summary

People aged 65 and over often suffer the most from Alzheimer’s disease, which leads to a decline in cognitive abilities such as memory and reasoning. Even though hereditary and environmental factors are suspected, the exact causes of Alzheimer’s disease are yet unknown.

The most significant predictor of Alzheimer’s disease is age. Heart disease, brain injuries, and inactivity are among well-documented dangers. There is currently no way to forecast who will acquire Alzheimer’s disease, despite the fact that new research are integrating more demographically varied people to do so.

The unknown nature of Alzheimer’s disease might be frightening, but keep in mind that scientific investigation into the condition is ongoing. If you or a loved one has been diagnosed, your doctor may offer further details on treatment and prognosis.