Alzheimer’s Disease (Kunkle, 2019) – Is Alzheimer’s genetic?

Woman's brain alzheimer's disease

Nebula Genomics DNA report for Alzheimer’s

Is Alzheimer’s genetic? We created a DNA report based on a study that attempted to answer this question. Below you can see a SAMPLE DNA report. To get your personalized DNA report, purchase our Whole Genome Sequencing!

Is Alzheimers genetic? Sample report from Nebula Genomics.
Is Alzheimers genetic? Sample variant analysis from Nebula Genomics

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What is Alzheimer’s (Part 1 of Is Alzheimer’s genetic?)

Alzheimer’s disease is a neurodegenerative disease, which occurs in its most common form in people over the age of 65 and is characterized by increasing dementia. 

Although they are often used interchangeably, the terms dementia and Alzheimer’s refer to different conditions. Dementia is the generic term for various diseases of the brain and is clearly described in the scientific discussion on the basis of diagnostic criteria. Common to all dementias is the increasing loss of cognitive functioning, emotional and social abilities. Alzheimer’s disease is a type of dementia, according to the current state of scientific knowledge the most common and generally the best known form. Alzheimer’s is the most common form of dementia, accounting for 60-80% of cases. 

This disease is progressive, where dementia symptoms gradually worsen over time. As of 2017, it was the sixth leading cause of death in the United States.  

A picture description of memory loss
Alzheimer’s disease affects memory and cognition processes.

Is Alzheimer’s genetic?

To date, the cause of Alzheimer’s disease has not been fully clarified, although a combination of factors are suspected. The greatest risk factors for Alzheimer’s are:

  • Older people of advanced age
  • Carrying the e4 form of the APOE gene
  • Family history

Genetically, a variant in the gene for ApoE has been identified as a risk factor for the development of Alzheimer’s disease. In addition, causal mutations in three different genes called presenilin-1 and -2 and amyloid precursor protein (APP). These mutations are thought to cause only a small percentage of Alzheimer’s cases (1 percent or less). However, patients inheriting an Alzheimer’s mutation to the APP gene or presenilin 1 gene are guaranteed to develop the disease and those inheriting an Alzheimer’s mutation to the presenilin 2 gene have a 95 percent chance of developing the disease.

Certain genetic mutations and the extra copy of chromosome 21 that characterizes Down syndrome are uncommon genetic factors that strongly influence Alzheimer’s risk. 

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Non-genetic risk factors (Part 3 of Is Alzheimer’s genetic?)

In addition to aging and genetic predisposition, other health and environmental factors for Alzheimer’s include disease risk:

  • Previous craniocerebral trauma
  • Metabolic diseases 
  • Insulin resistance and hyperinsulinemia
  • Diabetes 
  • High cholesterol levels 
  • Diseases of the cardiovascular system 
  • High blood pressure
  • Stroke

Individuals who are in good physical health and engage in physical activity are less at risk to develop Alzheimer’s. 

Mild cognitive impairment (MCI) is a different disease in which patients experience a slight but noticeable decline in cognitive abilities, including memory and thinking skills. A person with MCI is at an increased risk of developing Alzheimer’s or another dementia.

Epidemiology (Part 4 of Is Alzheimer’s genetic?)

According to the Alzheimer’s Association, there were around 5.8 million people living in the United States with Alzheimer’s in 2019 of which 97% of which are 65 or older. This number is based on clinical diagnostic criteria although it is acknowledged that the disease begins many years before the onset of symptoms, through biological changes in the brain that control memory and cognition. 

Women are significantly more likely to develop Alzheimer’s than men. One reason is their higher life expectancy. Moreover, recent research has revealed connections between fluctuations in hormone levels during menopause and the risk of developing Alzheimer’s. There is also a higher prevalence of Alzheimer’s in minorities compared with whites. A higher risk for  health conditions such as cardiovascular disease and diabetes, which are associated with an increased risk for Alzheimer’s and other dementias, are believed to account for these differences.

In 2017, 37,000 commercially insured Americans between the ages of 30-64 were diagnosed with early onset Alzheimer’s disease, which occurs in persons of a younger age than expected. 

According to estimates by Alzheimer’s Disease International, in 2015, approximately 46.8 million people worldwide were affected by dementia. According to the evaluation of computer models, this number, which is based on population projections by the United Nations, is expected to increase to around 131.5 million patients by 2050.

Characteristics and Symptoms (Part 5 of Is Alzheimer’s genetic?)

Alzheimer’s is characterized by an increasing deterioration in cognitive performance, usually accompanied by a decrease in the ability to cope with the activities of daily life, with increasing behavioral abnormalities and an increase in neuropsychiatric symptoms. Symptoms of Alzheimer’s such as memory loss may be mild early in the disease but often become more pronounced with late stage Alzheimer’s, with individuals losing the ability to carry on a conversation and respond to their environment. 

Many years before the first clinical symptoms become visible, plaques consisting of misfolded beta-amyloid (Aβ) peptides form in parts of the brain. Together with the amyloid plaques, neurofibrils, which are deposited in the neurons in the form of balls, are characteristic of the disease. Alzheimer’s disease belongs to the tauopathies, since in this neurodegenerative disease defective tau proteins attach themselves from the neuron (brain cell) body to the neuron axons, incapacitating the cells. As the disease progresses, brain cells die and connections among cells are lost, causing cognitive difficulties to worsen.

Neuron disease in Alzheimer's
An illustration of the neuropathology of Alzheimer’s disease. BruceBlaus. Attribution-Share Alike 4.0 International.

Alzheimer’s is not a normal part of aging. The first symptoms of Alzherimer’s vary among affected people. Memory problems are usually one of the first noticeable signs. Mild cognitive impairment may also be an early symptom. As the disease progresses, people experience greater memory loss and cognitive declines. 

According to the National Institute of Aging, a national center at the National Institutes of Health, people experience several symptoms of Alzheumers in various stages: mild (early-stage), moderate (middle stage), and severe (late-stage).

Early stage (mild)

A person with Alzheimer’s may function independently at this stage. They may experience some memory lapses, such as misplacing objects or forgetting familiar words. While the symptoms may not be widely apparent, they may be noticed by close family and friends. 

  • Memory loss
  • Poor judgment leading to bad decisions
  • Loss of spontaneity and sense of initiative
  • Taking longer to complete normal daily tasks
  • Repeating questions
  • Trouble handling money and paying bills
  • Wandering and getting lost
  • Losing things or misplacing them in odd places
  • Mood and personality changes
  • Increased anxiety and/or aggression

Middle stage (moderate)

This stage can last for many years. Dementia symptoms are more pronounced and the person may become confused, frustrated, or angry. 

  • Increased memory loss and confusion
  • Inability to learn new things
  • Difficulty with language and problems with reading, writing, and working with numbers
  • Difficulty organizing thoughts and thinking logically
  • Shortened attention span
  • Problems coping with new situations
  • Difficulty carrying out multi step tasks, such as getting dressed
  • Problems recognizing family and friends
  • Hallucinations, delusions, and paranoia
  • Impulsive behavior such as undressing at inappropriate times or places or using vulgar language
  • Inappropriate outbursts of anger
  • Restlessness, agitation, anxiety, tearfulness, wandering—especially in the late afternoon or evening
  • Repetitive statements or movement, occasional muscle twitches

Late stage (severe)

Individuals lose the ability to respond to their environment , carry out a conversation, and, eventually, to control movement. The individual normally has difficulty communicating and carrying out daily activities.

  • Inability to communicate
  • Weight loss
  • Seizures
  • Skin infections
  • Difficulty swallowing
  • Groaning, moaning, or grunting
  • Increased sleeping
  • Loss of bowel and bladder control

Diagnosis (Part 6 of Is Alzheimer’s genetic?)

Alzheimer’s is often diagnosed during the mild, or early-stage, of the disease. There is no single test for Alzheimer’s disease. Physicians use a variety of approaches and tools to make a diagnosis. Some of the most common diagnostic methods include: 

  • Medical and family history, including psychiatric history and history of cognitive and behavioral changes
  • A family member’s account of thinking and behavioral changes
  • Cognitive tests and physical and neurologic examinations
  • Blood tests and brain imaging to rule out other causes
  • Brain imaging to assess levels of beta-amyloid, a hallmark of Alzheimer’s
An Alzheimer's brain compared with a healthy brain
Healthy brain (bottom) versus brain of a donor with Alzheimer’s disease. Hersenbank. 3.0 Unported.

Treatment (Part 7 of Is Alzheimer’s genetic?)

There is currently no cure for Alzheimer’s. Some medications can treat the symptoms of the disease.  

The U.S. Food and Drug Administration (FDA) has approved two types of Alzheimer’s medications, cholinesterase inhibitors for early to moderate stage (Aricept®, Exelon®, Razadyne®) and memantine for late stage (Namenda®), to treat the cognitive symptoms (memory loss, confusion, and problems with thinking and reasoning) of Alzheimer’s disease. These medications may help lessen or stabilize symptoms for a limited time by affecting certain chemicals involved in carrying messages among the brain’s nerve cells. Sometimes, they are taken together. 

For behavioral and personality changes that accompany Alzheimer’s, such as anxiety, depression, emotional distress, and hallucinations, patients may undergo non-drug treatments that promote physical and emotional comfort. If appropriate and approved by a physician, some medication that can be used that includes antidepressants, anxiolytics, and antipsychotic medications. 

In recent years, many novel drugs have been used in clinical trials as possible treatments for early Alzheumer’s disease. However, none have been shown clinically effective. In November 2020, the FDA failed to endorse the newest candidate, Aducanumab. The FDA has not approved a new drug for Alzheimer’s in 17 years.

Prognosis (Part 8 of Is Alzheimer’s genetic?)

A common cause of death for people with Alzheimer’s is aspiration pneumonia, when pneumonia develops when a person cannot swallow properly and takes food or liquids, instead of air, into the lungs.

Once Alzheimer’s is diagnosed, the remaining life expectancy is about seven to ten years, although there are cases in which the final stage is reached after only four to five years. On the other hand, there have been patients who have lived for more than 20 years.

If you enjoyed this article, check out our other posts in the Nebula Research Library.

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