Alzheimer’s Disease: Understanding the Most Common Form of Dementia

Alzheimer’s Disease (AD) is the most well-known form of dementia. However, not all types of dementia are caused by Alzheimer’s, although it is the most common. Dementia is actually a syndrome that can be caused by one or more of several different diseases, and AD is only one of them. Dementia is typically recognized when a person has memory loss plus a gradual decline in cognitive ability, which is severe enough to affect daily functioning. It usually develops over many years, and as time goes on, it often becomes more severe. 

AD most often affects people above the age of 65 but is not a normal part of aging.  A delay in memory is a normal result of aging, but not being able to remember something at all is usually called mild cognitive impairment (MCI). It is not dementia unless it begins to interfere with daily life. 

Alzheimer’s Disease (AD) is a type of dementia that occurs when brain cells (neurons) are damaged and begin to shrink or die, likely due to a combination of genetic, environmental, and lifestyle-related changes in the brain. Risk factors that weaken the brain’s natural defenses may make it more likely for a person to show the symptoms of Alzheimer’s. These risk factors include brain injuries, substance or alcohol use, or chronic diseases like diabetes.

In this article, we will discuss the causes, types, signs and symptoms, diagnosis, treatment, and prevention of dementia caused by Alzheimer’s Disease.

What Is the Main Cause of Alzheimer’s Disease? 

The actual cause of the damage to the brain is unknown. The damage to neurons creates toxic substances in the brain called amyloid and tau proteins, which in turn clump up and form structures called plaques and tangles. These affect the function of multiple parts of the brain. This can interfere with memory, thinking, mood, communication, and learning abilities. 

There may be a genetic predisposition to developing AD. The apolipoprotein gene (APOE) is found in humans in three different forms: APOE 2, APOE 3, or APOE 4. Each one has a different risk for AD. The APOE 2 form decreases risk, the APOE 3 form is neutral, and the APOE 4 form increases risk. Like all other genes, each cell in our bodies contains two copies of the APOE gene.

About 25% of the population has one copy of APOE 4, and another 1% has two copies. Having one copy of APOE 4 is associated with 3 times the risk for AD, and having two copies is associated with 8 – 10 times the risk. It is important to note that APOE 4 does not cause AD; it just increases the risk of developing it. Not everybody with APOE 4 develops AD, and people who don’t have APOE 4 at all can still develop AD. Testing is not recommended because there is no preventive treatment developed at this time. 

Types of Alzheimer’s Disease 

The major form of AD usually starts with memory loss and may progress over the course of 8 – 20 years with the loss of other mental functions such as thinking, learning, and communicating, which leads to dependence on others for basic life activities. There is no permanent cure, but specific therapies or medications can sometimes help manage or slow down the symptoms. 

There are other “atypical” types of AD where the early symptoms come from a different area of function in the brain before going on to affect memory. These are:

Posterior cortical atrophy 

This type of Alzheimer’s often begins at an earlier age than usual, in the mid-50s or early 60s. The neurons in the back of the brain are affected before other areas, which is where our vision center is, as well as our sense of where things are in relation to each other. When damaged, the brain cannot correctly interpret and process the information received from the eyes. Early symptoms can include trouble reading, not being able to see or identify where one’s hand is in relation to other objects, and difficulty avoiding objects while walking.

Corticobasal syndrome 

This type of Alzheimer’s also often begins at an earlier age than usual, in the early 60s. The neurons on the sides and at the bottom of the brain are affected before other areas, which is where our language skills and body senses are located. Early symptoms can include stiffness and difficulty making a limb move. This can cause difficulty with the actual act of walking or keeping one’s balance, as well as difficulty in both speaking and understanding. 

Logopenic Primary Progressive Aphasia  

The neurons on the lower sides of the brain are affected before other areas, where the language centers are. Early symptoms include difficulty with finding the right word that is so severe that the person cannot name common objects, and has trouble following lengthy directions. People can usually continue to understand words for a long time, although this may get worse over time. There are also other forms of primary progressive aphasia.

Early-Onset Familial Alzheimer’s Disease 

This form of Alzheimer’s can start at an early age, in one’s 30s or 40s. It is inherited through families because of a single genetic mutation that gives a child a 50% chance of having the disease. Less than 5% of Alzheimer’s Disease is caused by this type. It is different from the gene commonly reported in the media, which is apolipoprotein (APOE), as explained above. The symptoms are like the main form of AD but start much sooner and progress faster. 

What Are the Signs and Symptoms of Alzheimer’s Disease? 

The most common signs and symptoms of AD include: 

• Forgetting recent life events or activities 
• Difficulty communicating, such as choosing the right words or understanding directions
• Personality or mood changes, often becoming anxious, irritated, or aggressive
• Difficulty performing personal care 
• Delusions or hallucinations 
• Confusion or disorientation to time or place
• Difficulty in handling complex tasks

Diagnosis of Alzheimer’s Disease 

The diagnosis of AD is done by analyzing a person’s overall mental and physical health and performing specific brain imaging tests. There are blood and spinal fluid tests that have been recently developed to detect abnormal protein levels and do genetic testing, but they have not yet been widely tested for accuracy in the general population. 

The healthcare provider will often check the following to look for other possible causes for the person’s signs and symptoms:

• Medical history 
• Overall physical and mental health condition 
• Medication use
• Changes in mood or behavior
• Ability to perform day-to-day tasks
• Screening tests of memory, thinking, and spatial ability

The following brain imaging scans may be done:

• Computerized tomography (CT)
• Magnetic resonance imaging (MRI)
• Positron emission tomography (PET)

Alzheimer’s Disease Treatment 

There are certain prescription medications that may temporarily reduce the signs or symptoms of dementia and others that may slow down the speed at which the disease gets worse. There is no permanent cure. Most over-the-counter medications marketed for memory loss are vitamins or proteins that have not been proven to be effective and are not required to provide proof or go through review by the FDA.

1. Cholinesterase Inhibitors 

Acetylcholine is a chemical messenger in the brain that helps the neurons communicate with one another. It needs to last long enough to send the message but eventually must be erased to allow the next message to arrive. It is important in language, memory, thinking, and judgment. In AD, acetylcholine may be erased by the body before the message can be received. 

Cholinesterase inhibitors are drugs that slow down how fast the brain breaks down acetylcholine, making it last longer in the brain and sometimes easing dementia symptoms. They are available in multiple forms (pills, patches, etc.). As always, there are multiple side effects and drug interactions with other medications. It is usually recommended for mild cognitive impairment and early-stage dementia.

Some examples of cholinesterase inhibitors are: 

• Donepezil
• Rivastigmine
• Galantamine

2. Memantine 

Memantine is a drug that functions by decreasing the effects of another chemical messenger in the brain called glutamate. It helps by temporarily blocking the message from being received by the other neuron. Too much glutamate may damage nerve cells. It is usually used in the moderate to advanced stages of dementia to help reduce signs and symptoms. 

3. Other Medications 

Sometimes other drugs that are used for other conditions are recommended in AD to manage behavioral symptoms of dementia, such as wandering at night, anxiety, depression, or delusions that are distressing to the person with AD. These drugs are often tranquilizers, sedatives, or depression medications. It is very important to weigh the side effects and risks of these medicines against the possible benefits. They are also available in multiple forms and may include:

• Antipsychotics 
• Anti-anxiety drugs
• Antidepressants 
• Anticonvulsant drugs 

4. Anti-amyloid monoclonal antibodies

These medications have recently come on the market and are not widely available. They are reported to work by reducing the build-up of amyloid plaque in the brain by encouraging the brain’s immune system to attack and remove the amyloid. They are only available by intravenous (IV) administration and can only be given in the office of a healthcare provider. Because of the high risk of side effects, such as a small amount of brain bleeding, it takes a year to build up to the recommended dose and requires brain imaging several times a year. It is recommended only for persons with mild cognitive impairment (MCI) or persons in the mild stage of AD for prevention of the progression of the disease. These medications are very expensive. They include:

• Lecanemab 
• Donanemab

Prevention of Alzheimer’s Disease 

Maintaining a healthy lifestyle is key to preventing cognitive decline and AD. The following lifestyle changes may help reduce the risk of developing dementia: 

Staying Mentally Active

Exercise the brain with mental activities like socializing, learning something new, cooking, or playing brain games (like sudoku, chess, puzzles, or crossword games). These may strengthen cognitive functions, improving focus, memory, and concentration. 

Physical Activity 

Physical activity helps increase blood flow and oxygen to the brain, particularly to the hippocampus, an area of the brain involved in learning and memory. It is best to engage in moderate-intensity physical activity, like fast walking or cycling, for 150 minutes every week. However, any physical activity is better than none.

Maintaining a Healthy and Balanced Diet

Studies show that following a balanced diet is favorable for brain health. This may include specific diets, like the DASH diet, Mediterranean diet, or Nordic diet. These diets mainly include consuming whole grains, cheese, yogurt, fresh fruits, and vegetables.

It is also recommended that red meat should not be consumed more than a few times per month, and fish, chicken, and eggs should be consumed only a few times a week. Lastly, fats should be taken from unsaturated sources, like olive oil, fatty fish, seeds, and nuts.

References:

1. https://memory.ucsf.edu/what-dementia