Late-onset familial Alzheimer disease, is a form of familial Alzheimer disease, that begins after age 65. In general, Alzheimer disease (AD) is a degenerative disease of the brain that causes gradual loss of memory, judgement and the ability to function socially. The exact underlying cause of late-onset familial AD is not completely understood; however, researchers suspect that it is a complex condition, which is likely associated with multiple susceptibility genes in combination with environmental and lifestyle factors.

A gene called APOE has been studied extensively as a risk factor for the disease. In particular, a variant of this gene called the "e4 allele" seems to increase an individual's risk for developing late-onset Alzheimer disease (people who have this allele are said to have the late-onset familial AD type 2). It is important to understand that APOE is a susceptibility gene, not a determinative gene, which means that people having two copies of this allele have an increased risk of having AD but not necessarily will have it.

There is no cure for AD. Treatment is supportive and based on the signs and symptoms present in each person.

Some cases of early-onset Alzheimer's disease are caused by gene variants (also called mutations) that can be passed from parent to child. This results in what is known as early-onset familial Alzheimer's disease (FAD). Researchers have found that this form of the disorder can result from variants in the APP, PSEN1, or PSEN2 genes. When any of these genes is altered, large amounts of a toxic protein fragment called amyloid beta peptide are produced in the brain. This peptide can build up in the brain to form clumps called amyloid plaques, which are characteristic of Alzheimer's disease. A buildup of toxic amyloid beta peptide and amyloid plaques may lead to the death of nerve cells and the progressive signs and symptoms of this disorder. Other cases of early-onset Alzheimer's disease may be associated with changes in different genes, some of which have not been identified.

Some evidence indicates that people with Down syndrome have an increased risk of developing Alzheimer's disease. Down syndrome, a condition characterized by intellectual disability and other health problems, occurs when a person is born with an extra copy of chromosome 21 in each cell. As a result, people with Down syndrome have three copies of many genes in each cell, including the APP gene, instead of the usual two copies. Although the connection between Down syndrome and Alzheimer's disease is unclear, the production of excess amyloid beta peptide in cells may account for the increased risk. People with Down syndrome account for less than 1 percent of all cases of Alzheimer's disease. This type of Alzheimer's disease is not inherited.

The causes of late-onset Alzheimer's disease are less clear. The late-onset form does not clearly run in families, although clusters of cases have been reported in some families. Alzheimer's disease is probably related to variations in one or more genes in combination with lifestyle and environmental factors. A gene called APOE has been studied extensively as a risk factor for the disease. In particular, a variant of this gene called the e4 allele seems to increase an individual's risk for developing late-onset Alzheimer's disease.

Many more genes have been associated with Alzheimer's disease, and researchers are investigating the role that additional genes may play in Alzheimer's disease risk.

Many people wonder if Alzheimer’s disease runs in their family. Is it in your genes? This question isn’t easy to answer. Researchers have identified several genetic variants that are associated with Alzheimer’s and may increase or decrease a person’s risk of developing the disease. What does that mean? Let’s first learn about the role of genes.

What Are Genes?

Human cells contain the instructions needed for a cell to do its job. These instructions are made up of DNA, which is packed tightly into structures called chromosomes. Each chromosome has thousands of segments called genes.

Genes are passed down from a person’s biological parents. They carry information that defines traits such as eye color and height. Genes also play a role in keeping the body’s cells healthy.

Variations in genes — even small changes to a gene — can affect the likelihood of a person developing a disease such as Alzheimer’s.

Do Genes Cause Diseases?

Permanent changes in one or more specific genes are called genetic variants. Some of these variants are quite common in the human population. While most genetic variants don’t cause diseases, some do. In some cases, a person inherits a genetic variant that will almost certainly lead to that individual developing a disease. Sickle cell anemia, cystic fibrosis, and some cases of early-onset Alzheimer’s are examples of inherited genetic disorders. However, other variants may simply increase, or even decrease, a person’s risk of developing that disease. Identifying genetic variants and their effects can help researchers uncover the most effective ways to treat or prevent diseases in an individual.

Additionally, factors such as exercise, diet, chemicals, or smoking can have positive or negative effects by changing the way certain genes work. In the field of epigenetics, researchers are studying how such factors can alter a cell’s DNA in ways that affect gene activity.

Genetic research is a component of precision medicine, an emerging approach that considers individual variability in genes, environment, and lifestyle. Precision medicine will enable researchers and doctors to predict more accurately which treatment and prevention strategies will work in particular groups of people.

Genes and Alzheimer's Disease

In most cases, Alzheimer’s does not have a single genetic cause. Instead, it can be influenced by multiple genes in combination with lifestyle and environmental factors. Consequently, a person may carry more than one gene or group of genes that can either increase or reduce the risk of Alzheimer’s.

Importantly, people who develop Alzheimer’s do not always have a history of the disease in their families. Still, those who have a parent or sibling diagnosed with the disease have a higher risk of developing Alzheimer’s than those without that association.

Genetic variants that affect Alzheimer's disease risk

Ten years ago, researchers knew of only 10 genes linked with Alzheimer’s. Today, scientists have identified more than 70 genetic regions associated with Alzheimer’s. Understanding which genes play a role — and what role they play — may help identify new methods to prevent, delay, or treat dementia.

One well-known gene that influences Alzheimer’s risk is the apolipoprotein E (APOE) gene. The APOE gene is involved in making a protein that helps carry cholesterol and other types of fat in the bloodstream. Problems in this process are thought to contribute to the development of Alzheimer’s. APOE comes in several forms, called alleles (e.g., ε2, ε3).

• APOE ε2 may provide some protection against the disease. If Alzheimer’s occurs in a person with this allele, it usually develops later in life than it would in someone with the APOE ε4 gene. Roughly 5% to 10% of people have this allele.
• APOE ε3, the most common allele, is believed to have a neutral effect on the disease — neither decreasing nor increasing risk of Alzheimer’s.
• APOE ε4 increases risk for Alzheimer’s and is associated with an earlier age of disease onset in certain populations. About 15% to 25% of people have this allele, and 2% to 5% carry two copies.

Each person inherits two APOE alleles, one from each biological parent, meaning people can have one of six possible combinations: 2/2, 2/3, 2/4, 3/3, 3/4, and 4/4. Having two copies of APOE ε4 is associated with a higher risk of Alzheimer’s than having one copy. While inheriting APOE ε4 increases a person’s risk of Alzheimer’s, some people with an APOE ε4 allele never develop the disease.

Researchers are also finding other rare genetic variants, in addition to APOE ε2, that appear to provide some protection against developing Alzheimer’s.

However, prevalence and risk associated with APOE and other genetic variants may not be the same across all population groups. Research suggests that the degree of risk may be affected by genetic ancestry — the global geographic region from which a person is biologically descended — and differ among people of African, Asian, American Indian, and European descent. More research is needed to better understand how certain genetic variants might affect a person’s or group’s risk for Alzheimer’s and to identify treatment and prevention strategies that will work best for that particular group.

Genetic variants that cause Alzheimer's disease

Of the genetic variants so far associated with Alzheimer’s, three rare single-gene variants are known to cause the disease:

• Amyloid precursor protein (APP) on chromosome 21
• Presenilin 1 (PSEN1) on chromosome 14
• Presenilin 2 (PSEN2) on chromosome 1

A child whose biological parent carries a genetic variant for one of these three genes has a 50/50 chance of inheriting that altered version of the gene. If the variant is inherited, the child has a very strong probability of developing Alzheimer’s before age 65 and sometimes much earlier. When someone develops Alzheimer’s before age 65, it’s known as “early-onset Alzheimer’s” or sometimes “younger-onset Alzheimer’s” or “earlier-onset Alzheimer’s.” Less than 10% of all people with Alzheimer’s develop symptoms this early. Of those who do, 10% to 15% can be attributed to changes in APP, PSEN1, and PSEN2.

Changes in these three genes result in the production of abnormal proteins that are associated with the disease. Each of these mutations contributes to the breakdown of APP, a protein that’s function isn’t completely understood. The breakdown of APP is part of a process that makes harmful forms of sticky amyloid fragments. These fragments cluster to form plaques in the brain, which is a hallmark of Alzheimer’s.

In addition to the three genetic variants that are known to cause Alzheimer’s, people with Down syndrome have an extra copy of chromosome 21, which carries the APP gene, and a higher risk of developing early-onset Alzheimer’s. Estimates suggest that 50% or more of people living with Down syndrome will develop Alzheimer’s with symptoms appearing in their 50s and 60s.

Genetic testing for Alzheimer's disease

Genetic tests are not routinely used in clinical settings to diagnose or predict the risk of developing Alzheimer’s or a related dementia.

In some cases, if a person has symptoms at an early age with a strong family history of Alzheimer’s, a neurologist or other medical specialist may order a genetic test for APP, PSEN1, and PSEN2.

Although APOE testing is also available, the results cannot fully predict who will or won’t develop Alzheimer’s. Rather, this type of testing is used primarily in research settings to identify study participants who may have an increased risk of developing Alzheimer’s. This approach helps scientists look for early brain changes and compare the effectiveness of possible treatments for people with different APOE profiles.

Some people learn their APOE status through consumer genetic testing. These products are available for a fee and provide some information around the results and what they mean. While at-home genetic tests are convenient, people considering them may also benefit from talking with a doctor or genetic counselor to better understand this type of test and their test results.

Normal Function

The APP gene provides instructions for making a protein called amyloid precursor protein. This protein is found in many tissues and organs, including the brain and spinal cord (central nervous system). Little is known about the function of amyloid precursor protein. Researchers speculate that it may bind to other proteins on the surface of cells or help cells attach to one another. Studies suggest that in the brain, it helps direct the movement (migration) of nerve cells (neurons) during early development.

Amyloid precursor protein is cut by enzymes to create smaller fragments (peptides), some of which are released outside the cell. Two of these fragments are called soluble amyloid precursor protein (sAPP) and amyloid beta (β) peptide. Recent evidence suggests that sAPP has growth-promoting properties and may play a role in the formation of neurons in the brain both before and after birth. The sAPP peptide may also control the function of certain other proteins by turning off (inhibiting) their activity. Amyloid β peptide is likely involved in the ability of neurons to change and adapt over time (plasticity). Other functions of sAPP and amyloid β peptide are under investigation.

Health Conditions Related to Genetic Changes

Alzheimer's disease

Many variants (also called mutations) in the APP gene can cause early-onset Alzheimer's disease, which begins before age 65. These variants are responsible for less than 10 percent of all early-onset cases of Alzheimer's disease.

The most common APP gene variant changes one of the protein building blocks (amino acids) in the amyloid precursor protein. This variant replaces the amino acid valine with the amino acid isoleucine at protein position 717 (written as Val717Ile or V717I). Variants in the APP gene can lead to an increased amount of the amyloid β peptide or to the production of a slightly longer and stickier form of the peptide. When these protein fragments are released from the cell, they can accumulate in the brain and form clumps called amyloid plaques. These plaques are characteristic of Alzheimer's disease. A buildup of toxic amyloid β peptide and amyloid plaques may lead to the death of neurons and the progressive signs and symptoms of Alzheimer's disease.

Hereditary cerebral amyloid angiopathy

Variants in the APP gene have been found to cause hereditary cerebral amyloid angiopathy, a condition characterized by stroke and a decline in intellectual function (dementia), which begins in mid-adulthood. These variants change single amino acids in the amyloid precursor protein. Each of these variants causes a different type of the condition. The Dutch type, the most common of all the types, is caused by the replacement of the amino acid glutamic acid with the amino acid glutamine at position 22 in the protein sequence (written as Glu22Gln or E22Q). The Italian type and Arctic type are also caused by changes to glutamic acid at position 22. In the Italian type, glutamic acid is replaced with the amino acid lysine (written as Glu22Lys or E22K) and in the Arctic type, glutamic acid is replaced with the amino acid glycine (written as Glu22Gly or E22G). The Flemish type is caused by replacement of the amino acid alanine with glycine at position 21 (written as Ala21Gly or A21G). In the Iowa type, the amino acid aspartic acid is switched with the amino acid asparagine at position 23 (written as Asp23Asn or D23N). The Piedmont type of hereditary cerebral amyloid angiopathy is caused by the replacement of the amino acid leucine at position 34 with the amino acid valine (written as Leu34Val or L34V).

The result of all of these variants is the production of an amyloid β peptide that is more prone to cluster together (aggregate) than the normal peptide. The aggregated protein forms amyloid deposits that accumulate in the blood vessels of the brain. The amyloid deposits replace the muscle fibers and elastic fibers that give blood vessels flexibility, causing the blood vessels to become weak and prone to breakage. In the brain, such a break causes bleeding (hemorrhagic stroke), which can lead to brain damage and dementia or be life-threatening. Amyloid deposits in specific parts of the brain can interfere with normal brain function, leading to dementia, seizures, movement problems, and other neurological features in some people with hereditary cerebral amyloid angiopathy.

Other Names for This Gene

• A4_HUMAN
• AAA
• ABETA
• ABPP
• AD1
• amyloid beta (A4) precursor protein
• amyloid beta-peptide
• amyloid beta-protein precursor
• amyloid precursor protein
• APPI
• cerebral vascular amyloid peptide
• CVAP
• PN-II
• PN2
• protease nexin 2
• protease nexin-II

Genomic Location

Normal Function

The PSEN1 gene provides instructions for making a protein called presenilin 1. This protein is one part (subunit) of a complex called gamma- (γ-) secretase. Presenilin 1 carries out the major function of the complex, which is to cut apart (cleave) other proteins into smaller pieces called peptides. This process is called proteolysis, and presenilin 1 is described as the proteolytic subunit of γ-secretase.

The γ-secretase complex is located in the membrane that surrounds cells, where it cleaves many different proteins that span the cell membrane (transmembrane proteins). This cleavage is an important step in several chemical signaling pathways that transmit signals from outside the cell into the nucleus. One of these pathways, known as Notch signaling, is essential for the normal growth and maturation (differentiation) of hair follicle cells and other types of skin cells. Notch signaling is also involved in normal immune system function.

The γ-secretase complex may be best known for its role in processing amyloid precursor protein (APP), which is made in the brain and other tissues. γ-secretase cuts APP into smaller peptides, including soluble amyloid precursor protein (sAPP) and several versions of amyloid-beta (β) peptide. Evidence suggests that sAPP has growth-promoting properties and may play a role in the formation of nerve cells (neurons) in the brain both before and after birth. Other functions of sAPP and amyloid-β peptide are under investigation.

Health Conditions Related to Genetic Changes

Alzheimer's disease

Dozens of PSEN1 gene variants (also known as mutations) have been identified in patients with early-onset Alzheimer's disease, a degenerative brain condition that begins before age 65. Variants in the PSEN1 gene are the most common cause of early-onset Alzheimer's disease, accounting for up to 70 percent of cases.

Almost all PSEN1 gene variants change single building blocks of DNA (nucleotides) in a particular segment of the PSEN1 gene. These variants result in the production of an abnormal presenilin 1 protein. Defective presenilin 1 interferes with the function of the γ-secretase complex, which alters the processing of APP and leads to the overproduction of a longer, toxic version of amyloid-β peptide. Copies of this protein fragment stick together and build up in the brain, forming clumps called amyloid plaques that are a characteristic feature of Alzheimer's disease. A buildup of toxic amyloid-β peptide and the formation of amyloid plaques likely lead to the death of neurons and the progressive signs and symptoms of Alzheimer's disease.

Hidradenitis suppurativa

At least one variant (also known as a mutation) in the PSEN1 gene has been found to cause hidradenitis suppurativa, a chronic skin disease characterized by recurrent boil-like lumps (nodules) under the skin that develop in hair follicles. The nodules tend to become inflamed and painful, and they produce significant scarring as they heal.

The identified variant deletes a single DNA building block (nucleotide) from the PSEN1 gene, written as 725delC. This genetic change reduces the amount of functional presenilin 1 produced in cells, so less of this protein is available to act as part of the γ-secretase complex. The resulting shortage of normal γ-secretase impairs cell signaling pathways, including Notch signaling. Although little is known about the mechanism, studies suggest that abnormal Notch signaling may promote the development of recurrent nodules in hair follicles and trigger inflammation in the skin.

Studies suggest that the PSEN1 gene variant that causes hidradenitis suppurativa has a different effect on γ-secretase function than the variants that cause early-onset Alzheimer's disease. These differences may explain why no single PSEN1 gene variant has been reported to cause the signs and symptoms of both diseases.

Familial dilated cardiomyopathy

MedlinePlus Genetics provides information about Familial dilated cardiomyopathy

Other Names for This Gene

• AD3
• FAD
• presenilin 1 (Alzheimer disease 3)
• presenilin 1 protein
• PS1
• PSN1_HUMAN
• PSNL1 gene product
• S182 protein

Genomic Location

Normal Function

The PSEN2 gene provides instructions for making a protein called presenilin 2. Presenilin 2 helps process proteins that transmit chemical signals from the cell membrane into the nucleus. Once in the nucleus, these signals turn on (activate) genes that are important for cell growth and maturation.

Presenilin 2 is best known for its role in processing amyloid precursor protein, which is found in the brain and other tissues. Research suggests that presenilin 2 works together with other enzymes to cut amyloid precursor protein into smaller segments (peptides). One of these peptides is called soluble amyloid precursor protein (sAPP), and another is called amyloid beta peptide. Recent evidence suggests that sAPP has growth-promoting properties and may play a role in the formation of neurons in the brain both before and after birth. Other functions of sAPP and amyloid beta peptide are under investigation.

Health Conditions Related to Genetic Changes

Alzheimer's disease

At least 11 mutations in the PSEN2 gene have been shown to cause early-onset Alzheimer's disease. Mutations in this gene account for less than 5 percent of all early-onset cases of the disorder.

Two of the most common PSEN2 mutations that cause early-onset Alzheimer's disease change single protein building blocks (amino acids) used to make presenilin 2. One mutation replaces the amino acid asparagine with the amino acid isoleucine at position 141 (written as Asn141Ile or N141I). The other mutation changes the amino acid methionine to the amino acid valine at position 239 (written as Met239Val or M239V). These mutations appear to disrupt the processing of amyloid precursor protein, leading to the overproduction of amyloid beta peptide. This protein fragment can build up in the brain and form clumps called amyloid plaques that are characteristic of Alzheimer's disease. A buildup of toxic amyloid beta peptide and amyloid plaques may lead to the death of neurons and the progressive signs and symptoms of this disorder.

Familial dilated cardiomyopathy

MedlinePlus Genetics provides information about Familial dilated cardiomyopathy

Other Names for This Gene

• AD3-like protein
• AD3L
• AD3LP
• AD4
• AD5
• Alzheimer's disease 3-like
• E5-1
• presenilin 2 (Alzheimer disease 4)
• PS2 protein (alzheimer-associated)
• PSN2_HUMAN
• PSNL2
• STM2

Genomic Location

Normal Function

The APOE gene provides instructions for making a protein called apolipoprotein E. This protein combines with fats (lipids) in the body to form molecules called lipoproteins. Lipoproteins are responsible for packaging cholesterol and other fats and carrying them through the bloodstream. Maintaining normal levels of cholesterol is essential for the prevention of disorders that affect the heart and blood vessels (cardiovascular diseases), including heart attack and stroke.

There are at least three slightly different versions (alleles) of the APOE gene. The major alleles are called e2, e3, and e4. The most common allele is e3, which is found in more than half of the general population.

Health Conditions Related to Genetic Changes

Alzheimer's disease

The e4 version of the APOE gene increases an individual's risk for developing late-onset Alzheimer's disease. Alzheimer's disease is a degenerative disease of the brain that causes dementia, which is a gradual loss of memory, judgment, and ability to function. The late-onset form of the condition occurs in people older than age 65. People who inherit one copy of the APOE e4 allele have an increased chance of developing the disease; those who inherit two copies of the allele are at even greater risk. The APOE e4 allele may also be associated with an earlier onset of memory loss and other symptoms compared to individuals with Alzheimer's disease who do not have this allele.

It is not known how the APOE e4 allele is related to the risk of Alzheimer's disease. However, researchers have found that this allele is associated with an increased number of protein clumps, called amyloid plaques, in the brain tissue of affected people. A buildup of amyloid plaques may lead to the death of nerve cells (neurons) and the progressive signs and symptoms of Alzheimer's disease.

It is important to note that people with the APOE e4 allele inherit an increased risk of developing Alzheimer's disease, not the disease itself. Not all people with Alzheimer's disease have the APOE e4 allele, and not all people who have this allele will develop the disease.

Age-related hearing loss

MedlinePlus Genetics provides information about Age-related hearing loss

Age-related macular degeneration

MedlinePlus Genetics provides information about Age-related macular degeneration

Dementia with Lewy bodies

The e4 version of the APOE gene can increase the risk of developing a form of dementia called dementia with Lewy bodies; however, some people with the APOE e4 allele never develop this condition. Dementia with Lewy bodies is characterized by intellectual decline; visual hallucinations; sudden changes in attention and mood; and movement problems characteristic of Parkinson's disease such as rigidity of limbs, tremors, and impaired balance and coordination.

People who inherit one copy of the APOE e4 allele have an increased chance of developing dementia with Lewy bodies. It is unclear how the APOE e4 allele contributes to the development of this condition. It is thought that the apolipoprotein E produced from the e4 allele of the APOE gene may disrupt the transport of a protein called alpha-synuclein into and out of cells. When alpha-synuclein is trapped inside or outside of cells, it accumulates in clusters, creating Lewy bodies. Accumulation of these clusters throughout the brain impairs neuron function and ultimately causes cell death. Over time, the loss of neurons increasingly impairs intellectual and motor function and the regulation of emotions, resulting in the signs and symptoms of dementia with Lewy bodies.

It is unclear why some people with the APOE e4 allele develop Alzheimer's disease while others develop dementia with Lewy bodies.

Other disorders

Variants of apolipoprotein E have been studied extensively as risk factors for many different conditions. For example, APOE alleles have been shown to influence the risk of cardiovascular diseases. People who carry at least one copy of the APOE e4 allele have an increased chance of developing atherosclerosis, which is an accumulation of fatty deposits and scar-like tissue in the lining of the arteries. This progressive narrowing of the arteries increases the risk of heart attack and stroke.

The APOE e2 allele has been shown to greatly increase the risk of a rare condition called hyperlipoproteinemia type III. Most people with this disorder have two copies of the APOE e2 allele, leading researchers to conclude that the e2 allele plays a critical role in the development of the condition. Hyperlipoproteinemia type III is characterized by increased blood levels of cholesterol, certain fats called triglycerides, and molecules called beta-very low-density lipoproteins (beta-VLDLs), which carry cholesterol and lipoproteins in the bloodstream. A buildup of cholesterol and other fatty materials can lead to the formation of small, yellow skin growths called xanthomas and the development of atherosclerosis.

Other Names for This Gene

• Apo-E
• APOE_HUMAN
• Apolipoproteins E

Genomic Location

Early-onset familial Alzheimer's disease is inherited in an autosomal dominant pattern, which means one copy of an altered gene in each cell is sufficient to cause the disorder. In most cases, an affected person inherits the altered gene from one affected parent.

The inheritance pattern of late-onset Alzheimer's disease is uncertain. People who inherit one copy of the APOE e4 allele have an increased chance of developing the disease; those who inherit two copies of the allele are at even greater risk. It is important to note that people with the APOE e4 allele inherit an increased risk of developing Alzheimer's disease, not the disease itself. Not all people with Alzheimer's disease have the e4 allele, and not all people who have the e4 allele will develop the disease.

Families have many things in common, including their genes, environment, and lifestyle. Together, these things may offer clues to diseases, like late- and early-onset Alzheimer’s, that can run in a family.

Late-Onset Alzheimer’s Disease

There is no test yet to predict if someone will get late-onset Alzheimer’s, in which symptoms become apparent in a person’s mid-60s. If someone is worried about changes in his or her memory or other problems with thinking, he or she should talk with a doctor.

A doctor may ask the patient to make a family health history. A family health history can help a person know if Alzheimer’s disease runs in the family. It lists health facts about a person and close relatives. It is a written record of:

• A family’s health conditions
• Lifestyle habits like smoking and exercise
• Where and how family members grew up

A family health history can show patterns of disease and risk factors. Try to include health facts about three generations—grandparents, parents, and children.

People can’t change the genes they inherit from their parents, but they can change things like diet, physical activity, and medical care to prevent diseases that may run in the family.

Steps to Maintain Cognitive Health

A doctor may suggest steps to stay healthy and watch for changes in memory and thinking. Steps include:

• Exercise regularly.
• Eat a healthy diet that is rich in fruits and vegetables.
• Spend time with family and friends.
• Keep one’s mind active.
• Control type 2 diabetes.
• Keep blood pressure and cholesterol at healthy levels.
• Maintain a healthy body weight.
• Stop smoking.
• Get help for depression.
• Avoid drinking a lot of alcohol.
• Get plenty of sleep.

Early-Onset Alzheimer’s Disease

There is a test to learn if a person has one of the three genetic mutations associated with early-onset Alzheimer's disease, which occurs between a person’s 30s and mid-60s.

If someone has a family history of early-onset Alzheimer's, he or she should talk with a doctor about getting tested.

A doctor may suggest meeting first with a genetic counselor. This type of counselor helps people learn the risk of getting genetic conditions. They also help people make decisions about testing and what comes next.

When a person moves to the later stages of Alzheimer's disease, caregiving may become more difficult. This article offers ways to adjust to the changes that take place during severe or late-stage Alzheimer's.

How to connect with the person

Communicating with a person with late-stage Alzheimer’s disease can take effort and patience. Though that person’s ability to respond may be limited, it is important to continue to interact:

• Continue to visit with the person even if responses are limited.
• Try to speak calmly and slowly; be aware of the tone and volume of your voice.
• Consider sharing familiar stories with the person.
• Make eye contact, say the person’s name and smile.
• Use other methods of communication besides speaking, such as gentle touching or massage.
• Have the person listen to music or calming nature sounds.

When the person with Alzheimers can't move

During the later stages of Alzheimer’s disease, a person may lose the ability to move and spend much of his or her time in a bed or chair. This lack of movement can cause problems such as pressure sores or bedsores, and stiffness of the arms, hands, and legs.

If the person with Alzheimer’s cannot move around on his or her own, contact a home health aide, physical therapist, or nurse for help. These professionals can show you how to move the person safely, such as changing positions in bed or in a chair.

A physical therapist can also show you how to move the person's body joints using range-of-motion exercises. During these exercises, you hold the person's arms or legs, one at a time, and move and bend it several times a day. Movement prevents stiffness of the arms, hands, and legs. It also prevents pressure sores or bedsores.

To make the person more comfortable:

• Buy special mattresses and wedge-shaped seat cushions that reduce pressure sores. You can purchase these at a medical supply store or drugstore or online. Ask the home health aide, nurse, or physical therapist how to use the equipment.
• Move the person at least once every 2 hours if he or she is sitting up.
• Move the person at least once every hour if he or she is lying down.
• Use a lap board to rest the person's arms and support the upper body when he or she is sitting up in bed or in a chair.
• Use a chair with arm rests to help reduce the chances of the person falling. The arms of a chair may also help with standing.
• Give the person something to hold, such as a washcloth, while being moved. The person will be less likely to grab onto you or the furniture. If he or she is weak on one side, stand on the weak side to support the stronger side and help the person change positions.

To keep from hurting yourself when moving someone with Alzheimer's disease:

• Know your strength when lifting or moving the person and don't try to do too much.
• Try to explain to the person what you plan to do before you begin to move them.
• Bend at the knees and then straighten up by using your thigh muscles instead of your back.
• Keep your back straight and don't bend at the waist.
• Hold the person as close as possible to avoid reaching away from your body.
• Place one foot in front of the other, or space your feet comfortably apart for a wide base of support.
• Take small steps to move the person from one seat to another. Don't twist your body.
• Consider using a transfer belt to help move the person. You can find transfer belts at a medical supply store, drugstore, or online.
• Read more tips on how to move the person safely from a bed to a wheelchair.

How to ensure the person eats well

In the later stages of Alzheimer’s disease, many people lose interest in food and caregivers may notice changes in how or when they eat. They may not be aware of mealtimes, know when they've had enough food, or remember to cook. If they are not eating enough different kinds of foods, they may not be getting the nutrients they need to stay healthy.

Here are some suggestions to help a person with late-stage Alzheimer's eat better. Remember that these are just tips—try different things and see what works best for the person:

• Serve bigger portions at breakfast because it's the first meal of the day.
• Offer several smaller meals throughout the day.
• Serve meals at the same time each day.
• Make the eating area quiet. Turn off the TV or radio.
• Control between-meal snacks. Lock the refrigerator door and food cabinets if necessary.
• If the person has dentures, make sure they fit. Loose dentures or dentures with bumps or cracks may cause choking or pain, making it harder to eat. Remove poorly fitting dentures until the person can get some that fit.
• Let the person's doctor know if they lose a lot of weight, for example, if he or she loses 10 pounds in a month.

You can also try different ways of preparing the person's plate. For example:

• Put food on the plate before placing it in front of the person.
• Offer just one food at a time instead of filling the plate or table with too many things.
• Use colorful plates that contrast with the color of the food to help the person see what is on the plate.
• If additional utensils cause confusion, try giving just a spoon to the person.
• Use a plate guard (sometimes called a "spill guard") if the person has trouble getting food onto utensil.
• Move the plate around if he or she seems to only eat from one side of the plate.

If the person needs help eating, you might try to:

• Give the person small amounts of food at a time.
• Describe the food he or she is eating.
• Sit to the side of the person while helping him or her eat because sitting in front may be intimidating.
• Encourage eating by switching between a bite of the meal and a bite of something sweet.
• Make sure the person has swallowed before introducing more food. Sometimes food can be pocketed in the cheeks.

When choosing foods to eat and liquids to drink, these suggestions might help:

• Give the person finger foods to eat such as cheese, small sandwiches, small pieces of chicken, fresh fruits, or vegetables. Sandwiches made with pita bread are easier to handle.
• If weight loss is a concern, give him or her high-calorie, healthy foods to eat or drink, such as protein milk shakes. You can buy high-protein drinks and powders at grocery stores, drugstores, discount stores, and online. You can also mix healthy foods in a blender and let the person drink his or her meal. Use diet supplements if he or she is not getting enough calories. Talk with the doctor or nurse about what kinds of supplements might be best.
• If a person is not getting enough calories, talk with the doctor or nurse about diet supplements and what kinds might be best.
• Consider adding extra healthy fats, such as olive oil and avocados, into a person's diet if they need more calories. Check with the doctor about how much and what kinds of fat to use.
• If the person has heart diseasediabetes or high blood pressure, check with the doctor or a nutrition specialist about which foods to limit.
• Have the person take a multivitamin — these come in different forms such as a tablet, capsule, powder, liquid, or injection — that adds vitamins, minerals, and other important nutrients to a person's diet. Consider which will be easiest for the person to take.

What to do about swallowing problems

As Alzheimer's disease progresses to later stages, the person may no longer be able to chew and swallow easily. This is a serious problem. Difficulty with swallowing may lead to choking or cause food or liquid to go into the lungs, which is known as aspiration. This can cause pneumonia, which can lead to death.

The following suggestions may help with swallowing:

• Make sure to cut food into small pieces and that it is soft enough for the person to eat.
• Grind or blend food to make it easier to eat.
• Offer soft foods, such as yogurt, applesauce, mashed avocado, sweet potatoes, and bananas.
• Don't use a straw, which may cause more swallowing problems. Instead, have the person drink small sips from a cup.
• Offer drinks of different temperatures — warm, cold, and room temperature—to see which might be easiest for the person to drink.
• Don't hurry the person. He or she needs time to chew and swallow each mouthful before taking another bite.

• Encourage the person to feed themselves as much as possible during meals. If the person needs support, try using overhand, underhand, or direct hand feeding approaches.
• Don't feed a person who is drowsy or lying down. He or she should be in an upright, seated position during the meal and for at least 20 minutes after the meal.
• Say "swallow" to remind him or her to swallow.
• Find out if the person's pills can be crushed or taken in another form.

If you are concerned about the person's swallowing, speak with his or her doctor, who may recommend a speech-language pathologist or other specialists for evaluation.

Helping the person with Alzheimer's eat can be exhausting. Planning meals ahead and having the food ready can make this task a little easier for caregivers. Also, remember that people with Alzheimer's disease may not eat much at certain times and then feel more like eating at other times. It helps to make mealtime as pleasant and enjoyable as possible. But no matter how well you plan, keep in mind that the person may not be hungry when you're ready to serve food.

What to do about incontinence

Incontinence means a person can't control his or her bladder and/or bowels. This may happen at any stage of Alzheimer's disease, but it is more often a problem in the later stages. Signs of this problem are leaking urine, problems emptying the bladder, and soiled underwear and bed sheets. Be sure to let the doctor know if this happens. He or she may be able to treat the cause of the problem.

Accidents happen. Try to be understanding when they occur. Stay calm and reassure the person if he or she is upset. Incontinence supplies, such as adult disposable briefs or underwear, bed protectors, and waterproof mattress covers, may be helpful.

Dental, skin, and foot problems

Dental, skin, and foot problems may take place in early and moderate stages of Alzheimer's disease, but most often happen during late-stage Alzheimer's disease.

Dental problems. As Alzheimer's disease symptoms worsen, people will need help taking care of their teeth or dentures. Brushing and flossing help to maintain oral health and reduce bacteria in the mouth, which may decrease the risk of pneumonia.

Make sure the person's teeth and teeth surfaces are gently brushed at least twice a day with fluoride toothpaste. The last brushing session should take place after the evening meal or after any medication is given at night. You may find that using a child's size toothbrush is easier for the person.
It is also best to floss once per day, if possible. If this is distressing to the person, an interdental brush, which is a small brush designed to clean between the teeth. Try to check the person's mouth for any problems such as:

• Sores
• Decayed teeth
• Food "pocketed" in the cheek or on the roof of the mouth
• Lumps

Be sure to take the person for regular dental checkups for as long as possible. Some people need medicine to calm them before they can see the dentist. Calling the dentist beforehand to discuss potential sensitivities may also be helpful.

Skin problems. Once the person stops walking or stays in one position too long, he or she may get skin or pressure sores. To prevent them, you can:

• Move the person at least once every 2 hours if he or she is sitting up.
• Move the person at least once every hour if he or she is lying down.
• Put a 4-inch foam pad on top of the mattress.
• Check to make sure that the foam pad is comfortable for the person. Some people find these pads too hot for sleeping or may be allergic to them. If the foam pad is a problem, you can get pads filled with gel, air, or water.
• Check to make sure the person sinks a little when lying down on the pad. Also, the pad should fit snugly around his or her body.

To check for pressure sores:

• Look at the person's heels, hips, buttocks, shoulders, back, and elbows for redness or sores.
• Ask the doctor what to do if you find pressure sores.
• Try to keep the person off the affected area.

Foot care. It's important for the person with Alzheimer's to take care of his or her feet. If the person cannot, you will need to do it. Here's what to do:

• Soak the person's feet in warm water. Wash the feet with a mild soap; and check for cuts, corns, and calluses.
• Put lotion on the feet so that the skin doesn't become dry and cracked.
• Cut or file their toenails.
• Talk to a foot care doctor, called a podiatrist, if the person has diabetes or sores on the feet.

What to do about body jerking

Sudden twitching or jerking, known as myoclonus, is another condition that sometimes happens with Alzheimer's. The person's arms, legs, or whole body may jerk. This can look like a seizure, but the person doesn't pass out. Tell the doctor right away if you see these signs. The doctor may prescribe one or more medicines to help reduce symptoms.

Learn more about care decisions and medical options at the end of life.

How to find help for caregiving

As the person moves through the stages of Alzheimer's, he or she will need more care. You may not be able to meet all his or her needs at home anymore. It's important to know your limits, take care of yourself, and to seek help whenever you need it. Learn more about getting help with Alzheimer's caregiving and finding ways to care for yourself. If caring for the person has become too much for you, you can also learn more about finding long-term care for a person with Alzheimer's.