Alzheimer's disease (AD) is the most common form of dementia among older people. Dementia is a brain disorder that seriously affects a person's ability to carry out daily activities.

AD begins slowly. It first involves the parts of the brain that control thought, memory and language. People with AD may have trouble remembering things that happened recently or names of people they know. A related problem, mild cognitive impairment (MCI), causes more memory problems than normal for people of the same age. Many, but not all, people with MCI will develop AD.

In AD, over time, symptoms get worse. People may not recognize family members. They may have trouble speaking, reading or writing. They may forget how to brush their teeth or comb their hair. Later on, they may become anxious or aggressive, or wander away from home. Eventually, they need total care. This can cause great stress for family members who must care for them.

AD usually begins after age 60. The risk goes up as you get older. Your risk is also higher if a family member has had the disease.

No treatment can stop the disease. However, some drugs may help keep symptoms from getting worse for a limited time.

Alzheimer’s disease, a type of dementia, is an irreversible, progressive brain disease that affects an estimated 5.7 million Americans. It is the sixth leading cause of death among all adults and the fifth leading cause for those aged 65 or older.

The causes of Alzheimer’s disease and other dementias are not completely understood, but researchers believe they include a combination of genetic, environmental, and lifestyle factors. In more than 90% of people with Alzheimer’s, symptoms do not appear until after age 60. The incidence of the disease increases with age and doubles every 5 years beyond age 65.

The Centers for Disease Control and Prevention (CDC) leads our nation’s public health efforts to help older adults with dementia to remain active, independent, and involved in their community by:

• Helping to promote awareness of Alzheimer’s disease and other dementias, including the importance of early diagnosis.
• Studying the societal and economic burden of dementias in states and communities.
• Supporting data collection on cognitive decline and caregiving.
• Working to ensure that caregivers have the resources to provide quality care to people with dementia.

Public Health Problem

Alzheimer’s disease affects mainly older adults, and the growth in the number of older adults is unprecedented. In 2016, 49 million adults living in the United States—15% of the population—were 65 or older. By 2060, that number is expected to climb to about 95 million, or nearly 1 in 4 US residents. In 2018, total payments for health care, long-term care, and hospice for people with Alzheimer’s and other dementias are estimated to be $277 billion. Medicare pays almost half of these costs. Unless scientists discover how to prevent Alzheimer’s and other dementias, the number of people with these conditions, and the costs, will increase substantially.

Compromised Health and Quality of Life for Adults With Alzheimer’s Disease and Other Dementias

Alzheimer’s disease slowly destroys brain function, leading to cognitive decline (e.g., memory loss, language difficulty, poor executive function), behavioral and psychiatric disorders (e.g., depression, delusions, agitation), and declines in functional status (e.g., ability to engage in activities of daily living and self-care). People with Alzheimer’s gradually lose the ability to care for themselves and to remain independent. Twice as many Americans fear the loss of mental capabilities as the loss of physical ability.

Compromised Health and Quality of Life for Caregivers

Given longer life spans and the growing prevalence of conditions like Alzheimer’s, the need for caregivers, both informal (i.e., family and friends) and formal (i.e., paid professionals), will likely increase significantly as the US population ages. Although caregiving may be rewarding, caregivers are at an increased risk of increased stress, depression, unhealthy behaviors, and poor attention to their own health. Caregivers of people with dementias are at even higher risk of these problems, and they may delay their own health needs.

Informal or unpaid caregivers are the backbone of long-term care provided in people’s homes. According to 2009 data from the Behavioral Risk Factor Surveillance System (BRFSS), about 25% of US adults aged 18 or older reported providing care or assistance to a person with a long-term illness or disability in the past 30 days. In 2018, the value of this unpaid caregiver activity is an estimated $232 billion.

Fast Facts

• 15% of the US population is 65 or older.
• Adjusting for age, rates of Alzheimer’s disease deaths increased more than 50% between 1999 and 2014. Alzheimer’s disease is the sixth leading cause of death among all US adults.
• Americans fear losing their mental capabilities twice as much as they fear losing their physical abilities.
• In 2018, total payments for health care, long-term care, and hospice for people with Alzheimer’s and other dementias are estimated to be $277 billion.
• In 2018, more than 16 million Americans are providing more than 18.4 billion hours of unpaid care for family and friends with Alzheimer’s and other dementias. The total value of that care is over $232 billion.

Alzheimer's disease (AD) is a neurological disorder that involves irreversible worsening changes in the ability to think and remember. It is the most common cause of dementia—the loss of the ability to reason, learn new skills, and plan and prioritize to the point which it interferes with a person's daily life and activities—in older adults.

AD develops over many years, with damage to the brain that may start a decade or more before memory problems appear. Initially, people experience memory loss and confusion, which may be mistaken for the kinds of memory changes that are sometimes associated with normal aging. However, the symptoms of AD gradually lead to:

• Behavior and personality changes
• Decline in cognitive abilities such as decision-making and language skills
• Problems recognizing family and friends.

AD ultimately leads to a severe loss of mental function. These losses are believed to be related to certain proteins that abnormally clump together and damage healthy neurons and their connections, causing them to die. People with severe AD cannot communicate and are completely dependent on others for their care.

The risk of AD increases with age, but it can also occur in midlife, between a person's 30s and mid-60s. We don't yet completely understand the causes of late-onset AD, but they probably include genetic, environmental, and lifestyle factors.

There are no treatments that can stop the progression of AD, but certain drugs can temporarily slow worsening of some symptoms.

Scientists don't yet fully understand what causes Alzheimer's disease in most people. The causes probably include a combination of age-related changes in the brain, along with genetic, environmental, and lifestyle factors. The importance of any one of these factors in increasing or decreasing the risk of Alzheimer's disease may differ from person to person.

Alzheimer's disease is a progressive brain disease. It is characterized by changes in the brain—including amyloid plaques and neurofibrillary, or tau, tangles—that result in loss of neurons and their connections. These and other changes affect a person’s ability to remember and think and, eventually, to live independently.

Aging and Alzheimer's Risk

Older age does not cause Alzheimer’s, but it is the most important known risk factor for the disease. The number of people with Alzheimer’s disease doubles about every 5 years beyond age 65. About one-third of all people age 85 and older may have Alzheimer's disease.

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, vascular damage, production of unstable molecules called free radicals, and breakdown of energy production within cells.

However, age is only one risk factor for Alzheimer’s disease. Many people live into their 90s and beyond without ever developing dementia.

Genetics of Alzheimer's Disease

Many people worry about developing Alzheimer’s disease, especially if a family member has had it. Having a family history of the disease does not mean for sure that you’ll have it, too. But it may mean you are more likely to develop it.

People’s genes, which are inherited from their biological parents, can affect how likely they are to develop Alzheimer’s disease. Genetic risk factors are changes or differences in genes that can influence the chance of getting a disease. These risk factors are the reason some diseases run in families.

There are two types of Alzheimer's—early-onset and late-onset. Both types have a genetic component.

Late-Onset Alzheimer's Disease

Most people with Alzheimer's have late-onset Alzheimer's disease, in which symptoms become apparent in their mid-60s. Researchers have not found a specific gene that directly causes the late-onset form of the disease. However, one genetic risk factor—having one form, or allele, of the apolipoprotein E (APOE) gene on chromosome 19—does increase a person's risk. APOE ɛ4 is called a risk-factor gene because it increases a person's risk of developing the disease. However, inheriting an APOE ɛ4 allele does not mean that a person will definitely develop Alzheimer's. Some people with an APOE ɛ4 allele never get the disease, and others who develop Alzheimer's do not have any APOE ɛ4 alleles.

Early-Onset Alzheimer's Disease

Early-onset Alzheimer's disease occurs between a person's 30s to mid-60s and represents less than 10 percent of all people with Alzheimer's. Some cases are caused by an inherited change in one of three genes. For other cases, research shows that other genetic components are involved. Researchers are working to identify additional genetic risk variants for early-onset Alzheimer's disease.

Health, Environmental, and Lifestyle Factors that May Contribute to Alzheimer's Disease

Research suggests that a host of factors beyond genetics may play a role in the development and course of Alzheimer's disease. There is a great deal of interest, for example, in the relationship between cognitive decline and vascular conditions such as heart disease, stroke, and high blood pressure, as well as metabolic conditions such as diabetes and obesity. Ongoing research will help us understand whether and how reducing risk factors for these conditions may also reduce the risk of Alzheimer's.

A nutritious diet, physical activity, social engagement, sleep, and mentally stimulating pursuits have all been associated with helping people stay healthy as they age. These factors might also help reduce the risk of cognitive decline and Alzheimer's disease. Clinical trials are testing some of these possibilities.

Early-life factors may also play a role. For example, studies have linked higher levels of education with a decreased risk of dementia. There are also differences in dementia risk among racial groups and sexes—all of which are being studied to better understand the causes of Alzheimer’s disease and to develop effective treatments and preventions for all people.

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

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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

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

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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

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.

Scientists continue to unravel the complex brain changes involved in the onset and progression of Alzheimer’s disease. It seems likely that damage to the brain starts a decade or more before memory and other cognitive problems appear. During this preclinical stage of Alzheimer’s disease, people seem to be symptom-free, but toxic changes are taking place in the brain.

Damage occurring in the brain of someone with Alzheimer’s disease begins to show itself in very early clinical signs and symptoms. For most people with Alzheimer’s—those who have the late-onset variety—symptoms first appear in their mid-60s. Signs of early-onset Alzheimer’s begin between a person’s 30s and mid-60s.

The first symptoms of Alzheimer’s vary from person to person. Memory problems are typically one of the first signs of cognitive impairment related to Alzheimer’s disease. Decline in non-memory aspects of cognition, such as word-finding, vision/spatial issues, and impaired reasoning or judgment, may also signal the very early stages of Alzheimer’s disease. And some people may be diagnosed with mild cognitive impairment. As the disease progresses, people experience greater memory loss and other cognitive difficulties.

Alzheimer’s disease progresses in several stages: preclinical, mild (sometimes called early-stage), moderate, and severe (sometimes called late-stage).

Signs of Mild Alzheimer’s Disease

In mild Alzheimer’s disease, a person may seem to be healthy but has more and more trouble making sense of the world around him or her. The realization that something is wrong often comes gradually to the person and his or her family. Problems can include:

• 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

Alzheimer’s disease is often diagnosed at this stage.

Signs of Moderate Alzheimer’s Disease

In this stage, more intensive supervision and care become necessary, which can be difficult for many spouses and families. Symptoms may include:

• 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 multistep 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

Signs of Severe Alzheimer’s Disease

People with severe Alzheimer’s cannot communicate and are completely dependent on others for their care. Near the end, the person may be in bed most or all of the time as the body shuts down. Their symptoms often include:

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

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

There is currently no cure for Alzheimer’s, though there are medicines that can treat the symptoms of the disease.

Memory often changes as people grow older. Some people notice changes in themselves before anyone else does. For other people, friends and family are the first to see changes in memory, behavior, or abilities. Memory loss that disrupts daily life is not a typical part of aging. People with one or more of these 10 warning signs should see a doctor to find the cause. Early diagnosis gives them a chance to seek treatment and plan for the future.

1. Memory loss that disrupts daily life: forgetting events, repeating yourself or relying on more aids to help you remember (like sticky notes or reminders).

2.Challenges in planning or solving problems: having trouble paying bills or cooking recipes you have used for years.

3.Difficulty completing familiar tasks at home, at work, or at leisure: having problems with cooking, driving places, using a cell phone, or shopping.

4.Confusion with time or place: having trouble understanding an event that is happening later, or losing track of dates.

5.Trouble understanding visual images and spatial relations: having more difficulty with balance or judging distance, tripping over things at home, or spilling or dropping things more often.

6.New problems with words in speaking or writing: having trouble following or joining a conversation or struggling to find a word you are looking for (saying “that thing on your wrist that tells time” instead of “watch”).

7.Misplacing things and losing the ability to retrace steps: placing car keys in the washer or dryer or not being able to retrace steps to find something.

8.Decreased or poor judgment: being a victim of a scam, not managing money well, paying less attention to hygiene, or having trouble taking care of a pet.

9.Withdrawal from work or social activities: not wanting to go to church or other activities as you usually do, not being able to follow football games or keep up with what’s happening.

10.Changes in mood and personality: getting easily upset in common situations or being fearful or suspicious.

Chances are you’ve walked into a room and forgotten why you went there. And misplaced your keys or eyeglasses at least a few times. Many people worry about these memory lapses. They fear they’re heading toward a serious condition like Alzheimer’s disease, an irreversible brain illness.

Occasional forgetfulness is a normal part of life that becomes more common as we grow older. In most cases, it’s no cause for alarm—unless it begins to hamper daily activities. Forgetting where you left the car keys is one thing; forgetting what they do is quite another.

Over the past few years, scientists have learned a lot about memory and why some memory problems are serious but others are not. As we age, changes occur throughout the body, including the brain. As a result, you may begin to notice that it takes longer to learn new things. Perhaps you can’t remember information as well as before, or you may misplace things. These memory lapses may be signs of normal aging. But if increasing forgetfulness begins to worry you, it’s a good idea to check with your doctor. If a medical problem exists, it’s best to start treatment as early as possible.

No matter what your age, several underlying causes can bring about memory problems. Forgetfulness can arise from stress, depression , lack of sleep or thyroid problems. Other causes include side effects from certain medicines, an unhealthy diet or not having enough fluids in your body (dehydration). Taking care of these underlying causes may help resolve your memory problems.

For some older people, though, episodes of memory loss may be a sign of a more serious problem called dementia . Two of the most common forms of dementia in older people are Alzheimer’s disease and multi-infarct dementia (or vascular dementia).

In Alzheimer’s disease, memory loss begins slowly and gets worse over time. People with Alzheimer’s disease have trouble thinking clearly. They find it hard to do everyday things like shopping, driving, cooking or having a conversation. Medications can help during the early or middle stages. As the illness progresses, though, patients may need someone to take care of all their needs (like feeding and bathing) at home or in a nursing home.

Vascular dementia also causes serious memory problems. But unlike Alzheimer’s disease, the signs of vascular dementia may appear suddenly. This is because the memory loss and confusion are caused by small strokes or changes in the blood supply to the brain. Further strokes can make the situation worse. Taking care of your high blood pressure can lower your chances of getting this illness.

See your doctor if you’re concerned that you or someone you know has a memory problem. Your doctor may be able to diagnose the problem or refer you to an expert who specializes in memory problems.

Forgetfulness: When To Seek Help

People who have a sudden loss of memory or become very confused should get medical help right away. Make an appointment to see a doctor if you notice these symptoms:

• Asking the same question or repeating the same story over and over
• Becoming lost in familiar places
• Not being able to follow directions
• Getting confused about time, people and places
• Not taking care of yourself—eating poorly, not bathing or being unsafe
• Having memory or concentration problems that concern you

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.

While a direct-to-consumer genetic test can estimate your risk, it cannot tell you for certain whether you will or will not develop Alzheimer disease. Variations in multiple genes, together with lifestyle factors such as diet and exercise, all play a role in determining a person’s risk.

The U.S. Food and Drug Administration (FDA) has allowed at least one direct-to-consumer genetic testing company, 23andMe, to offer a test for Alzheimer disease risk. The test analyzes a gene calledAPOE. Certain variations in this gene are associated with the likelihood of developing late-onset Alzheimer disease (the most common form of the condition, which begins after age 65). Specifically, the test allows you to find out how many copies (zero, one, or two) you have of a version of the gene called the e4 allele. People who have zero copies of the e4 allele have the same risk of late-onset Alzheimer disease as the general population. The risk increases with the number of copies of the e4 allele, so people with one copy have an increased chance of developing the disease, and people with two copies have an even greater risk. However, many people who have one or two copies of the e4 allele never develop Alzheimer disease, and many people with no copies of this allele ultimately get the disease.

Variations in the APOE gene are among many factors that influence a person’s overall risk of developing Alzheimer disease. Variations in many other genes, which are not reported in the FDA-approved direct-to-consumer genetic test, also contribute to disease risk. Additionally, there are risk factors for Alzheimer disease that have yet to be discovered. Therefore the APOE e4 allele represents only one piece of your overall Alzheimer disease risk.

Currently, there are no effective approaches for preventing Alzheimer disease, and while the disease can be treated, it has no cure. For these reasons, the National Institute on Aging recommends against genetic testing for Alzheimer disease except in a research setting (such as a clinical trial). Patient advocacy groups strongly recommend that people considering genetic testing for Alzheimer disease, including direct-to-consumer genetic testing, talk with a genetic counselor about the reasons they want to undergo testing and how they would cope with the results.