Alzheimer's Disease
Alzheimer's disease (AD) is a progressive neurocognitive disease that slowly erodes an individual's memory, judgment, cognition, learning, and, eventually, ability to function. It is the leading cause of dementia in the elderly. Alzheimer's disease can affects a person's mood, thinking, and behavior, as well as their overall personality, disposition, and sense of self.
The condition is characterized by language deterioration, impaired ability to mentally manipulate visual information, poor judgment, confusion, and restlessness. It is most commonly found in adults over age 60, but it can at times occur in younger adults as well. It is not considered a normal process of aging. According to 2021 figures published in the journal Alzheimer's & Dementia, it is estimated to occur in 5 percent of individuals between the ages of 65 and 75. One's risk of developing the disease tends to increase with age: Nearly 14 percent of those between ages 75 and 84 may develop Alzheimer's; for adults 85 years or older, prevalence approaches 35 percent.
Early signs of the condition may include forgetting important dates or events, misplacing things, finding it hard to complete familiar tasks at home or work, being confused about time or place, becoming easily lost in places one knows well, developing problems using words, losing planning or problem-solving abilities, and showing mood or personality changes. Because some of these symptoms may occur as part of normal aging, they sometimes go unrecognized or undiagnosed for a significant period of time. As the condition progresses, its symptoms tend to become more noticeable and disruptive.
Common symptoms of Alzheimer’s disease include:
- Forgetting appointments or events
- Feeling confused or overwhelmed by routine tasks, like paying bills or going grocery shopping
- Difficulty performing basic hygiene or self-care tasks, such as getting dressed or taking a shower
- Poor short-term memory for conversations; repeating statements, stories, or questions over and over
- Routinely losing possessions; may put them in strange locations without realizing
- Struggling to express thoughts or ideas; may forget frequently used words or names for objects
- Forgetting names of loved ones, especially in the later stages of the disease
- Poor judgment—for example, ventures outdoors in bad weather without adequate clothing
- Inappropriate social behavior
- Sudden personality changes, such as uncharacteristic anger
- Depression, apathy or social withdrawal
- An increasing tendency to be distrustful or paranoid
- Hallucinations or delusions, particularly in the later stages of the disease
According to the DSM-5, Alzheimer's disease can be classified as either a major or mild neurocognitive disorder, based on the severity of cognitive decline that is observed. It is typically diagnosed based on symptoms, family history, or following genetic testing to determine a causative genetic mutation. Though genetic testing is not always conducted, if a mutation is found to be present and/or there is a known family history of Alzheimer’s, the diagnosis is deemed “probable”; if not, the diagnosis is considered “possible.” Alzheimer’s can only be definitively diagnosed after death when the brain is examined for plaques and other visible markers of the disease; however, many doctors feel comfortable offering a probable diagnosis based on symptoms and family history.
To qualify as a major neurocognitive disorder, there must be:
- Clear evidence of a decline in memory and learning
- A steady progression of symptoms
- A gradual decline in cognition
- An inability to live independently
- The absence of other neurodegenerative, cerebrovascular, or neurological or mental diseases
To qualify as a mild neurocognitive disorder, there may or may not be evidence of genetic mutation from family history or testing, but the following symptoms should be present:
- Clear evidence of a decline in memory and learning
- A steady progression of symptoms
- A gradual decline in cognition
- The absence of other neurodegenerative, cerebrovascular, or neurological or mental diseases
The deficits must cause significant impairment in social or occupational functioning and represent a notable decline from a previous level of functioning.
Mild stages of Alzheimer's may include depression and/or apathy. With moderately severe Alzheimer's, psychotic features such as hallucinations or delusions, irritability, agitation, combativeness, and wandering behaviors may be observed. With severe Alzheimer's, gait disturbance, incontinence, seizures, difficulty swallowing, and sudden muscle contractions may occur.
Alzheimer’s disease is one possible cause of dementia, a broad category of related symptoms that include memory loss, language challenges, mood changes, and a general loss of functioning. While Alzheimer’s is not the only cause of dementia, it is the most common; nearly 70 percent of those with dementia are thought to have AD. Other causes of dementia include vascular disease, Parkinson’s disease, and HIV.
It is common in the early stages of Alzheimer’s for the person with the disease to be aware that something is wrong. They may recognize that they are having difficulty remembering things or getting lost frequently, and may become frustrated or agitated as a result. Many people who are formally diagnosed with Alzheimer’s are cognizant of their diagnosis and may be able to take steps to prepare themselves and their loved ones for their future decline. As the disease progresses, many people with Alzheimer’s often seem to become less aware of their symptoms, though they may still express frustration or seem to feel that something is wrong. They may also become depressed as a result of this continual frustration and ongoing sense of decline.
Genetic testing for Alzheimer’s is not yet an exact science, and many doctors do not include genetic tests in the battery of assessments they use when diagnosing someone with Alzheimer’s. Some people seek genetic testing before they start showing symptoms, in order to estimate their risk of developing the condition later on; however, many experts advise against this except in certain cases, as learning that one could be genetically vulnerable to Alzheimer’s can be psychologically burdensome. Genetic testing may be most useful in diagnosing early-onset Alzheimer's, as this condition is far rarer and may help young people and their families make sense of confusing symptoms.
Age is the strongest risk factor for Alzheimer's, although the condition is not a typical or normal aspect of aging.
Genetic susceptibility to Alzheimer's is another important variable. Those who have a parent or sibling with Alzheimer’s are more likely to develop it themselves. Genetic variants (alleles) such as apolipoprotein E4 (APOE), Amyloid precursor protein (APP), Presenilin-1 (PS-1), and Presenilin-2 (PS-2) can increase an individual's chance of developing Alzheimer's. These proteins can cause or exacerbate both structural and chemical problems in the brain, disconnecting areas of the brain that normally work together.
In addition to age and family history, risk factors for AD may include longstanding high blood pressure, head trauma, and neuronal injury. Medical conditions such as heart disease, diabetes, stroke, high blood pressure, and high cholesterol can damage the heart and blood vessels, which raises the risk. Because women usually live longer than men, they are more likely to develop Alzheimer's.
The genetic roots of Alzheimer’s are not yet fully understood. However, individuals who have a parent or sibling with the disease do appear to be at higher risk, suggesting that genetics do play a significant role. In addition, certain genes and genetic variants appear to confer additional risk, such as the e4 variant of the APOE gene.
Several specific genes have been implicated in Alzheimer’s disease, including apolipoprotein E gene (APOE), which is involved in making a protein that helps move cholesterol and other fats through the bloodstream. APOE is located on chromosome 19, and each person carries two copies of it (one inherited from each parent). There are currently three known variants of the APOE gene: e2, e3, and e4. The most common variant, e3, is not thought to increase or decrease the risk of Alzheimer’s. The e2 variant is relatively rare but appears to offer some protection against the disease. The e4 variant (one copy of which is carried by approximately a quarter of the population) is associated with a heightened risk of Alzheimer's in certain populations; having two copies of the variant confers even greater risk, but occurs in only 2 to 3 percent of people.
Having either one or two copies of the e4 variant does not automatically mean that someone will develop Alzheimer’s, simply that they are more vulnerable than others who carry different variants; indeed, many people with this gene variant do not go on to develop any kind of dementia. Targeting modifiable risk factors such as blood pressure, mental stimulation, and leading a generally healthy lifestyle could greatly reduce risk in someone with either one or two copies of the e4 variant.
More women than men have Alzheimer’s disease. However, whether this reflects a significant difference in risk between the genders is still a matter of debate. Many experts posit that the observed gender differences may simply be due to women living longer than men, on average, as getting older is the greatest known risk factor for developing Alzheimer’s disease.
Individuals with Down syndrome are at significantly greater risk of developing Alzheimer’s disease as they age, often at an earlier age than their counterparts without Down syndrome. According to the National Down Syndrome Society, approximately 30 percent of people in their 50s who have Down syndrome also have Alzheimer’s; by the time they reach their 60s, the prevalence nears 50 percent. The exact reason for this comorbidity is not fully understood; however, Down syndrome is known to decrease life span and increase the risk of other diseases, such as leukemia or epilepsy. In addition, chromosome 21—of which individuals with Down syndrome have an extra copy—is responsible for the amyloid precursor protein (APP). Having an extra copy is thought to increase production of beta-amyloid, a key component of the brain plaques that are thought to be responsible for Alzheimer’s disease.
There is no surefire way to prevent Alzheimer’s disease, but certain modifiable lifestyle factors are thought to significantly reduce risk. Because cardiovascular conditions such as heart disease greatly increase the risk of Alzheimer’s, protecting heart health by getting regular exercise, not smoking, and eating a diet low in sugar and saturated fats are often recommended prevention strategies. Maintaining social connections and staying mentally active as one ages are also thought to reduce the risk of dementia later in life. Taking steps to avoid serious head trauma—such as always wearing a seatbelt or wearing a helmet when riding a bicycle—could also have potent protective effects.
The progression of Alzheimer's disease cannot be slowed down, as the disease cannot be cured and impaired functions may not be restored. However, symptoms can be targeted to improve the quality of a person's life and reduce the impact of the more troubling aspects of the illness.
Cholinesterase inhibitors are a class of drugs prescribed to treat symptoms related to memory, thinking, language, judgment, and other thought processes. Three cholinesterase inhibitors commonly prescribed include Donepezil (Aricept) approved to treat all stages of Alzheimer's; Rivastigmine (Exelon) approved to treat mild to moderate Alzheimer's; and Galantamine (Razadyne) approved to treat mild to moderate Alzheimer's. A second type of medication, memantine (Namenda), is approved by the FDA for the treatment of moderate to severe Alzheimer’s. Memantine is prescribed to improve memory, attention, reason, language, and the ability to perform simple tasks. It can be used alone or with other Alzheimer’s disease treatments. In mid-2021, the FDA approved another Alzheimer's drug, aducanumab; however, this approval was widely criticized and evidence of the drug's efficacy is contested.
Treatment may also focus on managing a patient's behavioral problems, confusion, and agitation; modifying the home environment; and supporting the family. Underlying disorders that contribute to confusion should also be identified and treated. Behavior modification may be helpful for some patients in controlling unacceptable or dangerous activity.
Currently, there are no treatments that can cure Alzheimer’s disease or meaningfully slow its progression. Existing treatments may, however, improve quality of life and may help alleviate some symptoms of the disease.
Alzheimer’s disease does not follow an exact timeline, and individuals may lose independence at different rates. In the early stage of Alzheimer’s, many people with the disease are still able to carry out many basic tasks, such as eating and bathing, on their own, and may only need assistance with certain activities, such as paying bills or driving. As the disease progresses, however, more intensive care will likely be needed.
If the person with Alzheimer's is behaving in ways that endanger their health or safety—such as wandering without knowing how to get home, leaving the stove on frequently, or forgetting to take critical medications—begins to seriously neglect their personal hygiene, or is no longer able to perform basic daily tasks like getting dressed or preparing a meal, full-time care may be required. When, in the later stages of Alzheimer’s, movement becomes impaired, eating becomes difficult, and/or the person begins to behave in ways that are increasingly dangerous to themselves or others, placement in a 24-hour memory facility may be deemed necessary.
In 2021, the FDA approved an intravenous drug called aducanumab (sold under the brand name Aduhelm), which targets beta-amyloid in the brain to reduce the build-up of plaques that are thought to be responsible for Alzheimer’s. It is the first new Alzheimer’s drug in nearly two decades. Its approval, however, was met with some skepticism from the medical community, as the results of two large studies on its efficacy were inconclusive, and its $56,000/year price tag may put it out of reach for many families who are affected by AD, many of whom may not have insurance that can offset much of the cost. Experts emphasize that aducanumab is indicated for people with mild cognitive impairment, and may have little effect on patients whose Alzheimer’s has progressed beyond the early stages. Patients and their families are advised to talk to their doctor to determine whether aducanumab would be a helpful addition to their treatment plan.