Alzheimer's Disease

Alzheimer’s disease is the leading cause of dementia, a brain disorder that robs people of the ability to think, learn, and remember, and eventually robs them of their very selves. More than six million Americans currently have Alzheimer’s.


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What is Alzheimer’s disease?

Dementia and Alzheimer's disease are often used interchangeably, but they are different.

Dementia is a loss over time of memory or other mental functions or a change in mood or behavior that is severe enough to interfere with a person’s ability to function at home, socially, or at work. This umbrella term covers a range of cognitive problems, such as memory loss, problem-solving difficulty, and other impairments in thinking skills. Alzheimer’s disease is one type of dementia and the most common. In fact, Alzheimer’s disease accounts for 60% to 80% of all dementia cases. 

Alzheimer’s causes a decline in cognition and memory loss accompanied by changes in mood and behavior. The disease is caused by the accumulation of two types of protein in the brain: tangles (tau) and plaques (amyloid-beta). These tangles and plaques make it difficult for brain cells (neurons) to communicate with one another, impeding memory and other mental functions. Eventually, Alzheimer’s destroys enough brain cells that people die.

After an Alzheimer’s diagnosis, people have an average life expectancy of eight to 10 years in an increasingly dependent state as the disease progresses. There is no cure for Alzheimer’s disease, though some treatments temporarily improve symptoms.

It’s impossible to predict exactly how Alzheimer’s will affect each individual because the symptoms and rate of progression vary. Some develop severe mood and behavior problems; others do not. A symptom can show up early or not appear until much later. For some people, the decline is slow and gradual over a decade or longer; others experience a rapid downhill course that ends in death within a few years. 

What are the risk factors for Alzheimer’s disease?

Several factors raise the risk of developing Alzheimer’s disease. These include age, gender, family history, genetics, and health conditions. Some you can control, while others you cannot. 

Age, gender, and family history. The risk of developing Alzheimer’s disease rises steadily after age 65. Women appear to have a higher rate of Alzheimer’s than men, with women accounting for nearly two-thirds of cases. The disease is also hereditary. In general, having a first-degree relative (parent or sibling) with Alzheimer’s disease doubles the risk. 

Genes. Those who inherit specific gene mutations will inevitably develop Alzheimer’s disease, usually at relatively young ages (45 on average). This genetically-determined form of the disease—known as early-onset Alzheimer’s—accounts for roughly 1% of total cases of Alzheimer’s in the United States. Other genes do not necessarily cause Alzheimer’s but do increase your chances of developing the typical late-onset form, which accounts for 99% of cases. While researchers have identified many such genes, one that stands out is the apolipoprotein E (ApoE) gene. This gene has three variants: E2, E3, and E4. The problematic one is E4, which scientists believe may play a role in the faulty clearing of beta-amyloid deposits from the brain. 

Health conditions. Many studies show that the same conditions that harm the heart and blood vessels also increase the risk of Alzheimer’s. These include high blood pressure, high cholesterol, obesity, diabetes, and metabolic syndrome (the presence of three or more of the following factors: a large waistline, high blood pressure, high triglycerides, low HDL [good] cholesterol, and difficulty regulating blood sugar.) Other health conditions that raise one’s risk include smoking, head injury, depression, and hearing loss.

What are the signs and symptoms of Alzheimer’s disease?

Alzheimer’s disease is rarely identified in its early stages. One reason is that people and their families frequently don’t tell a doctor about early signs or symptoms. They may confuse them with typical signs of aging like forgetfulness, or the symptoms may emerge so gradually that they go unnoticed. Also, if a person is aware of symptoms, they may go to great lengths to conceal or compensate for them. 

Still, recognizing the signs and symptoms of Alzheimer’s is key to early diagnosis, which is confirmed through various physical and mental tests. While the course of Alzheimer’s can vary, the following are common symptoms. 

Progressive memory loss. This is the most characteristic and earliest symptom of Alzheimer’s. Only short-term memory (recent events and new information) is initially impaired. People may forget the content of conversations and ask the same questions repeatedly. The impairment soon interferes with the ability to interact socially and perform work. Long-term memories may be retained longer, but they grow increasingly fragmented. 

Disorientation. The sense of time becomes more distorted as the disease progresses. People may insist it’s time to leave immediately after arriving at a location or complain of not being fed as soon as a meal has ended. 

Decline in judgment and problem-solving. The ability to solve day-to-day problems, make decisions, and exercise judgment is noticeably impaired. Deterioration of these skills can begin subtly as poor performance in an activity the person once did well. People frequently have difficulty planning and carrying out tasks that require more than one step. Poor judgment and lack of insight can lead to victimization from scams and vulnerability to accidents. 

Language difficulties. People with Alzheimer’s typically have difficulty using and understanding language as time passes. Some language skills may be retained longer than others. Difficulty with word-finding is a common and frequently frustrating early symptom. Unable to think of the right words, people with Alzheimer’s may try to cover up with long-winded descriptions that fail to reach the point, or they may angrily refuse to discuss the matter further. 

Visual and spatial dysfunction. The disease damages the brain’s ability to understand the visual information it receives. This can make it difficult to locate objects and get a sense of surroundings and place, which makes driving more difficult and hazardous. People also may be unable to recognize familiar objects or how to use them, like a toothbrush. They also may fail to recognize familiar faces. 

Changes in mood, behavior, and personality.  Apathy is common, and many people with Alzheimer’s lose interest in their usual activities, are less motivated, and are more socially withdrawn. A person may become anxious, irritable, or inexplicably hostile. Depression is common. 

Decline in daily functioning. These include routine tasks such as working, managing finances, driving, using public transportation, shopping, preparing meals, cleaning, and making simple repairs. 

What are the stages of Alzheimer’s disease?

Alzheimer’s disease unfolds in five stages as symptoms progressively worsen.

Stage 1: Mild cognitive impairment 

Memory lapses occur but may seem like slight absentmindedness and often go unnoticed by others. Individuals may lose or misplace objects. They may not fully absorb what they read or hear, and job performance and social skills begin to suffer. They may become confused in new surroundings, and struggle to find the right words when speaking. The first personality change is usually a loss of spontaneity. People may avoid situations that challenge their abilities and may grow withdrawn, apathetic, moody, depressed, irritable, or anxious. They typically deny their problems are serious, even to themselves, and may blame others for their failures. 

Stage 2: Mild dementia 

Problems with memory and other thinking skills are now apparent to others. People have difficulty retaining new information and lose the thread of conversations. They sometimes have trouble recalling current events, like who the president is, and their personal history, such as where they attended school. They may no longer be able to manage their finances. Depression often becomes prominent. People can have a striking lack of insight into their cognitive problems. They may insist on driving despite a series of fender-benders or continue to cook but repeatedly scorch empty pots on the stove. 

Stage 3: Mild to moderate dementia 

Memory fluctuates daily or even hourly. People sometimes forget significant life events, but deny having memory problems. They often are unaware of the date or the time of year, and their conversation may become disjointed and contain irrelevant content. The continuing deterioration of memory gives people a sense of insecurity, which they may express with paranoia or anger. They may accuse others of hiding things, stealing, or plotting against them. 

Although able to manage many fundamental activities of daily living, such as using the bathroom and eating, they may only partially complete tasks because they cannot remember all the steps involved. 

Stage 4: Moderate to severe dementia 

Dramatic changes occur. People may begin to look ill, language skills are considerably reduced, and memory impairment becomes so profound that everything can seem unfamiliar and threatening to them. Individuals often have difficulty comprehending what others say or do, which can lead to a variety of emotional reactions, including delusions (accusing a spouse of infidelity or talking to imaginary people), obsessive behavior (repeatedly cleaning an object, endlessly removing and replacing the contents of a drawer), agitation (pacing, hostile behavior, asking the same question repeatedly), and catastrophic reactions. People may walk with slow, shuffling steps and require assistance with bathing, dressing, and eating. Sleep disturbances are common. 

Stage 5: Severe dementia 

The final stage is known as “the long goodbye.” All language skills are gone, and there seems to be little left of the person’s “self.” Behavior problems diminish, and motor skills decline until the person can no longer walk, sit up, chew and swallow food, or control bladder and bowel movements. The person often chokes on their own saliva, which can get into the lungs, causing pneumonia. Because of lack of movement, bed sores may develop, which can get infected. Pneumonia and infections are common causes of death. 

How is Alzheimer’s disease treated?

While there is no cure for Alzheimer’s disease, there are treatment options to help alleviate symptoms and sometimes slow its progression. 

Medications are often the first-line treatment. Some drugs target cognitive function or decline. Others are used to help with mood and behavior problems, such as agitation and outbursts of anger. 

Medications to treat Alzheimer’s disease

There are four drugs with longstanding FDA approval to treat Alzheimer’s disease. These are donepezil (Aricept), galantamine (Razadyne), rivastigmine (Exelon), and memantine (Namenda)—all available as both brand-name drugs and lower-cost generics. A single-pill combination of donepezil and memantine is sold under the brand name Namzaric. 

All these prescription medications affect particular brain chemicals and offer modest and temporary (often six months or less) improvements in memory, other cognitive functions, and daily functioning in some people. Donepezil and rivastigmine have been approved for use in mild, moderate, or severe Alzheimer’s, while galantamine is approved for use in mild to moderate cases. Memantine is approved for use in people with moderate to severe Alzheimer’s.

Another FDA-approved drug, aducanumab (Aduhelm), helps clear beta-amyloid—one of the hallmarks of Alzheimer’s disease—from the brain. It’s given by intravenous infusion. Aducanumab is for people with mild cognitive impairment or mild dementia. Lecanemab (Leqembi) is another intravenous drug that aims to reduce the burden of amyloid protein in the brains of patients with early-stage Alzheimer’s disease, but it is expensive and it is unclear how effectively it can slow cognitive decline.

Medications to treat mood and behavior problems associated with Alzheimer’s disease

Other medications may help with mood and behavior problems associated with Alzheimer’s. Three main classes of drugs are used: antidepressants, mood stabilizers, and antipsychotics.

Antidepressants. When depression, anxiety, irritability, agitation, or behavior problems arise in a person with dementia, doctors often turn to antidepressant drugs first. In addition to relieving mood symptoms, antidepressants may enhance the social functioning of a person with Alzheimer’s. They may improve appetite and sleep and increase energy, too. 

Doctors often choose a particular antidepressant drug based on its ability to improve various problems. For example, a class of drugs called selective serotonin reuptake inhibitors (SSRIs)—including sertraline (Zoloft), citalopram (Celexa), and escitalopram (Lexapro)—help with depression, anxiety, irritability, and agitation. If a person with dementia has both depression and apathy, the more activating antidepressant drugs venlafaxine (Effexor), desvenlafaxine (Khedezla, Pristiq), or bupropion (Wellbutrin) may be used. People with both depression and pain may be given duloxetine (Cymbalta). When symptoms disrupt sleep, the antidepressant drugs trazodone (Desyrel, Oleptro) or mirtazapine (Remeron) may help. 

Mood stabilizers. When antidepressants do not adequately address behavior problems, mood stabilizers are an option. These drugs can reduce agitation and mood swings. Examples include divalproex sodium (Depakote), gabapentin (Gralise), and lamotrigine (Lamictal).

Antipsychotics. Antipsychotic drugs may help manage specific behavior problems, such as severe agitation and hostility, that result from delusions or hallucinations. They are used with caution because of possible serious side effects, such as symptoms that mimic Parkinson’s disease (slowed movements, tremors, rigid muscles, shuffling walk, drooling, and a masklike expression) and tardive dyskinesia (a syndrome of involuntary writhing movements of the arms, legs, and tongue). Newer antipsychotic drugs— such as aripiprazole (Abilify), olanzapine (Zyprexa), quetiapine (Seroquel), and risperidone (Risperdal)— are less likely to cause these symptoms.

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