Alzheimer's Disease Symptoms, Test, Stages, Early Signs, Treatment

What is Alzheimer’s Disease?

Alzheimer's disease (AD), also known in medical literature as Alzheimer disease, is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death. It was first described by German psychiatrist and neuropathologist Alois Alzheimer in 1906 and was named after him. Most often, AD is diagnosed in people over 65 years of age, although the less-prevalent early-onset Alzheimer's can occur much earlier. In 2006, there were 26.6 million sufferers worldwide. Alzheimer's is predicted to affect 1 in 85 people globally by 2050.

Although Alzheimer's disease develops differently for every individual, there are many common symptoms. Early symptoms are often mistakenly thought to be 'age-related' concerns, or manifestations of stress. In the early stages, the most common symptom is difficulty in remembering recent events. When AD is suspected, the diagnosis is usually confirmed with tests that evaluate behaviour and thinking abilities, often followed by a brain scan if available. As the disease advances, symptoms can include confusion, irritability and aggression, mood swings, trouble with language, and long-term memory loss. As the sufferer declines they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Since the disease is different for each individual, predicting how it will affect the person is difficult. AD develops for an unknown and variable amount of time before becoming fully apparent, and it can progress undiagnosed for years. On average, the life expectancy following diagnosis is approximately seven years. Fewer than three percent of individuals live more than fourteen years after diagnosis.

The cause and progression of Alzheimer's disease are not well understood. Research indicates that the disease is associated with plaques and tangles in the brain. Current treatments only help with the symptoms of the disease. There are no available treatments that stop or reverse the progression of the disease. As of 2012, more than 1000 clinical trials have been or are being conducted to find ways to treat the disease, but it is unknown if any of the tested treatments will work. Mental stimulation, exercise, and a balanced diet have been suggested as ways to delay cognitive symptoms (though not brain pathology) in healthy older individuals, but there is no conclusive evidence supporting an effect.

Because AD cannot be cured and is degenerative, the sufferer relies on others for assistance. The role of the main caregiver is often taken by the spouse or a close relative. Alzheimer's disease is known for placing a great burden on caregivers; the pressures can be wide-ranging, involving social, psychological, physical, and economic elements of the caregiver's life. In developed countries, AD is one of the most costly diseases to society.

Alzheimer's Disease Fact Sheet

Alzheimer’s disease is an irreversible, progressive brain disease that slowly destroys memory and thinking skills, and eventually even the ability to carry out the simplest tasks. In most people with Alzheimer’s, symptoms first appear after age 60. Estimates vary, but experts suggest that as many as 5.1 million Americans may have Alzheimer’s disease.

Alzheimer’s disease is the most common cause of dementia among older people. Dementia is the loss of cognitive functioning—thinking, remembering, and reasoning—and behavioral abilities, to such an extent that it interferes with a person’s daily life and activities. Dementia ranges in severity from the mildest stage, when it is just beginning to affect a person’s functioning, to the most severe stage, when the person must depend completely on others for basic activities of daily living.

Alzheimer’s disease is named after Dr. Alois Alzheimer. In 1906, Dr. Alzheimer noticed changes in the brain tissue of a woman who had died of an unusual mental illness. Her symptoms included memory loss, language problems, and unpredictable behavior. After she died, he examined her brain and found many abnormal clumps (now called amyloid plaques) and tangled bundles of fibers (now called neurofibrillary tangles). Plaques and tangles in the brain are two of the main features of Alzheimer’s disease. The third is the loss of connections between nerve cells (neurons) in the brain.

Signs and symptoms of Alzheimer's disease

For many people, detecting the first signs of memory problems in themselves or a loved one brings an immediate fear of Alzheimer’s disease. However, most people over 65 experience some level of forgetfulness. It is normal for age-related brain shrinkage to produce changes in processing speed, attention, and short term memory, creating so-called “senior moments.” Forgetfulness is merely inconvenient, though, and generally involves unimportant information. Understanding the significance of these age-related changes begins with knowing the difference between what is normal and what is an early symptom of Alzheimer’s.

Signs and Alzheimer’s Symptoms

Symptoms that mimic early Alzheimer’s disease may result from:

  • Central nervous system and other degenerative disorders, including head injuries, brain tumors, stroke, epilepsy, Pick’s disease, Parkinson’s disease, Huntington’s disease.

  • Metabolic ailments, such as hypothyroidism, hypoglycemia, malnutrition, vitamin deficiencies, dehydration, kidney or liver failure.

  • Substance-induced conditions, such as drug interactions, medication side-effects, alcohol and drug abuse.

  • Psychological factors, such as dementia syndrome, depression, emotional trauma, chronic stress, psychosis, chronic sleep deprivation, delirium.

  • Infections, such as meningitis, encephalitis, and syphilis.

Alzheimer's is diagnosed through a complete medical assessment. If you or a loved one have concerns about memory loss or other symptoms of Alzheimer's or dementia, it is important to be evaluated by a physician.

There is no single test that can show whether a person has Alzheimer's. While physicians can almost always determine if a person has dementia, it may be difficult to determine the exact cause. Diagnosing Alzheimer's requires careful medical evaluation, including:

  • A thorough medical history

  • Mental status testing

  • A physical and neurological exam

  • Tests (such as blood tests and brain imaging) to rule out other causes of dementia-like symptoms

Having trouble with memory does not mean you have Alzheimer's. Many health issues can cause problems with memory and thinking. When dementia-like symptoms are caused by treatable conditions — such as depression, drug interactions, thyroid problems, excess use of alcohol or certain vitamin deficiencies — they may be reversed.

How does a doctor make a diagnosis of Alzheimer's?

The primary tools a doctor use to diagnose Alzheimer's disease are tests that can be performed in the office or clinic. Additional laboratory tests or brain-imaging tests also provide useful information for diagnosis, including ruling out other diseases that cause similar symptoms. The doctor’s goal is to answer the following questions:

  • Does a person have an impairment in memory or other thinking skills?

  • Does a person exhibit changes in personality or behaviors?

  • What is the degree of impairment or change?

  • How do the problems affect the person's ability to function?

  • What is the cause of the symptoms?

What diseases are doctors trying to rule out?

They check the thyroid, to rule out problems there. And, in many cases, symptoms of depression can be mistaken for Alzheimer's — and vice versa. They also routinely look for vitamin B-12 deficiency.

And they always make sure that the person is generally healthy and doesn't have some other serious medical problem that would complicate the diagnosis. A lot of older people have other medical problems that just make things worse — such as heart disease, high blood pressure, strokes, diabetes, kidney disease, lung disease or any combination of these.

How do doctors assess memory problems and other symptoms?

They conduct relatively simple, objective tests in which they ask people to answer questions or perform tasks associated with memory, abstract thinking, problem solving, language usage and related skills that they collectively refer to as cognitive skills. Scores on such tests enable them to quantify with some reliability a person's degree of cognitive impairment.

  • Assessing daily living skills. Doctors use questionnaires to judge a person's ability to perform activities of daily living (ADLs). These tasks include such things as using a telephone, preparing meals, taking medications and handling finances. A family member, friend or caregiver may be asked to help with the questionnaire. An ADL score helps a doctor quantify how well a person functions.

  • Neuropsychological tests. These tests can help them identify and judge the severity of behaviors that are commonly observed in people with Alzheimer's disease. Doctors may also demonstrate that a person is experiencing depression or other mental health problems that may cause similar symptoms.

  • Talking with friends and family. Doctors may also have more general questions, particularly for a family member or friend of the person with cognitive symptoms. They're looking for things that don't fit with the individual's former level of function. The family member or friend can often explain how cognitive skills, functional abilities and behaviors have changed over time.

This series of clinical assessments and a general physical exam often provide enough information to make a diagnosis of Alzheimer's disease. But when the diagnosis isn't clear, they depend on additional tests.

What lab tests do you use?

The primary role of lab tests — usually with blood samples — is to rule out other disorders that can cause some symptoms similar to those of Alzheimer's disease, such as a thyroid disorder or vitamin B-12 deficiency.

What is the current role of brain-imaging tests?

Alzheimer's disease results from the progressive loss, or degeneration, of brain cells. This degeneration can show up in a variety of ways in brain scans. But these scans alone aren't enough to make a diagnosis. This is because there's a lot of overlap in what we consider normal age-related change in the brain and abnormal change.

But brain imaging can help:

  • Rule out other causes, such as hemorrhages, brain tumors or strokes

  • Distinguish between different types of degenerative brain disease

  • Establish a baseline about the degree of degeneration

The brain-imaging technologies most often used are:

  • Computerized tomography (CT), which is a specialized X-ray technology that produces thin cross-sectional images of the brain

  • Magnetic resonance imaging (MRI), which uses magnetic fields and radio waves to create either cross-sectional or 3-D images of the brain

What does the future of diagnosis look like?

Researchers are working on new diagnostic tools that may enable health care professionals to diagnose Alzheimer's disease earlier in the course of the disease, when symptoms are very mild or before symptoms appear. Scientists are investigating a number of disease markers — genes, disease-related proteins and imaging procedures — that may accurately and reliably indicate whether someone has Alzheimer's disease and how much the disease has progressed. However, more research on these tests is necessary.

What's the benefit of an early diagnosis?

Reluctance to go to the doctor when you or a family member has memory problems is understandable. People hide their symptoms, or family members cover for them. That's easy to understand because Alzheimer's is such a dreaded disease. And many people wonder if there's any point in a diagnosis if there's no cure for the disease.

It's true that if a person has Alzheimer's or a related disease, doctors can't offer a cure. But getting an early diagnosis can be beneficial. If a person has another treatable condition that's causing the cognitive impairment or somehow complicating the impairment, then they can start treatments.

And for those with Alzheimer's disease, drug and nondrug interventions can be offered that may ease the burden of the disease. Doctors usually prescribe drugs that may slow the decline in memory and other cognitive skills. Also, they can educate caregivers and a person with Alzheimer's about strategies to enhance the living environment, establish routines, plan activities and manage changes in skills in order to minimize the effect of the disease on everyday life.

Importantly, an early diagnosis also helps a person with Alzheimer's disease, family and caregivers plan for the future. They have the chance to make informed decisions on a number of issues, such as:

  • Appropriate community services and resources

  • Options for residential and at-home care

  • Plans for handling financial issues

  • Expectations for future care and medical decisions

When doctors tell a person and family members about an Alzheimer's diagnosis, they help them understand that Alzheimer's is not an all-or-nothing phenomenon. They talk about what capacities are preserved and look to keep a person as healthy and safe as possible.

Alzheimer's stages: How the disease progresses

Alzheimer's disease can last more than a decade. See what types of behaviors are common in each of the stages as the disease progresses.

Alzheimer's disease typically develops slowly and gradually gets worse over the course of several years. As it progresses it eventually affects most areas of your brain, including those important in memory, thinking, judgment, language, problem solving, personality and movement.

Doctors divide this progression into Alzheimer's stages to help you and your family understand what to expect and plan for the future. It's important to realize that Alzheimer's stages are rough guides based on averages and generalizations. The disease is a continuous process. Your experience with Alzheimer's, the symptoms you develop and when they appear may vary.

Keeping in mind that everyone's different, it's helpful to think about three Alzheimer's stages — mild, moderate and severe.

Mild Alzheimer's disease

Alzheimer's disease is often first diagnosed in the mild, or early, stage, when it becomes clear to family and doctors that a person is having significant trouble with memory and thinking.

In the mild Alzheimer's stage, people may experience:

  • Memory loss for recent events. Individuals may have an especially hard time remembering newly learned information and repeatedly ask the same question.

  • Difficulty with problem solving, complex tasks and sound judgments. Planning a family event or balancing a checkbook may become overwhelming. Many people experience lapses in judgment, such as when making financial decisions.

  • Changes in personality. People may become subdued or withdrawn — especially in socially challenging situations — or show uncharacteristic irritability or anger. Decreased attention span and reduced motivation to complete tasks also are common.

  • Difficulty organizing and expressing thoughts. Finding the right words to describe objects or clearly express ideas becomes increasingly challenging.

  • Getting lost or misplacing belongings. Individuals have increasing trouble finding their way around, even in familiar places. It's also common to lose or misplace things, including valuable items.

Moderate Alzheimer's disease

During the moderate, or middle, Alzheimer's stage, people grow more confused and forgetful and begin to need help with daily activities and self-care.

People with moderate Alzheimer's disease may:

  • Show increasingly poor judgment and deepening confusion. Individuals lose track of where they are, the day of the week or the season. They often lose the ability to recognize their own belongings and may inadvertently take things that don't belong to them.

  • They may confuse family members or close friends with one another, or mistake strangers for family. They often wander, possibly in search of surroundings that feel more familiar and "right." These difficulties make it unsafe to leave those in the moderate Alzheimer's stage on their own.

  • Experience even greater memory loss. People may forget details of their personal history, such as their address or phone number, or where they attended school. They repeat favorite stories or make up stories to fill gaps in memory.

  • Need help with some daily activities. Assistance may be required with choosing proper clothing for the occasion or the weather and with bathing, grooming, using the bathroom and other self-care. Some individuals occasionally lose control of their urine or bowel movements.

  • Undergo significant changes in personality and behavior. It's not unusual for people with moderate Alzheimer's to develop unfounded suspicions — for example, to become convinced that friends, family or professional caregivers are stealing from them, or that a spouse is having an affair. Others may see or hear things that aren't really there. Individuals often grow restless or agitated, especially late in the day. People may have outbursts of accusing, threatening or cursing. Others may bite, kick, scream or attempt inappropriate sexual activity.

Severe Alzheimer's disease

In the severe, or late, stage of Alzheimer's, mental function continues to decline and the disease has a growing impact on movement and physical capabilities.

In severe Alzheimer's, people generally:

  • Lose the ability to communicate coherently. An individual can no longer converse or speak coherently, although he or she may occasionally say words or phrases.

  • Require daily assistance with personal care. This includes total assistance with eating, dressing, using the bathroom and all other daily self-care tasks.

  • Experience a decline in physical abilities. A person may become unable to walk without assistance, then unable to sit or hold up his or her head without support. Muscles may become rigid and reflexes abnormal. Eventually, a person loses the ability to swallow and to control bladder and bowel functions.

Rate of progression through Alzheimer's stages

The rate of progression for Alzheimer's disease varies widely. Alzheimer's tends to progress more slowly in those who are diagnosed at a younger age and in those who don't have other serious health issues.

On average, people with Alzheimer's disease live four to six years after diagnosis, but some survive as long as 20 years. Pneumonia is a common cause of death because impaired swallowing allows food or beverages to enter the lungs, where they can cause an infection. Other common causes of death include complications from urinary tract infections and falls.

Treatment

Currently, there is no cure for Alzheimer's. But drug and non-drug treatments may help with both cognitive and behavioral symptoms.

Researchers are looking for new treatments to alter the course of the disease and improve the quality of life for people with dementia.

There are no drug treatments available that can provide a cure for Alzheimer's disease. However, medicines have been developed that can improve symptoms, or temporarily slow down their progression, in some people.

What are the main drugs used?

There are two main types of medication used to treat Alzheimer's disease - cholinesterase inhibitors and NMDA receptor antagonists - which work in different ways. Cholinesterase inhibitors include donepezil hydrochloride (Aricept), rivastigmine (Exelon) and galantamine (Reminyl). The NMDA receptor antagonist is memantine (Ebixa).

How do they work?

Donepezil (Aricept), rivastigmine (Exelon) and galantamine (Reminyl)

Research has shown that the brains of people with Alzheimer's disease show a loss of nerve cells that use a chemical called acetylcholine as a chemical messenger. The loss of these nerve cells is related to the severity of symptoms that people experience.

Donepezil, rivastigmine and galantamine prevent an enzyme known as acetylcholinesterase from breaking down acetylcholine in the brain. Increased concentrations of acetylcholine lead to increased communication between the nerve cells that use acetylcholine as a chemical messenger, which may in turn temporarily improve or stabilise the symptoms of Alzheimer's disease.

All three cholinesterase inhibitors work in a similar way, but one might suit an individual better than another, particularly in terms of side-effects experienced. (Current guidance for NHS treatment is that the cheapest of these drugs is generally tried first, see 'NICE guidance' below.)

Memantine (Ebixa)

The action of memantine is quite different from, and more complex than, that of donepezil, rivastigmine and galantamine. Memantine blocks a messenger chemical known as glutamate. Glutamate is released in excessive amounts when brain cells are damaged by Alzheimer's disease and this causes the brain cells to be damaged further. Memantine can protect brain cells by blocking these effects of excess glutamate.

Are these drugs effective for everyone with Alzheimer's disease?

The latest (2011) guidance from the National Institute for Health and Clinical Excellence (NICE) recommends that donepezil, rivastigmine and galantamine are available as part of NHS care for people with mild-to-moderate Alzheimer's disease. There are also now several studies − including work supported by Alzheimer's Society − which suggest that cholinesterase inhibitors may also help people with more severe Alzheimer's disease. However, these drugs are not licensed in the UK for the treatment of severe Alzheimer's disease.

Between 40 and 70 per cent of people with Alzheimer's disease benefit from cholinesterase inhibitor treatment, but it is not effective for everyone and may improve symptoms only temporarily, between six and 12 months in most cases. According to an Alzheimer's Society survey of 4,000 people, those using these treatments often experience improvements in motivation, anxiety levels and confidence, in addition to daily living, memory and thinking.

It is not clear whether the cholinesterase inhibitors bring benefits for behavioural symptoms such as agitation or aggression. Trials have given mixed results here. Research does suggest that these drugs (and memantine) bring some relief from the carer's perspective.

Memantine is licensed for the treatment of moderate-to-severe Alzheimer's disease. It can temporarily slow down the progression of symptoms, including everyday function, in people in the middle and later stages of the disease. There is evidence that memantine may also help behavioural symptoms such as aggression and agitation.

The 2011 NICE guidance (see below) recommends use of memantine as part of NHS care for severe Alzheimer's disease and for patients with moderate disease who cannot take the cholinesterase inhibitor drugs.

Can memantine be taken at the same time as donepezil, rivastigmine or galantamine?

A few studies have looked, with a range of conclusions, at whether combining donepezil with memantine is more effective than taking donepezil alone in moderate-to-severe Alzheimer's disease. A recent trial provides strong evidence that, for people already on donepezil, there are important benefits for both patient and carer of the person remaining on donepezil when their Alzheimer's disease has become severe and treatment with memantine is started.

Memantine works in a completely different way from the acetylcholinesterase inhibitors and, if a person stopped taking donepezil in order to try memantine, their symptoms could become worse, which could then make it difficult to assess their suitability for memantine.

This latest research was not reflected in the 2011 guidance from NICE which does not recommend the combination treatment. Whether doctors will prescribe both medicines together, especially on the NHS, is unclear.

Are there any side-effects?

Generally, cholinesterase inhibitors and memantine can be taken without too many side-effects. Not everyone experiences the same side-effects, or has them for the same length of time, if they have them at all.

The most frequent side-effects of donepezil, rivastigmine and galantamine are loss of appetite, nausea, vomiting and diarrhoea. Other side-effects include stomach cramps, headaches, dizziness, fatigue and insomnia. Side-effects can be less likely for people who start treatment by taking the lower prescribed dose for at least a month.

The side-effects of memantine are less common and less severe than for the cholinesterase inhibitors. They include dizziness, headaches, tiredness, increased blood pressure and constipation.

It is important to discuss any side-effects with the doctor and/or the dispensing pharmacist.

None of these drugs are addictive.

How can these drugs be obtained?

In the first instance, these drugs can only be prescribed by a consultant. A general practitioner will need to refer the person to a hospital for a specialist assessment. A consultant will carry out a series of tests to assess whether the person is suitable for treatment and will write the first prescription, if appropriate. Subsequent prescriptions may be written by the general practitioner or the consultant.

Some people may wish to obtain these drugs privately. Private prescriptions can be obtained through a consultant, a general practitioner or a private hospital. Private prescriptions are subject to consultation fees, prescription charges and dispensing fees, which vary.

The current cost of these drugs to the NHS ranges from £800 to £1,000 per patient each year. However, the UK patents for all these drugs are expiring during 2012 and prices will start to fall dramatically as competing 'generic' versions are introduced. Whether these drugs are obtained on the NHS or privately, the patient must be willing to take the treatment, and should discuss any possible benefits, risks or side-effects with the doctor.

Are these drugs effective for other types of dementia?

The acetylcholinesterase inhibitors were developed specifically to treat Alzheimer's disease. We do not yet know whether they can be helpful for people with other forms of dementia, although there is evidence that they may be effective in dementia with Lewy bodies and dementia related to Parkinson's disease, for which rivastigmine is licensed. NICE guidelines allow acetylcholinesterase inhibitors to be offered to people with Lewy body or Parkinson's disease dementia if they have distressing symptoms or challenging behaviours.

There are several trials examining cholinesterase inhibitors for the treatment of vascular dementia, but the benefits are very modest, except in the individuals with a combination of both Alzheimer's disease and vascular dementia. Cholinesterase inhibitors are not licensed for the treatment of vascular dementia.

NICE guidance

The National Institute for Health and Clinical Excellence (NICE) reviews drugs and decides whether they represent good enough value for money to be available as part of NHS treatment.

In March 2011, NICE issued new guidance recommending that people with Alzheimer's disease should now have increased access to the available drugs. 

The latest NICE guidance on drug treatments for Alzheimer's disease recommends that people in the mild-to-moderate stages of the disease should be given treatment with donepezil (Aricept), galantamine (Reminyl) or rivastigmine (Exelon), including individuals with both Alzheimer's disease and learning disabilities.

This differs from the previous (2006) NICE guidance, which indicated these drugs could be prescribed only to people in the moderate stage of Alzheimer's disease.

The 2011 NICE guidance further recommends that memantine (Ebixa) should be prescribed as part of NHS care for patients with severe Alzheimer's disease, or for those with moderate disease who cannot take the cholinesterase inhibitor drugs. This differs from the previous NICE guidance, which stated that memantine should not be prescribed as part of NHS care, but emphasised further studies as an important research priority.

The clinical care guideline on the care and treatment of people with dementia, which NICE publishes alongside its guidance, stresses that the severity of a person's dementia should not be determined by cognition scores alone (eg Mini Mental State Examination), but by a more holistic view of the patient's condition.

NICE guidelines permit people with dementia with Lewy bodies or dementia associated with Parkinson's disease to be offered an acetylcholinesterase inhibitor if their non-cognitive symptoms (eg hallucinations, agitation) are causing distress or leading to challenging behaviour. The decision as to whether these treatments are appropriate for particular individuals lies with the specialist doctor.

In relation to the drugs for Alzheimer's disease, NICE recommends that:

  • treatment is started by a doctor who specialises in the care of people with dementia

  • patients who are started on one of the drugs are checked regularly, usually by a specialist team

  • the check-up includes an assessment of the patient's cognition, behaviour and ability to cope with daily life

  • the views of carers on the patient's condition are discussed at the start of drug treatment and at check-ups

  • treatment is continued as long as it is judged to be having a worthwhile effect

  • where a cholinesterase inhibitor is given, the least expensive of the three drugs is prescribed first. However, if it is not suitable for the patient another cholinesterase inhibitor could be chosen.

Printed copies of CG42 Dementia: supporting people with dementia and their carers, or of Donepezil, galantamine, rivastigmine and memantine for the treatment of Alzheimer's disease, can be ordered from NICE by calling 0845 003 7780, or downloaded from www.nice.org.uk

Alzheimer's Society continues to campaign for drugs to be made freely available to anyone who may benefit from them. For more information, see alzheimers.org.uk/accesstodrugs

For details of Alzheimer's Society services in your area, visit alzheimers.org.uk/localinfo 

For information about a wide range of dementia-related topics, visit alzheimers.org.uk/factsheets

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