What causes Alzheimer's disease?

Like all types of dementia, Alzheimer's is caused by brain cell death.3 It is a neurodegenerative disease, which means there is progressive brain cell death that happens over a course of time.
The total brain size shrinks with Alzheimer's - the tissue has progressively fewer nerve cells and connections.
While they cannot be seen or tested in the living brain affected by Alzheimer's disease, postmortem/autopsy will always show tiny inclusions in the nerve tissue, called plaques and tangles:
1. Plaques are found between the dying cells in the brain - from the build-up of a protein called beta-amyloid (you may hear the term "amyloid plaques").
2. The tangles are within the brain neurons - from a disintegration of another protein, called tau.
For a detailed visualization of what goes on in the Alzheimer's disease process, progressing from the normal brain to increasing dementia changes, the Alzheimer's Association has produced a journey of 16 slides. See the illustrations: Inside the brain: an interactive tour.

Risk factors

Some things are more commonly associated with Alzheimer's disease - not seen so often in people without the disorder. These factors may therefore have some direct connection. Some are preventable or modifiable factors (for example, reducing the risk of diabetes or heart disease may in turn cut the risk of dementia).
If researchers gain more understanding of the risk factors, or scientifically prove any "cause" relationships for Alzheimer's, this could help to find ways to prevent it or develop treatments.
Risk factors associated with Alzheimer's disease include:
Unavoidable risk factors
1. Age - the disorder is more likely in older people, and a greater proportion of over-85-year-olds have it than of over-65s
2. Family history (inheritance of genes) - having Alzheimer's in the family is associated with higher risk. This is the second biggest risk factor after age.
3. Having a certain gene (the apolipoprotein E or APOE gene) puts a person, depending on their specific genetics, at three to eight times more risk than a person without the gene.6 Numerous other genes have been found to be associated with Alzheimer's disease, even recently (see developments below).
4. Being female (more women than men are affected).
Potentially avoidable or modifiable factors
5. Factors that increase blood vessel (vascular) risk - including diabetes, high cholesterol and high blood pressure. (These also increase the risk of stroke, which itself can lead to another type of dementia.)
6. Low educational and occupational attainment.
7. Prior head injury. (While a traumatic brain injury does not necessarily lead to Alzheimer's, some research links have been drawn, with increasing risk tied to the severity of trauma history.)
8. Sleep disorders (the breathing problem sleep apnea, for example).
9. Estrogen hormone replacement therapy.

Signs and symptoms

The information in this section connects closely to some of that about tests and diagnosis below because symptoms noticed by patients, or people close to them, are exactly the same signs that healthcare professionals look for during testing. Symptoms can be diagnosed at any stage of Alzheimer's dementia and the progression through the stages of the disease is monitored after an initial diagnosis, too, when the developing symptoms dictate how care is managed. For doctors to make an initial diagnosis of Alzheimer's disease, they must first be satisfied that there is dementia - guidelines spell out what dementia consists of. It involves cognitive or behavioral symptoms that show a decline from previous levels of "functioning and performing" and interfere with ability "to function at work or at usual activities." The cognitive decline is in at least TWO of the five symptom areas listed below (from guidelines jointly produced by the National Institute on Aging and the Alzheimer's Association):
1. Worsened ability to take in and remember new information, for example:
# "Repetitive questions or conversations
# Misplacing personal belongings
# Forgetting events or appointments
# Getting lost on a familiar route."
2. Impairments to reasoning, complex tasking, exercising judgment:
# "Poor understanding of safety risks
# Inability to manage finances
# Poor decision-making ability
# Inability to plan complex or sequential activities."
3. Impaired visuospatial abilities (but not, for example, due to eye sight problems):
# "Inability to recognize faces or common objects or to find objects in direct view
# Inability to operate simple implements, or orient clothing to the body."
4. Impaired speaking, reading and writing:
# "Difficulty thinking of common words while speaking, hesitations
# Speech, spelling, and writing errors."
5. Changes in personality and behavior, for example:
# Out-of-character mood changes, including agitation; less interest, motivation or initiative; apathy; social withdrawal
# Loss of empathy
# Compulsive, obsessive or socially unacceptable behavior.
Once the number and severity of these example symptoms confirm dementia, the best certainty that they are because of Alzheimer's disease is given by:
A gradual onset "over months to years" rather than hours or days (the case with some other problems)
A marked worsening of the individual person's normal level of cognition in particular areas.
The most common presentation marking Alzheimer's dementia is where symptoms of memory loss are the most prominent, especially in the area of learning and recalling new information. But the initial presentation can also be one of mainly language problems, in which case the greatest symptom is struggling to find the right words.11
If visuospatial deficits are most prominent, meanwhile, these would include inability to recognize objects and faces, to comprehend separate parts of a scene at once (simultanagnosia), and a type of difficulty with reading text (alexia). Finally, the most prominent deficits in "executive dysfunction" would be to do with reasoning, judgment and problem-solving.11 Stages of Alzheimer's disease
The progression of Alzheimer's can be broken down into three basic stages:
# Preclinical (no signs or symptoms yet)
# Mild cognitive impairment
# Dementia.
The Alzheimer's Association has broken this down further, describing seven stages along a continuum of cognitive decline based on symptom severity - from a state of no impairment, through mild and moderate decline, and eventually reaching "very severe decline." The association has published the seven stages online. It is not usually until stage four that a diagnosis is clear - here it is called mild or early-stage Alzheimer's disease, and "a careful medical interview should be able to detect clear-cut symptoms in several areas."