Alzheimer's disease

Alzheimer's disease
Post-autopsy brain scans: A brain with Alzheimer's disease (left) as compared to a normal brain (right)
ICD-10	ICD10 F84.0-F84.1, ICD10 F84.0-F84.1
ICD-9	331.0 -290.1
OMIM	104300
MedlinePlus	000760

Alzheimer's disease is also known as Alzheimer disease, Alzheimer's and simply AD.

Alzheimer's is the most common cause of dementia, afflicting at least 44 million people worldwide, as of 2016. Alzheimer's is a terminal disease for which there is currently no known cure. It is most commonly found in people over 65 years old, although a less-common form called Familial Alzheimer's disease, or "early-onset Alzheimer's", also occurs, affecting about 1%—5% of the total of Alzheimer's sufferers.

Typically, the disease begins many years before it is diagnosed. In its early stages, short-term memory loss is the most common symptom, which is often initially thought by the sufferer to be caused by other factors, such as aging or stress. Later symptoms of the disease include confusion, anger, mood swings, language breakdown, long-term memory loss, and the general "withdrawal" of the sufferer as his or her senses decline. Gradually the sufferer will lose minor, and then major bodily functions, until death finally occurs. Survival after diagnosis has been estimated to be between 5 and 20 years.

Symptoms

Common symptoms of dementia include:

   A decline in memory
   Changes in thinking skills
   Poor judgment and reasoning
   Decreased focus and attention
   Decreased language ability
   Negative changes in behavior

Although the symptoms are common, they are typically experienced in unique ways. "Stages" are commonly referred to by professionals to describe the progressive nature of Alzheimer's (typically "early", "mid" and "late onset") but the symptoms can cross over these "boundaries" for many sufferers.

Diagnosis

The symptoms of Alzheimer's disease are generally reported to a doctor or physician when memory-loss (or symptoms surrounding memory loss) begins to pose a serious concern. When Alzheimer's disease is suspected, diagnosis is typically confirmed by a behavioural assessment, and some form of cognitive test. Often this is followed by a brain scan, such as a PET scan.

Criteria

There are three sets of criteria for the clinical diagnoses of the spectrum of Alzheimer's disease: the 2013 fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5); the National Institute on Aging-Alzheimer's Association (NIA-AA) definition as revised in 2011; and the International Working Group criteria as revised in 2010. Three periods, which can span decades, define the progression of Alzheimer's disease from the preclinical phase, to mild cognitive impairment (MCI), followed by Alzheimer's disease dementia.

Eight intellectual domains are most commonly impaired in AD: memory, language, perceptual skills, attention, motor skills, orientation, problem solving, and executive functional abilities, as listed in the fourth text revision of the DSM (DSM-IV-TR).

The DSM-5 defines criteria for probable or possible Alzheimer's for both major and mild neurocognitive disorder. Major or mild neurocognitive disorder must be present along with at least one cognitive deficit for a diagnosis of either probable or possible AD.

Laboratory tests

Apolipoprotein E4

Although apolipoprotein E4 is an important susceptibility gene for Alzheimer's disease], its sensitivity and specificity are insufficient (65 and 68 percent, respectively) to be used as a diagnostic test.

However, the level of apolipoprotein E4 in cerebrospinal fluid may be predictive.

Amyloid-beta protein

Amyloid-beta protein may be elevated in the cerebrospinal fluid of some patients.

Autopsy

Completely reliable confirmation of a Alzheimer's diagnosis has traditionally only been possible upon the death of the patient. The brain tissue will be examined by a pathologist, and there are two unique lesions that are unmistakable signs of Alzheimer's that will give definite confirmation.

Cause/etiology

The etiology of Alzheimer's disease is incompletely understood. Alzheimer's disease is associated with senile plaques and neurofibrillary tangles in the brain. The incorrect folding of proteins leads to the formation of amyloid plaques. The prion protein (PrP^C) may be the cellular receptor for amyloid-beta oligomer. Current research aims to determine if such plaques are the result of, or the cause of, Alzheimer's disease.

Regarding biomarkers, one study found that "a reduction in the cerebrospinal fluid (CSF) Aβ42 level denotes a pathophysiological process that significantly departs from normality (i.e., becomes dynamic) early, whereas the CSF total tau level and the adjusted hippocampal volume are biomarkers of downstream pathophysiological processes".

Although there is a genetic susceptibility in a small percentage of people, Alzheimer's is not considered a genetic illness. The greatest risk factor for developing Alzheimer's is age, as the percentage of people developing it dramatically increases after age 65 and beyond. Major environmental/lifestyle risk factors include a diet high in saturated fats that are typical of the standard western diet, smoking, and long-term exposure to environmental toxins such as aluminium. Research is ongoing.

Alzheimer's appears to be a disease of the modern world, especially developed societies. Prior to the early 20th century, this dementia was completely unknown to science and was never described in elder members of traditional societies.

Individuals with the genetic disease Down syndrome (trisomy 21) are at much higher risk for developing Alzheimer's in their middle age. According to the National Down Syndrome Society, about 30% of people with Down syndrome who are in their 50s, and about 50% of those in their 60s, have Alzheimer’s disease. The lifetime risk is over 90%.

Epidemiology

In the United States in 2020, Alzheimer's dementia prevalence was estimated to be 5% for those in the 60–74 age group, with the rate increasing to 14% in the 74–84 group and to 35% in those greater than 85.

Advancing age is a primary risk factor for the disease and incidence rates are not equal for all ages: every 5 years after the age of 65, the risk of acquiring the disease approximately doubles, in developed societies such as Spain and Italy.

Treatment

As of 2024, no treatment has been found to stop progression or completely reverse the disease, but some treatments do slow the progression. Many preventive measures have been suggested for Alzheimer's disease, but their values are uncertain: mental stimulation, exercise, and a Mediterranean style diet are usually recommended, both as possible prevention and as a sensible way of managing the disease.

Medications

As of 2023, available medications offer relatively small symptomatic benefit for some patients but generally do not slow disease progression. Newer monoclonal antibody treatments against beta-amyloid protein, for example, the drug Leqembi, have been approved in the United States, but they only slightly reduce the rate of disease progression and have significant side effects, including brain bleeding and in rare cases, death. These drugs cost over $20,000 a year, which could be prohibitively expensive for many patients.

Randomized controlled trials showed either small or absent benefit from acetylcholinesterase inhibitors such as donepezil.

The N-methyl-d-aspartate receptor antagonist memantine has shown some effectiveness but does not add benefit to donepezil .

Care management

Due to the incurable and degenerative nature of the disease care-management of Alzheimer's is essential. The role of the main caregiver is often taken by the spouse or a close relative. Caregivers may themselves suffer from stress, over-work, depression, and from being physically assailed.

Alzheimer's in society

Famous people who have, or have died of Alzheimer's disease, are the US president Ronald Reagan, the UK Prime minister Harold Wilson, the writers Terry Pratchett and Iris Murdoch, and the film stars Rita Hayworth and Charlton Heston.

History

Auguste D, first recorded patient with the newly recognised form of dementia.

Alzheimer’s disease is named after Dr. Alois Alzheimer, the German physician who first described it. In 1901, Alzheimer observed a 51-year-old patient at the Frankfurt asylum named Auguste Deter. Her symptoms included memory loss, language problems, and unpredictable behavior. In 1906, she died and Dr. Alzheimer noticed unusual pathology in her brain tissue; he found many abnormal clumps (now called amyloid plaques) and tangled bundles of fibers (now called neurofibrillary, or tau, tangles).

Prior to the early 20th century, Alzheimer's was undescribed in world medical literature. Other dementias and brain and behavioral disorders, however, were well documented by then.