Alzheimer’s disease is a brain disorder that gets worse over time and usually affects middle-aged to older adults. It causes the memory to get worse over time and can’t be fixed. It also makes other cognitive skills worse. The disease is marked by the loss of a lot of brain mass and the death of nerve cells and connections in the cerebral cortex of the brain.
Find out about Alzheimer’s disease and how to prevent it.
A look at Alzheimer’s disease.
In 1906, a German neuropathologist named Alois Alzheimer was the first person to describe the disease. At the beginning of the 21st century, it was known that it was the most common form of dementia in older people. In 2016, there were about 47.5 million people with dementia around the world. By 2030, that number was expected to rise to 75.6 million.
The disease’s stages
Alzheimer’s disease is known to have three stages: the early stage, mild cognitive impairment (MCI), and Alzheimer’s dementia. MCI and dementia are the two stages that are most important for clinical diagnosis. Recognizing the preclinical stage acknowledges that Alzheimer’s disease starts before symptoms show up and look forward to improvements in diagnostic tests that may one day make it possible to diagnose at the preclinical stage.
MCI is often broken down into two types: those who forget things and those who don’t. Forgetting things is one of the first signs that you are moving from normal aging to Alzheimer’s disease. This transitional stage is called amnestic MCI, and it’s marked by memory problems that are easy to see. However, judgment, reasoning, and perception are still normal. In MCI that doesn’t affect memory, problems with attention, perception, and language are more common than memory problems. But as MCI turns into Alzheimer’s disease, language, perception, and motor skills get worse and memory loss gets worse. The person’s mood becomes unstable, and they tend to get irritable and more sensitive to stress. They may also feel angry, anxious, or sad from time to time. These changes are the start of Alzheimer’s dementia, which in its later stages causes the person to stop responding and lose the ability to move and control their bodily functions. After 2 to 20 years of having the disease, the person dies.
About 10% of the people who get the disease are under the age of 60. These cases, which are called “early-onset familial Alzheimer disease,” seem to be caused by a genetic mutation that is passed down from parent to child. Most cases of Alzheimer’s disease, however, happen after age 60 (late-onset) and are usually sporadic, meaning they don’t run in families. However, a genetic factor has been found that is thought to make some of these people more likely to get the disorder. Rosacea is an inflammatory skin condition that lasts for a long time. People with rosacea are more likely to get Alzheimer’s disease, especially if they are 60 or older.
Neuritic plaques and neurofibrillary tangles
Autopsies are used to find out if a person has Alzheimer’s disease by looking for neuritic plaques and neurofibrillary tangles in the brain. Neuritic plaques, also called senile plaques, dendritic plaques, or amyloid plaques, are made up of neuronal material that is breaking down and deposits of a sticky protein called amyloid-beta (or beta-amyloid). This protein comes from a bigger molecule called amyloid precursor protein. The amyloid precursor protein is a normal part of nerve cells. Neurofibrillary tangles are made up of twisted protein fibers that are found inside nerve cells. These fibers are made of tau, a protein that is usually found in neurons. Tau molecules form tangles when they are processed in the wrong way.
Neuritic plaques and neurofibrillary tangles, which can also be found in small amounts in the brains of healthy older people, are both thought to interfere with the normal way cells work in some way. But it is not known if the plaques and tangles are a cause of the disease or a result of it. Animal studies suggest that amyloid-beta plaques form in the brain naturally when there is an infection. These plaques trap microorganisms. The idea that amyloid beta acts as a natural antibiotic suggests that Alzheimer’s disease may be linked in some way to brain infections since people with Alzheimer’s develop too much plaque or have some other kind of abnormal plaque buildup.
Many people with Alzheimer’s disease have brains that have other changes. One of these is a lack of the neurotransmitter acetylcholine. Neurons with acetylcholine are important for remembering things.
Alzheimer’s disease has been linked to insulin signals in the brain that don’t work right. Under normal circumstances, insulin binds to insulin receptors, which are found in large numbers on the membranes of neurons. This makes it easier for neurons to take in glucose, which is needed for the brain to do all of its many jobs. But neurons in the brains of people with Alzheimer’s disease don’t have many or any insulin receptors, so insulin doesn’t work as well on them. Because insulin can’t stick to the nerve cells, it builds up in the blood serum, causing a condition called hyperinsulinemia (abnormally high serum levels of insulin). Hyperinsulinemia is thought to cause inflammation in the brain, which leads to the growth of neuritic plaques. Aside from nerve cell damage and death, abnormal insulin signaling in the brain has also been linked to lower levels of acetylcholine and transthyretin, a protein that normally binds to amyloid-beta proteins and moves them out of the brain.
Both late-onset and early-onset cases of Alzheimer’s disease have been linked to genetic flaws. Finding and describing these flaws has given us important information about how Alzheimer’s disease works and has led to the development of new ways to diagnose and treat the disease.
A problem with a gene called APP, which codes for amyloid precursor protein, may cause more amyloid-beta, which is at the center of neuritic plaques, to be made or build up. It is thought, though, that this gene is only to blame for a very small number of early-onset cases of the disease.
Most cases of late-onset Alzheimer’s may be caused by a problem with the gene that tells the body to make apolipoprotein E (ApoE), which helps move cholesterol. This gene comes in three different forms: APOE2, APOE3, and APOE4. Two of these forms, APOE3 and APOE4, are linked to a higher risk of disease and affect the age at which the disease starts.
Functional magnetic resonance imaging (fMRI) studies have shown that the hippocampus of the brain is often more active in people between the ages of 20 and 35 who have the APOE4 variant. This part of the brain is very important for making and remembering memories and for feeling emotions. Scientists think that in some APOE4 carriers, a hyperactive hippocampus early in life leads to a dysfunctional hippocampus later in life, which can lead to Alzheimer’s disease. Brain imaging with fMRI in young people who have APOE4 may help find the people who are most likely to get sick.
By looking at the status of a gene called TOMM40 (translocase of outer mitochondrial membrane 40 homologs [yeast]), genetic testing can give more information about the risk of Alzheimer’s disease and predict when it will start. There are different versions of this gene, and their lengths vary because of differences in the number of times a certain set of base pairs is repeated in the gene sequence. People who have inherited TOMM40 variants are more likely to get the disease before they turn 80 if they have a long form of the gene and either APOE3 or APOE4. On the other hand, short forms of TOMM40 were linked to getting the disease after the age of 80.
Alzheimer’s disease has also been linked to several other genes. CD33, which codes for a cell surface protein with the same name; PICALM, which codes for a protein involved in endocytosis (the process by which cells take in substances); and CD2AP, which codes for a protein that interacts with the cell membrane and may play a role in endocytosis.
Alzheimer’s disease can’t be cured. But several medicines can be used to stop the disease from getting worse or to ease its symptoms. Drugs called acetylcholinesterase inhibitors can stop amnestic MCI from getting worse in about half of patients for about a year (or anticholinesterases). Galantamine, donepezil, and rivastigmine are examples of these drugs. They work by slowing the breakdown of acetylcholine. Acetylcholinesterase inhibitors often cause nausea, vomiting, and diarrhea as side effects. Some people with Alzheimer’s disease can feel better when they take the drug memantine. This is because it stops glutamate, an excitatory neurotransmitter, from binding to certain receptors in the brain. This drug can make people smarter and more involved in their daily lives, but it can also make some people very angry or believe things that aren’t true. Other treatments try to get rid of the depression, bad behavior, and lack of sleep that often come with the disease.
There are also several new drugs being tested in early and late-stage clinical trials for Alzheimer’s disease. Methylthioninium chloride (Rember), which is more commonly known as methylene blue (an organic dye), is a drug that has had some success. It works by targeting the tau protein in neurofibrillary tangles. In clinical trials, people with Alzheimer’s disease who took methylthioninium chloride either stopped their mental decline or slowed it down by a lot. It is the first drug that can break up tau protein fibers and stop neurofibrillary tangles from forming. In animal studies, a derivative of the flavonoid fisetin, which is found in onions, cucumbers, and fruits like strawberries and apples, showed that it might be able to reverse memory loss in people with Alzheimer’s disease.
Scientists are working hard to find ways to find Alzheimer’s disease earlier and treat it better. Progress in early detection has been especially important and has led to important changes in how Alzheimer’s disease is diagnosed. The first set of rules, which were put in place in 1984, said that clinical diagnosis could only be done in the last stage of dementia, which was usually confirmed by an autopsy. But in 2011, because diagnostic methods and scientists’ understanding of the pathophysiology of Alzheimer’s disease had improved, new guidelines were made for diagnosing the disease at three different stages: preclinical, MCI, and dementia. This made it easier to use new or experimental diagnostic technologies and to find the disease earlier.
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The ability to find Alzheimer’s disease early is mostly due to improvements in diagnostic imaging, the discovery of biomarkers (physiological changes that are unique to the disease and show that it is there), and the development of ways to measure these biomarkers. Some of the ways that Alzheimer’s disease is being found are blood tests that measure how much a protein is being expressed by certain white blood cells and positron emission tomography, which looks for higher levels of an enzyme in cerebrospinal fluid.
A test that looks for biomarkers in spinal fluid that are linked to Alzheimer’s disease has shown promise in finding the disease early. A lumbar puncture is used to get fluid for the test (spinal tap). The test is sensitive enough to find people who have mild cognitive impairment and are therefore most likely to get the disease in the future. This gives time for intervention strategies to be put in place to delay the disease’s onset.
How people live and how to stop it
Having a healthy heart and living a healthy lifestyle are both linked to a lower risk of dementia and Alzheimer’s disease. Some of these factors are regular exercise, a healthy diet, and not being too stressed out. On the other hand, people who have genes that make them more likely to get Alzheimer’s disease are thought to have a bad effect on their brains by making it easier for neuritic plaques to form.
Some foods, like vitamin B, caffeine, and alcohol, have also been linked to a lower risk of Alzheimer’s disease. For instance, a small clinical trial showed that vitamin B12 can slow the rate of brain atrophy in some people with MCI. This happens because vitamin B12 can control how much of an amino acid called homocysteine is in the blood. High levels of homocysteine have been linked to a higher chance of getting Alzheimer’s disease. In studies of mice with Alzheimer’s, when the mice drank the equivalent of five cups of coffee’s worth of caffeine, the levels of amyloid-beta proteins in the brain and blood went down. Mice with MCI were the ones who felt the effects of caffeine the most. The substance also helped these animals remember things a lot better. Moderate alcohol use, which is between 8 and 14 drinks per week for people 75 and older with normal cognitive function (one drink is 0.5 ounces of 100 percent alcohol), has been shown to cut the risk of dementia by almost 40 percent in people with normal cognitive function. But drinking alcohol is linked to a faster progression toward dementia in people who are in the early stages of Alzheimer’s disease and have MCI symptoms.
Rheumatoid arthritis, a chronic inflammatory disease of the connective tissues of the body, is another thing that is linked to a lower risk of Alzheimer’s disease. People with arthritis have a protein called GM-CSF (granulocyte-macrophage colony-stimulating factor). This protein is thought to cause the immune system to make more cells that destroy amyloid-beta proteins. In studies of mice with cognitive impairment similar to Alzheimer’s disease in people, treatment with GM-CSF decreased the number of amyloid plaques in the brain and led to better results on tests of memory and learning. A type of GM-CSF called sargramostim is used to treat people with acute myelogenous leukemia. It has also been looked into as a way to help people with Alzheimer’s disease. Periodontitis, a type of gum disease, may increase the chance of getting Alzheimer’s disease. Research has shown that people with chronic periodontitis are much more likely to get Alzheimer’s disease than people who don’t have gum disease. Porphyromonas gingivalis, a bacterium linked to gum disease, has also been found in the brains of people with Alzheimer’s disease. Gingipain is a protein that is made by P. gingivalis. It is toxic to neurons and is linked to more amyloid-beta being made in the brain. It is still not clear whether Alzheimer’s disease is caused by periodontitis and P. gingivalis getting into the brain or is a result of it.