Into the Brain: Alzheimer's in Women
Alzheimer’s is a type of dementia that causes problems with memory, thinking, and behavior. Dementia is caused by damage to brain cells.
When cells in a region of the brain are damaged, that region cannot carry out functions normally. Alzheimer’s is the most common form of dementia, accounting for sixty to eighty percent of dementia cases. The majority of people with this disease are age sixty-five or older and female (Alzheimer’s Disease Fact Sheet). Alzheimer’s is a progressive disease where symptoms gradually worsen over time. Researchers have determined that the APOE-e4 gene is a primary indicator of an individual’s susceptibility to developing the disease (“About Alzheimer’s Disease: Alzheimer’s”). Estrogen, a female hormone, plays a role in reducing the plaques in the brain as well as triggering a decline in the brain’s ability to burn glucose for energy.
Variables such as education and susceptibility to depression, that affects women more than men, play a part in the development of Alzheimer’s (“Alzheimer’s Genes: Are you at risk?”). The APOE-e4 gene, estrogen, and plaques and tangles are multiple risk factors that lead to the progression of Alzheimer’s. There are seven stages of Alzheimer’s. Unfortunately, in the first stage no mental impairment is evident – a person does not experience any memory problems. In this stage, the disease is not medically detectable. Stage two is very mild cognitive decline in which the disease still cannot be easily detected.
Cognitive decline or impairment is when a person has trouble remembering and learning new things. In this stage a person may feel as if objects or words have been forgotten. The third stage is mild cognitive decline in which doctors may be able to detect the disease. In this stage family or friends will start to notice difficulties in remembering things like words, objects, or preforming every day tasks (“10 Early Signs and Symptoms”). In the rest of the stages, doctors will be able to clearly detect the symptoms of Alzheimer’s.
The fourth stage is moderate cognitive decline in which symptoms can clearly be detected. In this stage a person will have trouble remembering events and history, will have a harder time completing tasks, and may become withdrawn in socially or mentally challenging situations. The fifth stage is moderately severe cognitive decline. In this stage a person will start to need help with day-to-day activities. The individual may not be able to recall the home address or telephone number, become confused as to their whereabouts or what day it is, and may have trouble with math as in counting back from forty. Stage six is severe cognitive decline.
In this stage memory continues to worsen and personalities may begin to change. A person may lose awareness of the surroundings around them, have trouble remembering names of family members, and need help with dressing and going to the bathroom. At this stage individuals may need extensive help with daily activities. The last stage, stage seven, is very severe cognitive decline. In this stage individuals lose the ability to respond to their environment, to carry on a conversation, and to control their movement.
A person may lose the ability to smile, talk, or to hold their head up. At this stage individuals need help with almost all of their daily care (“Early Signs of Alzheimer’s/Dementia”). Knowing the stage an individual is in will allow the person to get the proper treatment available for that specific stage. Although initial symptoms are often mistaken for normal aging or dementia because forgetfulness increases with age, some treatments are now available that slow down the progression of Alzheimer’s. There is no single test that can show whether a person has Alzheimer’s. To diagnosis Alzheimer’s, a careful medical examination of an individual’s family medical history, mental status testing, physical and neurological exam, and blood test, as well as brain imaging will be performed (CNN Wire).
Advanced medical imaging with magnetic resonance imaging can be used to help exclude other cerebral pathology of dementia. The imaging may predict conversion from early dementia to Alzheimer’s disease. An early and accurate diagnosis of Alzheimer’s disease is an important first step to help ensure that a person has appropriate treatment, care, family education, and plans for the future. Early diagnosis and treatment can delay symptoms for up to twelve months, helping to maintain thinking skills and memory (MedLexicon International Ltd). Unfortunately, there are no current cures for Alzheimer’s but a variety of treatments may help with both cognitive and behavioral symptoms. The FDA has approved the drugs cholinesterase inhibitors and memantine to treat cognitive symptoms of Alzheimer’s disease.
Cholinesterase inhibitors prevent the breakdown of acetylcholine, a chemical messenger important for learning and memory. Acetylcholine, a primary neurotransmitter in the body, is one of the chemicals that neurons use to communicate with each other. Acetylcholine is used by nerve cells to signal muscles to initiate or cease movement. Acetylcholine-producing cells in the forebrain are damaged in the early stages of Alzheimer’s disease. Normal aging causes a slight decrease in acetylcholine concentration, causing periodic forgetfulness.
However, in Alzheimer’s, the concentration can be decreased by as much as ninety-percent, resulting in significant memory and behavioral decline (“Preventing Memory Loss”). Memantine, another drug the FDA has approved to treat cognitive symptoms of Alzheimer’s disease, regulate the activity of glutamate, a different messenger chemical involved in learning and memory, in the brain. Glutamate is a powerful excitatory neurotransmitter that is released by nerve cells in the brain and is responsible for sending signals between nerve cells (Stanford). Glutamate can actually be damaging to nerve cells when there are abnormally high concentrations of the neurotransmitter. Cells activated by glutamate become overexcited, which can lead to effects that can cause cell damage or death.
Medications that slow down the progression of Alzheimer’s are most effective when treatment is started in the early stages of the disease. Methods of treatments that do not involve drugs include writing with your non-dominant hand, brain games, pet therapy, and altering one’s environment to resolve challenges and obstacles (Dador). The APOE-e4 gene is a known factor that increases the rick of developing Alzheimer’s. The APOE gene provides instructions for making a protein called Apolipoprotein E. This protein helps carry lipids, cholesterol, and other fats in the bloodstream to the liver, where the lipids from the blood are excreted.
The APOE gene is located on the long arm of chromosome 19 (ALZinfo.org). The three major alleles of the APOE gene are e2, e3, and e4. An allele is one or two or more alternative forms of a gene that arises by mutation and is found at the same place on the chromosome. The most common allele is e3, which is found in more than half the population.
People inherit one APOE allele from each parent. Having one APOE-e4 gene increases one’s risk of developing this disease and having two of the APOE-e4 genes doubles one’s risk of developing Alzheimer’s (“APOE”). A blood test can identify which APOE alleles a person has but cannot predict who will or will not develop Alzheimer’s (Goldman). Women with the APOE-e4 gene have close to twice the likelihood of progressing to mild cognitive impairment as those who didn’t posses the gene. Scientists suspect the APOE-e4 gene interacts with estrogen after women undergo menopause, to create conditions that lead to Alzheimer’s (Emling). Individuals with Alzheimer’s have damaged brain cells.
Plaques and tangles damage the brain cells. Although many older individuals develop some plaques and tangles as a consequence of aging, the brains of people with Alzheimer’s have a greater number of plaques and tangles in specific regions such as the temporal lobe. Plaques build up between nerve cells in the brain. Plaques form when protein pieces called beta-amyloid clump together. Beta-amyloid is chemically sticky and gradually builds up into plaques. Beta-amyloid is formed when certain proteins travel through a part of the cell known as the trans-Golgi network while on the way to the cell surface.
Scientists believe that the longer the proteins stay in the trans-Golgi network, the more likely the proteins are to develop into beta amyloid (Whiteman). Researchers have found that estrogen appears to reduce the formation of beta-amyloid, which in turn slows down the progression of Alzheimer’s. Estrogen pushes key proteins through normal pathways before the proteins have the time to form debilitating plaques (Goldman). Dead and dying nerve cells contain tangles, which are made up of another protein. Every neuron has a cytoskeleton, an internal support structure made up of structures called microtubules. Microtubules act as tracks, guiding nutrients and molecules from the body of the cell to the ends of the axon, the long threadlike part of a nerve cell along which impulses are conducted from the cell body to other cells, and back.
In areas where tangles have formed in the brain, tau, a protein that stabilizes microtubules, collapses into twisted strands. When tau proteins become defective and fail to stabilize microtubules, pathologies of the nervous system can develop, such as Alzheimer’s disease. Tangles also destroy a vital cell transport system made of proteins involved with the transportation of food molecules, cell parts, and other key molecules (Stanford). Plaques and tangles spread through the brain’s cortex in a pattern as Alzheimer’s disease progresses. In the early stages, plaques and tangles begin to form in brain areas involved in learning, memory, thinking, and planning. In mild to moderate stages, brain areas that were affected in the early stages begin to develop more plaques and tangles.
The plaques and tangles have now spread to areas involved in speaking, understanding speech, and sense of where your body is in relation to objects around you. In severe stages, most of the cortex is seriously damaged. The brain then begins to shrink due to widespread cell death (MedLexicon International Ltd). A shrunken brain causes the different regions in the brain to not function properly. Alzheimer’s disease is characterized by loss of neurons and synapses, connections between neurons through which information flows from one neuron to another, in the cerebral cortex and certain subcortical regions.
This loss results in atrophy of the affected regions, including degeneration in the temporal lobe and parietal lobe, and part of the frontal cortex. In a brain with Alzheimer’s, the cortex shrivels up, damaging areas involved in thinking, planning, and remembering. Shrinkage is also severe in the hippocampus, an area of the cortex that plays a key role in the formation of new memories (Whiteman). In the United States, Alzheimer’s disease is the sixth leading cause of death and is projected to affect 13.8 million Americans by 2050. As of right now there are no known cures, but treatments for symptoms are available and research continues.
Currently some studies suggest that estrogen therapy may help to delay or prevent Alzheimer’s in women who do not yet have the disease. After menopause, the low estrogen levels trigger a series of effects, including a decline in the brain’s ability to burn glucose for energy. Without glucose, the backup energy system keeps the brain running but creates byproducts that damage the brain cells, which lead to a decrease in memory. The backup energy system burns ketone bodies, which are compounds produced from carbohydrates and fat in the liver (Emling). Alzheimer’s is a serious disease that can affect anyone, but women have a higher risk of developing the disease than men partly because women live longer and the chances of developing this disease increases with age.
Research has found that the risks of dementia rise for women whose ovaries were removed because of the low estrogen levels. The stages of Alzheimer’s are the same for men as women. Being able to identify the stages of Alzheimer’s can alert an individual to seek early medical diagnosis. Early treatment is key in slowing the progression of Alzheimer’s and will give an individual more time to plan for the future (MedLexicon International Ltd).