What Part Of The Brain Is Affected In Alzheimer’s Disease

Is There Treatment Available

At present there is no cure for Alzheimer’s disease. However, one group of drugs called cholinergeric drugs appears to be providing some temporary improvement in cognitive functioning for some people with mild to moderate Alzheimer’s disease.

Drugs can also be prescribed for secondary symptoms such as restlessness or depression or to help the person with dementia sleep better.

Community support is available for the person with Alzheimer’s disease, their families and carers. This support can make a positive difference to managing dementia. Dementia Australia provides support, information and counselling for people affected by dementia. Dementia Australia also aims to provide up-to-date information about drug treatments.

Further help

For more information contact the National Dementia Helpline on 1800 100 500.

For a range of books and videos contact our Library.

For advice, common sense approaches and practical strategies on the issues most commonly raised about dementia, read our Help Sheets.

Prevention Of Alzheimer Disease

Some research tentatively suggests certain measures that may help prevent Alzheimer disease:

• Controlling cholesterol levels: Some evidence suggests that having high cholesterol levels may be related to developing Alzheimer disease. Thus, people may benefit from a diet low in saturated fats and, if needed, drugs to lower cholesterol and other fats .

• Controlling high blood pressure: High blood pressure may damage blood vessels that carry blood to the brain and thus reduce the brains oxygen supply, possibly disrupting connections between nerve cells.

• Exercising: Exercising helps the heart function better and, for unclear reasons, may help the brain function better.

• Keeping mentally active: People are encouraged to continue doing activities that challenge the mind, such as learning new skills, doing crossword puzzles, and reading the newspaper. These activities may promote the growth of new connections between nerve cells and thus help delay dementia.

• Drinking alcohol in modest amounts: In modest amounts , alcohol may help lower cholesterol and maintain blood flow. Alcohol may even help with thinking and memory by stimulating the release of acetylcholine and causing other changes in nerve cells in the brain. However, there is no convincing evidence that people who do not drink alcohol should start drinking to prevent Alzheimer disease. Once dementia develops, abstaining from alcohol is usually best because it can make symptoms of dementia worse.

Amyloid Accelerates Tau Toxicity

NEW YORK, NY Using high-resolution functional MRI imaging in patients with Alzheimer’s disease and in mouse models of the disease, Columbia University Medical Center researchers have clarified three fundamental issues about Alzheimer’s: where it starts, why it starts there, and how it spreads. In addition to advancing understanding of Alzheimer’s, the findings could improve early detection of the disease, when drugs may be most effective. The study was published today in the online edition of the journal Nature Neuroscience.

It has been known for years that Alzheimer’s starts in a brain region known as the entorhinal cortex, said co-senior author Scott A. Small, MD, Boris and Rose Katz Professor of Neurology, professor of radiology, and director of the Alzheimer’s Disease Research Center. But this study is the first to show in living patients that it begins specifically in the lateral entorhinal cortex, or LEC. The LEC is considered to be a gateway to the hippocampus, which plays a key role in the consolidation of long-term memory, among other functions. If the LEC is affected, other aspects of the hippocampus will also be affected.

In the study, the researchers used a high-resolution variant of fMRI to map metabolic defects in the brains of 96 adults enrolled in the Washington Heights-Inwood Columbia Aging Project . All of the adults were free of dementia at the time of enrollment.

The authors declare no financial or other conflicts of interests.

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How Is Alzheimer’s Disease Diagnosed

There is currently no single test to identify Alzheimer’s disease. The diagnosis is made only after careful clinical consultation.

The clinical diagnosis might include:

• A detailed medical history
• Lumbar puncture for cerebral spinal fluid tests
• Medical imaging

These tests will help to eliminate other conditions with similar symptoms such as nutritional deficiencies or depression. After eliminating other causes, a clinical diagnosis of Alzheimer’s disease can be made with about 80% to 90% accuracy if the symptoms and signs are appropriate. The diagnosis can only be confirmed after death by examination of the brain tissue.

It is important to have an early and accurate diagnosis to determine whether a treatable condition other than Alzheimer’s disease, is causing the symptoms. If Alzheimer’s disease is diagnosed, medical treatment and other assistance can be discussed.

What Happens In Alzheimer Disease

You probably know that your brain works by sending signals. Chemical messengers, called neurotransmitters , allow brain cells to talk to each other. But a person with Alzheimer disease has lower amounts of neurotransmitters.

People with Alzheimer disease also develop deposits of stuff that prevent the cells from working properly. When this happens, the cells can’t send the right signals to other parts of the brain. Over time, brain cells affected by Alzheimer disease also begin to shrink and die.

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Neurofibrillary Tangles And Neuropil Threads

Fig. 4

Neurofibrillary Tangles. Neurofibrillary tangles develop from intracellular pre-tangles containing misfolded tau and small tau aggregates to mature NFTs containing bundles of cross-linked tau filaments before the neuron dies and an extracellular ghost tangle remains. Silver staining and Thioflavin S capture many mature tangles and some pre-tangles along with amyloid plaques and tau neuropil threads. Development of NFTS from the pre-tangles is more easily visualized using tau immunohistochemistry . This allows the mis-localized somal tau to be distinguished readily from the bundles of PHFs in NFTS in addition to the neuropil threads that can also be pronounced . The scale bars are 40m

Alzheimers Disease Research Efforts

Because the diagnosis of Alzheimers has been challenging, its been hard for clinical trials to make sure theyre including people with the disease. As advances in the field make it easier to diagnose Alzheimers, it will be easier for clinical trials to study new treatments.

Current research is looking at how the brain works and changes with age, how dementia affects the brain, how we can predict who will develop dementia, as well as prevention and treatment options.

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Who Has Alzheimers Disease

• In 2020, as many as 5.8 million Americans were living with Alzheimers disease.1
• Younger people may get Alzheimers disease, but it is less common.
• The number of people living with the disease doubles every 5 years beyond age 65.
• This number is projected to nearly triple to 14 million people by 2060.1
• Symptoms of the disease can first appear after age 60, and the risk increases with age.

Figure 1 Main Parts Of The Brain

The cerebrum is the largest part of the brain and is involved in higher functions like touch, vision, and hearing, along with speech, fine motor movement, reasoning, memory, and emotions.1 The cerebellum coordinates muscle movements, helps maintain posture, and aids in balance.1 The brainstem coordinates automatic functions like breathing, heart rate, swallowing, wake and sleep cycles, digestion, and body temperature.1 It also connects the cerebrum and cerebellum with the spinal cord, acting as a sort of center of communication between them.

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Rarer Causes Of Dementia

There are many rarer diseases and conditions that can lead to dementia, or dementia-like symptoms.

These conditions account for only 5% of dementia cases in the UK.

They include:

• problems with planning and reasoning

These symptoms are not severe enough to cause problems in everyday life.

MCI can be caused by an underlying illness, such as depression, anxiety or thyroid problems.

If the underlying illness is treated or managed, symptoms of MCI often disappear and cause no further problems.

But in some cases, people with MCI are at increased risk of going on to develop dementia, which is usually caused by Alzheimer’s disease.

Read more about how to prevent dementia.

Final Stages Of Alzheimer’s

In the final stages, people may lose the ability to feed themselves, speak, recognize people and control bodily functions. Memory worsens and may become almost non-existent. Constant care is typically necessary. On average, those with Alzheimer’s live for 8 to 10 years after diagnosis, but this terminal disease can last for as long as 20 years.

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Causes Of Vascular Dementia

Vascular dementia is caused by reduced blood flow to the brain, which damages and eventually kills brain cells.

This can happen as a result of:

• narrowing and blockage of the small blood vessels inside the brain
• a single stroke, where the blood supply to part of the brain is suddenly cut off
• lots of “mini strokes” that cause tiny but widespread damage to the brain

Not everyone who has a stroke will go on to develop vascular dementia.

Read more about vascular dementia.

Pathway Breakdown Leading To Alzheimer’s Damage

In the second breakdown pathway APP is split by enzymes B-secretase then y-secretase . Some of the fragments that result stick together and form a short chain called an oligomer. Oligomers are also known as ADDL, amyloid-beta derived diffusible ligands. Oligomers of amyloid beta 42 have been shown to cause problems in the communication between neurons. Amyloid beta 42 also produces tiny fibers, or fibrils. When they stick together they form amyloid plaque. Some of these plaques can insert themselves into the membrane of the neuron cell causing substances outside the cell to leak into it, causing further damage. This damage results in a buildup of Amyloid beta 42 peptides leading to neuron dysfunction.

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Exchange Of Information In Brain Is Affected In Alzheimers Disease

Alzheimers disease also greatly affects the transmission and exchange of information inside the brain. The process of thinking and memory depends on the transmission of signals among and across the neurons. Alzheimers affects the brain by interfering with the signal transmission within the cells, activity of neurotransmitters or brain chemicals. This results in faulty signaling and affects the brain, resulting in impaired ability to communicate, learn and remember.

Cholinergic Neurotransmission And Alzheimer Disease

The cholinergic system is involved in memory function, and cholinergic deficiency has been implicated in the cognitive decline and behavioral changes of AD. Activity of the synthetic enzyme choline acetyltransferase and the catabolic enzyme acetylcholinesterase are significantly reduced in the cerebral cortex, hippocampus, and amygdala in patients with AD.

The nucleus basalis of Meynert and diagonal band of Broca provide the main cholinergic input to the hippocampus, amygdala, and neocortex, which are lost in patients with AD. Loss of cortical CAT and decline in acetylcholine synthesis in biopsy specimens have been found to correlate with cognitive impairment and reaction-time performance. Because cholinergic dysfunction may contribute to the symptoms of patients with AD, enhancing cholinergic neurotransmission constitutes a rational basis for symptomatic treatment.

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Granulovacuolar Degeneration And Neuropil Threads

Granulovacuolar degeneration occurs almost exclusively in the hippocampus. Neuropil threads are an array of dystrophic neurites diffusely distributed in the cortical neuropil, more or less independently of plaques and tangles. This lesion suggests neuropil alterations beyond those merely due to NFTs and SPs and indicates an even more widespread insult to the cortical circuitry than that visualized by studying only plaques and tangles.

In The Alzheimer’s Brain

Scientists have identified several hallmark brain abnormalities in people affected by Alzheimer’s:

• Amyloid plaques, which are microscopic clumps of a protein called beta-amyloid peptide. These abnormal clusters of protein fragments build up between nerve cells which disrupts electrical signals. Diseased tissue has many fewer nerve cells and synapses compared to healthy brain tissue.
• Dead and dying nerve cells contain neurofibrillary tangles, which are made up of twisted strands of another protein called tau .
• These plaques and tangles tend to spread through the cortex in a predictable pattern as AD progresses.
• There is a profound loss of connections among brain cells called synapses. These connections transmit information from cell to cell and are responsible for memory, learning and communication.
• Inflammation results from the brain’s efforts to fend off the lethal effects of these and other neurological changes.
• Brain cells eventually die, resulting in significant tissue shrinkage or atrophy.

Scientists are not absolutely sure what mechanism specifically causes cell death and tissue loss in a diseased brain, but plaques and tangles are the prime suspects.

There are several larger scale effects on the brain as well:

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The Role Of Amyloid Plaques

Amyloid plaques are mostly made up of a protein called B-amyloid protein which is itself part of a much larger protein called APP . These are amino acids.

We do not know what APP does. But we do know that APP is made in the cell, transported to the cell membrane and later broken down. Two major pathways are involved in breakdown of APP . One pathway is normal and causes no problem. The second results in the changes seen in Alzheimer’s and in some of the other dementias.

The Locus Coeruleus Is Among The First Parts Of The Brain Affected By Alzheimer’s Disease

LOS ANGELES, Feb. 17 — Researchers found the part of the brain affected by Alzheimer’s disease first, and think engaging in mentally challenging activities could help prevent its development.

The locus coeruleus was found by researchers at the University of Southern California to be susceptible to the disease first because of its job regulating blood vessel activity in the brain and interconnectedness to the entire organ.

Previous research has shown that both cognitive and physical activity can help slow or prevent the build-up of fats and proteins that disrupt brain and memory function in people with dementia-type diseases.

For the new study, , researchers reviewed previous studies on cognitive aging and the development of related diseases such as Alzheimer’s.

They found the locus coeruleus, a small part of the brain that releases norepinephrine, a neurotransmitter responsible for regulating heart rate, attention, memory and cognition, is among the first parts of the brain affected by Alzheimer’s disease. Part of the reason, they said, is its location and branch-like axons that extend through much of the brain, making it more susceptible to toxins and infections in other parts of the organ.

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Early In Alzheimer Disease

Symptoms develop gradually, so for a while, many people continue to enjoy much of what they enjoyed before developing Alzheimer disease.

Symptoms usually begin subtly. People whose disease develops while they are still employed may not do as well in their jobs. In people who are retired and not very active, the changes may not be as noticeable.

The first and most noticeable symptom may be

• Forgetting recent events because forming new memories is difficult

• Sometimes changes in personality

Early in the disease, people become less able to use good judgment and think abstractly. Speech patterns may change slightly. People may use simpler words, a general word or many words rather than a specific word, or use words incorrectly. They may be unable to find the right word.

People with Alzheimer disease have difficulty interpreting visual and audio cues. Thus, they may become disoriented and confused. Such disorientation may make driving a car difficult. They may get lost on their way to the store. People may be able to function socially but may behave unusually. For example, they may forget the name of a recent visitor, and their emotions may change unpredictably and rapidly.

Many people with Alzheimer disease often have insomnia. They have trouble falling or staying asleep. Some people become confused about day and night.

At some point, psychotic behavior develops in many people with Alzheimer disease.

What Is Known About Alzheimers Disease

Scientists do not yet fully understand what causes Alzheimers disease. There likely is not a single cause but rather several factors that can affect each person differently.

• Age is the best known risk factor for Alzheimers disease.
• Family historyresearchers believe that genetics may play a role in developing Alzheimers disease. However, genes do not equal destiny. A healthy lifestyle may help reduce your risk of developing Alzheimers disease. Two large, long term studies indicate that adequate physical activity, a nutritious diet, limited alcohol consumption, and not smoking may help people. To learn more about the study, you can listen to a short podcast.
• Changes in the brain can begin years before the first symptoms appear.
• Researchers are studying whether education, diet, and environment play a role in developing Alzheimers disease.
• There is growing scientific evidence that healthy behaviors, which have been shown to prevent cancer, diabetes, and heart disease, may also reduce risk for subjective cognitive decline. Heres 8 ways.

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Alzheimers Disease Risk Factors

Age is the top risk factor, and the risk of developing Alzheimers doubles every five years after age 65. However, about 200,000 people under age 65 have early-onset Alzheimers.

Genetic, environmental, and lifestyle factors can play a role in causing dementia-related diseases like Alzheimers. The most significant factor in early-onset dementia is genetics. If a person has a parent or sibling with Alzheimers, that person has double the likelihood of developing it.

Cardiovascular conditions like high blood pressure, diabetes and high cholesterol may also be contributing factors to Alzheimers. In addition, secondary conditions such as stroke can be factors.

Causes Of Dementia With Lewy Bodies

Lewy bodies are tiny clumps of a protein called alpha-synuclein that can develop inside brain cells.

These clumps damage the way the cells work and communicate with each other, and the brain cells eventually die.

Dementia with Lewy bodies is closely related to Parkinson’s disease and often has some of the same symptoms, including difficulty with movement and a higher risk of falls.

Read more about dementia with Lewy bodies.

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