SYMPTOMS OF ALZHEIMERS DISEASE

Many people experience some decline in memory with age, which stems from slower processing speed in the brain, along with a decline in attention and retrieval of information.   Word finding, for example, can become problematic with age, but the information is not lost and typically the word or missing information will be remembered later.

Episodes of simple forgetfulness are quite normal and differ from dementia, with Alzheimer’s disease the most common form of age-related dementia, says Harvard Medical School in a special report on Alzheimer’s disease.   Alzheimer’s is a disease in the true sense of the word (and not “insanity”), as it causes irreversible neurological damage in the brain.  It is a progressive disease and symptoms get worse as more of the brain functions are lost over time. 

Early warning signs of Alzheimer’s disease.

Harvard says that one or more common warning signs can indicate the early stages of Alzheimer’s, instead of normal age-related forgetfulness.

• Memory:  Initially, short-term memory may be affected, such as forgetting appointments, or forgetting where the person has left things, or leaving things in odd places.  (Long-term memory will eventually be impaired, with the person unable to recognize friends and family members.)
• Mood and personality changes:  The individual may display personality changes, such as becoming unsocial and withdrawn, but may also become distrustful and hostile, while losing interest in favourite activities.
• Having trouble with daily tasks:  Normal tasks can become challenging, for example having difficulty driving or using appliances.
• Communication:  The individual will start to have trouble with language, initially having difficulty finding words and trying to describe the object instead of using its name.   Reading and writing can also become impaired as the disease progresses.
• Judgment:  Judgment may become impaired and the individual may start having difficulty making decisions or solving problems.
• Disorientation:  The person may start to get lost in familiar areas or forget where he or she was going, as well as losing track of date and time.
• Unusual behaviour:  The person may start to dress incompletely or not appropriately, may wander around, or engage in unsafe actions.

Early symptoms of Alzheimer’s disease.

Family members and friends may not recognize the early symptoms of Alzheimer’s, as they may emerge gradually or be mistaken for normal signs of aging.  According to Harvard, some symptoms typically begin early in the development of the disease and are more severe than the early warning signs.

• Progressive memory loss: The most prominent early symptom is the progressive loss of memory.  Short-term memory of recent events and new information may become impaired, with the person asking the same questions or repeating the same story regularly  The inability to absorb new information starts to interfere with the person’s work, along with the ability to interact socially the way they used to.  Long-term memories may be retained longer but can become fragmented over time.
• Disorientation:  Memory problems may lead to increasing disorientation in terms of time, places, and people.  Initially the person is losing track of time and the sense of time may become distorted, such as insisting on leaving a place soon after arrival.  The disorientation may later extend to not recognizing places or people.
• Decline in judgment and problem solving:  An increasing decline in the ability to plan and to carry out complex tasks or solve the problems of daily life may be observed.  A lack of insight and poor judgement may also be seen.
• Language difficulties:  Initial difficulty with word-finding may worsen into an increasing difficulty to use and understand language.
• Visual and spatial dysfunction:  The disease can damage the ability of the brain to make sense of the visual information it receives, which affects the person’s sense of his or her surroundings and their place in it.  This can result in the person getting lost easily.  The ability to recognize objects and what they are used for may also become impaired, for example in later stages of the disease not recognizing a toothbrush or what it is used for.  Familiar faces may not be recognizing any longer.
• Changes in mood, behaviour, and personality:  These symptoms are usually the most obvious indications to family members that something is wrong with the individual.  Apathy is a common symptom, and the person may become socially withdrawn and lose interest in his or her usual activities.  Other common indications of Alzheimer’s manifest in the person becoming inexplicably anxious and irritable, or even hostile.  Depression may often accompany Alzheimer’s, partly due to the biological changes in the brain and partly due to a psychological reaction to the person’s realisation of the loss of mental abilities.
• Decline in daily functioning:  The person may develop difficulties with the normal activities of daily living, such as working, driving, shopping, preparing meals, cleaning, or other chores.

Later symptoms of Alzheimer’s.

Harvard says as the disease progresses and greater damage occur in the brain, some symptoms are typical of the later stages of the disease:

• Motor skills dysfunction:  The person gradually forgets how to perform learned motor skills, such as dressing, using tools, using a phone, or even using utensils to eat.  Later in the course of the disease further motor skills dysfunction may include difficulties starting and sustaining movements, such as walking.  With advanced Alzheimer’s the person may become bedridden and lose control over bodily functions.
• Behavioural and psychological problems:  Changes in behaviour may become troublesome, such as being stubborn, resisting care, using uncharacteristic abusive or foul language, hiding things, or urinating in unsuitable places.  Strong emotional responses can occur, even for minor problems, such as crying, shouting, agitated pacing, or striking another person.  Brain dysfunction lies at the bottom of this behaviour and may well be the response of an overwhelmed and frightened person, trying to protect himself or herself.  This behaviour usually gets worse in the late afternoon and evening and may be due to tiredness.  Some Alzheimer’s patients (about 40%) may experience delusions or hallucinations.

How Alzheimer’s disease affects systems in the brain.

The human brain is the most sophisticated and complex system in the known universe.  The brain consists of a web of an estimated 100 billion interconnecting brain cells, called neurons and the wide range of symptoms caused by Alzheimer’s disease results from damage to brain cells in different regions of the brain. 

T

he brain regions can be categorized into three different systems, each with unique functions:

• The most basic system in the brain consists of the brainstem and cerebellum, which control basic bodily functions that are needed for survival.  The brain stem controls vital life functions such as body temperature, heartbeat, breathing, eye movement, swallowing, and blood pressure, while the cerebellum (also known as the “little brain”) is associated with the regulation and coordination of movement, posture, balance, as well as cardiac and respiratory functions.  This basic system usually only gets affected in the final stages of Alzheimer’s disease.
• The limbic system is situated deep inside the brain and is involved in memory and learning, as well as our emotional and behavioural responses.  The two major components of the limbic system (apart from smaller components such as the thalamus, hypothalamus, and basal ganglia) are the hippocampus and the amygdala.  The hippocampus is in essence the memory center of the brain and is key to learning new things.  The amygdala plays a central role in emotional responses and feelings, as well as attaching emotional content to our memories.
• The cerebral cortex is the outtermost layer of the brain and is made up of three types of areas, which accounts for most of human cognition and behaviour.  The sensory areas receive information from the five senses (sight, sound, smell, taste, and touch), the motor areas are involved in the initiation of movement, while association areas are involved in the integration of information from multiple brain regions.  The cerebral cortex plays an essential role in the healthy functioning of the brain.

Alzheimer’s disease affects the three systems differently.  The limbic system is affected first, then the cerebral cortex, then the brain stem and cerebellum.

• Damage to the limbic system impairs memory and cause mood swings.
• Damage to the cerebral cortex can lead to uncontrolled emotional outbursts and at this stage of the disease people may need help with daily activities, such as eating and dressing.
• Damage to the brain stem occurs late during Alzheimer’s disease and can impair the function of organs such as the heart, lungs, and other bodily processes.

How Alzheimer’s disease affects brain cells:

The Alzheimer’s symptoms result from changes to the brain cells and structure of the brain.  Dementia Care Central describes the disease by way of picturing a city at night, with all the lights on.  When flying over the city, all these lights make the city glow.  Should a problem occur in the wiring or circuits of the city’s electrical system, the lights will go out one by one, with the power outage gradually disabling the city light by light, house by house, suburb by suburb.

The individual light bulbs in the city represent individual brain cells (neurons) and the city represent the whole brain.  Alzheimer’s disease gradually “turns off” individual neurons in the brain, just like a gradual power outage in a city tuns off individual lights.  Unlike the electrical circuits in the city that can be repaired, severe damage in the brain caused by Alzheimer’s is permanent.

At cellular level, the neurons have tiny spaces between them, called synapses, which facilitates the conveying of signals between neurons via brain chemicals called neurotransmitters.  These neurotransmitters are released by neurons and deposited into the synapses, where it acts as “electrical conductors” to forward signals to the next neuron.  Alzheimer’s disease affects the neurons in the brain, leading to cellular damage and the inability of damaged neurons to communicate with other neurons, affecting brain function.  Damaged neurons eventually die.

A microscopic view of the brain of an Alzheimer’s patient displays tangles and plaques that affects brain cells and the transfer of impulses between neurons.  The tangles and plaques are the main contributors to Alzheimer’s disease, and these were identified by researchers as tau protein tangles and beta-amyloid plaque build-up.  When these tangles and plaques start to form in the brain, it may not immediately affect memory, but these individuals are at a higher risk of developing Alzheimer’s disease.

Tau is a normal protein found in brain cells which helps to transports nutrients into- and move waste products out of brain cells.  Aging, or errant genes, can cause tau to become abnormal, resulting in pieces of the tau protein collapsing and forming twisted fibers (called neurofibrillary tangles), which tangle and clump together.  In this event the nutrients and toxic waste products can no longer move freely within brain cells.  The tangles eventually disintegrate.  Affected cells cannot function properly anymore and eventually die.

The fatty membrane that surrounds brain cells contain a protein molecule called beta-amyloid, whose small fragments are naturally sticky and, together with debris from dying neurons, can cause plaque build-up outside the cells of the brain, clumping together into “sticky globs” of amyloid.  Clumps of beta-amyloid can block cell-to-cell signalling at synapses and may also activate cells in the immune system to trigger inflammation, which can devour disabled cells.

In the earliest stages of Alzheimer’s disease, the tangles and plaque usually first form in the regions in the brain that is used for memory, learning, thinking, and planning.

In mild to moderate stages of the disease, more tangles and plaque form in these areas, while spreading to areas involved in speaking and understanding speech, as well as the sense of where your body is in relation to objects around you.

In advanced stages of Alzheimer’s disease, the cortex is severely damaged and widespread cell death cause the brain to shrink.  Individuals lose the ability to recognise familiar people and can lose the ability to communicate and care for themselves.

What causes Alzheimer’s disease?

According to Bredesen, Alzheimer’s is what happens when the brain tries to protect itself from of a wide range of metabolic and toxic threats, that can be summarized in three main categories:

1. Inflammation:  The body’s immune system mounts an inflammatory response when under acute threat from invading pathogens (such as viruses, bacteria, fungi, parasites).  When the threat is chronic, the inflammatory response is continuously activated, leading to the accumulation of amyloid in the brain.  Inflammation is also triggered by food such as trans fats (artificial fats in pre-packaged foods and fried foods) or sugar.  Sugar toxicity (high intake) is accompanied by insulin resistance, which is linked to Alzheimer’s.

2. A shortage of brain-boosting nutrients, hormones, and other cognition-supporting molecules:  In order to function optimally, the brain needs optimal levels of neuron- and synapse-supporting factors, which includes a wide range of nutrients and hormones.

3. Toxic exposure: When the brain is infiltrated by toxic metals such as copper and mercury, or by biotoxins such as produced by mold, amyloid plays a protective role by binding to these toxins to prevent them from damaging the neurons.  Chronic exposure to toxic substances, however, results in the brain churning out too much amyloid.

The brain is normally able to protect itself from these threats.  When these threats are chronic and intense in nature, the intrinsic defense mechanism in the brain (that fights invading pathogens by producing amyloid) crosses the line from being a defense mechanism into causing harm to the brain’s synapses.  When high concentrations of amyloid-beta accumulate in the brain, it triggers the defense receptors to reduce the connections (synapses) and ultimately kill the neurons.

Conclusions

Some questions about Alzheimer’s disease remain unanswered, for instance is the forming of beta-amyloid plaque the trigger for the forming of tau tangles, or are the two not influenced by each other?  Not everybody with high levels of beta-amyloid develop problems with tau tangles or Alzheimer’s disease.  These two conditions may not be the only detrimental changes in the brain due to Alzheimer’s, as autopsies have revealed other types of damage, such as damage to small blood vessels in the brain of some patients.  

The disease not only affects the individual, but also has dramatic effects on family members and loved ones.  There is a ray of hope to slow down or halt the progression of the disease in the early stages.  Please see the Health Insight blog “Some insights into Alzheimer’s” for more information.

References:

Alzheimer’s Disease.  A guide to diagnosis, treatment, and caregiving.  A Special Health Report, published 2018, by Harvard Medical School.   (www.health.harvard.edu)

The End of Alzheimer’s.  The first programme to prevent and reverse the cognitive decline of dementia.  Author: Dr Dale Bredesen.  Book published 2017 by Penguin Random House UK.  P. 308

The limbic system.  Published online.  Queensland Brain Institute.  The University of Queensland.  Australia.  (www.qbi.uq.edu.au)

Know your brain: Cerebral cortex.  Published 5 December 2014.  Neuroscientifically Challenged.  (www.neuroscientificallychallenged.com)

Alzheimer’s Disease 101:  How is the disease diagnosed and how is the disease treated?  Published online and updated 4 August 2020.  Dementia Care Central.  USA.  (www.dementiacarecentral.com)

Inside the brain.  A tour of how the brain works.  Published online.  Alzheimer’s Association.  USA.  (www.alz.org)

The structure and function of the human brain.  Published online.  Northern Brain Injury Association.  British Columbia.  Canada.  (www.nbia.ca)

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