What’s in a baby’s kick?

I am delighted to have been able to attend a Royal Institution ‘Summer School’ workshop on bioengineering this August. The focus in this workshop was on refining drug delivery systems and using mathematics to determine whether a foetus is developing properly.

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The first half of the session was lead by Rachel Dorris, a medical physicist, and was centred on how drugs can be better designed for use in inhalers.

Asthma is an autoimmune disease caused by the spontaneous contracting of the smooth muscles that surround the bronchioles in the lungs which results in constricted airways. Inhalers contain a drug (a bronchodilator) that can ‘open up’ the airways.

 

(credit: slideplayer)

In order for this treatment to be effective, the drug uptake (the retention of the drug in the necessary organ) must be at its optimum. To measure the drug uptake, a medical imaging technique that suits this purpose must be chosen. After some collaboration, our team decided that a Nuclear Medicine Scan was the ideal technique. It involves giving the patient the bronchodilator with a small amount of a radioactive tracer (Technetium-99m) and then observing the patient with a gamma camera. The image quality is relatively low but provides functional information and can be easily used to observe drug uptake.

This is an example of a Nuclear Medicine Scan of the lungs. The whitest areas show the highest drug uptake. (credit: slideshare)

From Nuclear Medicine Scans of 4 different drug particle sizes in patients’ lungs, we performed a qualitative analysis of the images- determining which particle size we believed would have the optimum drug uptake in the bronchioles. We then performed a quantitative deposition analysis of the images to confirm our ideas. The conclusion we arrived at is that a bronchodilator with a particle size of 1.5μm was best suited to use in inhalers.

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The second half of the workshop was lead by Dr. Stefaan Verbruggen, who is currently researching the effects of kicking in the womb during pregnancy on the development of musculoskeletal diseases, and, in particular, developmental dysplasia of the hip (DDH).

The hip is a type of “ball-and-socket” joint. In a normal hip, the ball at the upper end of the femur fits firmly into its socket in the pelvis. In babies with DDH, this joint is not properly formed and so the ball does not fit well in the socket and is easily dislocated. In all cases of DDH, the socket (acetabulum) is shallow which means that the ball cannot fit inside it comfortably.

 

(Credit: Oxford University Hospitals)

1 in every 1000 babies are born with a form of DDH. There are varying degrees of severity in DDH cases:

• Subluxatable- the ball of joint is simply loose in the socket
• Dislocatable- the ball lies within the socket but can be dislocated easily
• Dislocated- the ball is completely out of the socket.

(Credit: helpmegrowutah.blogspot.co.uk)

DDH is not genetic, but the risk of a baby having DDH greatly increases if there was not enough room in the womb whilst its bones and joints were developing.

A foetus’ bones and muscles, like in adults, react to stress by growing. In adults and children, the main stressor acting on the hip joint is gravity, but this is not the case in foetuses. Instead, the main way that foetuses can ‘exercise’ their hip joints, is by kicking. Considered one of the most endearing interactions between a foetus and the outside world, kicking is vital to its development; if there is not enough room for a foetus to kick, complications with joint development and DDH can arise.

• It is a ‘breech baby’ (the foetus is positioned feet first). In scans, it is revealed that these babies cannot fully extend their legs when kicking.
• There are issues with oligohydramnios (in which there is less amniotic fluid- normally due to a fault in the foetus’ urine production so that it ingests the amniotic fluid but does not pass it out). Notice how, in scans, these babies don’t appear to kick at all.

Cine-MRI scans of baby kicks

 

Curiously enough, foetal twins tend to have enough space to kick comfortably, despite having to share the womb. (They also are unable to kick each other due to a membrane wall separating them!)

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The progress of a foetus’ joint growth and muscle activity is measured to ensure that the pregnancy is going well and to calculate the risk of DDH. However, when foetuses are in the womb, experimental equipment, naturally, cannot be used and only images can be used. This means that mathematics must be employed in a fascinating manner to calculate strength of a kick from only two MRI scans.

 

Start of kick (Frame 76)

End of kick (Frame 83)

First we must work out the change in angle from the start to the finish of the kick. At the start of the kick, the angle between the hip and the ankle is 87°. At the finish, it is 153°. This means that the change in angle is 66°. Then, this must be converted to radians, making the value 1.15192 radians.

The MRI scan was taken at 3 frames per second and the kick took 8 frames. Using this, we can calculate that the length of the kick in seconds is (to three decimal places) 2.667 seconds.

Speed is found by dividing the distance by time taken to complete the distance. In this case, the distance is the change in angle. Therefore, the speed (or velocity) of the baby’s kick is  1.15192 / 2.667 = 0.432 radians/s.

The length of the lower leg is 58.4 millimetres and it can be considered a radius in this case. Acceleration is found by multiplying the square of the velocity by the radius. So the acceleration of the kick was 0.432² x 58.4 = 10.899 mm/s²

The foetal leg would weigh 0.321 kg. Since force = mass x acceleration, we can now also find the force that the foetus must generate to perform this kick- 3.498 N.

This example demonstrates just how powerful mathematics is; using only 6 relatively simple calculations, we can quickly work out the force of a foetus’ kick from just 2 basic MRI scan frames.

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Overall, the workshop was an incredible introduction into the field of bioengineering. Without a doubt, the second half of the workshop was my favourite as I found the exploration of DDH in babies very interesting and I was amazed by how easy a seemingly impossible task was made by using formulae that I had already learnt in school but had never seen being used to solve ‘real-life’ problems.

 

Serology in Mumbai (Part II)

I was incredibly fortunate to observe another serology lab whilst in Mumbai. Learning in the Sunflower Laboratory was a completely different to experience to my previous lab observation as the Sunflower Laboratory was much better equipped with over 30 fully automated diagnostic tools. Also, at this lab the staff actually spoke English- making it a lot easier to learn!

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One of the most important automated diagnostic tools at the Sunflower Laboratory was the GeneXpert Machine as it was capable of, very accurately, diagnosing tuberculosis (TB) and producing results in under 2 hours.

To understand why this is so important, it is necessary to know about India’s history with TB and the nature of the bacterium itself.

TB is a horrific disease caused by Mycobacterium tuberculosis that severely affects the lungs and causes those with the illness to cough up blood as well as experience fevers, among other torturous symptoms. It also is a granulomatous inflammatory diseases- meaning that it causes many different types of white blood cells to clump together (aggregate) to form a  giant multinucleated cell that can block blood vessels. Bacteria actually use these granulomas to essentially ‘hide’ behind- preventing themselves from being destroyed by the body’s immune system.

Mycobacterium TB as seen under an electron microscope (Credit: louisville.edu)

Granuloma as viewed under a microscope (Credit:http://pathhsw5m54.ucsf.edu/overview/text.html)

India is the country with the highest burden of TB- around 40% of the Indian population have TB. Whilst observing the lab, I had the chance to talk to the lab assistants as well as some of the local people and discovered the complex cultural factors that affect the spread of TB. TB used to be considered a “poor man’s disease” due to the fact that it spread remarkably quickly in slums. This is because slums are poorly ventilated and overcrowded. In addition to this,  poor people are more susceptible to TB due to malnutrition. If a person in these conditions also has any prior diseases, such as HIV, they  are even more likely to contract TB.

TB has only recently lost its reputation as exclusively a disease of poverty as the rich have begun to contract TB from their maids, drivers, etc. This is also, in part, because the rich and the poor have started to occupy the same areas. For instance, my native city, Mumbai, is the location of hundreds of stylish skyscrapers, four luxurious shopping centres  and a grand airport- but also home to 10% of all slums in India (Source: Times of India).

A well-known industrialist from Pune was shocked when he was detected with TB. He said that he used AC car and always ensured to keep safe distance from crowd. But then when we enquired and checked people around him, we found that his driver who lives in a city slum had TB

– Times of India

Excessive coughing caused by the high levels of pollution in India, coupled with the fact that the country is very overcrowded, allows Mycobacterium tuberculosis to spread easily through the air. In addition to this, India is, for the most part, impoverished- meaning that the majority of TB sufferers cannot afford treatments. Leaving TB untreated means that not only will their condition worsen but also, they will likely spread the disease to others around them. According to tbalert.org,  “just one person with untreated infectious TB can pass the illness on to 10-15 people annually”.

(This problem is currently being combated as the government is providing free drugs to any citizen who has TB.)

Prevention of diseases via vaccine was, originally, thoroughly researched; in fact, ever since the late 1970s, the BCG vaccine that was designed to give immunity against TB has been administered to almost all citizens of India. Unfortunately, exactly 20 years later, the final results of a 15-year-long BCG trial were released, confirming that the vaccine provided no protection against TB.

(I, myself, was given the BCG vaccine as a newborn- it left a small scar that, surprisingly, is still visible 15 years later!)

Even getting a diagnosis for TB is not usually very easy; diagnosing tuberculosis based only on signs and symptoms is difficult as the typical symptoms are also shared by other major diseases. The only definite way to diagnose the disease is to actually see the mycobacterium under the microscope. This can be impractical, however, as culturing this slow-growing bacteria takes anywhere from two to six weeks.

Moreover, in some areas of India, few people actually seek a diagnosis due to the overwhelming stigma surrounding TB. People could lose jobs and women may be divorced if they were found out to have TB.

So, to recap, TB is an airborne disease that affects just under half of the Indian population and is easily spread due to the high pollution levels and population density. Many of the people who contract TB are too poor to get it treated- allowing them to get worse in their ill state and to spread it to those around them. Even if the people who suspect that they have TB were to try to get a diagnosis, they would have to wait for around a month to get a formal diagnosis and start an effective treatment course. Essentially, contracting TB in India is a terrible, even life-threatening disease, that is shockingly easy to contract.

Enter the GeneXpert Machine.

This diagnostic tool detects the Mycobacteria TB complex DNA in sputum samples and Rifampicin (an antibiotic used to treat TB) resistance associated with mutations of the patient’s genes. This impressive machine automates sample processing, nucleic acid amplification, and detects target sequences in samples using real time polymerase chain reactions (PCR) and reverse transcriptase PCR.

The GeneXpert Machine at Sunflower Laboratory

 

The machine uses cartridges (which the sample is added to) that hold the PCR reagents and host the PCR process. This means that the process is entirely self-contained meaning there is no risk of cross-contamination.

A cartridge that is ready to be processed by the machine

 

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The diagnostic tools were truly awesome to learn about, however I found the manual processes for detecting other pathogens equally exciting!

One of these processes was the culturing of bacteria for visual analysis or analysis by one of the other diagnostic tools.

In order for cultured pathogens to thrive, they must grow on a culture medium that is well suited to the pathogens’ needs.

The lab mainly used three different types of Agar (a gelatinous substance derived from algae).

• Blood agar- an enriched medium consisting of a low concentration of blood that is used for growing fastidious organisms (those which have complex nutrient needs) and detecting haemolytic activity as the RBCs are digested.
• Chocolate agar- a type of blood agar plate made up of lysed RBCs that is used for fastidious respiratory bacteria.
• MacConkey agar- a selective medium specially designed for culturing gram negative bacteria

In order to transfer the pathogens that need to be cultured onto the growth medium, a streaking method that is well-suited to the process must be chosen. At the lab, I was introduced to quadrant streaking.

(Credit : Pinterest)

After this, the cultures are incubated for a certain amount of time depending on what bacteria is being cultured. After this incubation period, the cultures can be examined by eye or a colony from the culture can be processed by one of the automated diagnostic tools. I even got to handle some of the cultures!

 

Quadrant Streaking on Blood Agar

…And on Chocolate Agar (This patient’s sample shows profuse bacterial growth)

Quadrant Streaking on a split plate of Blood Agar and MacConkey Agar

(Interestingly enough, in the above photo, the pink appearance of the bacterial colonies on the MacConkey Agar indicates that the bacteria is lactose-fermenting. )

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All in all, I had a wonderful experience observing the Sunflower Laboratory for a total of 3 days- learning about how TB and other bacteria are being identified at this clinic in both manual and automated procedures. Learning about TB in this depth enriched my understanding of the specific disease and of how diseases can be spread, prevented, and cured. Being introduced to quadrant streaking will certainly help in the required practicals I’ll complete this year in GCSE Biology!

 I am extremely thankful to Dr Aditi Salunke and Reema for this fantastic opportunity.

Shukriya (thanks!)

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(A quick selfie in the microbiology lab)

A Tour of the Brain

The human brain, despite its vast complexities, has a relatively straightforward architecture. This post will explore the structure of one of the most important organs of the body.

Imagine that you are looking at a human brain sitting on the lab worktop before you.

At first sight, the brain appears to consist entirely of a large mass of spongy tissue. These deeply folded outer layers of the brain make up the cerebral cortex and take up nearly two thirds of the entire volume of the brain. Observe the seemingly erratic pattern of curved  grooves on the surface (the sulci) and you will be able to identify the major divisions of the cerebral cortex. Divided into two hemispheres (which are bridged by a bundle of fibres called the corpus callosum), the cerebral cortex houses the majority of the ‘grey matter’ and is separated into a few important lobes.

The first lobes you notice are the frontal lobes. They are aptly named considering that they are found at the front of the brain (near the forehead). The lobes (one in each hemisphere) are responsible for decision making, planning, memory, voluntary action, and even personality.

(Credit: Wikipedia)

Next, you spot the parietal lobes which are located at the crown of the head. These lobes are heavily involved in perception and interpretation of all sensory information. They are also necessary for spatial awareness and attention.

(Credit: Wikipedia)

Below the parietal lobes lie the occipital lobes. Found at the back of the brain, the occipital lobes are mainly involved in vision. Damage to the occipital lobes often leads to blindness as well as other vision-related defects.

The last of the main divisions of the cerebral cortex are the temporal lobes. In vivo, they are found near the ears. The temporal lobes are essential for object recognition, memory formation, and language.

(Credit: Wikipedia)

Now imagine picking up the brain (whilst wearing latex gloves- naturally). Raise it above eye level and you will see the prominent brain stem emerging from the base of the brain. In vivo, this would be connected to the spinal cord- linking the brain to the body.

Nestled just behind the brain stem is the cerebellum. Literally meaning ‘little brain’, the cauliflower-shaped brain structure plays an important role in not only movement, fine motor control, and posture but also in memory, mood, and language processing as well as Pavlovian learning. The cerebellum is comprised of two hemispheres which are connected via a narrow structure known as the vermis.

(Credit: Quizlet)

Now place the brain back down on the worktop and carefully pry apart the hemispheres to observe the hidden inner structures of the brain. Remember the brain stem? Look above it and you will discover the midbrain and then, above the midbrain, the egg-shaped thalamus. Heavily interconnected with several other regions in the cortex, most sensory information first passes through here before moving on to the relevant parts of the cortex.

Our last stop on this tour of the brain is the hippocampus. To access this, you must cut into the temporal lobes as this seahorse shaped region is located deep within these lobes. The hippocampus is highly involved in the formation and consolidation of memories and in spatial navigation. Damage to the hippocampus can cause severe amnesia.

(Credit: Pinterest)

You have now observed all of the basic architecture of the brain. Knowing this makes it much easier to comprehend diseases of the brain and to discover cures.

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This post  is part of the Neuroscience Crash Course (a mini series about the brain created in preparation for the Brain Bee).

Next post in the Neuroscience Crash Course

Serology in Mumbai (Part I)

Recently, I have been offered the fantastic opportunity to observe a couple of diagnostics labs in India. This past week has been an amazing, immersive learning experience in the field of diagnostics and serology, in particular.

I have been observing Marve Clinical Laboratory in Malad West, Mumbai in order to understand more about the practical aspect of diagnosing diseases. Initially, I was apprehensive about this undertaking as my knowledge of diagnostics beforehand was limited only to what has been covered in the GCSE course and the occasional article I have read in the NewScientist. Thankfully, my apprehension subsided quickly as the staff were keen to give me a tour of the lab and talk about the facilities at their disposal as well as briefly go over the basics of serology and diagnostics.

The main difficulty was communication; the majority of the lab technicians could only speak Hindi and, despite being of Indian origin, I barely know enough to get by. While they were very willing to explain procedures, I could only understand the gist of it (and that’s only because the more scientific words are in English). This meant that I frequently bombarded the doctor with questions (which he very kindly answered in spite of his busy schedule) and turned to the Internet for more information.

Despite this, I gained a lot from this experience and I am eager to share this newfound knowledge with you.

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Most diagnostic labs use serology diagnostics. Serology is the study of serum (the blood plasma, not including fibrinogens) and other bodily fluids. Diagnostic labs identify antibodies formed due to infection in the serum and other bodily fluids in order to diagnose diseases. At Marve Clinical Laboratory, I learnt about various techniques used to diagnose disease using serum and urine.

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On my first day, I was introduced to the diagnostic tool known as a Complete Blood Count.  A Complete Blood Count has a range of uses from diagnosing deficiency diseases (by looking at the patient’s hemoglobin concentration) to assessing whether the patient’s immune system is fighting a disease (by checking their lymphocyte count). This process is fully automated through the use of a CBC Machine; the machine simply takes a sample of the blood and produces the result within a minute.

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After this, I learnt about Erythrocyte Sedimentation; when blood is contained in a tall, thin tube, erythrocytes (red blood cells) gradually settle to bottom (sedimentation). When a patient is suffering inflammation, their erythrocytes clump together, becoming a denser mass of cells- meaning they settle to the bottom faster. In order to measure the progression of an inflammation, the erythrocyte sediment rate is recorded; the greater the amount of sedimentation, the greater the inflammation.

An ESR Tube

 

At Marve Clinical Laboratory, two methods for measuring the ESR were used: the Westergren Method and an automated method. The Westergren Method entails putting 2ml of blood into a test tube containing 0.5ml of sodium citrate and storing it at room temperature for 2 hours before transferring the blood to a Westergren-Katz tube (filling it to the 200mm mark). This tube is then placed upright for 1 hour at which point the distance ‘travelled’ by the erythrocyte sediment is measured. The ESR is expressed as mm/hour.

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Another important role of the lab is to carry out ABO typing (blood typing)- in some cases, knowing your blood type can be vital to survival. Your blood type depends on which antigens (proteins), if any, you have on your red blood cells. In ABO typing, the person’s blood is mixed with a reagent containing antibodies against type A and B blood. If the blood cells clump together (agglutinate), it means that the blood has reacted with the antibodies. For instance, if a person’s blood type is B, agglutination will occur with the antibodies against type B blood. The same is true with type A blood also. If a person’s blood type is AB, agglutination will occur with both sets of antibodies. If their blood is type O, there will be no agglutination. Blood typing can also tell you whether you have a substance known as Rh Factor on your red blood cells. If agglutination occurs when your blood is mixed with a reagent containing antibodies against Rh Factor, your blood is Rh positi

Since there is agglutination when the blood is mixed with antibodies against type B blood and antibodies against the Rh Factor, the blood type is B positive

In this blood sample, no agglutination occurs with antibodies against both type A blood and type B blood – so the blood type is O

Can you tell which blood type this test shows?

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By far the most fascinating machine in the lab was the Biochemistry Analyser. Capable of doing an impressive 400 tests an hour, this machine was able to process samples and produce results rapidly and with very little human involvement. It is used to test renal function (RFT) and liver function (LFT) as well as to carry out Lipid Profile Tests and Blood Sugar Tests.

The specific model was the Mindray BS-210

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Urine analysis, necessary to diagnose renal diseases and endocrine disorders, is often done at Marve Clinical Laboratory as well. Important factors used in diagnosis are volume of urine as well as the presence of ketone bodies, occult blood, cells, casts, and crystals in the urine.

In 24 hours, a healthy person passes 1.5 to 1.8 litres of urine. However, if a person has kidney or blood sugar problems, they will pass 2.5 to 5.6 litres. This abnormal increase in urine is known as polyuria. The opposite extreme is known as oliguria and is seen in patients with acute nephritis (nerve damage). Anuria, the complete suppression of urine, is seen in patients with renal failure.

Ketone bodies are water-soluble molecules produced by the liver from fatty acids. Ketone bodies are only produced when the body is lacking glucose as a fuel. They are present in the urine of patients with diabetes mellitus- early detection of this is paramount.

Pus cells in the urine are essentially white blood cells (mainly neutrophils), dead skin cells, and bacteria. In order to confirm the diagnosis of a disease, the number of pus cells in a urine sample must be counted; at this laboratory, this task is done manually and so I was fortunate to have the  chance to try this myself. The presence of high levels (more than 10 per microlitre of urine) of pus cells in the urine is known as pyuria and it indicates infection in the lower or upper urinary tract.

Stained pus cells as seen under a microscope

Urinary casts (microscopic cylindrical structures) are formed by a diseased kidney. There are several different types of urinary casts including hyaline casts (which suggest renal disease), RBC and WBC cells (which point to glomerular issues), granular casts, waxy casts, and fatty casts (which are caused by the degeneration of tubular epithelium).

(Credit: Medical-Labs.net )

In addition to casts, crystals can also be found in acidic urine. Calcium oxylate crystals (which is seen in patients with kidney stones) is the most commonly encountered at Marve Clinical Laboratory.

Calcium Oxalate Crystals viewed under a standard light microscope. This is very similar to the crystals I have observed in some of the urine samples at the lab. (Credit: Medical-labs.net)

Upon researching this crystal further, I found the surprisingly dramatic image of these crystals under an electron microscope.

(Credit: Wikipedia)

Fascinatingly enough, Calcium oxalate monohydrate crystals can also be found in the major organs of ethylene glycol (better known as a primary agent of Antifreeze) poisoning victims. When ethylene glycol is metabolised by the body these crystals are produced in spindle or ‘picket fence’ structures.

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In total, I spent 4 days observing Marve Clinical Laboratory and gained an incredibly valuable insight into the field of diagnostics and serology in particular. I discovered the practical side of many processes (such as blood typing) that I had, up until now, only read about in textbooks.  On the whole, the experience was amazing and I am incredibly grateful to Dr. Thakkar and the rest of the laboratory staff for giving me this opportunity.

Shukriya (thanks!)

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(In case you were wondering, the blood type in the last test is B Positive)

 

 

A Closer Look at ‘Still Alice’

Lisa Genova’s ‘Still Alice’ is a powerful novel about how Alzheimer’s disease affects one woman and gradually damages her relationship with her family and reality. It is told through the point of view of Alice, the patient, which gives the narrative a poignancy that is simply unattainable with typical pathologies. To this day, it is the only book that had me in tears.

Alice, a brilliantly bright professor at Harvard and expert in the field of linguistics, is only fifty when she falls head-first into a downward spiral of dementia. It starts with very small things: forgetting a single word in an important speech, becoming disorientated in Harvard Square, forgetting references on her to-do list. But insidiously, Alzheimer’s disease starts to take hold of her life by stealing her memories and leaving her disorientated and dependent. In addition to detailing the impact Alzheimer’s has on Alice’s life, Genova refers to the causes, diagnosis, and (sadly unsuccessful) treatments available to her. Fascinated, I decided to delve deeper into the topic.

(Before we get started, I should warn you that there are spoilers ahead.)

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Alzheimer’s disease is a disease of the brain and one of the most common forms of dementia. Over 520,000 people in the UK have some form of Alzheimer’s disease. A the disease progresses, proteins structures (amyloid plaques and neurofibrillary tangles) build up in the brain which results in the patient losing connections between nerve cells and, ultimately, in nerve cell death. This, in turn, causes loss of brain tissue in the cerebral cortex (see the diagram below). Patients also are deficient in  an important chemical of the brain called acetylcholine, meaning that signals cannot be effectively transmitted around the brain. Alzheimer’s is a progressive disease; gradually, the damage spreads to different parts of the brain. This causes the identifiable, severe symptoms.

(Credit: plasmogen.me)

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Symptoms of Alzheimer’s disease include:

• Memory loss
  • There are many occurrences of this in the book, one of the most notable being when the disease corrupts Alice’s long-term memory- resulting in her forgetting that her mother and sister had died decades ago and fully expecting them to arrive for dinner
• Loss of spontaneity and sense of initiative
  • Alice is rendered unable to go for a run ( or do any other activity) on whim as she needs her husband, John, to monitor her
• Repeating questions
  • This occurs frequently in the latter half of the book
• Wandering and getting lost
  • The most significant and upsetting example of this is when Alice is unable to find the toilet in her own home which lead to a situation that was both embarrassing and depressing
• Losing things or misplacing them in odd places
  • A key example of this is when Alice loses her Blackberry, causing her to panic, only for John to find that she had stored it in the freezer
• Mood and personality changes
  • Once independent, outgoing, and confident of her own intelligence, Alice becomes increasingly introverted
• Increased anxiety and/or aggression
  • In the book, this is the primary consequence of her loss of independence

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Although still largely unknown, certain factors increase the risk of Alzheimer’s disease. In Alice’s case, as she had early-onset Alzheimer’s disease,  the main factor was genetics. Early on in the book, Alice is screened for the APP (amyloid precursor protein), PS1 (presenilin-1) , and PS2 (presenilin-2) mutations. These mutated genes are infamous for creating proteins that form plaques and tangles. Alice is mutation positive for PS1 meaning that she definitely has Alzheimer’s disease. If her test result came back negative, there would still have been a 50% chance that she does have Alzheimer’s disease as, currently, we do not know all the mutated genes that could be responsible for Alzheimer’s disease.

The PS1 mutation is autosomal dominant, meaning that her children each have a 50% chance of inheriting early-onset Alzheimer’s disease. In the book, two of Alice’s children opt to have themselves screened for the mutation as well, however certain ethical issues arise from this. Anna, one of Alice’s daughters who has the mutation, used to be desperate to have children. Now she must consider if it is right for her to have children despite their being a very high risk of them inheriting Alzheimer’s disease from her.

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Throughout the book, Alice undergoes many tests (initially for diagnosis and, later on, to monitor the progression of the disease). These include the Stroop test, the Raven’s Coloured Progressive Matrices, the Luria Mental Rotation test, the Boston Naming test, the WAIS-R Picture Arrangement test, the Benton Visual Retention test, and the NYU Story Recall. In order to understand these further, I have included a sample of each test below.

But first, remember this name and address: John Black, 42 West Street, Brighton.

First, let’s review the Stroop test. The purpose of the Stroop test is to assess reaction times. The Stroop test is fairly straight-forward- name the colours of the following words aloud as quickly as you can. Do NOT read the words, instead name the colours of the words.

(Credit: Snap!-Wordpress)

 

Raven’s Progressive Matrices is a nonverbal test designed to measure abstract reasoning and perception. In the Test A, select the piece with the same pattern and, in the red-coloured test, shade in the correct part of the diamond to complete the pattern.

Test A

Test B

 

Luria Mental Rotation is used to judge perception and general intelligence as well as spatial processing. In the example below, choose the object which is a rotated view of the original object

 

(Credit: ProProfs)

The Boston Naming Test involves showing a patient flashcards with common items on it and asking them to provide the names of the items- it is used to assess word retrieval.

Before I discuss the Benton Visual Retention test, study this image carefully for 10 seconds:

 

(Credit: Wikipedia)

 

 

Now scroll down until you can no longer see the image.

The Benton Visual Retention test assesses visual perception and visual memory. The patient is shown an image (like the one you just saw) for an allotted amount of time. Then, after a short waiting period, they are asked to either reproduce the image themselves or select a copy of the original image from a series of visually similar images.

Now, choose which image is a copy of the original.

(Credit: Wikipedia)

 

You have now seen most of the tests used to diagnose and monitor Alzheimer’s disease and other neurological diseases. (If you are wondering how well you fared, the answers are at the end of the post.)

Before we move on to possible treatments of this disease, I have one last test for you. Earlier, I gave you a name and address to remember. Can you still recall it?

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At present, there are five FDA approved medications for treating the symptoms of Alzheimer’s disease. There are currently no approved medications that can actually stop or reverse the progression of Alzheimer’s. Three of these medications (donepezil, galantamine, and rivastigmine) are Cholinesterase inhibitors. They work by slowing down the break-down of neurotransmitters.

Clinical trials are important in treating Alzheimer’s as, if successful, they could lead to the availability of new, approved drugs that actually treat the disease instead of just masking the symptoms.

Most of the new, promising therapies are focussed on lowering levels of Beta-amyloid (a major component of plaques in the brain). One of the current drugs in research uses Solanezumab (a monoclonal antibody that binds to beta-amyloid and carries it away from the brain).

With greater funding towards this cause and more clinical trialling, we will find a cure for Alzheimer’s disease- hopefully in the near future.

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Solutions to the tests:

• Raven’s Progressive Matrices- Option 4
• Luria Mental Rotation- Option 4
• Benton Visual Retention- Option 2
• The name and address- John Black, 42 West Street, Brighton
  • (This is the same name and address Alice was asked to recall in the novel)