Alzheimer Dementia Causes and Treatments

 Alzheimer's is typically thought of a disease that affects the elderly, but ten per cent of people with Alzheimer's have the early-onset form and are under the age of sixty-five. While about 50% of early-onset Alzheimer's cases do not show specific mutations, there is a strong genetic linkage. Mutation positive for genes APP, PS1 or PS2 is a solid confirmation of the diagnosis. It is possible that those without these mutated genes may have other mutated genes that also cause the disease. Sadly, the genetic element means that any offspring may have inherited the mutated form of a gene. This can only be diagnosed by genetic screening.

2012: Current drugs for treating Alzheimer's dementia can slow its progression for a significant period of time but are not a cure. The sooner someone is diagnosed and put on medication the more likely they will be able to benefit if better treatments become available. Examples are Aricept (boosts cholinergic functioning) and Namenda.

Diagnosis: finding amyloid plaques and/or neurofibrillary tangles in the brain.

The cognitive deficits - the symptoms of dementia - occur before the plaques form and neurons die. 

In the brain of someone with Alzheimer's, there is too much of a soluble protein called amyloid-beta 42. Either too much is made or not enough is cleared away. When too much is present, these individual little peptides stick together and form small oligomers. These gluey oligomers of amyloid-beta 42 lodge in synapses - the spaces between neurons - and interfere with synaptic transmission, the ability of neuron number one to 'talk' to neuron number two. And when this happens, new information isn't learned. Or old information can't be accessed. Synaptic plasticity suffers. Over time because this synapse isn't working properly and because of inflammation and other problems, that nerve axon terminal will retract. Eventually, unable to function, the neuron will die, leaving behind empty space (the atrophy seen on MRI scans) and possibly a heap of amyloid-beta 42 in an amyloid plaque.

The degree of dementia correlates only with  synapse dysfunction, not with neuronal loss, not with number of plaques, not with atrophy on an MRI scan.

The cure (disease altering) treatments will need to:

• impede production of amyloid-beta 42,
• increase clearance of already produced amyloid-beta 42,
• prevent amyloid-beta 42 from sticking to itself so it can't form oligomers, or
• rip these already formed oligomers apart.

If such treatments are found, the hope is that people suffering from symptoms of dementia can be treated before they've experienced any neuron death. If the synapses are fixed, neurotransmission can work again.

Source: Still Alice by Lisa Genova (Simon & Schuster, 20012)

Cataracts

What are cataracts?

Cataracts are cloudy patches on the lens in the eye, which cause blurred vision and eventual blindness if left untreated. It is estimated that in the UK one in three people aged 65 has a cataract in one or both eyes.

Most develop due to age-related changes in the lens

• An imbalance between free radicals (unstable atoms that damage cells) and antioxidants (which keep free radicals in check). Cells in the body produce both, but smoking, drinking too much alcohol and exposure to chemicals can speed up production of the damaging free radicals.
• As we age, fewer antioxidants are produced, resulting in oxidative stress, leading to tissue damage; proteins and fibres in the lens start to break down and calcium builds up in the lens.
• Cataracts are also linked to conditions such as diabetes and to medications, includinglong-term use of steroids.

Current treatment

The current treatment is to replace the cloudy lens in a 30-minute operation under local anaesthetic. The cloudy lens is removed through a small cut in the eye, and replaced with a plastic one. About 350,000 cataract operations are performed in the UK each year.

New treatment developed

Scientists at US-based Nacuity Pharmaceuticals have developed a 'pellet' implant (NPI-002) that is injected into the eye to prevent cataracts forming, and might even reverse the growth of existing cataracts without surgery. This is now being tested in the first clinical trial.

• The implant is thought to work by lowering calcium levels in the eye.
• The implant is loaded with antioxidants and injected into the vitreous, the gel-like fluid between the lens and the retina (the light-sensitive area in the eye). The solution includes N-acetylcysteine amide (NACA), an effective antioxidant.
• The implant slowly releases its contents into the vitreous, which carries them to the lens where it acts on the cataract. 

First clinical trial

An animal study by ophthalmologists at Washington University, US, and other centres, reported in the journal BMC Ophthalmology in 2018, showed that the implant prevented and reduced the severity of cataracts. It also led to an increase in protective antioxidants, and reduced calcium levels to 2.5 times lower than a control group.

The first human trial, in the US, will start soon (late 2021) and will involve 30 patients aged 65 and over with cataracts.

Initial interest in the implant is tempered with caution. Gwyn Williams, a consultant ophthalmologist at Singleton Hospital in Swansea, said "It is a very interesting idea and I look forward to seeing the results. Cataracts are multi-factorial and I am sceptical that this one approach will be effective by itself, though this remains to be seen."

Source: Scientists develop 'pellet' that can be injected into patient's eye to prevent cataracts forming - and could even reverse existing traces. Daily Mail (5 Oct. 2021) 

Long Covid Facts

While many people recover from Covid-19 without further problems, some report having long-term health problems. A large range of symptoms are reported by these sufferers, for varying periods after the infection. Symptoms typically fall into four groups.

Types of Long Covid

Post intensive care syndrome (PICS)
Critically ill patients can suffer a range of health problems after a long time in hospital. This can include muscle weakness, and anxiety or another mental health problem. They may also have memory problems, which can affect whether they can return to work.

Post viral fatigue syndrome (PVFS)
Similar to problems following enteritis or rubella, fatigue and 'brain fog' may make it difficult to concentrate or remember things. 

Permanent organ damage (POD)
The lungs and heart, and also liver and pancreas, may have permanent damage.

Long-term Covid syndrome (LTCS)
This group report 'floating' symptoms which mean they do not fit into the other three groups. They suffer illness linked to one part of the body (e.g. respiratory system, brain, cardiovascular system and heart, kidneys, gut, liver or skin), which later abates, but then new symptoms arise in a different part of the body.

Why does this happen? 
Latest: A small study (at Stellenbosch University, South Africa) comparing blood collected from 11 people with long Covid and 13 healthy individuals found that those with long Covid have a large amount of tiny clots of inflammatory molecules trapped in their bloodstream. These blockages have the potential to disrupt the body's ability to distribute oxygen and vital nutrients, which could explain - or help to explain - the most common symptoms of fatigue, headaches and breathing difficulties. Some of the trapped molecules contain clotting proteins such as fibrinogen (helps the body to make clots to stop bleeding) and alpha(2)-antiplasmin (helps prevent blood clots from breaking down). Under normal conditions, the body maintains a balance of clotting and anti-clotting material to help the body reduce blood loss after injury, and preventing clots from growing too large and restricting oxygen flow. High amounts of alpha(2)-antiplasmin stuck in the blood mean the body's ability to break down clots is severely reduced. Other recent studies have also highlighted that the body's clotting system could be involved, while Covid itself has been linked to clotting disorders during the initial infection. More research with larger samples is needed to confirm these findings, and research to identify the type of treatment for the problem.

There are three possible reasons, and long covid may even be a combination of these.

1. Direct damage by the virus. For example, the heart and lungs can be permanently damaged, which could explain prolonged shortness of breath and chest pains. 
2. It is even possible that the virus could hide in some body tissues, and continually reactivate; some studies are looking into this possibility.
3.  Inadvertent damage that the body can do when it responds to the virus.

Long Covid is less common than first feared.
Initially it was unclear how many people might be affected, nor how long symptoms might last and whether there might be permanent damage. It it is possible to have serious Covid-19 symptoms and not experience long-term syndromes, and for those with mild cases to develop one of the syndromes.

The UK Office for National Statistics (ONS) has been monitoring this, by testing people at random which ensures that the comparison between Covid sufferers and non-sufferers is good. Additionally they carry out long-term follow-ups of those with long covid. Their latest (September 2021), large and comprehensive analysis suggests that one in 40 (2.5%) people with coronavirus has symptoms lasting at least three months.

Those most likely to suffer long-term (at least 3 months after infection) health conditions are:

• Women aged 35 to 69
• Those aged 50 to 69
• People with high levels of virus in their body when testing positive.

Long Covid in children: An Australian study indicates that long covid symptoms in children and teens resolve in four to twelve weeks.

Sources: BBC News 18 Sept. 2021 (link). Article in Daily Mail, (link) 15 Oct. 2020. Article in New Scientist, 31 Oct. 2020. Article in Daily Mail (link) 5 Oct. 2021.

The Perils of MisInformation

Social media networks are playing an increasing role in spreading misinformation about coronavirus Covid-19, and the vaccines that have been developed to prevent infection.

Despite the widespread availability of vaccines in the US, only about half of the people are fully vaccinated. Many of the unvaccinated don't plan to get the vaccine.

A handful of influencers on Facebook, Twitter and other social media are responsible for falsely claiming that the virus does not exist, and that vaccines will harm you. Influencers can reach millions of people, some directly but also many indirectly as people forward their posts to others.

Tagging posts as False often happens after the post has been forwarded multiple times. The problem is how to identify such material quickly and reduce its spread to a minimum.

Social media platforms want to continue to allow "free speech" but in most countries free speech exemptions must also take account of laws controlling certain views, especially if it involves endangering others. Social media platforms also encourage people to participate in debate by bringing to your attention emotional content that encourages people to respond.

Social media platforms, governments and sociologists are currently grappling with how to allow and even encourage free debate, without trolling others for simply holding opposing views, or spreading misinformation that has harmful effects on other people.

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Wider Fit Ladies Shoe Brands in UK

 As we get older, our feet get wider and an added complication is that many people develop bunions (this is now known to be down to genetics and not wearing the wrong footwear). Many high fashion brands don't come in wider sizes, and until recently the styles on offer veered to the 'comfy' rather than the stylish. Here are the ones available in the UK that I have discovered.

• James Inglis Collections from Italy and USA. Free specialist fitting service. Extra narrow to extra wide widths. Sizes 4 to 10 including 1/2 sizes.
• Van-Dal Width fittings are slightly more generous than usual. Van Dal 'D' fit is wider than the average high street shoe. Van-Dal E fit are classed as wide fitting. Van-Dal EE fit are wider again; they also tend to have a lower heel.
• Hotter Offer four width fittings - Slim, Standard, Wide and Extra Wide in UK whole and half sizes.
• Sole Bliss On-trend shoes for women with bunions, wide feet and sensitive soles. Initial range focused on heels, but now offer flats, sandals and trainers.

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