What is alzheimer's disease?

Alzheimer’s disease is a progressive neurodegenerative disease and is most common in people over 65.¹ Alzheimer’s can vary in its symptoms and speed of progression. Still, it is closely associated with cognitive decline, e.g., memory loss, poor judgement, confusion and the inability to carry out daily tasks independently. 

The average time someone lives with Alzheimer’s disease after diagnosis is between 4 and 8 years, however, this is highly variable and some patients live much longer.¹ Alzheimer’s disease can be very hard for friends and family, too, who often help in caring for their loved ones as the disease progresses.

What causes alzheimer's disease?

Alzheimer's disease is thought to be caused by abnormal protein lumps which form in the brain and cause damage to neurons. As a result, this causes a loss of brain volume. There are two types of protein clumps seen in Alzheimer’s: amyloid plaques and tau neurofibrillary tangles.³

Amyloid plaques are sticky clumps of beta-amyloid protein which become insoluble (impossible for the body to remove) and are found on the outside of neurons.³ This disrupts the functions of the neurons. 

Within a neuron, signalling messengers and nutrients are carried down the axon. This function is facilitated by microtubules, which are stabilised by tau in a healthy neuron. However, in Alzheimer’s disease, abnormal tau tangles which are formed from clumps of tau protein disrupt this transport system and impair signalling within and between neurons.³

Both types of protein clumps impair the healthy functioning of neurons and eventually cause neuron death. There is a pattern in which these protein clumps tend to form in Alzheimer’s as the disease progresses. Abnormal proteins typically form first in the hippocampus and entorhinal cortex (brain areas involved in memory) and later affect the cerebral cortex which is associated with language, problem-solving, and the regulation of behaviour and mood.³

Inflammation is also thought to contribute to Alzheimer’s disease and lots of research is currently instigating the role it plays in disease development and progression.³ It is also thought that the blood-brain barrier may be impaired when amyloid plaques form, which may disrupt glucose entry into the brain, making it harder for immune cells to clear them and causing inflammation.

Alzheimer’s disease symptoms

Alzheimer’s usually progresses from mild to moderate and later severe symptoms.

Early signs of the disease include:

• Memory loss
• Loss of their sense of initiative
• Repeating conversations 
• An individual getting lost or forgetting where they are
• Anxiety
• Mood changes
• Problems with keeping up with dates and planning
• Misplacing things
• Some difficulty with daily tasks, e.g. handling money or bathing

As the disease progresses, symptoms may worsen and include:

• Confusion and memory loss for personally significant memories – for example forgetting the names of friends and family or even forgetting one's personal history
• Changes to the body’s sleep and wake cycle – e.g. sleeping a lot during the day and being up at night
• Moderate anxiety, delusions or paranoia
• Difficulty regulating emotions - increased irritability, loss of temper and emotional outbursts.
• Problems with executive function – this may include difficulty when planning and problem-solving, losing the ability to control impulsive behaviour or acting in a way which is vulgar or inappropriate in social situations
• Problems with speech and language comprehension

In its later stages, Alzheimer’s symptoms become severe. Some symptoms of severe Alzheimer’s include:

• Seizures
• Loss of control for swallowing can lead to inhalation of food and increased risk of aspiration pneumonia
• Physical decline – this can include severe weight loss and reduced dental and bodily hygiene, which can lead to other health conditions such as skin infections, gum disease, and malnutrition
• Sudden increase in sleep both in the day and night
• Urinary incontinence (loss of bladder control) and loss of bowel control
• Loss of the ability to communicate verbally
• Loss of awareness of surroundings, personal history, or recent memories

Mild cognitive impairment

Some people with Alzheimer’s may be diagnosed with mild cognitive impairment (MCI). MCI refers to a milder cognitive decline than dementia, which does not fully impact an individual’s ability to continue to carry out all daily activities independently. Patients with MCI may still need help with one or two tasks and demonstrate mild loss of memory and cognitive abilities.

Dementia

Dementia refers to a group of symptoms which co-occur and affect several cognitive functions including memory, problem-solving, language, concentration, and decision-making.⁴ Alzheimer’s is the leading cause of dementia worldwide thought to cause between 60% and 80% of all dementia cases,¹ but is not the only cause of dementia - see the later section ‘Alzheimer’s vs dementia: what's the difference?’ to learn more about other causes of dementia.⁵ However, not everyone with Alzheimer’s will develop dementia in their lifetime.

Diagnosis of alzheimer’s disease

To diagnose Alzheimer's disease, a doctor will evaluate your symptoms and medical history, conduct tests to rule out other causes for symptoms, and may use cognitive and behavioural assessments alongside biomarker tests⁷ to confirm the diagnosis and severity of Alzheimer’s.⁶

Neurological assessments can be used to check that symptoms cannot be explained better by other conditions that impair elements of cognition.⁶ For example, speech difficulties can be a consequence of stroke, so it is important to rule out stroke as an alternative cause. Brain imaging may also be involved in this process, to investigate whether any structural changes to the brain (e.g. a brain tumour) may contribute to symptoms.

Psychological disorders are also investigated as disorders such as depression and anxiety can also give rise to memory loss, loss of concentration and behavioural change. This helps to rule out alternative causes and assess whether mood disorders may be related to Alzheimer’s disease and require specialised treatment.

Patients may also be given cognitive and behavioural tests which assess the presence and severity of symptoms affecting problem-solving, memory, reasoning, and daily functioning.⁹

Finally, a lumbar puncture may be performed to collect cerebrospinal fluid (CSF) for analysis and can be used to identify high levels of tau or beta-amyloid proteins.⁸ There are also blood tests that are still in the very early stages of their development.⁷ Researchers are trying to improve the accuracy and sensitivity of both ‘biomarker tests’ for Alzheimer’s disease. This means that they are more often used in clinical trials and research settings than in clinics.

Treatments for alzheimer's disease

Current treatments aim to alleviate the symptoms of Alzheimer’s disease rather than the cause.

Acetylcholinesterase (AChE) inhibitors are drugs which work to increase a substance called acetylcholine in the brain which plays a large role in neuron signalling. This aims to alleviate some cognitive symptoms by increasing signalling between neurons.

Another drug which acts on signalling substances in the brain is memantine which is used to lower the effects of excessive glutamate in the brain.¹⁰ Glutamate is the main excitatory messenger in the brain and is involved in healthy functioning. However, too much glutamate causes overexcitation of the neurons in the brain which has a toxic effect on these cells.

Additionally, drugs can be prescribed to help alleviate psychological symptoms associated with Alzheimer’s disease-related dementia. This includes antipsychotics and/or antidepressants to target symptoms such as delusions, paranoia, anxiety, depression and extreme distress.¹²

A new treatment for Alzheimer's has not been approved in the UK for over 20 years,¹³ but there are currently several drugs which aim to target the cause of the disease (the sticky protein clumps) which are currently on trial. These drugs have not been approved yet in the UK, but have applied for approval by the MHRA and NICE this year. 

This includes Lecanemab and Donanemab – two humanised immunoglobulin-G1 monoclonal antibodies which target amyloid plaques before they become insoluble and work with the body’s immune system to clear them from the brain.¹⁰ So far, clinical trials using these drugs have had promising effects on slowing disease progression and lowering the amount of amyloid seen in the brain in specialised PET scans, but do not stop or reverse disease progression.¹³

FAQs

Alzheimer’s and dementia – what’s the difference?

Sometimes people use the terms Alzheimer’s and dementia interchangeably but there are key differences between Alzheimer’s disease and dementia, and they refer to two different things. Alzheimer’s is a progressive neurodegenerative disease caused by the abnormal aggregation of amyloid and tau proteins which can cause a loss of neurons in the brain. 

Dementia is not a condition in itself but is instead a label given to a group of symptoms which typically co-occur and relate to cognitive functions.⁴ Although Alzheimer’s disease is thought to be the leading cause of dementia, there are many other causes of dementia, each presenting slightly different symptom profiles.⁵ For example:

• Dementia with Lewy bodies (DLB) is another type of dementia where different protein clumps called Lewy bodies are thought to cause dementia
• Vascular dementia is thought to be caused by restrictions to blood flow in the brain
• Behavioural variant frontotemporal dementia (bvFTD) is more likely to be early-onset, is related to tau and TDP-43 genes, and has symptoms that begin as mainly behavioural (e.g., mood changes, and impulsive behaviour), with memory being affected later.¹¹ This type of dementia is more closely associated with motor neuron disease than with Alzheimer’s

Summary

Alzheimer’s Disease is a progressive neurodegenerative disease which causes cognitive decline, although symptoms and severity can vary on a case-by-case basis. It is caused by abnormal protein clumps in the brain which damage neurons (the cells which carry messages and make up the brain) and impair their functions in signalling. Current treatments for Alzheimer’s are limited and target symptoms, although there are a few new drugs being trialled that target the cause.