Understanding Alzheimer's disease

Dementia affects around 50 million people globally [1] and over 9 million in the UK alone [2]. Whilst there are several forms of dementia, Alzheimer’s disease is the commonest cause. The incidence of dementia and Alzheimer’s specifically, is increasing year on year as people are living longer than ever before, with numbers now expected to double every 20 years [1]. At present, there is no ‘cure’ for Alzheimer’s disease, but certain medicines have been shown to slow the progression of the condition. Greater awareness, early diagnosis and prevention where possible, is therefore of paramount importance.

What is Alzheimer’s disease?

Alzheimer’s disease is the commonest form of dementia. Dementia is an umbrella term describing a set of symptoms associated with progressive decline in brain function, most commonly affecting older people over 65. The symptoms of dementia are progressive, meaning they get worse over time and may include memory loss, difficulties with daily tasks (particularly executive functions and problem-solving), difficulties with language and understanding, and changes in behaviour [3].

Dementia is caused by damage to the nerve cells (neurons) in the brain, which prevents them from functioning properly and can result from several different disease processes. However, dementia is not synonymous with normal ageing and has very specific symptoms. The commonest disease that causes dementia is Alzheimer’s disease, followed by vascular dementia [4].

What causes Alzheimer’s disease?

The precise cause (aetiology) of Alzheimer’s disease is not well understood and remains the subject of intensive research internationally. However, at the cellular level, it is known that the disease is linked to the abnormal accumulation of specific proteins in the brain, which prevent the normal functioning of neurons. Signalling pathways between neurons are interrupted by the accumulation of two types of pathological lesions: beta-amyloid plaques and neurofibrillary tangles associated with tau proteins. Over time, these lesions become widespread throughout the brain’s tissues, leading to disruption of neural communication pathways, neuron degeneration, tissue breakdown (atrophy) and functional loss [5]. Exactly what triggers these pathological processes in the brain remains unclear, but scientists now know that the process begins many years, possibly even decades, before the onset of symptoms. Additionally, several factors that increase the risk of developing Alzheimer’s disease are known.

Risk factors for Alzheimer’s disease

Risk factors for Alzheimer’s and other forms of dementia can be divided into ‘modifiable’ and ‘non-modifiable’ categories, depending on whether the outcome can be changed (modified) by the individual. Starting with the non-modifiable factors, the most significant risk factor for developing all forms of dementia is age, with likelihood doubling every 5 years beyond the age of 65 and rising even more sharply beyond the age of 80.

However, Alzheimer’s can also affect younger people, with 1 in 20 cases occurring in people under the age of 65. This is known as ‘early-onset Alzheimer’s disease’ and can affect people over the age of 40 [3].

A person’s genetics can also influence their likelihood of developing Alzheimer’s disease, albeit to a minor degree. In small number of families, Alzheimer’s disease is caused by a single faulty gene that is inherited from one’s parents and can be passed on to subsequent generations [6]. This gene mutation can be associated with early-onset dementia and people from affected families may be encouraged to seek genetic counselling for further advice on their risk of developing Alzheimer’s.

People with Down’s syndrome are also more likely to develop Alzheimer’s disease than the general population and are also likely to be affected at a younger age [7]. Additionally, people who have suffered severe head injuries in the past may be more likely to develop Alzheimer’s, although further research is required in this area.

When considering modifiable risk factors, many factors associated with the development of cardiovascular disease, such as smoking, obesity, diabetes, high blood pressure and high cholesterol, are also associated with the development of Alzheimer’s disease [3]. Additionally, recent research shows that the presence of certain risk factors at specific stages of life, are particularly influential on the development of dementia later in life.

For example, in mid-life (ages 45 – 65) the presence of hearing loss, obesity and hypertension increase dementia risk more than at other stages in life, and in later life (over age 65) smoking, physical inactivity, depression, social isolation and diabetes increase risk disproportionately [8]. That is not to say that the presence of these factors at other stages of life do not influence overall dementia risk, but rather they show particularly profound effect on disease risk at the stages of life specified.

Prolonged, chronic stress has also been implicated in the development of Alzheimer’s disease, specifically the progression of mild age-related cognitive impairment to clinically diagnosable Alzheimer’s disease. This is thought to be related to immune system dysregulation and brain inflammation associated with chronic stress [9][10], but further research is required to draw definitive conclusions.

There is also an association between poor sleep and dementia risk, which experts agree is likely a bidirectional relationship. This means that whilst poor sleep may increase dementia risk, dementia itself also has negative effects on sleep [11]. From a preventive medicine perspective, the evidence linking poor sleep with dementia risk is growing. A large study (Whitehall II study) conducted over a 25-year follow-up period, suggested that consistently reduced sleep duration of 6 hours or less (opposed to an average of 7 hours) between the ages 50 – 60, increased the risk of dementia in later life by up to 30% [12].

Other studies have shown that poor sleep is associated with the accumulation of beta-Amyloid plaques in the central nervous system, proteins that are linked to the development of Alzheimer’s disease [13]. However, some experts feel there is insufficient evidence to conclusively link poor sleep with dementia risk in later life [8] and further research is needed in this area. To read more about the importance of sleep for overall health, please see our dedicated article here.

Alzheimer's treatments & prognosis

At present, there is still no cure for Alzheimer’s disease despite decades of research, but there are medicines and specialist therapies available that can help reduce symptoms and slow disease progression. Alzheimer’s is a progressive condition, meaning that its symptoms get worse over time and cannot be reversed. As symptoms worsen, people diagnosed with Alzheimer’s may require additional support with everyday activities such as shopping, cooking, cleaning and ultimately personal-care and hygiene too.

Medicines used to relieve the symptoms of Alzheimer’s disease fall broadly into two classes. The first are acetylcholinesterase (AchE) inhibitors such as donepezil or galantamine. These medicines increase levels of a neurotransmitter in the brain called acetylcholine, allowing better communication between neurons.

The second medicine commonly used is memantine, which works by reducing the amount of another neurotransmitter in the brain called glutamate, which otherwise would suppress neuronal activity further. Memantine is usually used for more advanced stages of Alzheimer’s, or those who cannot tolerate AchE inhibitors due to side-effects.

Non-pharmacological treatments for Alzheimer’s disease include specialist therapies such as cognitive stimulation therapy, cognitive rehabilitation, and reminiscence & life-story work. These techniques may be used in conjunction with pharmacological treatment and are designed to reduce the rate of cognitive decline and improve overall mood and wellbeing [3][4].

Unfortunately, the prognosis of Alzheimer’s disease (and most other forms of dementia) remains very poor. As the disease progresses and symptoms worsen, those affected usually need increasing levels of care, many ultimately requiring round-the-clock residential support. Witnessing the progression of Alzheimer’s disease in a loved one can be extremely difficult for families, as the behaviour and independence of their loved one declines over time. There are however a number of specialist support services available via the NHS (here) and dedicated charities (here).

Reducing the risk of developing Alzheimer’s - the latest research

As the exact cause of Alzheimer’s disease remains unclear, there is no absolute way to prevent the condition. However, minimising modifiable risk-factors is likely to be helpful. This includes maintaining good cardiovascular health by eating a healthy diet, exercising regularly, stopping smoking, reducing alcohol intake and maintaining diabetes control where applicable. Additionally, taking steps to improve sleep, avoid social isolation, treating depression, reducing sedentary time and staying socially and mentally active as we get older, is all likely to help reduce our risk.

Whilst exercise is important to brain and overall health, and research has shown that older adults who exercise regularly are more likely to maintain cognition than those who don’t, there is insufficient evidence to state that exercise can reliably prevent dementia onset [8]. However, in those with genetic pre-disposition to early-onset Alzheimer’s, regular aerobic exercise (over 150 mins weekly) has been show to delay disease onset by up to 15 years [14]. Regarding diet, there is some evidence suggesting that the adoption of a Mediterranean diet may have protective effects against the development of dementia [15][8].

The very latest research into the biology of ageing may also point towards future opportunities for Alzheimer’s disease prevention. The primary risk factor for developing Alzheimer’s disease is increasing age, therefore it follows that if we can slow the rate of cellular ageing through certain lifestyle modifications, this may reduce our risk of developing the condition.

Research in animal models has shown that intermittent fasting reduces metabolic changes leading to the development of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease as well as a host of other conditions including heart disease, diabetes, cancer and age-related memory decline [16][17][18][19][20]. However, there are currently no long-term studies in humans that convincingly demonstrate the effectiveness of fasting in preventing Alzheimer’s disease, but this may present new and exciting avenues for prevention in the near future.

The bottom line

Alzheimer’s disease is the commonest cause of dementia. It is a progressive disease with no known cure. Dementia affects approximately 50 million people globally and around 9 million people in the UK.

The global incidence of dementia is increasing year on year, with numbers of people affected expected to double every 20 years, primarily due to the average age of the global population increasing.

The exact cause (aetiology) of Alzheimer’s disease is unknown, but the metabolic and cellular processes that lead to the development of the disease involve abnormal accumulation of proteins in the brain (beta-amyloid plaques and tau-protein neurofibrillary tangles)

The primary risk factor for developing Alzheimer’s disease is increasing age, with risk doubling every 5 years beyond the age of 65 and rising even more sharply after the age of 80

Other risk factors include genetic predisposition, poor cardiovascular health (plus associated lifestyle factors) and Down’s syndrome. Social isolation, depression, hearing loss, sedentary lifestyle, diet and sleep quality may also influence Alzheimer’s disease development.

Treatments for Alzheimer’s are aimed at reducing unpleasant symptoms (rather than cure) and include medications and specialist therapies.

Due to the uncertain aetiology, complete prevention of Alzheimer’s is not currently possible, but reducing modifiable risk factors, such as improving cardiovascular health and maintaining social and mental functioning as we age, is likely to be helpful.

Research in animal models suggests that fasting and caloric restriction reduces the rate of metabolic processes underlying the development Alzheimer’s disease (and other age-related diseases), but there is no conclusive evidence that this approach is effective in humans. However, this may present exciting avenues for preventive medicine in future.

Useful Links:

NHS website - Alzheimer's disease

https://www.nhs.uk/conditions/alzheimers-disease/

Alzheimer's Society - What is dementia?

https://www.alzheimers.org.uk/about-dementia/types-dementia/what-is-dementia

References:

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