Alcohol use and dementia

  • Dementia has emerged as one of the biggest killer diseases of the 21st century
  • Studies suggest that moderate alcohol use significantly increases the risk of dementia
  • There are no treatments that slow or stop the progression of dementia
  • There are 50m people worldwide living with dementia, by 2050 there will be 132m
  • 0.85m people in the UK are living with dementia and this is expected to rise to 1m by 2025
  • Public policies alone are not sufficient to limit and control alcohol use
  • This increases the importance of a medical solution for dementia
  • Recent innovative research on neurodegenerative disorders provide some hope for future dementia sufferers
 
Alcohol use and dementia

Two significant recent studies described in this Commentary link alcohol use and the onset of dementia. One study published in the June 2017 edition of the British Medical Journal (BMJ) suggests that moderate alcohol use increases the risk of adverse brain outcomes and a steeper decline in cognitive abilities. The other, published in the February 2018 edition of the Lancet Public Health, suggests that excessive alcohol consumption is a significant risk of early onset dementia.

Dementia is a chronic progressive disorder, which has emerged as one of the biggest killers and the only leading cause of death without a treatment that can slow or stop its progression. Of the 529,655 deaths recorded in the UK in 2015, dementia accounted for 61,686 (11.6%): the majority are women, 41,283, compared to 20,403 men.
 
In this Commentary
 
In this Commentary we outline how alcohol affects you, explain its misuse and describe some of the UK’s drinking patterns and their consequent costs. We then suggest that public policies alone, which are aimed at both the individual and population levels to reduce and control alcohol use in order to save lives and reduce healthcare costs, are insufficient. This shifts the burden of a solution for alcohol related dementia onto potential medical treatments. We describe dementia and provide a few epidemiological facts before describing the findings of the 2 studies. We suggest that the studies are significant because there are no effective treatments or cures for dementia despite the vast amounts of money spent on neurodegenerative diseases over the past 2 decades. We end by mentioning a couple of significant UK-based innovative dementia research initiatives, which signal hope for future dementia sufferers.
 
How alcohol affects you and its misuse

Alcohol is a dependence-producing psychoactive beverage, which has been widely used throughout the world for centuries. Problems associated with the consumption of alcohol have been around since the beginning of recorded history. There are 3 mechanisms by which alcohol can affect you: (i) alcohol has toxic effects on your brain and other organs and tissue, (ii) alcohol has intoxicating effects, which manifest themselves in physical and mental impairment and (iii) you may become dependent of alcohol, which means control over your drinking habit is impaired. Alcohol’s harmful impact is influenced by, (i) the volume you consume, (ii) your pattern of drinking and (iii) the quality of the alcohol. When your body takes in more alcohol than it can metabolize, the excess builds up in your bloodstream. Your heart circulates the blood alcohol throughout your body leading to changes in your body’s chemistry and normal functions. 

Studies have consistently suggested that heavy alcohol consumption is detrimental to health and a leading preventable cause of death. There is an increasing awareness of the harmful impact of alcohol misuse on individuals and societies. According to the 2011 World Health Organization’s (WHO) Global status report on alcohol and health, only about 50% of the world's population consumes alcohol, and most users are in the wealthier northern hemisphere countries, although alcohol use is increasingly becoming a problem in emerging economies. Eastern European countries have the highest consumption, riskiest patterns of drinking and the highest levels of alcohol-related deaths and disabilities. According to a February 2018 WHO report, an estimated 3.3m people a year worldwide die as a result of alcohol misuse, which accounts for about as much death and disability worldwide as tobacco and hypertension. 
 
Drinking in the UK and its costs
 
The latest available data suggest that the total alcohol consumption in the UK is 9.5 litres per person aged 15 years and older and 7.8 litres per person on average throughout the entire population in 2015. This forms part of a recent downward trend from a peak of 11.6 and 9.5 litres per head respectively in 2004 and positions the UK 16th out of the 34 OEDC countries. 21m people in the UK do not drink alcohol. According to NHS Digital, in 2014 there were 1.1m hospital admissions in England wholly or partially attributable to alcohol use: more than double the number recorded a decade earlier. In 2014 about 6,600 people in England died from causes related to alcohol and about 115,000 adults received specialist alcohol treatment. Treating alcohol related conditions is estimated to cost NHS England about £3.5bn per year: around 3.6% of its annual budget. About 6% of adults in England are dependent on alcohol. 195,000 prescriptions were written in 2014 by the NHS to treat alcohol dependence at a cost of £3.4m. Over the past decade these prescription costs, measured in 2014 prices, have increased by nearly 80% from £1.9m in 2004.
 
Public policies to curb alcohol use are insufficient

In May 2018, Scotland became the first country in the world to introduce legislation for minimum pricing on cheap, high-strength alcohol. The government said it was an endeavour to cut the consumption of alcohol and save lives. For several decades, similar alcohol reduction and prevention measures have been available at both the individual and population levels in the UK and elsewhere. The most effective include alcohol taxes, restrictions on alcohol availability, and drink-driving countermeasures. Despite the success of these policies, alcohol problems continue to present a major challenge to medicine and public health. In part, this is because population-based public health alcohol control policies tend to be overlooked in favour of approaches aimed at the individual and these have tended to be more palliative than preventative. It is reasonable to assume therefore that, in the near- to medium-term, alcohol related dementia will neither be significantly slowed nor reduced by public policies alone. This shifts the emphasis to a medical solution for alcohol related dementia.
 
Dementia

Dementia is an umbrella term, which describes a group of symptoms that impair your cognitive functions and behavioural abilities severely enough to interfere with your daily life and activities. It is a chronic, progressive and incurable disorder, which ranges in severity from ‘mild’, when it is just beginning to affect your functioning, to ‘severe’, when you depend completely on others for basic activities of living. Dementia involves damage of nerve cells in your brain, which can occur in several areas and affect people differently, depending on the area of the brain affected. Alzheimer's, a neurodegenerative disease, is the most common irreversible cause of dementia, accounting for 60% to 80% of all dementia cases.
The biggest risk factor for dementia is age. We are living in the age of the aged, which represents the successes of improved healthcare over the past century. There are some 50m people worldwide living with dementia. The total number of people with dementia worldwide is projected to increase to 75m by 2030 and 132m by 2050, with the largest proportion of these in low- and middle-income countries. There are 0.85m people diagnosed with dementia in the UK, with numbers set to rise to over 1m by 2025 and to 2m by 2050. 225,000 people in Britain will develop dementia this year. There is a similar story to be told in most wealthy developed countries. For example, in the US an estimated 6m people have Alzheimer's, which equates to 10% of people aged 65 and older. The current annual cost of dementia globally is estimated to be about US$1tr: 1% of global GDP. The annual cost of the condition in the US is US$259bn, which is expected to rise to US$1tr by 2025. Dementia costs the UK exchequer about £26bn each year.
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Dementia is not an inevitable part of ageing. The notion that dementia is a disease rather than a side-effect of aging has been around for 100 years. Early onset of the disease can begin when people are in their 30s, 40s, or 50s. For example, over 42,000 people under 65 have dementia in the UK. Age, family histories and heredity are factors of dementia that we cannot change. But lifestyle factors such as alcohol use are modifiable risks. There is no cure for the condition and no therapy that slows or stops its progression although some drug treatments may temporarily improve its symptoms.
 
The BMJ study

For some time, scientists have suggested that moderate alcohol consumption could delay the onset of cognitive impairments in ageing, but few studies have examined the effects of modest consumption of alcohol on the brain. This increases the significance on the BMJ study, which includes an analysis of the relationship between moderate alcohol consumption and dementia. Researchers from Oxford University  and University College London studied a cohort of 550 healthy adult civil servants over a 30 year period between 1985 and 2015. At the beginning of the study the average age of the cohort was 43 and none were dependent on alcohol. At regular intervals during the study tests were administered to assess participants’ levels of alcohol consumption and cognition. At the end of the study participants underwent an MRI brain scan, which enabled researchers to analyse correlations between average alcohol consumption, cognition and brain structure. Findings suggest that alcohol use is associated with reduced right hippocampal volume. The hippocampus is a small region of your brain associated with memory and spatial navigation. Poor memory is linked with small hippocampal volume as measured by an MRI scan. The more you drink, the more you are likely to have hippocampal atrophy, which is regarded as an early marker for dementia. Significantly, the study found that even moderate drinkers were 3 times more likely to have hippocampal atrophy than abstainers.

The principal strength of the study is that it is a longitudinal observational analysis of a specific cohort, which yielded detailed information on long term alcohol consumption and cognition and confounding variables. These are “extra” variables, which are important to know in order to avoid bias. Because this was an observational study the researchers were unable to draw any conclusions on cause and effect. Notwithstanding, they were able to conclude that moderate alcohol use is associated with adverse brain outcomes and, “Alcohol might represent a modifiable risk factor for cognitive impairment, and primary prevention interventions targeted to later life could be too late.” In an editorial note in the same BMJ, Killian Welch, a consultant neuropsychiatrist at the Royal Edinburgh Hospital suggests the findings of the study, “strengthen the argument that drinking habits many people regard as normal, have adverse consequences for health.”
 
The Lancet Public Health study
 
The second study from The Lancet Public Health presents findings of a large retrospective study predicated upon data of more than 1m adults diagnosed with dementia between 2008-2013 from the French National Hospital Discharge database. These data provide details on all hospital admissions, including patient demographics, reasons and durations for hospital stays and treatments received. Findings suggest that being hospitalised with alcohol dependence or a health issue caused by continuous heavy drinking is a significant risk factor for dementia. Although the condition is more common in people over the age of 65, the study identified and examined 57,000 cases, which presented with the onset of dementia before 65. Of these, 57% were heavy drinkers, 39% regularly consumed alcohol and 18% had an alcohol use disorder as an additional diagnosis. “Heavy drinkers” were found to be more than 3 times likelier to develop dementia. Excluding alcohol-related brain damage, alcohol use disorders were still found to be associated with a 2 times greater risk of dementia.

According to Michael Schwarzinger, the lead author of the study, who is the director of the French Translational Health Economics Network and a researcher at the Universite Paris Diderot, France, “Chronic heavy drinking was the most important modifiable risk factor for dementia onset in both genders and remained so after controlling for all known risk factors for dementia onset.” While other studies have reached similar conclusions, some research suggest that drinking one or two units of alcohol a day - a small glass of red wine particularly - could be of benefit to brain health and slow the onset cognitive deterioration. Indeed, the Lancet Commission on dementia, associates light to moderate alcohol use with a healthier brain. Schwarzinger and his colleagues however are clear, “Our findings suggest the burden of dementia attributable to alcohol use disorders is much larger than previously thought . . .. Chronic heavy drinking leads to irreversible brain damage [and even] heavy drinkers who got sober didn’t have a lower dementia risk than their peers who remained problem drinkers. . . Additionally, clinicians should be better aware of the role of alcohol use disorders in dementia onset over the lifetime, which seems to be a risk factor often omitted.”
 
Why there is no cure for dementia

Over the past 2 decades pharmaceutical companies, biotech’s, governments, universities and charities have devoted vast amounts of money, time and effort to the dementia challenge, but without being able to develop any credible treatment let alone cure. This partly reflects the complexity of neurodegenerative disorders. The brain is a complex organ, which scientists are still endeavouring to understand. This lack of understanding is one of the main obstacles preventing the development of effective treatments for dementia. The disorder seems to present as a result of an intricate interaction of genes, lifestyle factors and other environmental influences. But, without knowing the exact mechanisms that cause damage, especially in Alzheimer's, it is impossible to target the disease process effectively.

In addition to our rudimentary understanding of the brain there are some specific challenges faced by researchers into neurodegenerative disorders. One is the blood-brain barrier, which is formed by brain endothelial cells, which protect the brain by preventing toxins from reaching it. This presents dementia researchers with a significant challenge because the blood-brain barrier also prevents treatments getting through to the brain and working effectively. Newer immunotherapy drugs, also known as biologics, are large complex molecules or mixtures of molecules, which because of their size and shape may only partly cross the blood-brain barrier. This suggests that dangerous doses would be needed for them to work effectively. And even if the biologics could penetrate the blood-brain barrier and target the proteins causing damage to brain cells, dementia is irreversible and may have started to develop decades before the presentation of symptoms and before the administration of drugs. Further, there is no test for dementia, which means the disorder is difficult to diagnose. This leads some health professionals to suggest that with no effective treatments, early diagnosis has no benefits. A significant proportion of those living with dementia have not received a formal diagnosis, which presents further challenges not least for clinical studies.
 
The amyloid hypothesis

For the past 2 decades dementia drug development has been dominated by the ‘amyloid hypothesis’, which suggests that Alzheimer’s can be treated by attacking the sticky plaques of beta amyloid protein that builds up in patients’ brains. The pharmaceutical industry has lost billions in failed development of drugs designed to target amyloid, and there is still no treatment that affects the underlying progression of the disease. In January 2018 Pfizer, the world’s largest pharmaceutical company, which has spent billions on dementia R&D, announced that it was pulling out of research into drugs to treat complex neurological disorders. Notwithstanding, many pharmaceutical companies, driven by the potential financial gains from finding a medicine that can arrest the disease of 50m people, continue to work on treatments for neurodegenerative diseases.
 
Innovative research endeavours that target dementia

The UK’s 2013 presidency of the G8, (an inter-governmental political forum comprised of the major industrialized democracies) focused on dementia. This resulted in the condition rising up global political agendas and the UK Government unlocking more money for research into neurodegenerative disorders. In 2015 the UK government with the help of JP Morgan, an American multinational investment bank, set-up the Dementia Discovery Fund, with an initial investment of £15m and the commitment from several big pharmaceutical companies to invest. The fund’s strategy was to raise £100m for dementia R&D and move beyond the amyloid hypothesis. It has invested in some 12 start-ups and projects investigating novel ways to stop or reverse the complex biological processes that lead to dementia. In November 2017 the Bill and Melinda Gates Foundation invested US$50m into the fund, which took its total to £130m. Other well-funded novel research projects include the UK Dementia Research Institute, which brings together the Medical Research Council, Alzheimer’s Society and Alzheimer’s Research UK in a £250m initiative involving more than 400 scientists, who are leading efforts to transform the treatment and care for people with dementia.
 
Takeaways

Dementia is a 21st century Damocles Sword positioned to bankrupt healthcare systems in the developed world. Dementia is a vast, fast growing global killer disease effecting about 7% of people living in wealthy nations and costing billions. Despite billions spent on dementia R&D over the past 2 decades there are no viable treatments to either slow or stop the progression of the disorder. Alcohol use has been suggested as a significant contributory factor for the onset dementia. Public policies to curb the use of alcohol are insufficient to significantly dent the vast and escalating burden of dementia. This shifts the emphasis for a solution to medicine. Despite the dearth of medical solutions, things are beginning to change with some recent novel research initiatives specifically targeting neurodegenerative disorders, which might help to lift the Damocles Sword. 

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