Gene Expression Altered By Alcohol
Lead author Dr. Douglas Feinstein and colleagues used rat microglial cells immune cells found in the brain and the spinal chord to identify which genes would be affected both by exposure to alcohol and by high levels of inflammation in said cells.
The reason they chose to work with microglial cells specifically is because these cells are normally tasked with that forms plaques in Alzheimers.
This process is known as phagocytosis, which roughly translates as the action of cells eating.
At the same time, microglial cells are known to become active when exposed to alcohol, coming to express high levels of inflammatory markers.
Taking this into account, the researchers experimented with microglial cells from rats by exposing them to alcohol, cytokines , or both alcohol and cytokines.
The exposure lasted, in each case, 24 hours, after which point Dr. Feinstein and team investigated any changes that had occurred in gene expression as a result of each of these experiments.
Also, the researchers scrutinized the effect that alcohol had on microglias ability to clear amyloid beta.
They found that 312 genes presented altered expression following exposure to alcohol only, while the same was true for 3,082 genes after cytokine-only exposure, and 3,552 genes following concomitant exposure to both cytokines and alcohol.
Dementia Or Alzheimers Like Phenotypes
Expression of TLR7, HMGB1, and microglia activation marker are increased in post-mortem human alcoholic hippocampal tissue and expression of TLR7 was correlated with alcohol intake. Consistent with human findings, TLR7, HMGB1, IL-1, TNF-, and let-b are also highly expressed in rat HEC brain slice culture following alcohol intake. Alcohol increased the release of let-7b in microglia-derived microvesicles and binding of let-7b to the chaperone HMGB1 and DAMP, and reduced the binding of let-7b to its classical target, Ago2. Together, the findings suggest that alcohol may mediate hippocampal neurodegeneration via let-7b/HMGB1/TLR7-associated signaling pathways . MicroRNA let-7b is highly expressed in CSF of AD patients . Intrathecal injection of CSF from AD patients into the CSF of wild-type mice resulted in neurodegeneration, whereas injection into CSF of mice lacking TLR7 did not result in neurodegeneration, suggesting the pivotal role of microRNAs such as let-7b in TLR7 signaling mediated CNS damage .
Is There Treatment Available
At an early stage of the disease, problems may be reduced or reversed if the person abstains from alcohol, improves their diet and replace vitamins especially thiamine and vitamin B1. Thiamine is important to limit some of the toxic effects of alcohol, and is an important supplement for heavy drinkers.
Community support is available for the person with dementia, their family and carers. This support can make a positive difference to managing dementia.
Many people who develop alcohol related dementia are young, and this can mean that they and their family and carers will need extra consideration. It may be helpful to talk to a counsellor at Dementia Australia. Contact the National Dementia Helpline on 1800 100 500.
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Alcohol Related Brain Damage
The term alcohol related brain damage incorporates a range of psychoneurological and cognitive conditions that are associated with long-term alcohol misuse and related vitamin deficiencies. At one extreme is WernickeKorsakoff syndrome and at the other, the more frequent milder and often less obvious subtle dysfunctions of executive and memory processes due to the vulnerability of the frontal lobe and hippocampus to adverse effects of alcohol. Notably, these regions are especially vulnerable to A pathology.
Parkinsons Disease And Alcohol: Your Guide
If you have Parkinsons disease , you may be wondering whether alcohol consumption affects the development or progression of your condition. Some people may wonder if they should avoid drinking completely. As one MyParkinsonsTeam member asked, How does alcohol affect Parkinsons how much can I drink? Or should I avoid drinking altogether?
Some studies havent found that small amounts of alcohol are associated with a higher PD risk, while others highlight the dangers alcohol can pose for anyone with a chronic condition. In addition, there may be adverse interactions between alcohol and common Parkinsons medications. Because of conflicting information, people with PD may feel confused about whether or not to drink.
Ive been told by more than one doctor that I should not have any alcohol, one MyParkinsonsTeam member wrote. And at this point, I dont remember which doctor or specifically why.
So, how do you decide what approach to take?
If you have Parkinsons disease and are trying to decide whether or not to reduce your drinking or quit alcohol completely here are some things to consider.
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Inadequate Ability To Absorb Nutrients
The current research and understanding of Wernicke-Korsakoff syndrome and memory damage due to alcohol has to do with how alcohol affects the individuals ability to absorb nutrients. Specifically, the development of Wernicke-Korsakoff syndrome in general is the result of inadequate levels of thiamine, or B1, as explained by the National Library of Medicine. This deficiency can be caused by alcohol interrupting the bodys ability to absorb thiamine from the diet, leading to inadequate levels of the vitamin in the body.
While the relationship between thiamine and memory isnt fully understood, what is apparent is that a deficiency in this essential vitamin interrupts the brains ability to recall old memories or create new ones.
What Is The Current Advice
According to the UK chief medical officers, we should stick to drinking no more than 14 units of alcohol a week. This keeps health risks to a low and safe level.
- Large glass of wine – 3 units
- Pint of higher-strength lager or beer – 3 units
- Standard glass of wine – 2 units
- Pint of lower-strength lager or beer – 2 units
- Bottle of lager or beer – 1.7 units
- Single shot of spirits – 1 unit
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How Much Alcohol Is Too Much Alcohol
A unit is a measure of alcohol. You can find out how many units are in an alcoholic drink by reading the label. The NHS recommends not drinking more than 14 units of alcohol each week. This should ideally be spread over three or more days because binge-drinking is particularly harmful to the brain.
When a person starts drinking more than around 25 units per week on a regular basis, it may start to affect their ability to think and function properly.
Drinking a large amount of alcohol in a short space of time is known as binge-drinking. It is equivalent to drinking 8 units or more for men and 6 units or more for women. It has been suggested that older people should have lower limits because they are at greater risk of the damaging effects of alcohol.
Get support with ARBD
Light To Moderate Amounts Of Alcohol
Moderate alcohol drinking is classified as drinking one alcoholic drink a day for women and two a day for men. Light drinking describes those who drink less than moderate drinkers but more than those who totally abstain from alcohol.
In a study that involved over 3000 adults over the age of 75, light to moderate drinking was associated with a 42% lower risk of Alzheimer’s disease and a 29% lower risk of all types of dementia.
One study found that among women who were over the age of 90, a decrease in alcohol consumption was associated with an increase in the development of mild cognitive impairment and dementia.
Another study considered how alcohol consumption affected people with a diagnosis of mild cognitive impairment . This study demonstrated that light to moderate alcohol consumption was associated with a decreased chance of mild cognitive impairment progressing into full dementia. Participants who never drank alcohol had a higher chance of developing dementia than those who were light to moderate drinkers, while heavy drinkers were the most likely to progress to dementia.
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Testing And Treatment For Alcoholic Dementia
There are several medical tests that can be performed to help determine if a person has alcoholic dementia. Examining a persons nervous and muscular system can help shed light on any nerve damage caused by alcoholic dementia. Many physicians will also administer blood tests to test a persons nutrition levels.
Tests that may be used to diagnose alcoholic dementia include:
- nervous/muscular system testing, such as looking for abnormal eye movement, increased pulse, muscle weakness, and low blood pressure
- blood testing to detect vitamin B1 levels and transketolase activity
- liver enzyme testing
If alcoholic dementia is detected and still in the early stages, significant improvement may be made through treatment. Quitting drinking is often the first step in treating this condition. Additionally, thiamine may be administered to improve eye movement and vision problems, confusion, and muscle coordination.
Improvement can take several weeks or months to be felt, and many people will remain in the hospital or treatment facility until their major symptoms subside. Individuals who have been diagnosed with Wernicke-Korsakoff syndrome may never regain complete cognitive function.
What Is Moderate Alcohol Consumption
These reviews typically defined moderate alcohol consumption as 1-14 units of alcohol per week for women and 1-21 units a week for men. NHS guidelines published in 2016 state that both men and women should limit their intake to 14 units a week. A unit is dependent on the amount of pure alcohol in a given volume and can be calculated for specific drinks here. According to the NHS, a basic guideline for units of alcohol is as follows:
- A typical glass of wine: 2 units
- A pint of lower alcohol beer or cider: 2 units
- A pint of higher alcohol beer or cider: 3 units
- A single shot of spirits such as whisky, gin or vodka : 1 unit
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Majority Reported Passing Out From Drinking
Scientists examined seven European cohort studies from the U.K., France, Sweden, and Finland to include 131,415 people.
The participants, aged between 18 and 77 years, werent diagnosed with dementia during the years when they reported their alcohol consumption .
At follow-up, an average of 14 years later, they were examined for symptoms of dementia.
Over 96,000 people in this group reported passing out due to alcohol. Of these, over 10,000 reported having lost consciousness from drinking in the past year.
Binge drinking tends to be most problematic among college aged youth and young adults, Dr. Scott Krakower, unit chief of psychiatry at Zucker Hillside Hospital, Glen Oaks, New York, told Healthline.
The moderate drinkers who hadnt passed out while drinking were used as the reference group. Compared with other participants, those who reported alcohol-induced loss of consciousness were more likely to drink hard liquor and beer, rather than wine.
After excluding participants with early or late onset Alzheimers, and cardiovascular conditions to find risk of cognitive impairment, the study authors concluded, The findings of this study suggest that alcohol-induced loss of consciousness, irrespective of overall alcohol consumption, is associated with a subsequent increase in the risk of dementia.
Can Alcoholic Amnesia Be Reversed
Individuals who experience blackouts based on binge drinking are generally unable to recover those memories, but they do not usually have other memory issues afterward. Unfortunately, this is not the case with the long-term damage of alcoholic amnestic disorders. The National Library of Medicine explains that the brain damage caused by thiamine deficiency resulting from alcohol abuse is generally permanent damage to those areas of the brain. In other words, the memories lost will not return, and the inability to learn or form new memories will not diminish. According to a study from Innovations in Clinical Neuroscience, 80 percent of people who are diagnosed with Wernicke-Korsakoff syndrome end up with a permanent memory disorder.
Permanent memory loss and damage to memory and learning centers is a life-changing situation. People who struggle with this condition are likely to need ongoing care to function. Many people who develop this condition are not diagnosed until it has reached a dangerous point. Death can result from this disorder over time. Because of the severity of this conditions effect on quality of life and long-term health, it is important to recognize the risks of this disorder and stop drinking alcohol if the risk of developing Wernicke-Korsakoff syndrome is high.
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Alcohol Cytokines And The Peripheral Immune System
Alcohol affects both cytokines and the peripheral immune system. Alcohol-induced neuroinflammation includes increased brain levels of pro-inflammatory cytokines interleukin 1 and tumour necrosis factor alpha . Reduced anti-inflammatory cytokine IL-10 have been observed in response to chronic high alcohol administration in short-term pre-clinical models. Notably, these persisted for several days while peripheral circulating plasma cytokines were undetectable, favouring a pro-inflammatory milieu in the brain .
In pre-clinical models, the impact of ethanol may have dichotomous effects on the peripheral immune system depending on the concentrationhaving a suppressive effect at high and stimulatory effect at low concentration .
Clinical studies show that serum pro-inflammatory cytokines have been increased in patients with chronic alcoholism . Increased pro-inflammatory and anti-inflammatory cytokines early in abstinence have been described , as has increased pro-inflammatory cytokine production by dendritic cells from alcohol-dependent participants. In addition to the pathways above, peripheral inflammation is highly likely due to alcohol-related increase in gut bacteria translocation. These peripheral cytokines are known to affect microglial phenotypes .
American Addiction Centers Inc
- Inability to remember recent events
- Lack of awareness that there are problems with memory
- Confabulation, or making up information that has been forgotten
The individual who is confabulating to fill in missing information may not be lying in the literal sense of the word. Instead, the person may truly believe that the confabulated memories are real. There is little understanding of why confabulation occurs in Wernicke-Korsakoff syndrome.
A study from the International Journal of Geriatric Psychiatry indicates there are other, problematic behavioral symptoms that can occur with alcoholic amnestic disorder, including aggression, agitation, and depression. However, not much is known about how these symptoms are connected and whether or not there are ways to support individuals with these symptoms.
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Is There A Treatment Or Cure
While theres no cure, and most forms of dementia are irreversible,2 alcohol-related dementia is an exception.1
If the disease is diagnosed early enough, symptoms may be improved or reversed if the person stops drinking alcohol and starts replacing thiamine in the body.1
To reduce the risk of all health problems related to alcohol, the National Health and Medical Research Council of Australia recommends adults drink no more than 10 standard drinks per week.10
If youre worried about a friend or family member who is experiencing memory problems, confusion and/or personality changes, take them to see their doctor or a medical professional.
Early dementia diagnosis can help the person and their family understand, manage and treat the condition.
For more information on dementia and alcohol-related dementia, visit Dementia Australia.
Alcohol Aids Accumulation Of Harmful Protein
That being said, only very few genes played a role in both the phagocytosis of amyloid beta and inflammatory processes at cellular level.
Among the genes we saw altered were many involved in phagocytosis, says Dr. Feinstein, which is the first time this has been shown.
While these studies were performed in isolated cells, he goes on to explain, our results suggest that alcohol impedes the ability of microglia to keep the brain clear of amyloid beta and may contribute to the development of Alzheimers disease.
Importantly, when the team tried exposing the microglia to alcohol levels consistent with those that might be seen in humans who binge drink or who have a heavy drinking habit they saw that the microglial cells ability to clear amyloid beta was suppressed by approximately 15 percent following only 1 hour of exposure.
This led the researchers to conclude that it may be impaired microglial phagocytosis due to the effect of alcohol that could leave the brain vulnerable to neurodegeneration.
We didnt continue the study to see whether phagocytosis was further impaired after longer exposures to alcohol, but it appears that these changes in microglial cells could be a contributing factor to the development of Alzheimers disease.
Dr. Douglas Feinstein
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Scope Of The Systematic Search
Following the PRISMA guidelines , a systematic search was performed by using OVID to identify all systematic reviews published from January 2000 to October 2017 on Medline, Embase, and PsycINFO and by using a combination of keywords and Medical Subject Headings terms related to alcohol use, dementia, AD, brain function, memory, and cognitive health. Additional file : Tables S1 to S3 in the Additional file outline the exact search strategy used for each database a PRISMA checklist is also provided in the Additional file . The World Alzheimer Reports were additionally used to identify potential systematic reviews . A systematic search of grey literature was performed via Google but provided no contributions which fulfilled our inclusion criteria . It is highly unlikely that systematic reviews and meta-analyses would not be published in scientific journals .
What Is Alcoholic Dementia
Alcoholic dementia involves memory loss and a variety of other cognitive impairments.
Both short- and long-term memory is affected by alcoholic dementia. This means its challenging to learn new information and remember things already learned.
Along with memory issues, there are a host of other cognitive issues.
The Diagnostic and Statistical Manual of Mental Disorders is the official handbook used by the American Psychiatric Association.
According to the DSM-V, a person with alcoholic dementia may exhibit memory impairment and one or more of these cognitive impairments1:
- Aphasia Loss of ability to use or understand spoken or written language
- Inability to perform specific physical actions despite will and knowledge to do so and relevant muscles being intact
- Agnosia Failure to recognize individuals, objects, or sounds, despite senses being functional
- Executive Functioning Deficits Impaired ability to plan, organize, or think abstractly
Aphasia seems to be less common with alcoholic dementia compared to other dementias.9
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