Introduction
Alzheimer’s disease (AD) is a neurodegenerative disease (degeneration of the neurons of the brain) with increased global prevalence. It is a chronic and progressive disease that decreases the patient’s quality of life and carries a heavy economic burden on society. The identification of factors that lead to dementia (memory loss) in AD is of paramount concern. Environmental factors play a pertinent role in neurodegenerative diseases such as AD. Alcohol acts as one of the factors that promote these diseases. It is because the brain is a prominent target for alcohol, and excessive alcohol consumption is associated with brain damage.
What Are the Underlying Mechanisms That Link Alcohol With Alzheimer's Disease?
Mild to moderate alcohol consumption may be beneficial. However, chronic (long-term) and excessive alcohol drinking leads to various problems, including an altered nervous system. Excessive amounts of ethanol (alcohol) increase Aβ and Tau protein accumulation (proteins that trigger the progression of AD). Various mechanisms implicated in alcohol causing brain damage are:
1. Glutamate-Induced Excitotoxicity: Glutamate (a neurotransmitter) plays a pivotal role in brain perception and produces an excitatory response. The response is generated following the interaction of glutamate with receptors. However, excessive activation of glutamate receptors can result in excitotoxicity (nerve cell death). In AD, there is an excess of glutamate and glutamatergic activity. Chronic alcoholism similarly affects glutamate activity.
2. Oxidative Stress: Oxidative stress leads to mitochondrial (mitochondria are cell organelles that produce energy) damage in AD and increased free radical (highly reactive molecules) production. Chronic ethanol administration in animal models supports the oxidative stress mechanism. Oxidative stress leads to brain atrophy, inflammation, and oxidative damage. Further, postmortem examination of brain tissues from alcoholics shows blood-brain barrier (BBB) dysfunction. Studies suggest that BBB is involved in AD disease mechanisms. The BBB is a selectively permeable barrier that ensures a stable brain environment and prevents foreign bodies from invading the brain. BBB dysfunction inhibits the transport of Aβ protein from the brain to the peripheral blood for removal.
3. Permanent Neuronal Damage Secondary to Malnutrition: Alcohol enters the bloodstream from the stomach within five minutes of drinking. One of the inhibitory effects of chronic alcohol use is malnutrition. Alcoholics tend to consume fewer calories and have poor nutrient absorption in the gastrointestinal tract (GIT). Research suggests that people with alcoholism obtain about 50 percent of their calories from ethanol. Alcohol inhibits many nutrients, including thiamine (vitamin B1). Thiamine serves a vital role in brain neuron development. Heavy alcohol consumption can also result in Korsakoff's syndrome (a short-term memory disorder).
4. Altered Gut Microbiota: The gut-brain axis (GBA) consists of dual communication between the central nervous system and the intestine. It links the emotional centers of the brain with the intestine. Evidence states that alcohol intake changes the microbiota (microorganisms within a specific environment) and the microbiota-gut-brain axis. Alcohol-induced microbiome alterations can cause neuroinflammation and alter the neuroimmune balance. Excessive amounts of alcohol also increase blood-brain barrier (BBB) permeability, resulting in brain damage. Further, the gut microbiota plays a role in the pathogenesis of AD. Recent research shows that probiotics may improve the symptoms of AD, suggesting a link between gastrointestinal alterations and AD.
5. Neurotoxic Effects: Ethanol metabolism leads to the formation of the active metabolite acetaldehyde. Acetaldehyde can induce DNA and nerve cell damage in the brain. One must note that the damage is reversible in acute alcohol exposure. However, chronic alcoholism leads to extensive DNA damage and chromosomal instability (risk factors for neurodegeneration). Hence, alcoholism increases the risk for cognitive impairment and dementia by structural damage to the brain through alcohol-induced chromosomal instability. Studies also show a direct and toxic effect of alcohol and its metabolites on the brain caused by free radicals, inflammatory mediators, and oxidative stress.
What Are the Effects of Alcohol on Alzheimer's Disease Pathology?
Only a few studies exist regarding the effects of alcohol on Alzheimer’s disease (AD) pathology.
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In rats, alcohol administration affects the hippocampus (a brain structure involved in learning and memory) of the brain. The hippocampus is affected early in AD by abnormal protein accumulation and neurodegeneration. Hence, it leads to the early symptom of the inability to memorize new information.
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Alcohol can enhance neuroinflammation and neurotoxicity in AD. Some studies suggest that alcohol may inhibit phagocytosis (cell-eating) of ß-amyloid by brain immune cells and promote AD.
Many studies explain risk reduction through reduced alcohol consumption for AD. However, data regarding the alcohol impact on AD pathology is contradictory.
What Is the Dual Role of Alcohol in Alzheimer's Disease?
Studies show a relationship between dementia development and progression and alcohol abuse. But, the link between alcohol consumption with cognitive outcomes is controversial. Heavy alcohol consumption is related to dementia and deterioration of cognitive function.
On the other hand, some studies suggest that low or moderate alcohol intake has a protective effect on brain cells. Some protective effects of alcohol on the brain are reduced blood thickness (called plasma viscosity) and increased high-density lipoprotein cholesterol levels (also known as good cholesterol). Studies suggest that these effects can lower the risk of dementia.
A study examining the association between moderate alcohol intake and cognitive function in women stated that less than one drink per day could reduce cognitive impairment risk. However, the effect of alcohol on AD is related to the amount, pattern, frequency, type of alcohol, nutritional state, and genetics. Concerning the protective effects of low alcohol consumption, it is not recommended to increase alcohol consumption in advancing age because:
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The results of studies depicting the positive effects of alcohol are not consistent.
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Alcohol has detrimental effects on other organs. Further, there is an increased risk of addiction in individuals.
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Individual metabolism depends on gender, body weight, the presence of enzymes for alcohol metabolism, and genetic susceptibility.
Conclusion
Alcohol consumption exists worldwide, and 50 to 75 percent of chronic alcoholics show cognitive decline and brain damage. Hence, these findings make chronic alcoholism a leading cause of dementia due to Alzheimer’s disease. Although the link between alcohol use and Alzheimer’s disease has been studied, further research can elucidate the molecular mechanisms underlying the interaction. Also, more studies are needed to clarify the causative role of alcohol intake in neurodegenerative disorders such as Alzheimer’s disease. Future research must differentiate between non-drinkers and individuals who have given up drinking in developing Alzheimer’s disease. As a result, it will lead to newer treatment modalities targeting the same.
