1
Exploring the Impact of Alcohol Abuse on Cognitive Decline
Name of Student
Course
Institution Name
Name of Instructor
Due Date
2
Exploring the Impact of Alcohol Abuse on Cognitive Decline
Alcoholism is a disease characterized by uncontrolled preoccupation with alcohol and
drinking. Alcoholism usually stems from habitual and chronic alcohol consumption which leads
to physical and psychological dependence. Chronic alcohol use disorder is associated with a
myriad of harmful health implications, including liver diseases (steatosis, hepatitis and cirrhosis),
cardiovascular diseases, malnutrition, and neurological disorders (Zahr et al., 2011). Studies have
clearly elucidated the effects of alcohol on the brain, both on acute and chronic use. According to
Woods et al., alcohol’s direct effects on the brain include depression of central nervous system
(CNS) activity, alterations in cerebrovascular function, and neurotoxicity (2016). Alcohol also
has well-documented neurocognitive effects on the brain.
Cognition can be defined as the mental processes related to acquiring, processing,
storing, and using information. Cognitive brain functions include learning, comprehension,
perception, attention, memory, expression, language, communication, and execution (Yen et al.,
2022). Cognition utilizes key neurotransmitters including glutamate and acetylcholine, which are
vital for memory and learning; serotonin, which impacts mood and emotion regulation; and
dopamine, which is linked to reward and motivation. Several brain structures are crucial for
cognition including the prefrontal cortex which governs executive functions like decisionmaking, the hippocampus which is crucial for memory consolidation, the amygdala which is
responsible for processing emotions, and the thalamus which relays sensory information needed
for cognitive processes.
Alcohol-mediated cognitive impairment will therefore affect important mental functions
such decision-making, potentially leading to severe morbidity and mortality outcomes. Martin et
al. (1986) report that following neuropsychological testing, 50 to 70 percent of individuals with
3
alcohol use disorder exhibited cognitive deficits. Other than neurotoxicity from ethanol, chronic
alcohol use can also affect the brain indirectly through coexisting nutritional deficiency, liver
disease, or trauma. The detrimental impact of alcoholism on cognitive brain functions
underscores the significant threat it poses to the health of individuals as well as the need to
address it to reduce fatal outcomes.
Underlying Neurobiological Mechanisms in Alcohol Brain Damage
Neuroinflammation
Chronic alcohol consumption usually induces complex, multi-organ responses such as the
activation of a variety of immune responses. In the brain, alcohol use can mediate cognitive
decline by inducing neuroinflammation. In alcohol-related brain damage (ARBD), the activation
of certain brain cells such as the microglia leads to the release of proinflammatory cytokines
which mediate neuroinflammation (Zahr et al., 2011). In a study cited by Zahr et al. (2011),
findings reported various patterns of positive signs of neuroinflammation in the ventral tegmental
area, substantia nigra, and hippocampus of alcoholic individuals. When used on a chronic basis,
alcohol will induce the infiltration of inflammatory mediators into the CNS, and these, in turn,
will cause cytokine expression and microglial activation. Inflamed neurons are eventually
degenerated, contributing to neuronal and brain damage which is usually seen in imaging
techniques such as compute tomography (CT), and magnetic resonance imaging (MRI) scans.
Nutritional Deficiency
Alcohol-related brain damage can also be mediated through nutritional deficiency,
particularly thiamine (vitamin B1), whose deficiency famously leads to Wernicke’s
encephalopathy. If diagnosed early, Wernicke’s encephalopathy (WE) can be reversed by the
administration of parenteral thiamine; however, when inadequately treated, it progresses to the
4
chronic disease state, Korsakoff’s Syndrome (KS) (Thomson et al., 2012). Thiamine deficiency
in alcoholism can result from several factors. The first factor is poor nutrition among alcoholics.
This is because alcoholics typically have poor feeding habits, underscored by a glaring lack of a
well-balanced diet. The second factor is impaired absorption of thiamine from the
gastrointestinal tract. Impaired absorption results from alcohol-induced damage to the intestine
lining, which subsequently inhibits the thiamine transport and absorption mechanism in the gut.
The third factor leading to thiamine deficiency is the depletion of liver stores. This is usually due
to a reduction in the rate of conversion of thiamine into the active metabolite, thiamine
pyrophosphate (TPP) (Zahr et al., 2011).
Usually, one or more of the three factors is implicated in the development of Wernicke’s
encephalopathy. Ultimately, diminished levels of thiamine pyrophosphate – the active form of
the vitamin – disrupts several metabolic processes occurring in the neurons. TPP deficiency
interrupts energy production by interfering with the Kreb’s cycle and the pentose-phosphatepathway (PPP) in carbohydrate metabolism. TPP inadequacy also disrupts lipid metabolism
which consequently hinders adequate production of myelin which is an integral sheath for
neurons. Finally, TPP deficiency hampers protein metabolism which interferes with the
production of glucose-derived neurotransmitters (Zahr et al., 2011). The disruption in the
aforementioned metabolic processes leads to a deficiency of essential biomolecules required for
normal neuronal cell functioning. Therefore, the metabolic deficits can contribute to neuronal
and white matter damage.
Ethanol Neurotoxicity
Ethanol can mediate direct neurotoxic effects through its metabolites. In the brain,
methanol is degraded into different metabolites such as acetaldehyde and ethyl esters. In chronic
5
alcohol use, these metabolites can accumulate to toxic levels which may then interrupt important
cellular processes such as mitochondrial function. This subsequently leads to neuronal cell death.
Acetaldehyde can also form adducts with cellular proteins, which in turn can activate
neuroinflammation, causing cell degeneration. Ethanol also induces the generation of reactive
oxygen species (ROS) in the neurons which can catalyze the degradation of essential cellular
biomolecules such as the DNA. This can impair gene expression and protein synthesis,
subsequently leading to neuronal cell death. According to Zahr et al. (2011), ethanol can also
reduce the levels of brain-derived neurotrophic factor (BDNF) thereby impairing intracellular
signaling pathways involved in cell survival, hence enhancing neuronal cell death. Finally,
according to Thomson et al., repeated bouts of drinking and withdrawal are likely to lead to
glutamate-induced excitability which results in lasting neuronal damage (2012).
Liver Dysfunction
Chronic alcohol use can severely impact the liver, causing alcoholic fatty liver disease,
alcoholic hepatitis, cirrhosis and liver failure. Alcohol-induced liver damage impairs the liver's
ability to eliminate neurotoxic substances like ammonia and manganese. The compromised liver
fails to efficiently clear these substances from the bloodstream. Elevated ammonia levels can
disrupt cerebral blood flow, metabolism, and astrocytic function, adversely impacting brain
function. Similarly, elevated levels of manganese, resulting from impaired liver function, can
negatively affect the dopaminergic system, intensify oxidative stress, and induce neurotoxicity
(Zahr et al., 2011). Consequently, alcohol-related brain damage is mediated through the liver's
inability to detoxify harmful substances, allowing the accumulation of these neurotoxins to levels
that disrupt normal cell function and induce cell death. This leads to brain damage and ultimately
contributes to cognitive impairment.
6
Risk Factors to Brain Damage in Alcohol Use
Age
Advanced age serves as a risk factor to may human diseases, including cognitive decline.
Yen et al. (2022) claim that the rate of cognitive impairment and dementia increases with age,
with about 4–19% of persons aged 65 years or older having cognitive impairment. Woods et al.,
on the other hand, reported that older individuals who were heavy drinkers “exhibited greater
cognitive deficits as a function of age compared to younger current heavy drinkers and compared
to adults who were current nonheavy drinkers or abstainers” (2016). Alcohol-associated
cognitive decline in older individuals can result from several factors such as age-related
physiological changes, decreased liver function, and altered metabolism, leading to prolonged
exposure to alcohol. Decreased liver and physiological functions would therefore result in the
accumulation of toxic substances such as acetaldehyde which mediate neurodegeneration
through inflammation and direct neurotoxicity. Additionally, aging brains experience diminished
neuroplasticity, making them more prone to cognitive decline and structural damage caused by
excessive alcohol consumption. At the same time, older individuals are more likely to have
comorbid conditions such as hypertension and diabetes which have been linked to elevated risk
of ARBD. These factors heighten the risk of developing alcohol-related brain disorders,
emphasizing the importance of age-sensitive interventions for mitigating potential cognitive
impairments in the elderly.
Comorbidities
Comorbid conditions such as diabetes, hypertension, cardiovascular diseases, and chronic
kidney disease significantly increase the risk of cognitive impairment. Comorbidities amplify the
risk of alcohol-related brain disorders, either by synergistically exacerbating the detrimental
7
effects of alcohol or by contributing to an underlying cognitive impairment. In patients with
diabetes, cognitive decline is associated with hyperglycemia and insulin resistance, with research
evidence showing a higher risk of new-onset cognitive impairment among diabetic individuals as
compared to non-diabetics (Yen et al., 2022). This could be because insulin resistance – a
prominent feature in diabetes – can impair regional glucose metabolism and utilization in the
brain.
Hypertension, in turn, can cause cognitive decline by increasing the risk of stroke and
cerebral white matter lesions. Further, hypertension is one of the leading causes of global
dementia. Atherosclerosis, arterial stiffness, and hypoperfusion of the brain are all hypertensionassociated factors that mediate neuronal injury. Notably, heavy alcohol intake is associated with
increased hypertension incidence. Chronic kidney disease is usually associated with
accompanied risks of cardiovascular diseases and accumulation of uremic metabolites which
significantly increase the risk of neurodegeneration and cognitive dysfunction. In their study,
Yen et al. posited that moderate to heavy alcohol consumption can potentially aggravate brain
injury caused by comorbid conditions. They concluded that “moderate to heavy alcohol drinking
was associated with a higher risk of cognitive impairment compared to light drinking” among
patients with diabetes, hypertension and CKD (2022).
Genetic Factors
Genetics can significantly influence susceptibility to alcohol-related cognitive decline
(Yen et al., 2022). Genetics play an important role in determining factors that influence an
individual's response to alcohol such as metabolism, tolerance, and predisposition to addiction.
For example, individuals who are genetically predisposed to alcohol addiction are more likely to
become chronic alcohol abusers and hence more likely to experience cognitive decline associated
8
with ethanol consumption. Furthermore, genetic variations in enzymes involved in alcohol
metabolism, neurotransmitter systems, and neuronal pathways contribute to diverse reactions to
alcohol exposure. For example, individuals who are slow-acetylators will metabolize alcohol
much less efficiently, leaving room for accumulation of toxic metabolites upon chronic, heavy
ethanol consumption. These toxic metabolites would in turn mediate neurodegeneration through
adduct formation or generation of reactive oxygen species. Understanding genetic factors is
therefore crucial for targeted prevention and personalized interventions to mitigate the
neurological consequences of alcohol consumption.
Clinical Features of Alcohol-mediated Cognitive Decline
Cognitive decline resulting from chronic alcohol abuse can present with different clinical
pictures, including dementia, Wernicke’s encephalopathy, and Korsakoff syndrome. Dementia is
a disorder characterized by a decline in cognitive brain functions such as learning, memory,
language, and executive functions. Koch et al. (2019) elaborate that alcohol consumption can be
a significant risk factor to dementia, and that “the associations of alcohol consumption with
dementia risk may vary with the absence or presence of apolipoprotein E.” There are several
causes of dementia but the clinical features are typically similar. Common symptoms include
memory impairment, language difficulties, inability to handle complex tasks, altered behavior,
and impaired reasoning.
Wernicke’s encephalopathy is an acute neurologic disorder caused by thiamine
deficiency. It typically manifests through a clinical triad of encephalopathy – which is
characterized by profound disorientation, indifference, and inattentiveness – oculomotor
dysfunction, and gait ataxia. The prognosis of Wernicke’s encephalopathy is usually good if
9
thiamine is promptly administered to a patient with an acute alcohol intoxication, as clinical
improvement is usually experienced within hours to days (Thomson et al., 2012).
Korsakoff syndrome (KS) can be categorized as a late neuropsychiatric manifestation of
Wernicke’s encephalopathy. KS primarily affects the language aspect of cognition, with its
hallmark feature being selective anterograde and retrograde amnesia. Confabulation is also a
common feature in KS. It is imperative to note that other cognitive aspects such as attention and
social behavior remain relatively intact in KS. Importantly, most patients with KS do not attain
complete recovery, with many requiring at least some form of supervision and social support.
Conclusion
Chronic alcohol abuse poses a significant threat to cognitive function, impacting vital
brain structures and neurotransmitter systems. The neurobiological mechanisms underlying
alcohol-related brain damage involve neuroinflammation, nutritional deficiency, ethanol
neurotoxicity, and liver dysfunction. These factors contribute to cognitive impairment by
inducing neuronal cell death and disrupting essential metabolic processes. Age, comorbidities,
and genetic factors further amplify the risk of alcohol-mediated cognitive decline. Clinical
picture of cognitive decline include dementia, Wernicke’s encephalopathy, and Korsakoff
syndrome, each of which presents with distinct symptoms and mandate unique treatment
measures. Recognizing the intricate interplay of the associated risk factors is crucial for targeted
prevention and personalized interventions to mitigate the neurological consequences of alcohol
consumption. Addressing alcoholism not only promotes individual well-being but also
contributes to reducing the societal burden of cognitive decline and associated disorders.
10
References
Koch, M., Fitzpatrick, A. L., Rapp, S. R., Nahin, R. L., Williamson, J. D., Lopez, O. L., ... &
Sink, K. M. (2019). Alcohol consumption and risk of dementia and cognitive decline
among older adults with or without mild cognitive impairment. JAMA Network
Open, 2(9), e1910319-e1910319. doi:10.1001/jamanetworkopen.2019.10319
Martin, P. R., Adinoff, B., Weingartner, H., Mukherjee, A. B., & Eckardt, M. J. (1986).
Alcoholic organic brain disease: nosology and pathophysiologic mechanisms. Progress in
Neuro-Psychopharmacology and Biological Psychiatry, 10(2), 147-164.
Thomson, A. D., Guerrini, I., & Marshall, E. J. (2012). The evolution and treatment of
Korsakoff's syndrome: out of sight, out of mind?. Neuropsychology review, 22, 81-92.
https://doi.org/10.1007/s11065-012-9196-z
Woods, A. J., Porges, E. C., Bryant, V. E., Seider, T., Gongvatana, A., Kahler, C. W., ... &
Cohen, R. A. (2016). Current heavy alcohol consumption is associated with greater
cognitive impairment in older adults. Alcoholism: clinical and experimental
research, 40(11), 2435-2444. https://doi.org/10.1111/acer.13211
Yen, F. S., Wang, S. I., Lin, S. Y., Chao, Y. H., & Wei, J. C. C. (2022). The Impact of Alcohol
Consumption on Cognitive Impairment in Patients With Diabetes, Hypertension, or
Chronic Kidney Disease. Frontiers in Medicine, 9,
861145. doi: 10.3389/fmed.2022.861145
Zahr, N. M., Kaufman, K. L., & Harper, C. G. (2011). Clinical and pathological features of
alcohol-related brain damage. Nature Reviews Neurology, 7(5), 284-294.
https://doi.org/10.1038/nrneurol.2011.42