The long-term impact of alcohol on the brain encompasses a wide range of effects, varying by drinking patterns, age, genetics, and other health factors. Among the many organs alcohol affects, the brain is particularly vulnerable. Heavy drinking causes alcohol-related brain damage, with alcohol acting as a direct neurotoxin to nerve cells, while low levels of alcohol consumption can cause decreases in brain volume, regional gray matter volume, and white matter microstructure. Low-to-moderate alcohol intake may be associated with certain cognitive benefits or neuroprotection in older adults. Social and psychological factors can offer minor protective effects. The overall relationship between alcohol use and brain health is complex, reflecting the balance between alcohol's neurotoxic effects and potential modulatory influences.
Classification
The neurological consequences of long-term alcohol use can be broadly classified into harmful outcomes (e.g., brain atrophy, cognitive decline, dementia), potential neutral effects, and, in limited cases, minor protective effects associated with low-to-moderate consumption. Severe manifestations are often categorized under alcohol-related brain damage (ARBD), including conditions such as Wernicke-Korsakoff syndrome and alcohol-related dementia.
Alcoholics can typically be divided into two categories, uncomplicated and complicated.
Uncomplicated alcoholics do not have nutritional deficiency states or liver disease, but have a reduction in overall brain volume due to
white matter
White matter refers to areas of the central nervous system that are mainly made up of myelinated axons, also called Nerve tract, tracts. Long thought to be passive tissue, white matter affects learning and brain functions, modulating the distr ...
cerebral atrophy. The severity of atrophy sustained from alcohol consumption is proportional to the rate and amount of alcohol consumed during a person's life.
Complicated alcoholics may have liver damage that impacts brain structure and function and nutritional deficiencies "that can cause severe brain damage and dysfunction".
Characteristics

Excessive alcohol consumption is associated with widespread and significant brain
lesion
A lesion is any damage or abnormal change in the tissue of an organism, usually caused by injury or diseases. The term ''Lesion'' is derived from the Latin meaning "injury". Lesions may occur in both plants and animals.
Types
There is no de ...
s, specifically damage to brain regions including the
frontal lobe
The frontal lobe is the largest of the four major lobes of the brain in mammals, and is located at the front of each cerebral hemisphere (in front of the parietal lobe and the temporal lobe). It is parted from the parietal lobe by a Sulcus (neur ...
,
limbic system
The limbic system, also known as the paleomammalian cortex, is a set of brain structures located on both sides of the thalamus, immediately beneath the medial temporal lobe of the cerebrum primarily in the forebrain.Schacter, Daniel L. 2012. ''P ...
, and
cerebellum
The cerebellum (: cerebella or cerebellums; Latin for 'little brain') is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as it or eve ...
,
with widespread
cerebral atrophy, or brain shrinkage caused by
neuron degeneration. This damage can be seen on neuroimaging scans. Alcohol alters both the structure and function of the brain as a result of the direct
neurotoxic
Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specifical ...
effects of
alcohol intoxication
Alcohol intoxication, commonly described in higher doses as drunkenness or inebriation, and known in overdose as alcohol poisoning, is the behavior and physical effects caused by recent consumption of Alcohol (drug), alcohol. The technical ter ...
or acute alcohol withdrawal. Increased
alcohol
Alcohol may refer to:
Common uses
* Alcohol (chemistry), a class of compounds
* Ethanol, one of several alcohols, commonly known as alcohol in everyday life
** Alcohol (drug), intoxicant found in alcoholic beverages
** Alcoholic beverage, an alco ...
intake is associated with damage to brain regions including the
frontal lobe
The frontal lobe is the largest of the four major lobes of the brain in mammals, and is located at the front of each cerebral hemisphere (in front of the parietal lobe and the temporal lobe). It is parted from the parietal lobe by a Sulcus (neur ...
,
limbic system
The limbic system, also known as the paleomammalian cortex, is a set of brain structures located on both sides of the thalamus, immediately beneath the medial temporal lobe of the cerebrum primarily in the forebrain.Schacter, Daniel L. 2012. ''P ...
, and
cerebellum
The cerebellum (: cerebella or cerebellums; Latin for 'little brain') is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as it or eve ...
,
with widespread
cerebral atrophy, or brain shrinkage caused by
neuron degeneration. Frontal lobe damage becomes the most prominent as alcoholics age and can lead to impaired neuropsychological performance in areas such as problem solving, good judgment, and goal-directed behaviors.
Impaired emotional processing results from damage to the limbic system. This may lead to troubles recognizing emotional facial expressions and "interpreting nonverbal emotional cues".
The effects can manifest much later—mid-life Alcohol Use Disorder has been found to correlate with increased risk of severe cognitive and memory deficits in later life.
Alcohol consumption can substantially impair
neurobiologically-beneficial and -demanding exercise.
In some cases occasional moderate consumption may have ancillary benefits on the brain due to social and psychological benefits if compared to alcohol abstinence and soberness. Researchers have found that moderate
alcohol
Alcohol may refer to:
Common uses
* Alcohol (chemistry), a class of compounds
* Ethanol, one of several alcohols, commonly known as alcohol in everyday life
** Alcohol (drug), intoxicant found in alcoholic beverages
** Alcoholic beverage, an alco ...
consumption in older adults is associated with better cognition and well-being than abstinence.
Complications
Serious complications include irreversible brain damage, psychiatric disorders (e.g., depression, anxiety), and increased risk of other neurodegenerative conditions, such as Alzheimer's disease.
Causes
Alcohol is known to have direct
neurotoxic
Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specifical ...
effects on brain matter, both during
alcohol intoxication
Alcohol intoxication, commonly described in higher doses as drunkenness or inebriation, and known in overdose as alcohol poisoning, is the behavior and physical effects caused by recent consumption of Alcohol (drug), alcohol. The technical ter ...
and alcohol withdrawal. While the extent of causation is difficult to prove, alcohol intake – even at levels often considered to be low – "is negatively associated with global brain volume measures, regional gray matter volumes, and white matter microstructure" and these associations become stronger as alcohol intake increases.
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Alcohol related brain damage is not only due to the direct toxic effects of alcohol; alcohol withdrawal, nutritional deficiency, electrolyte disturbances, and liver damage are also believed to contribute to alcohol-related brain damage.
Binge drinking
Binge drinking
Binge drinking, or heavy episodic drinking, is drinking alcoholic beverages with an intention of becoming intoxicated by heavy consumption of alcohol over a short period of time, but definitions vary considerably.
Binge drinking is a style of ...
, or heavy episodic drinking, can lead to damage in the limbic system that occurs after a relatively short period of time. This brain damage increases the risk of
alcohol-related dementia, and abnormalities in mood and cognitive abilities. Binge drinkers also have an increased risk of developing chronic alcoholism.
Alcoholism
Alcoholism is the continued drinking of alcohol despite it causing problems. Some definitions require evidence of dependence and withdrawal. Problematic use of alcohol has been mentioned in the earliest historical records. The World He ...
is a chronic relapsing disorder that can include extended periods of abstinence followed by relapse to heavy drinking. It is also associated with many other health problems including
memory disorders
Memory disorders are the result of damage to neuroanatomical structures that hinders the storage, retention and recollection of Memory, memories. Memory disorders can be progressive, including Alzheimer's disease, or they can be immediate including ...
,
high blood pressure
Hypertension, also known as high blood pressure, is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms itself. It is, however, a major ri ...
, muscle weakness, heart problems,
anaemia
Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availab ...
, low immune function,
liver disease
Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common.
Liver diseases
File:Ground gla ...
, disorders of the digestive system, and pancreatic problems. It has also been correlated with
depression, unemployment, and family problems with an increased risk of domestic abuse.
It is unclear how the frequency and length of binge drinking sessions impacts brain damage in humans. Humans who drank at least 100 drinks (male) or 80 drinks (female) per month (concentrated to 21 occasions or less per month) throughout a three-year period had impaired decision-making skills compared to non-binge drinkers.
Thiamine deficiency
Thiamine
Thiamine, also known as thiamin and vitamin B1, is a vitamin – an Nutrient#Micronutrients, essential micronutrient for humans and animals. It is found in food and commercially synthesized to be a dietary supplement or medication. Phosp ...
is a vitamin the body needs for growth, development, and cellular function, as well as converting food into energy. Thiamine is naturally present in some foods, added to some food products, and available as a dietary supplement. A nutritional deficiency in thiamine can worsen alcohol-related brain damage. There is a genetic component to
thiamine deficiency
Thiamine deficiency is a medical condition of low levels of thiamine (vitamin B1). A severe and chronic form is known as beriberi. The name beriberi was possibly borrowed in the 18th century from the Sinhala language, Sinhalese phrase (bæri ...
that causes intestinal
malabsorption
Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal (GI) tract. Impairment can be of single or multiple nutrients depending on the abnormality. This may lead to malnutrition and a varie ...
.
A nutritional vitamin deficiency state that is caused by thiamine deficiency which is seen most commonly in alcoholics leads to
Wernicke's encephalopathy and
Alcoholic Korsakoff syndrome (AKS) which frequently occur simultaneously, known as
Wernicke–Korsakoff syndrome
Wernicke-Korsakoff syndrome (WKS), colloquially referred to as wet brain syndrome, is the combined presence of Wernicke encephalopathy (WE) and Korsakoff syndrome. Due to the close relationship between these two disorders, people with either ar ...
(WKS). This disorder is preventable through supplementation of the diet by thiamine and an awareness by health professionals to treat 'at risk' patients with thiamine.
Thiamine deficiency may occur in upwards of 80% of patients with alcoholism however, only ≈13% of such individuals develop WKS, raising the possibility that a genetic predisposition to WKS may exist in some individuals.
Lesions
A lesion is any damage or abnormal change in the tissue of an organism, usually caused by injury or diseases. The term ''Lesion'' is derived from the Latin meaning "injury". Lesions may occur in both plants and animals.
Types
There is no de ...
, or brain abnormalities, are typically located in the
diencephalon
In the human brain, the diencephalon (or interbrain) is a division of the forebrain (embryonic ''prosencephalon''). It is situated between the telencephalon and the midbrain (embryonic ''mesencephalon''). The diencephalon has also been known as t ...
which result in
anterograde and
retrograde amnesia
In neurology, retrograde amnesia (RA) is the inability to access memories or information from before an injury or disease occurred. RA differs from a similar condition called anterograde amnesia (AA), which is the inability to form new memories f ...
, or memory loss.
Mechanisms of action

Alcohol affects the brain through multiple mechanisms. The cerebral atrophy that alcoholics often present with is due to alcohol induced neurotoxicity.
Evidence of neurodegeneration can be supported by an increased
microglia
Microglia are a type of glia, glial cell located throughout the brain and spinal cord of the central nervous system (CNS). Microglia account for about around 5–10% of cells found within the brain. As the resident macrophage cells, they act as t ...
density and expression of proinflammatory cytokines in the brain. Animal studies find that heavy and regular binge drinking causes neurodegeneration in corticolimbic brain regions areas which are involved in learning and spatial memory. The corticolimbic brain regions affected include the
olfactory bulb
The olfactory bulb (Latin: ''bulbus olfactorius'') is a neural structure of the vertebrate forebrain involved in olfaction, the sense of smell. It sends olfactory information to be further processed in the amygdala, the orbitofrontal cortex (OF ...
,
piriform cortex,
perirhinal cortex
The perirhinal cortex is a brain cortex, cortical region in the medial temporal lobe that is made up of Brodmann areas Brodmann area 35, 35 and Brodmann area 36, 36. It receives highly processed sensory information from all sensory regions, and i ...
,
entorhinal cortex
The entorhinal cortex (EC) is an area of the brain's allocortex, located in the medial temporal lobe, whose functions include being a widespread network hub for memory, navigation, and the perception of time.Integrating time from experience in t ...
, and the hippocampal
dentate gyrus
The dentate gyrus (DG) is one of the subfields of the hippocampus, in the hippocampal formation. The hippocampal formation is located in the temporal lobe of the brain, and includes the hippocampus (including CA1 to CA4) subfields, and other su ...
. It was found that a heavy two-day drinking binge caused extensive neurodegeneration in the entorhinal cortex with resultant learning deficits in rats.
Alcohol abuse affects neurons in the frontal cortex that typically have a large
soma, or cell body. This type of neuron is more susceptible to
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...
and normal aging. Research is still being conducted to determine whether there is a direct link between excessive alcohol consumption and Alzheimer's disease.
The volume of the
corpus callosum
The corpus callosum (Latin for "tough body"), also callosal commissure, is a wide, thick nerve tract, consisting of a flat bundle of commissural fibers, beneath the cerebral cortex in the brain. The corpus callosum is only found in placental ...
, a large white matter tract that connects the two cerebral hemispheres, is shown to decrease with alcohol abuse due to a loss of myelination. This integration between the two cerebral hemispheres and cognitive function is affected. A limited amount of myelin can be restored with alcohol abstinence, leading to transient neurological deficits.
The endocrine system includes the hypothalamic–pituitary–adrenal axis, the hypothalamic–pituitary–gonadal axis, the hypothalamic–pituitary–thyroid axis, the hypothalamic–pituitary–growth hormone/insulin-like growth factor-1 axis, and the hypothalamic–posterior pituitary axis, as well as other sources of hormones, such as the endocrine pancreas and endocrine adipose tissue. Alcohol abuse disrupts all of these systems and causes hormonal disturbances that may result in various disorders, such as stress intolerance, reproductive dysfunction, thyroid problems, immune abnormalities, and psychological and behavioral disorders.
Higher order functioning of the cerebral cortex is organized by the cerebellum. In those with cerebral atrophy,
Purkinje cell
Purkinje cells or Purkinje neurons, named for Czech physiologist Jan Evangelista Purkyně who identified them in 1837, are a unique type of prominent, large neuron located in the Cerebellum, cerebellar Cortex (anatomy), cortex of the brain. Wi ...
s, or the cerebellar output neurons, in the
vermis are reduced in number by 43%.
This large reduction in Purkinje cells causes a decrease in high order cerebral cortex organization. The cerebellum is also responsible for refining crude motor output from the
primary motor cortex
The primary motor cortex ( Brodmann area 4) is a brain region that in humans is located in the dorsal portion of the frontal lobe. It is the primary region of the motor system and works in association with other motor areas including premotor c ...
. When this refinement is missing, symptoms such as unsteadiness and
ataxia
Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...
will present. A potential cause of chronic alcoholic cerebellar dysfunction is an alteration of
GABA-A receptor. This dysfunction causes an increase in the neurotransmitter
GABA
GABA (gamma-aminobutyric acid, γ-aminobutyric acid) is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system.
GA ...
in cerebellar Purkinje cells,
granule cell
The name granule cell has been used for a number of different types of neurons whose only common feature is that they all have very small cell bodies. Granule cells are found within the granular layer of the cerebellum, the dentate gyrus of t ...
s, and
interneuron
Interneurons (also called internuncial neurons, association neurons, connector neurons, or intermediate neurons) are neurons that are not specifically motor neurons or sensory neurons. Interneurons are the central nodes of neural circuits, enab ...
s leading to a disruption in normal cell signaling.
An
MRI brain scan found that levels of
N-acetylaspartate
''N''-Acetylaspartic acid, or ''N''-acetylaspartate (NAA), is a derivative of aspartic acid with a formula of C6H9NO5 and a molecular weight of 175.139.
NAA is the second-most-concentrated molecule in the brain after the amino acid glutamate. ...
(NAA), a metabolite biomarker for neural integrity, was lower in binge drinkers. Additionally, abnormal brain metabolism, a loss of white brain matter in the frontal lobe, and higher parietal gray matter NAA levels were found. This shows a correlation between binge drinking, poor executive functioning, and working memory. A decrease in frontal lobe NAA levels is associated with impaired executive functioning and processing speed in neuro-performance tests.
Neuroinflammation
Ethanol can trigger the activation of
astroglial cells which can produce a proinflammatory response in the brain. Ethanol interacts with the
TLR4 and
IL-1RI receptors on these cells to activate intracellular signal transduction pathways. Specifically, ethanol induces the phosphorylation of IL-1R-associated kinase (IRAK),
ERK1/2, stress-activated protein kinase (SAPK)/
JNK, and
p38 mitogen-activated protein kinase (p38 MAPK). Activation of the IRAK/MAPK pathway leads to the stimulation of the
transcription factor
In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription (genetics), transcription of genetics, genetic information from DNA to messenger RNA, by binding t ...
s
NF-kappaB and
AP-1. These transcription factors cause the upregulation of
inducible nitric oxide synthase (iNOS) and
cyclooxygenase-2 (COX-2) expression.
The upregulation of these inflammatory mediators by ethanol is also associated with an increase in
caspase 3 activity and a corresponding increase in cell
apoptosis
Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
.
The exact mechanism by which various concentrations of ethanol either activates or inhibits TLR4/IL-1RI signaling is not currently known, though it may involve alterations in
lipid raft
The cell membrane, plasma membranes of cells contain combinations of glycosphingolipids, cholesterol and protein Receptor (biochemistry), receptors organized in glycolipoprotein lipid microdomains termed lipid rafts. Their existence in cellular me ...
clustering or
cell adhesion
Cell adhesion is the process by which cells interact and attach to neighbouring cells through specialised molecules of the cell surface. This process can occur either through direct contact between cell surfaces such as Cell_junction, cell junc ...
complexes and actin
cytoskeleton
The cytoskeleton is a complex, dynamic network of interlinking protein filaments present in the cytoplasm of all cells, including those of bacteria and archaea. In eukaryotes, it extends from the cell nucleus to the cell membrane and is compos ...
organization.
Changes in dopaminergic and glutamatergic signaling pathways
Intermittent ethanol treatment causes a decrease in expression of the
dopamine receptor type 2 (D2R) and a decrease in phosphorylation of 2B subunit of the
NMDA receptor
The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and predominantly Ca2+ ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other ...
(NMDAR2B) in the
prefrontal cortex
In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. It is the association cortex in the frontal lobe. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, ...
,
hippocampus
The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...
,
nucleus accumbens
The nucleus accumbens (NAc or NAcc; also known as the accumbens nucleus, or formerly as the ''nucleus accumbens septi'', Latin for ' nucleus adjacent to the septum') is a region in the basal forebrain rostral to the preoptic area of the hypo ...
, and for only D2R the
striatum
The striatum (: striata) or corpus striatum is a cluster of interconnected nuclei that make up the largest structure of the subcortical basal ganglia. The striatum is a critical component of the motor and reward systems; receives glutamat ...
. It also causes changes in the acetylation of
histone
In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei and in most Archaeal phyla. They act as spools around which DNA winds to create structural units called nucleosomes ...
s H3 and H4 in the prefrontal cortex, nucleus accumbens, and striatum, suggesting
chromatin
Chromatin is a complex of DNA and protein found in eukaryote, eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important r ...
remodeling changes which may mediate long-term alterations. Additionally, adolescent rats pre-exposed to ethanol have higher basal levels of dopamine in the nucleus accumbens, along with a prolonged dopamine response in this area in response to a challenge dose of ethanol. Together, these results suggest that alcohol exposure during adolescence can sensitize the
mesolimbic and
mesocortical dopamine pathways to cause changes in
dopaminergic
Dopaminergic means "related to dopamine" (literally, "working on dopamine"), a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain.
Dopaminergic pathways, Dopaminergic brain pathways facil ...
and glutamatergic signaling, which may affect the remodeling and functions of the adolescent brain. These changes are significant as alcohol’s effect on NMDARs could contribute to learning and memory dysfunction (''see
Effects of alcohol on memory'').
Inhibition of hippocampal neurogenesis
Excessive alcohol intake (
binge drinking
Binge drinking, or heavy episodic drinking, is drinking alcoholic beverages with an intention of becoming intoxicated by heavy consumption of alcohol over a short period of time, but definitions vary considerably.
Binge drinking is a style of ...
) causes a decrease in hippocampal
neurogenesis
Neurogenesis is the process by which nervous system cells, the neurons, are produced by neural stem cells (NSCs). This occurs in all species of animals except the porifera (sponges) and placozoans. Types of NSCs include neuroepithelial cells ( ...
, via decreases in neural stem cell proliferation and newborn cell survival.
Alcohol decreases the number of cells in S-phase of the
cell cycle
The cell cycle, or cell-division cycle, is the sequential series of events that take place in a cell (biology), cell that causes it to divide into two daughter cells. These events include the growth of the cell, duplication of its DNA (DNA re ...
, and may arrest cells in the G1 phase, thus inhibiting their proliferation.
Ethanol has different effects on different types of actively dividing hippocampal progenitors during their initial phases of neuronal development. Chronic alcohol exposure decreases the number of proliferating cells that are
radial glia-like, preneuronal, and intermediate types, while not affecting early neuronal type cells; suggesting ethanol treatment alters the precursor cell pool. Furthermore, there is a greater decrease in differentiation and immature neurons than there is in proliferating progenitors, suggesting that the abnormal decrease in the percentage of actively dividing preneuronal progenitors results in a greater reduction in the maturation and survival of postmitotic cells.
Additionally, alcohol exposure increased several markers of cell death. In these studies neural degeneration seems to be mediated by non-apoptotic pathways.
One of the proposed mechanisms for alcohol's neurotoxicity is the production of nitric oxide (NO), yet other studies have found alcohol-induced NO production to lead to apoptosis (''see
Neuroinflammation
Neuroinflammation is inflammation of the nervous tissue. It may be initiated in response to a variety of cues, including infection, traumatic brain injury,Ebert SE, Jensen P, Ozenne B, Armand S, Svarer C, Stenbaek DS ''et al.'' Molecular imaging of ...
section'').
Kindling and excitotoxicity
Repeated detoxifications ("
kindling
Kindling may refer to:
* Kindling, material for firelighting
* ''Kindling'' (album), a 1973 album by Gene Parsons
* ''Kindling'' (1915 film), a film by Cecil B. DeMille
* Kindling (2023 film), a British drama film
* ''Kindling'' (Mick Farren no ...
") can worsen withdrawal symptoms and amplify brain damage through hyperexcitability and excitotoxicity, leading to more severe cognitive and emotional dysfunction over time, particularly in the
prefrontal cortex
In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. It is the association cortex in the frontal lobe. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, ...
. Animal studies show that repeated alcohol withdrawals are associated with a significantly impaired ability to learn new information.
Alcohol's acute effects on
GABAergic
In molecular biology and physiology, something is GABAergic or GABAnergic if it pertains to or affects the neurotransmitter gamma-aminobutyric acid (GABA). For example, a synapse is GABAergic if it uses GABA as its neurotransmitter, and a GABAergic ...
enhancement and
NMDA suppression cause alcohol induced neurotoxicity, or worsening of alcohol withdrawal symptoms with each subsequent withdrawal period. This may cause CNS depression leading to acute tolerance to these withdrawal effects. This tolerance is followed by a damaging
rebound effect during withdrawal. This rebound causes hyperexcitability of neurotransmission systems. If this hyperexcitability state occurs multiple times, kindling and neurotoxicity can occur leading to increased alcohol-related brain damage. Damaging
excitotoxicity
In excitotoxicity, neuron, nerve cells suffer damage or death when the levels of otherwise necessary and safe neurotransmitters such as glutamic acid, glutamate become pathologically high, resulting in excessive stimulation of cell surface recept ...
may also occur as a result of repeated withdrawals. Similar to people who have gone through multiple detoxifications, binge drinkers show a higher rate of emotional disturbance due to these damaging effects.
Epigenetic changes
Long-term, the effects of chronic hazardous alcohol use are thought to be due to stable alterations of
gene expression
Gene expression is the process (including its Regulation of gene expression, regulation) by which information from a gene is used in the synthesis of a functional gene product that enables it to produce end products, proteins or non-coding RNA, ...
resulting from
epigenetic
In biology, epigenetics is the study of changes in gene expression that happen without changes to the DNA sequence. The Greek prefix ''epi-'' (ἐπι- "over, outside of, around") in ''epigenetics'' implies features that are "on top of" or "in ...
changes within particular regions of the brain.
For example, in rats exposed to alcohol for up to 5 days, there was an increase in histone 3 lysine 9 acetylation in the pronociceptin promoter in the brain amygdala complex. This acetylation is an activating mark for pronociceptin. The nociceptin/nociceptin opioid receptor system is involved in the reinforcing or conditioning effects of alcohol.
Diagnosis
Neurological impairment related to alcohol is typically diagnosed through clinical history, neuropsychological testing, neuroimaging, and laboratory tests. Differential diagnosis includes other causes of dementia, psychiatric disorders, and traumatic brain injury. Modern neuroimaging techniques in particular have revolutionized the understanding of alcohol-related brain damage. The two main imaging methods are hemodynamic and electromagnetic. These techniques have allowed for the study of the functional, biochemical, and anatomical changes of the brain due to prolonged alcohol abuse.
Neuroimaging provides valuable information in determining the risk an individual has for developing alcohol dependence and the efficacy of potential treatment.
In Korsakoff patients, MRI shows atrophy of the thalamus and mamillary bodies. PET showed decreased metabolism, and therefore decreased activity in the thalamus and other diencephalon structures.
Uncomplicated alcoholics, those with chronic Wernicke's encephalopathy (WE), and Korsakoff psychosis showed significant neuronal loss in the frontal cortex, white matter, hippocampus, and
basal forebrain.
Uncomplicated alcoholics were seen to have a shrinkage in
raphe
Raphe ( ; from ;Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon. revised and augmented throughout by Sir Henry Stuart Jones. with the assistance of. Roderick McKenzie.'' Oxford: Clarendon Press. : raphae or raphes) has several differe ...
neurons, the mamillary bodies, and the thalamus.
Hemodynamic methods
Hemodynamic methods record changes in blood volume, blood flow, blood oxygenation, and energy metabolism to produce images.
Positron emission tomography
Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, r ...
(PET) and
single-photon emission computed tomography
Single-photon emission computed tomography (SPECT, or less commonly, SPET) is a nuclear medicine tomography, tomographic imaging technique using gamma rays. It is very similar to conventional nuclear medicine planar imaging using a gamma camera ...
(SPECT) are common techniques that require the injection of a radioactively labeled molecule, such as glucose, to allow for proper visualization. After injection, the patient is then observed while performing mental tasks, such as a memory task. PET and SPECT studies have confirmed and expanded previous findings stating that the prefrontal cortex is particularly susceptible to decreased metabolism in alcohol abusing patients.
Magnetic resonance imaging
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to generate pictures of the anatomy and the physiological processes inside the body. MRI scanners use strong magnetic fields, magnetic field gradients, and ...
(MRI) and
functional magnetic resonance imaging
Functional magnetic resonance imaging or functional MRI (fMRI) measures brain activity by detecting changes associated with blood flow. This technique relies on the fact that cerebral blood flow and neuronal activation are coupled. When an area o ...
(fMRI) are other commonly used tenichiques. These methods are noninvasive, and have no radioactive risk involved. The fMRI method records the metabolic changes in a particular brain structure or region during a mental task. To detect damage to white matter, the standard MRI is not sufficient. An MRI derivative technique known as
diffusion tensor imaging (DTI) is used to determine the orientation and integrity of specific nerve pathways, allowing the detection of damage.
When imaging those with alcoholism, the DTI results show that heavy drinking disrupts the microstructure of nerve fibers.
Electromagnetic methods

While the hemo-dynamic methods are effective for observing spatial and chemical changes, they cannot show the time course of these changes. Electromagnetic imaging methods are capable of capturing real-time changes in the brain's electrical currents.
Electroencephalography
Electroencephalography (EEG)
is a method to record an electrogram of the spontaneous electrical activity of the brain. The biosignal, bio signals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in ...
(EEG) imaging utilizes small electrodes that are attached to the scalp. The recordings are averaged by a technique known as
event-related potential
An event-related potential (ERP) is the measured brain response that is the direct result of a specific sense, sensory, cognition, cognitive, or motor system, motor event. More formally, it is any stereotyped electrophysiology, electrophysiologi ...
s (ERP). This is done to determine the time sequence of activity after being exposed to a stimulus, such as a word or image.
These neuroimaging methods have found that alcohol alters the nervous system on multiple levels.
This includes impairment of lower order
brainstem
The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is conti ...
functions and higher order functioning, such as problem solving. These methods have also shown differences in electrical brain activity and responsiveness when comparing alcohol-dependent and healthy individuals.
Prevention
Primary prevention strategies include limiting alcohol intake in accordance with health guidelines, nutritional supplementation in at-risk individuals (especially thiamine), and early intervention for alcohol use disorder. Education on the prevention of alcoholism is the best supported method of avoiding alcohol-related brain damage.
By providing information that studies have found on risk factors and the mechanisms of damage, the efforts to find an effective treatment may increase. This may also reduce mortality by influencing doctors to pay closer attention to the warning signs.
Treatment
Treatment approaches include stopping alcohol use, thiamine and multivitamin supplementation, cognitive-behavioral therapy targeting memory, executive function, and motivation, and medications like naltrexone or acamprosate to aid in maintaining abstinence. Management of comorbid psychiatric conditions is also essential. Many negative physiologic consequences of
alcoholism
Alcoholism is the continued drinking of alcohol despite it causing problems. Some definitions require evidence of dependence and withdrawal. Problematic use of alcohol has been mentioned in the earliest historical records. The World He ...
are reversible during
abstinence
Abstinence is the practice of self-enforced restraint from indulging in bodily activities that are widely experienced as giving pleasure. Most frequently, the term refers to sexual abstinence, but it can also mean abstinence from alcohol (drug), ...
. As an example, long-term chronic alcoholics suffer a variety of cognitive deficiencies.
However, multiyear abstinence resolves most neurocognitive deficits, except for some lingering deficits in spatial processing.
Alcohol-related brain damage can have drastic effects on the individuals affected and their loved ones. The options for treatment are very limited compared to other disorders. Although limited, most patients with alcohol-related cognitive deficits experienced slight improvement of their symptoms over the first two to three months of treatment.
Others have said to see increase in cerebral metabolism as soon as one month after treatment.
Outcomes
Some consequences of frequent long-term drinking are not reversible with abstinence. Alcohol
craving (compulsive need to consume alcohol) is frequently present long-term among
alcoholics.
Among 461 individuals who sought help for alcohol problems, followup was provided for up to 16 years.
By 16 years, 54% of those who tried to remain abstinent ''without'' professional help had relapsed, and 39% of those who tried to remain abstinent ''with help'' had relapsed.
Epidemiology
Nearly half of American alcoholics exhibit "neuropsychological disabilities
hat
A hat is a Headgear, head covering which is worn for various reasons, including protection against weather conditions, ceremonial reasons such as university graduation, religious reasons, safety, or as a fashion accessory. Hats which incorpor ...
can range from mild to severe"
with approximately two million requiring lifelong care after developing permanent and debilitating conditions. Prolonged alcohol abstinence can lead to an improvement in these disabilities. For those with mild impairments, some improvement has been seen within a year, but this can take much longer in those with higher severity damage.
History
Recognition of alcohol's neurotoxic effects dates back to the 19th century. The identification of Wernicke’s encephalopathy and Korsakoff’s psychosis linked alcohol to specific brain disorders. Advances in neuroimaging in the late 20th century further clarified the structural impact of chronic alcohol use.
Society and culture
Alcohol use is deeply embedded in many cultures, and moderate consumption is often socially acceptable or even encouraged. However, stigma surrounds alcohol use disorder and alcohol-related cognitive impairment, complicating public health messaging.
Economic costs associated with alcohol-related brain damage include healthcare expenses, lost productivity, and caregiving burdens.
Special populations
Adolescents
Consuming large amounts of alcohol over a period of time can impair normal brain development in humans. Deficits in retrieval of verbal and nonverbal information and in visuospatial functioning were evident in youths with histories of heavy drinking during early and middle adolescence.
During adolescence critical stages of neurodevelopment occur, including remodeling and functional changes in
synaptic plasticity
In neuroscience, synaptic plasticity is the ability of synapses to Chemical synapse#Synaptic strength, strengthen or weaken over time, in response to increases or decreases in their activity. Since memory, memories are postulated to be represent ...
and neuronal connectivity in different brain regions. These changes may make adolescents especially susceptible to the harmful effects of alcohol. Compared to adults, adolescents exposed to alcohol are more likely to exhibit cognitive deficits (including learning and memory dysfunction). Some of these cognitive effects, such as learning impairments, may persist into adulthood.
The impulsivity and sensation seeking seen in adolescence may lead to increased alcohol intake and more frequent binge drinking episodes leaving adolescents particularly at risk for alcoholism. The still developing brain of adolescents is more vulnerable to the damaging neurotoxic and neurodegenerative effects of alcohol.
"High impulsivity has
lsobeen found in families with alcoholism, suggestive of a genetic link. Thus, the genetics of impulsivity overlaps with genetic risks for alcohol use disorder and possibly alcohol neurodegeneration".
Adolescents are much more vulnerable to alcohol-related brain damage in the form of persistent changes in neuroimmune signalling from binge drinking.
Genetics and family history
Gender and parental history of alcoholism and binge drinking has an influence on susceptibility to alcohol dependence as higher levels are typically seen in males and in those with a family history.
There is also a genetic risk for
proinflammatory cytokine mediated alcohol-related brain damage. There is evidence that variants of these genes are involved not only in contributing to brain damage but also to impulsivity and alcohol abuse. All three of these genetic traits contribute heavily to an alcohol use disorder.
References
{{Psychoactive substance use
Brain, long
Alcohol abuse
Neurology
Sedatives
Addiction psychiatry
Hypnotics