Alcohol-related Brain Damage Research Articles

Promising strategies for the prevention of alcohol-related brain damage through optimised management of acute alcohol withdrawal: A focussed literature review.

There is an increasing awareness of the link between chronic alcohol consumption and the development of cognitive, behavioural and functional deficits. Currently, preventative strategies are limited and require engagement in dedicated long-term rehabilitation and sobriety services, the availability of which is low. The acute alcohol withdrawal syndrome is an episode of neurochemical imbalance leading to autonomic dysregulation, increased seizure risk and cognitive disorientation. In addition to harm from symptoms of alcohol withdrawal (e.g. seizures), the underpinning neurochemical changes may also lead to cytotoxicity through various cellular mechanisms, which long-term, may translate to some of the cognitive impairments observed in Alcohol-Related Brain Damage (ARBD). Here we review some of the pharmacological and neurochemical mechanisms underpinning alcohol withdrawal. We discuss the cellular and pharmacological basis of various potential neuroprotective strategies that warrant further exploration in clinical populations with a view to preventing the development of ARBD. Such strategies, when integrated into the clinical management of acute alcohol withdrawal, may impact large populations of individuals, who currently face limited dedicated service delivery and healthcare resource.

Meeting the Needs: Description and Evaluation of an Alcohol Related Brain Damage (ARBD) Residential Rehabilitation Service

ABSTRACT To describe and evaluate a cost-effective, integrated model of service provision for people with Alcohol Related Brain Damage (ARBD). Participants identified by three large acute hospitals as having ARBD and suitable for recovery and rehabilitation were offered a 12-week recovery-focussed program at a residential unit. The unit is a collaboration between an NHS board, the local council, and a 3rd sector organization Participants’ pre-admission and post-admission medical data was gathered to analyze the effectiveness of the unit’s program on Emergency Department (ED) attendance and inpatient bed use. Improvement in cognition was measured by comparing the ACE-III results for all participants at admission and just prior to discharge from the program. Thirty-one participants met the inclusion criteria. Paired t-tests revealed the 12-week program overall significantly reduced attendance at ED, use of in-patient beds after discharge, and improved cognitive functioning. This integrated model of service provision provides clear benefits to residents’ cognitive functioning and to the NHS by freeing up inpatient beds and ED capacity. Therefore, it should be considered by commissioners when addressing the needs of people with ARBD.

Adolescent alcohol exposure alters age-related progression of behavioral and neurotrophic dysfunction in the TgF344-AD model in a sex-specific manner.

Alzheimer's Disease (AD) and heavy alcohol use are widely prevalent and lead to brain pathology. Both alcohol-related brain damage (ABRD) and AD result in cholinergic dysfunction, reductions in hippocampal neurogenesis, and the emergence of hippocampal-dependent cognitive impairments. It is still unknown how ARBD caused during a critical developmental timepoint, such as adolescence, interacts with AD-related pathologies to accelerate disease progression later in life. The current study utilized a longitudinal design to characterize behavioral and pathological changes in a transgenic rat model of AD (TgF344-AD) following adolescent intermittent ethanol (AIE) exposure. We found that AIE accelerates cognitive decline associated with AD transgenes in female rats at 6 months of age, and male AD-rats are impaired on spatial navigation by 3-months with no additional deficits due to AIE exposure. Protein levels of various AD-pathological markers were analyzed in the dorsal and ventral hippocampus of male and female rats. The data suggests that AIE-induced alterations of the tropomyosin-related kinase A receptor (TrkA) / p75 neurotrophin receptor (p75NTR) ratio creates a brain that is vulnerable to age- and AD-related pathologies, which leads to an acceleration of cognitive decline, particularly in female rats.

Cognitive impairment among alcohol treatment service users in South Wales: an exploratory examination of typologies of behaviour, impairment, and service attendance.

Alcohol dependence is a global issue with many negative consequences, including alcohol-related brain damage (ARBD). Assessment of the sociodemographic and cognitive characteristics of individuals with confirmed or suspected ARBD presenting to alcohol services warrants further investigation. This study retrospectively examined rates of cognitive impairment using Montreal Cognitive Assessment (MoCA) data from 300 adults who visited three alcohol support services. We demonstrate that 55.3% of the sample had significant levels of cognitive impairment. Females' cognitive performance was disproportionately negatively affected by historical alcohol use relative to males. The analysis identified four categories of participants, and the majority had a long history (+10 years) of alcohol use and were still actively drinking. Those taking part in active treatment for ARBD or practising abstinence demonstrated lower levels of cognitive impairment. Additionally, prior access to specialised ARBD care was associated with higher MoCA scores. This research has identified a range of key service engagement, sociodemographic and cognitive characteristics that could be used to optimise support for those with alcohol dependence, whilst also highlighting some critical questions to be addressed in future research.

Fasudil alleviates alcohol-induced cognitive deficits and hippocampal morphology injury partly by altering the assembly of the actin cytoskeleton and microtubules

Alcohol-Related Brain Damage (ARBD) manifests predominantly as cognitive impairment and brain atrophy with the hippocampus showing particular vulnerability. Fasudil, a Rho kinase (ROCK) inhibitor, has established neuroprotective properties; however, its impact on alcohol-induced cognitive dysfunction and hippocampal structural damage remains unelucidated. This study probes Fasudil’s neuroprotective potential and identifies its mechanism of action in an in vivo context. Male C57BL/6 J mice were exposed to 30% (v/v, 6.0 g/kg) ethanol by intragastric administration for four weeks. Concurrently, these mice received a co-treatment with Fasudil through intraperitoneal injections at a dosage of 10 mg/kg/day. Fasudil was found to mitigate alcohol-induced spatial and recognition memory deficits, which were quantified using Y maze, Morris water maze, and novel object recognition tests. Concurrently, Fasudil attenuated hippocampal structural damage prompted by chronic alcohol exposure. Notably, Fasudil moderated alcohol-induced disassembly of the actin cytoskeleton and microtubules—mechanisms central to the maintenance of hippocampal synaptic integrity. Collectively, our findings indicate that Fasudil partially reverses alcohol-induced cognitive and morphological detriments by modulating cytoskeletal dynamics, offering insights into potential therapeutic strategies for ARBD.

Phosphatidylethanol in post-mortem brain: Correlation with blood alcohol concentration and alcohol use disorder

Phosphatidylethanol (PEth) is an alcohol derivative that has been employed as a blood-based biomarker for regular alcohol use. This study investigates the utility of phosphatidylethanol (PEth) as a biomarker for assessing alcohol consumption in post-mortem brain tissue. Using samples from the New South Wales Brain Tissue Resource Centre, we analysed PEth(16:0/18:1) levels in the cerebellum and meninges of individuals with varying histories of alcohol use, including those diagnosed with alcohol use disorder (AUD) and controls. Our findings demonstrate a significant correlation between PEth levels and blood alcohol content (BAC) at the time of death, supporting the biomarker's sensitivity to recent alcohol intake. Furthermore, this study explores the potential of PEth levels in differentiating AUD cases from controls, taking into consideration the complexities of diagnosing AUD post-mortem. The study also examined the relationship between PEth levels and liver pathology, identifying a link with the severity of liver damage. These results underscore the value of PEth as a reliable indicator of alcohol consumption and its potential contributions to post-mortem diagnostics and consequently, research into alcohol-related brain damage.

Alcohol Triggers the Accumulation of Oxidatively Damaged Proteins in Neuronal Cells and Tissues.

Alcohol is toxic to neurons and can trigger alcohol-related brain damage, neuronal loss, and cognitive decline. Neuronal cells may be vulnerable to alcohol toxicity and damage from oxidative stress after differentiation. To consider this further, the toxicity of alcohol to undifferentiated SH-SY5Y cells was compared with that of cells that had been acutely differentiated. Cells were exposed to alcohol over a concentration range of 0-200 mM for up to 24 h and alcohol effects on cell viability were evaluated via MTT and LDH assays. Effects on mitochondrial morphology were examined via transmission electron microscopy, and mitochondrial functionality was examined using measurements of ATP and the production of reactive oxygen species (ROS). Alcohol reduced cell viability and depleted ATP levels in a concentration- and exposure duration-dependent manner, with undifferentiated cells more vulnerable to toxicity. Alcohol exposure resulted in neurite retraction, altered mitochondrial morphology, and increased the levels of ROS in proportion to alcohol concentration; these peaked after 3 and 6 h exposures and were significantly higher in differentiated cells. Protein carbonyl content (PCC) lagged behind ROS production and peaked after 12 and 24 h, increasing in proportion to alcohol concentration, with higher levels in differentiated cells. Carbonylated proteins were characterised by their denatured molecular weights and overlapped with those from adult post-mortem brain tissue, with levels of PCC higher in alcoholic subjects than matched controls. Hence, alcohol can potentially trigger cell and tissue damage from oxidative stress and the accumulation of oxidatively damaged proteins.

Enlarged perivascular spaces in alcohol-related brain damage induced by dyslipidemia

Perivascular spaces (PVSs) as the anatomical basis of the glymphatic system, are increasingly recognized as potential imaging biomarkers of neurological conditions. However, it is not clear whether enlarged PVSs are associated with alcohol-related brain damage (ARBD). We aimed to investigate the effect of long-term alcohol exposure on dyslipidemia and the glymphatic system in ARBD. We found that patients with ARBD exhibited significantly enlargement of PVSs in the frontal cortex and basal ganglia, as well as a notable increased levels of total cholesterol (TC) and triglycerides (TG). The anatomical changes of the glymphatic drainage system mentioned above were positively associated with TC and TG. To further explore whether enlarged PVSs affects the function of the glymphatic system in ARBD, we constructed long alcohol exposure and high fat diet mice models. The mouse model of long alcohol exposure exhibited increased levels of TC and TG, enlarged PVSs, the loss of aquaporin-4 polarity caused by reactive astrocytes and impaired glymphatic drainage function which ultimately caused cognitive deficits, in a similar way as high fat diet leading to impairment in glymphatic drainage. Our study highlights the contribution of dyslipidemia due to long-term alcohol abuse in the impairment of the glymphatic drainage system.

Exercise leads to sex-specific recovery of behavior and pathological AD markers following adolescent ethanol exposure in the TgF344-AD model.

Human epidemiological studies suggest that heavy alcohol consumption may lead to earlier onset of Alzheimer's Disease (AD), especially in individuals with a genetic predisposition for AD. Alcohol-related brain damage (ARBD) during a critical developmental timepoint, such as adolescence, interacts with AD-related pathologies to accelerate disease progression later in life. The current study investigates if voluntary exercise in mid-adulthood can recover memory deficits caused by the interactions between adolescence ethanol exposure and AD-transgenes. Male and female TgF344-AD and wildtype F344 rats were exposed to an intragastric gavage of water (control) or 5 g/kg of 20% ethanol (adolescent intermittent ethanol; AIE) for a 2 day on/off schedule throughout adolescence (PD27-57). At 6 months old, rats either remained in their home cage (stationary) or were placed in a voluntary wheel running apparatus for 4 weeks and then underwent several behavioral tests. The number of cholinergic neurons in the basal forebrain and measure of neurogenesis in the hippocampus were assessed. Voluntary wheel running recovers spatial working memory deficits selectively in female TgF344-AD rats exposed to AIE and improves pattern separation impairment seen in control TgF344-AD female rats. There were sex-dependent effects on brain pathology: Exercise improves the integration of recently born neurons in AIE-exposed TgF344-AD female rats. Exercise led to a decrease in amyloid burden in the hippocampus and entorhinal cortex, but only in male AIE-exposed TgF344-AD rats. Although the number of basal forebrain cholinergic neurons was not affected by AD-transgenes in either sex, AIE did reduce the number of basal forebrain cholinergic neurons in female rats. These data provide support that even after symptom onset, AIE and AD related cognitive decline and associated neuropathologies can be rescued with exercise in unique sex-specific ways.

"I Genuinely Believe This Is the Most Stigmatised Group within the Social Care Sector"-Health and Social Care Professionals' Experiences of Working with People with Alcohol-Related Brain Damage: A Qualitative Interview Study.

Appropriate diagnosis, treatment and care contribute to better service engagement, improvements to wellbeing, cost savings and reductions in morbidity and mortality for people with alcohol-related brain damage. In Northeast England, large amounts of alcohol are consumed; this is reflected in the number of alcohol-related deaths in the region. However, the pathway for people with alcohol-related brain damage to receive diagnosis, treatment and care is unknown and could be unwittingly influenced by stigma. Qualitative, in-depth, semi-structured interviews were completed with 25 health and social care professionals from organizations involved with people with alcohol-related brain damage recruited via snowball sampling. Interviews were recorded, transcribed verbatim, coded, and analysed. People with alcohol-related brain damage were found to be stigmatised by both society and professionals, inhibiting their entry into services. Therefore, alcohol-related brain damage remains underdiagnosed and misdiagnosed. There was found to be no dedicated service; silos with revolving doors and underfunded generic care with long waiting lists typically exclude those with alcohol-related or neurological problems. Reducing stigmatising processes associated with alcohol-related brain damage could counteract professionals' reluctance to provide care.

Shades of grey: choice, control and capacity in alcohol-related brain damage.

Liaison psychiatrists have identified that conducting capacity assessments in general hospital patients with alcohol-related brain damage (ARBD) can be challenging. This educational article uses the fictitious case of a man with ARBD, alcohol dependence and significant self-neglect, focusing on assessment of his capacity to decide about moving into a care home on discharge. We provide an overview of clinical, legal and ethical literature relevant to decision-making and capacity assessment in individuals with ARBD, with the aim of guiding clinicians approaching complex capacity assessments.

Alcohol-related brain damage: an umbrella (term) for the approaching post-COVID monsoon

Individuals with alcohol-related brain damage (ARBD) represent a population whose healthcare needs often go unmet. This is the result of a lack of not only an awareness surrounding the condition by healthcare professionals, but also healthcare service inclusion and delivery, more broadly. The Coronavirus 2019 (COVID-19) pandemic and the associated lockdowns dramatically affected the accessibility and availability of addiction services globally, while also driving changes in alcohol consumption among the most vulnerable. In the absence of change, this culmination of increased high-risk drinking behaviour, lack of awareness by healthcare professionals and severely limited service delivery for individuals living with ARBD post COVID-19, represents a perfect storm that is rapidly approaching our health and care services world-wide. Collectively, this will reduce positive health outcomes in an already at-risk group.

Neuropsychiatric and Neuropsychological Aspects of Alcohol-Related Cognitive Disorders: An In-Depth Review of Wernicke's Encephalopathy and Korsakoff's Syndrome.

Alcohol-related cognitive disorders have long been an area of study, yet they continue to pose challenges in the diagnosis, treatment, and understanding of underlying neuropsychiatric mechanisms. The present article offers a comprehensive review of Wernicke's Encephalopathy and Korsakoff's Syndrome, two conditions often seen on a continuum of alcohol-related brain damage. Drawing on current medical literature, neuroimaging studies, and clinical case reports, we explore the neuropsychiatric and neuropsychological profiles, symptomatology, and differential diagnoses of these disorders. We delve into the biochemical pathways implicated in the development of WE and KS, notably thiamine deficiency and its impact on neurotransmitter systems and neural networks. The article also addresses the challenges in early diagnosis, often complicated by non-specific symptoms and co-occurring psychiatric conditions. Furthermore, we review the current state of treatment protocols, including pharmacological and non-pharmacological interventions. Finally, the article highlights gaps in current knowledge and suggests directions for future research to improve diagnosis, treatment, and patient outcomes. Understanding the nuanced interplay between the neuropsychiatric and neuropsychological aspects of WE and KS is crucial for both clinicians and researchers alike, in order to provide effective treatment and to advance our understanding of these complex conditions.

Alcohol Withdrawal Is an Oxidative Stress Challenge for the Brain: Does It Pave the Way toward Severe Alcohol-Related Cognitive Impairment?

Alcohol use is a leading cause of mortality, brain morbidity, neurological complications and minor to major neurocognitive disorders. Alcohol-related neurocognitive disorders are consecutive to the direct effect of chronic and excessive alcohol use, but not only. Indeed, patients with severe alcohol use disorders (AUD) associated with pharmacological dependence suffer from repetitive events of alcohol withdrawal (AW). If those AW are not managed by adequate medical and pharmacological treatment, they may evolve into severe AW, or be complicated by epileptic seizure or delirium tremens (DT). In addition, we suggest that AW favors the occurrence of Wernicke’s encephalopathy (WE) in patients with known or unknown thiamine depletion. We reviewed the literature on oxidative stress as a core mechanism in brain suffering linked with those conditions: AW, epileptic seizure, DT and WE. Thus, we propose perspectives to further develop research projects aiming at better identifying oxidative stress brain damage related to AW, assessing the effect of repetitive episodes of AW, and their long-term cognitive consequences. This research field should develop neuroprotective strategies during AW itself or during the periwithdrawal period. This could contribute to the prevention of severe alcohol-related brain damage and cognitive impairments.

Alcohol-related brain damage: A mixed-method evaluation of an online awareness-raising programme for frontline care and support practitioners.

Alcohol-related brain damage (ARBD) is an umbrella term referring to the neurocognitive impairments caused by excessive and prolonged alcohol use and the associated nutritional deficiencies. This study evaluated the outcomes of an online research-informed training program for ARBD which aimed to improve client outcomes by promoting support staff's awareness and confidence in working with clients who may have (or who are at risk of developing) the condition. Staff working within a large non-governmental non-profit housing organisation (n=883) enrolled in the training program. Questionnaires were used pre- and post-training to collect self-reported awareness of ARBD and confidence in supporting individuals with the condition. Semi-structured interviews were conducted with 27 staff members approximately 10 weeks post-completion of the program. Interviews were audio-recorded, transcribed verbatim and analysed by employing qualitative content analysis. Findings from the questionnaires indicated a significant increase in all measures after completing the training program. Three main themes were developed based on the interview data: changes to awareness and understanding; professional practice; and training-specific characteristics. Participants reported changes in their ability to identify potential service users with ARBD and confidence in doing so. Our findings demonstrate that online training programs can be effective in improving support staff's ability to identify ARBD, potentially leading an increase in signposting service users to relevant services. The research-informed nature of the training demonstrates that translating research findings directly to frontline workers can have a substantial impact and may improve outcomes for this client group.

Alcohol Related Brain Damage Presentations in an Acute General Hospital

AimsAlcohol-related brain damage (ARBD) is used to describe a variety of clinical syndromes associated with excessive intake of alcohol. It can present with cognitive and neurological syndromes, including Wernicke's encephalopathy, Korsakoff's syndrome, alcohol dementia, cerebellar atrophy and frontal lobe dysfunction, Central pontine myelinolysis and Marchiafava Bignami disease. In up to 25% of cases ARBD can be complicated by traumatic head injury and brain blood supply disturbances. In the absence of clear national guidelines, standards or established pathways of care across most of the UK, most patients are unable to access appropriate service provision. The North Derbyshire mental health liaison team (MHLT) provides assessment and diagnosis of acute alcohol related brain injury, assess severity (based on clinical presentation, investigation findings, cognitive assessment) and provide a care plan with follow-up to various community services. Aim and objectives: To find out the discharge outcome for patients with ARBD diagnosis by the north MHLT, help us identify service gaps and look at ways to improve patient's care in this group.MethodsWe retrospectively analysed 300 patients who were referred to liaison team for drug and alcohol problems and were seen by the drug and alcohol lead nurse within the liaison team. Patients who were given a diagnosis of ARBD by the liaison team were included in the study.We looked at 1.Age and gender distribution2.Team who gave the initial diagnosis3.Discharge destination4.Community follow-up and engagementResultsWe identified 17 patients who were given diagnosis of ARBD. There was relatively equal distribution of male to female patients. Majority of diagnosis’ were given by liaison team. The discharge destination was variable with around half referred to ARBD rehabilitation unit and Derbyshire recovery partnership. Engagement was poor with only 20% of patients engaging with services.ConclusionRecommendations: 1.Detailed cognitive tests need doing for screening and to establish severity2. Consideration for which neuroimaging modalities can help aid diagnosis, if any, should be made. 3.ARBD leaflets to be given4.ARBD diagnosed patients who do not need rehabilitation unit, should be referred for social care assessment as an inpatient and / or be followed up in the community under Care Act5. Considerations with the Multi Disciplinary Team for ways to improve engagement in the community, perhaps with more frequent and robust follow-ups.

What is the Korsakoff syndrome? – a paper in tribute to Prof Alwyn Lishman

ABSTRACT Introduction Alwyn Lishman was interested in how memory research could be applied to clinical psychiatry. After a brief review of his major contributions, this paper will focus on his research on the alcoholic Korsakoff syndrome. It will consider how his findings relate to contemporary debates, particularly on how the syndrome should be defined, and its relationship to broader alcohol-induced cognitive impairments. Methods A review of the contribution of Alwyn Lishman, Robin Jacobson and colleagues to our knowledge of Korsakoff’s syndrome, together with a review of the pertinent recent literature. Results Lishman and colleagues followed earlier authors in defining the Korsakoff syndrome in terms of disproportionate memory impairment, but they also noted a variable degree of IQ, frontal-executive, and timed visuo-spatial impairment in their cases. More recent authors have included such features in their definitions of the syndrome. Lishman also argued for a specific “alcoholic dementia”. The present paper argues that recent definitions of the Korsakoff syndrome confound its core and associated features, and also fail to recognise the multifactorial basis of alcohol-related brain damage. Conclusions Korsakoff’s syndrome is best defined in terms of disproportionate memory impairment, and more widespread cognitive impairment is best encompassed within “alcohol-related brain damage”.

Diagnostic, management and nursing challenges of less common dementias: Frontotemporal dementia, alcohol-related dementia, HIV dementia and prion diseases

Background: Most cases of dementia are due to Alzheimer's disease or vascular dementia, but attention on these disorders means that other important causes of dementia may be relatively neglected. About 10–15% of people with dementia have other diagnoses, and there are numerous causes of the less common types of dementia. Aims: This paper provides information about the causes, symptoms, diagnosis and nursing management of some of the different types of less common dementias, with the aim of helping nurses to provide better care to patients and families affected. Methods: This is one of two connected papers and provides a narrative review of the literature on the clinical presentation of frontotemporal dementia, HIV dementia, prion dementias and alcohol-related dementia. Findings: Frontotemporal dementia has important clinical subtypes with distinct different presentations; for example, predominantly behavioural symptoms or progressive language dysfunction. Alcohol-related dementia is one of several types of alcohol-related brain damage. This is important as, with abstinence, its progression may be halted or even to some extent improved. HIV dementia has become less common since the introduction of effective antiretroviral therapy, but, nonetheless, the less severe picture of HIV-associated cognitive dysfunction remains prevalent despite treatment. Prion dementias encompass sporadic, familial and acquired Creutzfeldt-Jakob disease and are incurable, therefore requiring extensive palliative care. Conclusions: These forms of dementia all have different symptoms and courses from common types of dementia, such as Alzheimer's disease. It is important for nurses to be aware that dementia may have several causes and that people with different dementias will have different needs. Nonetheless, the general skills of nurses in supporting patients and families remain essential in order to develop appropriate care plans and to provide individualised, person-centred care.

Impact of Current Alcohol Consumption on Cognitive Function in Patients with Self-Perceived Memory Decline: A Comparative Study of Subjective Cognitive Decline, Mild Cognitive Impairment and Alzheimer-Type Dementia Groups

Background: Alcohol consumption has been considered as a modifiable risk factor for dementia development and alcohol-related brain damage may further impair cognitive abilities in dementia patients. This study aimed to find out the differences in cognitive function according to current alcohol drinking in patients with self-perceived memory decline, including subjective cognitive decline (SCD), mild cognitive impairment (MCI) and early Alzheimer-type dementia (ATD).Methods: From May 2018 to December 2019, retrospective chart review was performed in patients who visited CHA Bundang Medical Center for cognitive decline. A two-way analysis of variance with interaction test were used to analyze the impact of alcohol consumption on cognitive function between groups.Results: A total of 147 patients was classified into three groups of SCD (n=30), MCI (n=53), and ATD (n=64), and each group was divided into two subgroups of alcohol users and alcohol non-users, according to the current status of alcohol consumption. Between SCD, MCI and ATD groups, scores of clock drawing test and Go/No-go test were significantly lower in current alcohol users of ATD groups compared to the SCD and MCI groups (p<0.05).Conclusions: These results suggest that current alcohol consumption has detrimental effects especially on the frontal/executive function in early ATD patients. Considering the association between frontal/executive function and ADL, our finding suggests that cessation of alcohol intake may be a therapeutic strategy to prevent ADL deterioration in patients with ATD.

Lipidome changes in alcohol-related brain damage.

Alcohol-related brain injury is characterized by cognitive deficits and brain atrophy with the prefrontal cortex particularly susceptible. White matter in the human brain is lipid rich and a major target of damage from chronic alcohol abuse; yet, there is sparse information on how these lipids are affected. Here, we used untargeted lipidomics as a discovery tool to describe these changes in the prefrontal, middle temporal, and visual cortices of human subjects with alcohol use disorder and controls. Significant changes to the lipidome, predominantly in the prefrontal and visual cortices, and differences between the white and grey matter of each brain region were identified. These effects include broad decreases to phospholipids and ceramide, decreased polyunsaturated fatty acids, decreased sphingadiene backbones, and selective decreases in cholesteryl ester fatty acid chains. Our findings show that chronic alcohol abuse results in selective changes to the neurolipidome, which likely reflects both the directs effects on the brain and concurrent effects on the liver.