Academic literature on the topic 'Alcohol-related brain damage'

Alcohol-related dementia (ARD) is a controversial concept. Alcohol-related brain damage (ARBD) is a term used to cover a spectrum of conditions and disorders: this includes alcohol-related dementia, Korsakoff's syndrome, Wernicke's encephalopathy, alcohol-related brain injury, and alcohol amnesic syndrome. In other words, these are the conditions that have been induced by chronic alcohol consumption, resulting in some degree of brain damage. The prevalence data are varied.

Purpose – The purpose of this paper is to argue that alcohol-related brain damage (ARBD) is a neglected problem. ARBD is a term that has begun to be used over the past decade to describe prolonged cognitive impairment caused by alcohol use, including Wernicke's encephalopathy and Korsakoff syndrome, alcohol dementia and alcohol-related brain injury. Design/methodology/approach – The paper provides an overview of ARBD describing the research around its prevalence and prognosis. There is a consensus in the literature that there is little research and a lack of awareness of this condition. The author uses case studies from his own experience working with people with ARBD to describe the difficulties in accessing appropriate assessment and care for this group, and suggests that they are often excluded in a way that is familiar from the experience of the person with “dual diagnosis”. Findings – Recommendations are made including raising awareness, improving screening for cognitive impairment and developing specialist services. Originality/value – ARBD appears to have been neglected in the “dual diagnosis” world and this paper attempts to address this, and so should be of interest to a wide range of professionals working with substance use, mental health, homelessness and social work.

Doctor of Philosophy (PhD)
Proteomics is rapidly achieving recognition as a complimentary and perhaps superior approach to examine global changes in protein abundance in complex biological systems and the value of these techniques in neuropsychiatry is beginning to be acknowledged. Characterizing the brain’s regional proteomes provides a foundation for the detection of proteins that may be involved in disease-related processes. Firstly, optimal conditions were achieved for the application of two dimensional-gel electrophoresis (2D-GE)-based proteomics with postmortem human brain tissue. These optimized techniques were then applied to soluble fractions of adjacent grey and white matter of a single cytoarchitecturally defined area (Brodmann area 9; BA9) and of two adjacent regions of frontal white matter (BA9 and CC body) from healthy individuals. These normative proteomic comparisons highlighted the importance of correct tissue sampling, i.e. proper separation of regional white matter, as heterogeneity in the respective proteomes was demonstrated. Furthermore, they stressed the necessity for future molecular brain mapping studies. The main focus of this thesis however, was to examine the proteomes of brain regions specifically vulnerable to alcohol-induced damage underlying cognitive dysfunction. Alcoholic patients commonly experience mild to severe cognitive decline. It is postulated that cognitive dysfunction is caused by an alcohol-induced region selective brain damage, particularly to the prefrontal cortex. The cerebellum is increasingly recognized for its role in various aspects of cognition and alcohol–induced damage to the cerebellar vermis could indirectly affect neurocognitive functions attributed to the frontal lobe. We used a 2D-GE-based proteomics approach to compare protein abundance profiles of BA9 grey and white matter and the cerebellar vermis from human alcoholics (neurologically uncomplicated and alcoholics complicated with liver cirrhosis) and healthy control brains. Among the protein level changes observed are disturbances in the levels of a number of thiamine-dependent enzymes. A derangement in energy metabolism perhaps related to thiamine deficiency seems to be important in all regions analysed, even where there are no clinical or pathological findings of Wernicke-Korsakoff Syndrome. Evidence of oxidative changes was also seen in all regions and effects of liver dysfunction in the vermis found. However, overall, these results highlight the complexity of this disease process in that a number of different proteins from different cellular pathways appear to be affected. By identifying changes in protein abundance levels in the prefrontal grey and white matter and the cerebellar vermis, hypotheses may draw upon more mechanistic explanations as to how chronic ethanol consumption causes the structural and functional alterations associated with alcohol-related brain damage. Furthermore, by comparing these results, we may be able to isolate disturbances in molecular pathways specific to the brain damage caused by alcohol, severe liver dysfunction and thiamine deficiency.

Background: Alcohol Related Brain Damage (ARBD) is an umbrella term used to describe the range of effects that long-term consumption of alcohol can have on the structure and function of the brain. Despite the increasing prevalence of ARBD, there is a lack of research in this area, and as a result, there are no current guidelines and few services available for the treatment of this condition. There is therefore a need to increase the evidence base in this area, which will assist in the understanding, and ultimately treatment, of ARBD. Aims: This thesis consists of two parts. The first is a systematic review journal article which asks the question: “What is the impact of alcohol-abuse on memory function within the first three weeks of alcohol withdrawal?” The second part is a qualitative research project which aims to develop a grounded theory regarding the patient experience of ARBD, identifying and highlighting themes and concepts that are central to the experience. Methods: For the systematic review, four databases were searched. Studies that were included in the review had to have participants with alcohol-dependence; abstinence of less than or equal to three weeks; and to have undergone some form of neuropsychological assessment of memory function. Data from 15 articles were extracted and assessed for quality. For the qualitative study, participants (n=10) were interviewed regarding their experiences of ARBD and the data was then analysed using grounded theory methodology. Results: The results of the systematic review were somewhat ambiguous with some studies reporting impairments in verbal and visual memory, while other studies found no impairments. Episodic memory deficits were present in all studies reviewed. The results of the qualitative study propose a tentative model which describes “transformation through adaptation”. This model hypothesises that successful negotiation of the journey through ARBD hinges on the adaptations that need to be made in order to progress towards transformation. The model is understood in the framework of a number of phases, “Being diagnosed with ARBD, “Focusing on abstinence”, “Taking ownership of life with ARBD” and “Creating a valuable life”, all of which exist within a framework of being supported by specialist services. Conclusions and implications: The systematic review demonstrated some support for deficits in visual and episodic memory within the first three weeks of abstinence, while it appeared that verbal memory was relatively preserved. The heterogeneity of the studies, coupled with the methodological variability, meant that all conclusions need to be considered as tentative, and be interpreted with caution. The main difficulties with interpretation were to do with the confounding factors often found within this client group. The results reinforce the concept of tailored treatment programmes for individuals due to the large variability of the effect of alcohol (and other factors). The qualitative study proposes a model that shows how adaptation appears to play a key role in the successful negotiation of a diagnosis of ARBD. The study describes a series of categories that can be used as a framework to identify and support the changes that are necessary for recovery and reintegration. The value in this study is that the results are directly attributable to individuals who have been diagnosed, and are now successfully living, with ARBD.

Alkohol har funnits sedan urminnes tider och är något som de flesta ungdomar och vuxna är bekanta med. Flertalet vet också att för mycket alkohol på lång sikt kan orsaka skador, framförallt på lever (fettlever) och njurar. Men inte alla vet att alkohol skadar hjärnan och kan ge kramper samt epilepsi. Alkohol har olika effekter på kroppen. Akut kan det öka den inhiberande och minska den excitatoriska signaleringen i hjärnan. Långvarigt kan det öka den excitatoriska signaleringen, minska den inhibitoriska samt öka alkoholtoleransen. I hjärnan är balansen mellan den inhibitoriska och excitatoriska signaleringen mycket betydelsefull och rubbningar kan orsaka skador som i sin tur kan orsaka krampanfall. Dessa krampanfall kan bli allvarliga och ibland dödliga. Studier kring sambandet mellan alkohol och epilepsi utförda av Samokhvalov et al. (2010), Devetag et al. (1983), Bråthen et al. (1999), Tartara et al. (1983), Bartolomei et al. (1997), Victor och Brausch (1967) och Hillbom (1980) har visat på olika resultat, men trots skillnaden i resultaten har korrelationen mellan alkohol och epilepsi varit tydlig. I studien av Devetag et al. (1983) hade 58 % av 153 alkoholister anfall icke relaterade till abstinens, alkoholinducering eller sjukdom/skada. Av 60 patienter med krampanfall var 30 stycken (50 %) icke relaterade till abstinens, alkoholinducering eller sjukdom/skada i studien utförd av Bartolomei et al. (1997). Bråthen et al. (1999)  utförde en studie på 142 alkoholister med krampanfall där 16 stycken (36 %) var icke-relaterade till abstinens, alkoholinducering eller sjukdom/skada. Vidare påvisade Tartara et al. (1983) i sin studie 30 patienter med krampanfall där 3 stycken (10 %) inte var relaterade till abstinens, alkohlinducering eller sjukdom/skada. Krampanfall som inte är relaterade till abstinens, akoholinducering eller sjukdom/skada är kluriga och svåra att utreda. Många forskare har försökt få insikt i och reda ut frågan om alkohols influens över utvecklingen av epilepsi och hur det skulle tänkas gå till. När kan alkoholrelaterade krampanfall klassificeras som epilepsi, vad innebär ett alkoholrelaterat krampanfall och vilka orsaker existerar som leder till att sådanan krampanfall uppstår. I den här litteraturstudien utreds kopplingen mellan alkoholism och epilepsi för att bättre förstå sambandet. Till studien har 20 vetenskapliga artiklar använts för att förstå vilka effekter alkohol har på kroppen, vad det innebär att ha epilepsi och hur de båda är kopplade. För att komma fram till ett svar på den framförda frågeställningen i studien, om långvarigt bruk av alkohol ger kramper och epilepsi, användes 7 studier vars undersökingar huvudsakligen fokuserat på alkoholister inlagda med krampanfall. Resultaten från de 7 studierna indikerar sammantaget att alkohol sannolikt kan orsaka epilepsi. Ingen av studierna har visat motsatsen. Långvarigt bruk av alkohol ger kramper och kan även ge epilepsi, men hur det går till är inte klarlagt. Samtidigt finns det många individer som missbrukar alkohol och som inte får epilepsi eller aldrig ens upplever ett enda krampanfall.
Alcohol has been used for drinking for many years and is a substance that is well known to most teenagers and adults. Most people also know that alcohol, when misused, can cause damage to both the liver and the kidneys but not as many people know about the damage alcohol can cause the brain. The damage that alcohol causes in the brain can lead to conditions where the patient can experience seizures, whitch can further devlop into epilepsy. Alcohol has different effects on the body. An immidiate response to alcohol is that the inhibitory signaling in the brain increases and the excitatory signaling decreases. When it comes to a prolonged misuse of alcohol the effects on the brain are the opposite and it can also increase the tolerance for alcohol. Inhibitory and excitatory signaling in the brain are essential and disturbance of those signals can be very damaging to the brain. The damages can develop and become permanent and it can also trigger different kinds of seizures. The seizures can in turn become very serious and fatal. Studies on the connection between alcohol and epilepsy has been conducted by Samokhvalov et al. (2010), Devetag et al. (1983), Bråthen et al. (1999), Tartara et al. (1983), Bartolomei et al. (1997), Victor och Brausch (1967) och Hillbom (1980) and have shown different results. The results however have shown a clear correlation between alcohol and epilepsi. In the study performed by Devetag et al. (1983) 58 % of 153 patients experienced seizures not related to alcohol withdrawl, alcohol induction or injury/disease. Of 60 patients who presented seizures in the study conducted by Bartolomei et al. (1997), 30 (50 %) had seizures not related to alcohol withdrawl, alcohol induction or injury/disease. A study performed by Bråthen et al. (1999) showed  16 patients (36 %) of 142 with seizures not related to alcohol withdrawl, alcohol indiction or injury/disease. Furthermore, a study conducted by Tartara et al. (1983) showed 30 patients with seizures, where 3 (10 %) of them were not related to alcohol withdrawl, alcohol induction or injury/disease. Seizures not related to alcohol withdrawl, alcohol abuse or injury/disease are difficult to investigate. Many scientists have tried to get insight in as to how alcohol can influence the ethiopathogenesis of epilepsy. What is alcohol-related seizures, what is the cause behind the seizures and how does one decide if the seizures can be defines as epilepsy. This literature review investigates the link between alcoholism and epilepsy to better understand this connection. The question of issue was ”if prolonged misuse of alcohol can lead to epilepsy” and to unravel the question, 7 studies were used. The studies main focus was alcoholism and seizures. The results from the studies indicated in total that alcohol prabably can cause epilepsy since none of the studies showed the opposite. A prolonged misuse of alcohol can lead to seizures and even epilepsy, but how this comes to be is not clear and needs to be properly investigated. Not to forget, some people who misuse alcohol do not get epilepsy and some never experience even a single seizure.

Long-term heavy alcohol consumption causes significant brain abnormalities and impairs cognitive functioning. A number of terms have been used to describe these effects, including: ‘alcohol-related dementia’, ‘alcohol-induced dementia’, and ‘alcoholic dementia’. The more pragmatic umbrella term ‘alcohol-related brain damage’ (ARBD) is also used. The literature is beset with limitations, in particular the lack of a diagnostic gold standard, and the difficulty in making a clinical diagnosis. Many individuals labelled as having an alcohol-related dementia are, in fact, suffering from the Wernicke–Korsakoff syndrome (WKS). (This is a specific neuropathological disease caused by thiamine deficiency, which can occur secondary to alcohol misuse. It is considered in Chapter 4.1.12.) When considering the topic of ‘alcohol-related dementia’ it is probably sensible to take a broad clinically-based diagnostic view that includes both WKS and other cases of ‘dementia’ that appear to be alcohol-related. Alcohol-related dementia should be recognized as a preventable condition. However, identification is hampered by a lack of clarity in terminology, and a lack of standardized and specialized screening instruments and assessment procedures. These individuals make repeated use of Accident and Emergency Departments, general medical, and long stay wards. Early identification would reduce their need for these services. Abstinence is the key to recovery. Treatment services should be integrated and flexible.

Like the liver, the brain is commonly affected by long-term alcohol misuse. While neurocognitive dysfunctions are widely known in their most extreme presentations, such as Korsakoff’s syndrome and Wernicke’s encephalopathy (WE), there are other less explicit manifestations of neurocognitive damage which occur more frequently. This chapter explores these conditions under the umbrella term ‘alcohol-related brain damage’ (ARBD), more specifically employing the term Wernicke–Korsakoff’s syndrome (WK) when referring to the acute and chronic effects of thiamine deficiency. The correlation between excessive alcohol consumption and thiamine intake is explored, along with the body’s response of boosting gamma-aminobutyric acid (GABA)–benzodiazepine and NMDA receptors. In acute and non-acute cases of ARBD, prompt diagnosis and treatment are essential due to the risk of long-term cognitive and intellectual damage it can yield. As such, psychosocial treatment in the aftermath of the clinical phase is equally important, focusing on assessment, therapeutic intervention, adjustment, and social integration.

Alcohol is one of the most frequently used substances, and alcohol-related disorders are common, especially in western societies. While there is no safe lower drinking level, a clear dose–response relationship has been shown between alcohol intake and organ damage. Conceptualization and diagnostic classification of alcohol use disorders have changed over time, focusing most recently on aspects of craving, loss of control, and continued use despite negative consequences. Alcohol acts via various binding sites in the brain and via downstream effects, including glutamatergic, GABAergic, serotonergic, dopaminergic, opioid, and neuroendocrine pathways. For its long-lasting, habit-forming effects, sensitization within the mesolimbic–mesocortical system is crucial. Psychological treatments traditionally focus on motivational enhancement, cognitive behaviour therapy, and the community reinforcement approach. Pharmacological treatment approaches range from aversive and reward-inhibiting to anti-craving compounds and cognitive enhancers, which target opioid, glutamatergic, and monoamine receptors. Improvement of treatment effects can be achieved by polypharmacy and use of personalized medicine, based on clinical characteristics, biomarkers, and genetic indicators.

Alcohol produces a range of central-nervous-system-related biological effects, including anxiety reduction, euphoria, sedation, disinhibition, aggression, blackouts, tolerance, addiction, and withdrawal. The Chinese have used alcoholic drinks since 5000 B.C. Presumably, man ventured to drink the liquid from fermented grain, liked the intoxicating effect, and started to make it on purpose. Alcohol has been used as an anesthetic for millennia (see chapter 7). Alcohol is indispensable in medicine as a solvent. Laudanum, a staple of the medicine chest in the nineteenth century, was simply an alcoholic solution of opium. NyQuil, a cough syrup, and Listerine, an oral antiseptic, all contain copious amounts of ethanol. Alcohol has beneficial effects when consumed in moderate amounts. Research strongly suggests that moderate consumption of alcohol, especially red wine and dark beer, seems to have protective effects on the heart. The hallmarks of the Mediterranean diet are olive oil and red wine, and people from such countries have fewer cardiovascular events. Flavonoids, the active principle in red wine, are thought to exert beneficial cardiovascular effects. According to the Bible (Genesis 9:20–21), Noah was the first man who discovered wine: “Noah, a man of the soil, was the first to plant a vineyard. When he drank some of its wine, he became drunk and lay uncovered inside his tent.” The New Testament gives an account of Jesus performing his first miracle—turning water into wine. Despite the beneficial effects of moderate alcohol consumption, excessive use of alcohol damages the brain, heart, and liver. Even mild drunkenness can cause temporary loss of memory. The liver metabolizes alcohol with an enzyme called alcohol dehydrogenase, which turns alcohol into acetaldehyde. Because acetaldehyde is acutely toxic, people—including many Asians—who lack alcohol dehydrogenase cannot tolerate much alcohol. This is the reason that their faces become flush when they drink alcohol and that there are fewer incidents of alcoholism in Asians. Alcoholism is known to cause psychosis and alcoholic dementia. To fight the “demon rum,” on January 16, 1919, the U.S. Congress passed the Eighteenth Amendment, prohibiting “the manufacture, sale, or transportation of intoxicating liquors.” It was repealed 14 years later, the only amendment to the U.S. Constitution that has been repealed.

Luigino Troisi of the University of Salento found (Tetrahedron Lett. 2010, 51, 371) that a variety of primary and secondary amines could be coupled with a benzylic halide 1 under carbonylating conditions. Ilhyong Ryu of Osaka Prefecture University showed (Organic Lett. 2010, 12, 1548) that under reducing conditions, an iodide 3 coupled with CO to give the primary alcohol. Felicia A. Etzkorn of Virginia Tech observed (Organic Lett. 2010, 12, 696) that under Hg hydrolysis conditions, the orthothioester derived from 5 coupled with 6 to give 7. Yasuharu Yoshimi of the University of Fukui and Minoru Hatanaka of Iwate Medical University devised (Tetrahedron Lett. 2010, 51, 2332) conditions for the decarboxylative addition of the acid 8 to 9 to give 10. Yong-Min Liang and Xiaojun Yao of Lanzhou University and Chao-Jun Li of McGill University described (J. Org. Chem. 2010, 75, 783) a related procedure with α-amino acids. Yasutaka Ishii of Kansai University established (J. Am. Chem. Soc. 2010, 132, 2536) that t -butyl acetate 12 was an effective partner for the Ir-mediated oxidation-coupling-reduction of an alcohol 11. He used (J. Org. Chem. 2010, 75, 1803) a similar protocol to condense acetone with the diol 14, to give the long-chain diketone 16. The formation of allylic Grignard reagents can be inefficient because the excess reactive halide tends to couple with the Grignard reagent as it forms. Brandon L. Ashfeld of the University of Notre Dame found (Tetrahedron Lett. 2010, 51, 2427) a simple solution to this problem: inclusion of a catalytic amount of the inexpensive Cp2 TiCl2 to mediate the addition of 18 to 17. Brian T. Connell of Texas A&M University demonstrated (J. Am. Chem. Soc. 2010, 132, 7826) that with Mn, 21 could be added to 20. The acetate 21 is thus an easily prepared homoenolate equivalent. Note that although 21 is an E/Z mixture, the product 22 is cleanly Z. Gérard Cahiez of the Université de Paris 13 reported (Synlett 2010, 299) a detailed study of the Cu-catalyzed coupling of 24 with 23. Without supporting ligands, slow addition (syringe pump, 1 h) of 24 to 23 assured clean formation of 25. Manual slow addition (dropping funnel, 15 min) was not effective.