About half of the nearly 20 million alcoholics in the United States seem to be free of cognitive impairments. In the remaining half, however, neuropsychological difficulties can range from mild to severe. For example, up to 2 million alcoholics develop permanent and debilitating conditions that require lifetime custodial care (Rourke and Löberg 1996). Examples of such conditions include alcohol-induced persisting amnesic disorder (also called Wernicke-Korsakoff syndrome) and dementia, which seriously affects many mental functions in addition to memory (e.g., language, reasoning, and problem-solving abilities) (Rourke and Löberg 1996). Most alcoholics with neuropsychological impairments show at least some improvement in brain structure and functioning within a year of abstinence, but some people take much longer (Bates et al. 2002; Gansler et al. 2000; Sullivan et al. 2000).
- These potential differences deserve close scrutiny in the context of other variables such as age, drinking history, perceived social sanctions for drinking, impulsivity, genetic risk factors, etc. (Nolen-Hoeksema and Hilt 2006).
- Females can be more susceptible than males to many of the negative consequences of alcohol use, such as nerve damage, as they may begin to see effects from a lower amount of alcohol consumption.
- Such studies instead indicate limited metabolic pathway reactions and capacity of astrocytes to detoxify ammonia by glutamine synthesis and emphasize distortions of energy and neurotransmitter metabolism (Zwingmann 2007).
- Studies of alcohol-related central nervous system disorders are used as a framework for findings in uncomplicated alcoholism.
MRS Findings in Uncomplicated Alcoholism
- If you suspect an alcohol overdose and the person is unconscious, do not leave them alone.
- WKS is a brain disorder caused by a thiamine deficiency or lack of vitamin B-1.
- In one study, ERP abnormalities in alcoholics were particularly evident in the right frontal area (Porjesz and Begleiter 1982).
- Neuroimaging studies that measured gender differences in alcoholics’ brain functioning have yielded contradictory evidence, with some studies showing women to be more susceptible than men to brain impairments, and other studies showing no such distinction.
- The risk of brain damage and related neurobehavioral deficits varies from person to person.
- Anti-inflammatory and neuroprotective agents can be one of the novel therapeutic options to treat or diminish the progression of neurodegenerative disease.
Besides, immune therapy, N terminus-based antibodies immunization has a significant role in clearing the misfolded protein (Aβ and tau protein) but it is only effective at the earliest stage of disease 77. Active Aβ immunotherapy (AN1792 vaccine trial) provided evidence of progression of mild to moderate dementia prior to death with a clearance of brain plaque in post-mortem follow-up 129,130. Tau Immunotherapy ACI-35 blocks the oligomerization of tau protein and improves motor activity, neurological deficiency with extended life expectancy in the tau transgenic rodent model 131,132. Therefore, novel therapeutic options are needed to treat the single or multi-target molecules of misfolded protein formation, oxidative stress damage, cognitive impairments, and synaptic integrity as well as the pro-inflammatory response in alcohol-induced neurodegeneration.
How can alcohol-related neurologic disease be prevented?
Itself a complex construct, impulsivity has been commonly operationalized with tasks measuring inhibitory control of responses, i.e., go/no-go tasks, which require subjects to refrain from responding on some trials. Some evidence suggests that alcohol may have disinhibitory effects on behavior. Rather low alcohol doses (peak BAC of ~0.04%) decrease the latency of arousal to sexually explicit stimuli (Wilson and Niaura 1984).
Intoxication and behavioral control
MBD, a disease marked by mildly impaired mental status (e.g., confusion) and sometimes by dysarthria (Lee et al. 2011) or ataxia (Arbelaez et al. 2003), is poorly understood but may be related to nutritional deficiencies in addition to chronic alcohol consumption (Kawamura et al. 1985). Traditionally characterized by demyelination and necrosis of the corpus callosum, a number of reports identify cortical lesions in so-called MBD (Ihn et al. 2007; Johkura et al. 2005; Khaw and Heinrich 2006; Namekawa et al. 2013; Tuntiyatorn and Laothamatas 2008; Yoshizaki et al. 2010). Such data, however, represent single case studies and may reflect inaccurate MBD diagnoses.
Alcohol-induced disinhibition is also reflected in premature motor preparation based on incomplete stimulus evaluation (Marinkovic et al. 2000). The disinhibitory effects could result from the psychomotor stimulant properties of alcohol (Wise 1988), or may reflect a disruption in the inhibitory control of behavior subserved by prefrontal regions (Peterson et al. 1990). Indeed, alcohol decreases inhibitory control under the conditions of stop-signal imperative stimuli (Mulvihill et al. 1997) and a demanding vigilance task (Dougherty et al. 1999), as demonstrated by moderately intoxicated subjects who are impaired in withholding responses to inappropriate stimuli. Impairments in mental functions such as attention and vigilance can be detected at BAC levels much lower than the legal intoxication levels, such as 0.02–0.03% (Koelega 1995). Alcohol intoxication disrupts neurophysiological indices of stimulus processing in attentional (Grillon et al. 1995; Jääskeläinen et al. 1999; Marinkovic et al. 2001; Porjesz and Begleiter 1985), semantic, (Marinkovic et al. 2001, 2004), and psychomotor domains (Ridderinkhof et al. 2002). Furthermore, consistent with the evidence obtained alcohol overdose from chronic alcoholics, acute intoxication results in a disproportionate impairment of executive functions such as planning, working memory, or complex behavioral control (Peterson et al. 1990).
MRS studies of the human brain have revealed a reduced level of NAA in several brain regions of patients with AUD which indicates neuronal injury. Similarly, studies in AUD patients have shown an elevated level of choline-containing compounds that usually provide evidence of demyelination but it is not consistent with alcohol withdrawal syndrome 71,11. According to earlier studies, alcohol withdrawal seizures commonly occur due to an imbalance between glutamatergic and GABAergic neurotransmission which can be detected by MRS of the human brain 107. Studies on the rodent and human brain delineated that excessive ethanol intake induces neuronal injury during various developmental stages including neurodegeneration and this type of ethanol-induced neurodegeneration seems to be connected with glial activation and neuroinflammation 23,63,64. Astrocytes and oligodendrocytes play a crucial role in the molecular mechanism of signal conduction and neurotransmission in both gray and white matter. Besides, astrocytes, oligodendrocytes, and myelin protein take part in the maintenance of plasticity of gray and white matter 65.
HE caused by alcoholism compared with other forms of HE (e.g., as a result of viral infection or primary biliary cirrhosis) appears to have different effects on DTI parameters (Miese et al. 2006), with more widespread changes in FA and MD in alcoholic relative to nonalcoholic cirrhosis (Ahluwalia et al. 2015). When researchers induced hyperammonemia in cirrhotic patients, an increase in ADC in brain white matter was observed, supporting excess ammonia in the blood as a mechanism driving cerebral edema (Mardini et al. 2011). Thinning of the corpus callosum occurs in uncomplicated alcoholics and is more prominent in the anterior than posterior regions (Estruch et al. 1997; Pfefferbaum et al. 1996). As with WE and KS, evidence for MBD-like pathology in uncomplicated alcoholism raises the possibility that brain damage occurs on a continuum. The following section examines how brain structures and function respond when drinking stops.
- The heights of the peaks are measured in terms of the strength of the electrical signal (volts) recorded from the scalp over time (in thousandths of a second, or mS).
- Many of the effects of heavy alcohol use are reversible or can at least be significantly improved.
- Like PET and SPECT, fMRI permits observing the brain “in action,” as a person performs cognitive tasks or experiences emotions.
Other health conditions
This article reports key findings in humans, from macrostructural findings using magnetic resonance imaging (MRI), microstructural findings using diffusion tensor imaging (DTI), and metabolic findings from MR spectroscopy (MRS). Studies of alcohol-related central nervous system disorders are used as a framework for findings in uncomplicated alcoholism. The article also examines studies of abstinence and relapse and current imaging studies of animal models of alcoholism and co-occurring brain disorders. The evidence suggests that human studies are necessary to identify and classify the brain systems modified by concomitants of alcoholism versus alcoholism, per se, and that animal models of alcoholism and its co-occurring brain disorders are essential for a mechanistic understanding of vulnerable brain systems. The main goal of neuroimaging techniques is to diagnose cognitive and functional abnormalities of the brain.
Health
Magnetic resonance spectroscopy (MRS) provides additional information about the molecular concentration and ethanol metabolites in the brain 104. Proton-MRS can explore region-specific neurobiological status in combination with genetic mediated neurocognitive decline which has potential efficacy for future clinical management of AUD 105. The largest MRS signals arise from N-acetyl aspartate (NAA), glutamate, glutamine, and choline-containing compounds (Cho) which are considered to measure neuronal integrity and normal brain function 106,70.
Short-term effects
- Alcohol in the stomach and intestine continues to enter the bloodstream and circulate throughout the body.
- Thus, brain swelling in cirrhosis is thought to reflect an increase in astrocytic glutamine formation.
- Clearly, many questions remain concerning the nature and extent of gender differences in the effects of alcoholism on brain and behavior.
- A local increase in metabolic rate results in an increased delivery of blood and increased oxygenation of the region participating in a task.
Therefore, more studies are needed to establish the role of the NMDA receptor in the mechanism of neurodegeneration or neuro-regeneration in patients with AUD. Before discussing the effect of alcohol on BBB damage, we have to look through alcohol absorption and metabolism. The liver is the predominant organ for ethanol metabolism which usually occurs via two oxidative pathways mediated by alcohol dehydrogenase (ADH) and cytochrome P450 2E1 (CYP2E1) 30 (Figure 1). In brief, after drinking alcohol, absorption Occurs in the gastrointestinal tract then the liver converts the alcohol to acetaldehyde through the first-pass metabolism in the liver, this oxidation reaction is catalyzed by the alcohol dehydrogenase enzyme 31,32.