A protein may signal alcohol-related cognitive impairment

When diagnosing patients with alcohol use disorder (AUD), a physician usually asks about the person’s drinking habits, performs a physical examination, orders laboratory tests and may refer them for a psychological examination. In Spain, 20,000 people were diagnosed with AUD in 2020, according to a Ministry of Health report last year. Often, patients face an overworked healthcare system that lacks the necessary resources for comprehensive neuropsychological monitoring, says Laura Orío, a senior researcher at the Hospital 12 de Octubre’s I+12 Foundation in Madrid, Spain. The scientist is leading a research project that has discovered a biomarker that, through a blood test, can detect cognitive deterioration in those suffering from this disease.

The team observed that patients with lower cognitive levels also had higher levels of reelin, a protein found in the brain that helps its formation in early stages and its proper function and protects the brain when it suffers damage. “We were very surprised. In the scientific community, it is understood to be a good protein,” Orío explains. The scientists also found that people with the highest reelin levels also had another protein, called apolipoprotein E-4 (APOE-4), which is produced by a genetic mutation and only present in a very small percentage of the population. APOE-4 promotes alcohol’s toxic effects in those who have it, says Berta Escudero, the study’s other lead author, a psychologist and a researcher at the I+12 Foundation.

The study included a sample of 24 patients who had been diagnosed with AUD and were in the early abstinence period (four weeks without drinking) and a control group of 34 people. They assessed the subjects’ cognition using a screening test for alcoholism-related cognitive impairment. The test evaluates visuospatial skills (object representation), memory and executive function (everything related to attention, concentration and decision-making). Those with the worst results also had the highest levels of reelin. The study’s findings were published last June in the International Journal of Neuropsychopharmacology.

When patients enter a detoxification program, they are given pharmacological treatment and group therapies. The former focuses on alleviating withdrawal syndrome, although there are also abuse-deterrent drugs that instead seek to “reduce the desire to consume [alcohol],” explains Francisco Pascual, the president of Socidrogalcohol, a non-profit scientific organization dedicated to treating and preventing addictions.

The researchers found that both cognitive deterioration and reelin levels had been reduced in the worse-off patients after six months of abstinence. It is still too early to speak of causality, but it is possible to do so in relational terms, says the psychologist.

One of Orío’s hypotheses is that this protein appears with alcohol withdrawal as a response mechanism and then gradually decreases. “The body tries to produce more of [the protein] to increase the probability of it having a protective effect,” Escudero explains. That is why it is important to measure [reelin] during the first weeks of abstinence; it serves as a biomarker.

Each person’s reelin levels also depend on other factors, such as the length of time the patient has been drinking and the amount consumed. Persistent alcohol use causes inflammation, and the attendant changes in the brain, to spread over time and can lead to lesions in the brain structure, says Javier Carmiña, the spokesman for the Spanish Society of Neurology (SEN), which is not involved in the research.

Alcohol use disorder is linked to cancer, type 2 diabetes, liver disease and heart disease, but it can also damage mental health and lead to cognitive impairment and diseases like dementia. In addition to all these effects, it also causes social and occupational problems for those who suffer from the condition. However, the problem is underdiagnosed because society does not recognize that alcohol consumption causes diseases beyond addiction, laments Pascual, of Socidrogalcohol, who did not participate in this research project. “It is part of our traditions [and] our innermost being, we celebrate everything with alcoholic beverages.”

Patients who consume alcohol and have cognitive dysfunction should seek help because it can be improved

Cognitive rehabilitation treatment specifically trains executive function and short-term memory, which are necessary in most day-to-day activities, Carmiña explains. “Once alcohol consumption is discontinued, several areas tend to improve, especially attentional functions, at the beginning.” According to the neurologist, patients’ recovery of cognition depends heavily on how much alcohol they have consumed during their addiction.

The project is ongoing. Orío says that they are monitoring the patients long-term to find out the mechanism that links reelin and cognitive impairment due to alcohol use disorder. They are also continuing to search for new biomarkers that can serve as indicators.

All four experts agree that this finding can make an important difference for patients. Identifying people with cognitive impairment would make it easier to refer them directly to a cognitive stimulation program; instead of their cognition worsening, it could be maintained or even improved, says Escudero. Carmiña concludes: “Patients who consume alcohol and have cognitive dysfunction should ask for help because it can be improved.”

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