A systematic review of treatments for alcohol-related cognitive impairment: lessons from the past and gaps for future interventions.

Alcohol-related cognitive impairment (ARCI) is highly prevalent among patients with alcohol dependence. Although it negatively influences treatment outcome, this condition is underdiagnosed and undertreated. The aim of this systematic review is to investigate the existing evidence regarding both cognitive and pharmacological interventions for ARCI. We systematically reviewed PubMed, Scopus and Science direct databases up to May 2019 and followed the PRISMA guidelines. The quality of the studies was assessed using the Jadad Scale. Twenty-six studies were eligible for inclusion (14 referring to neuropsychological interventions and 12 to pharmacological treatments). Among neuropsychological interventions, computerised treatments, errorless learning and component method showed positive effects on working memory, memory measures and general cognitive function. On the other hand, thiamine, memantine and methylphenidate improved working memory, long-term memory and general cognitive function. Nevertheless, these studies have several limitations, such as small sample size, lack of replication of the results or low specificity of the interventions. Therefore, no gold-standard intervention can yet be recommended for clinical practice, and further research based on promising strategies (e.g. digital interventions, thiamine) is required.

Patients With Severe Alcohol-Related Cognitive Impairment Improve in Flexibility When Abstinence Is Maintained: A Comparative Study With Alzheimer's Disease.

The disease progression of severe alcohol-related cognitive impairment (ARCI) is debated. The aim of this study was to compare the cognitive change of patients with severe ARCI in inpatient setting to that of patients with Alzheimer's disease (AD). Fifteen consecutive patients with severe ARCI were recruited between 2013 and 2015. They received inpatient detoxification, neurological assessment, and inpatient cognitive rehabilitation in specialized facilities. Twelve patients, with documented AD matched on sex and initial cognitive impairment severity, were selected. All have benefited from two neuropsychological assessments. The neurocognitive change was tested in both groups with pair-wised Wilcoxon tests. ARCI and AD patients' time course was compared with Mann-Whitney-Wilcoxon test. In ARCI group, first assessment occurred at 2.9 (± 2.2) months of abstinence and follow-up 6.5 (± 2.9) months later, the mean age was 56.5 (± 7.4) years, and 12 were men. In AD group, follow-up occurred at 12.8 (± 2.9) months (p < 10-3), the mean age was 72.3 (± 8.4) years (p < 10-3), and 10 were men. ARCI patients significantly improved on one executive function test (TMT-B; p < 0.05), while AD patients have worsened memory subtests on Free-and-Cued-Selective-Reminding Test (p < 0.05). These tests showed a statistically different change between severe ARCI and AD group (p < 0.05). Severe ARCI patients have improved in executive functioning, discernible on the TMT-B test, in specific care setting, including abstinence maintenance and rehabilitation. The disease progression was different from that observed in AD patients.

Altered Global Signal Topography in Alcohol Use Disorders.

The most common symptom of patients with alcohol use disorders (AUD) is cognitive impairment that negatively affects abstinence. Presently, there is a lack of indicators for early diagnosis of alcohol-related cognitive impairment (ARCI). We aimed to assess the cognitive deficits in AUD patients with the help of a specific imaging marker for ARCI. Data-driven dynamic and static global signal topography (GST) methods were applied to explore the cross-talks between local and global neuronal activities in the AUD brain. Twenty-six ARCI, 54 AUD without cognitive impairment (AUD-NCI), and gender/age-matched 40 healthy control (HC) subjects were recruited for this study. We found that there was no significant difference with respect to voxel-based morphometry (VBM) and static GST between AUD-NCI and ARCI groups. And in dynamic GST measurements, the AUD-NCI patients had the highest coefficient of variation (CV) at the right insula, followed by ARCI and the HC subjects. In precuneus, the order was reversed. There was no significant correlation between the dynamic GST and behavioral scores or alcohol consumption. These results suggested that dynamic GST might have potential implications in understanding AUD pathogenesis and disease management.

The altered functional connectivity density related to cognitive impairment in alcoholics.

Alcohol use disorder (AUD) is one of the most common substance use disorders contributing to both behavioral and cognitive impairments in patients with AUD. Recent neuroimaging studies point out that AUD is a typical disorder featured by altered functional connectivity. However, the details about how voxel-wise functional coordination remain unknown. Here, we adopted a newly proposed method named functional connectivity density (FCD) to depict altered voxel-wise functional coordination in AUD. The novel functional imaging technique, FCD, provides a comprehensive analytical method for brain's "scale-free" networks. We applied resting-state functional MRI (rs-fMRI) toward subjects to obtain their FCD, including global FCD (gFCD), local FCD (lFCD), and long-range FCD (lrFCD). Sixty-one patients with AUD and 29 healthy controls (HC) were recruited, and patients with AUD were further divided into alcohol-related cognitive impairment group (ARCI, n = 11) and non-cognitive impairment group (AUD-NCI, n = 50). All subjects were asked to stay stationary during the scan in order to calculate the resting-state gFCD, lFCD, and lrFCD values, and further investigate the abnormal connectivity alterations among AUD-NCI, ARCI, and HC. Compared to HC, both AUD groups exhibited significantly altered gFCD in the left inferior occipital lobe, left calcarine, altered lFCD in right lingual, and altered lrFCD in ventromedial frontal gyrus (VMPFC). It is notable that gFCD of the ARCI group was found to be significantly deviated from AUD-NCI and HC in left medial frontal gyrus, which changes probably contributed by the impairment in cognition. In addition, no significant differences in gFCD were found between ARCI and HC in left parahippocampal, while ARCI and HC were profoundly deviated from AUD-NCI, possibly reflecting a compensation of cognition impairment. Further analysis showed that within patients with AUD, gFCD values in left medial frontal gyrus are negatively correlated with MMSE scores, while lFCD values in left inferior occipital lobe are positively related to ADS scores. In conclusion, patients with AUD exhibited significantly altered functional connectivity patterns mainly in several left hemisphere brain regions, while patients with AUD with or without cognitive impairment also demonstrated intergroup FCD differences which correlated with symptom severity, and patients with AUD cognitive impairment would suffer less severe alcohol dependence. This difference in symptom severity probably served as a compensation for cognitive impairment, suggesting a difference in pathological pathways. These findings assisted future AUD studies by providing insight into possible pathological mechanisms.

Identification and Evaluation of Neuropsychological Tools Used in the Assessment of Alcohol-Related Cognitive Impairment: A Systematic Review.

Background: Neuropsychological assessment is central to identifying and determining the extent of Alcohol-Related Cognitive Impairment (ARCI). The present systematic review aimed to synthesize and discuss the evidence appraising the neuropsychological tests used to assess ARCI in order to support clinicians and researchers in selecting appropriate tests for use with this population. Methods: We searched for studies investigating the psychometric, diagnostic and practical values of tools used in the screening, diagnosis, and assessment of Korsakoff's Syndrome (KS), Alcohol-Related Dementia (ARD), and those with a specific diagnosis of Alcohol-Related Brain Damage (ARBD). The following databases were searched in March 2016 and again in August 2018: MEDLINE, EMBASE, Psych-INFO, ProQuest Psychology, and Science Direct. Study quality was assessed using a checklist designed by the authors to evaluate the specific factors contributing to robust and clearly reported studies in this area. A total of 43 studies were included following the screening of 3646 studies by title and abstract and 360 at full-text. Meta-analysis was not appropriate due to heterogeneity in the tests and ARCI samples investigated in the studies reviewed. Instead, review findings were narratively synthesized and divided according to five domains of assessment: cognitive screening, memory, executive function, intelligence and test batteries, and premorbid ability. Effect sizes (d) were calculated to supplement findings. Results: Overall, several measures demonstrated sensitivity to the cognitive deficits associated with chronic alcoholism and an ability to differentiate between gradations of impairment. However, findings relating to the other psychometric qualities of the tests, including those important for the accurate assessment and monitoring of ARCI (e.g., test-retest reliability), were entirely absent or limited. Additionally, the synthesis of neuropsychological outcomes presented here supports the recent impetus for a move away from discrete diagnoses (e.g., KS, ARD) and the distinctions between them toward more broad and inclusive diagnostic conceptualizations of ARCI, thereby recognizing the heterogeneity in presentation. Conclusions: Based on the evidence reviewed, provisional recommendations for appropriate tests in each domain of assessment are presented, though further validation of most tests is warranted. Review findings can support efficient and evidenced-based test-selection and guide future research in this area.