Cognitive impairment in alcohol use disorder and clinical practice guidelines for management of long-stay alcohol use disorder patients

INTRODUCTION Cognitive disorders affect over half of patients with alcohol use disorder (AUD),[1] even without neurological impairments. Identifying these cognitive deficits is important for several reasons. First, some deficits can progress to severe conditions like Korsakoff syndrome (KS) (persisting amnestic disorder), which is difficult to recover from. Early detection and treatment during Wernicke encephalopathy (WE) may prevent this progression.[2] Second, while abstinence from alcohol can improve cognitive function, it may persist for longer periods in some individuals.[3–5] Third, recognizing cognitive impairment can help identify patients who are less likely to follow treatment plans. Studies show that these patients retain less treatment-related information[6] and learn fewer skills to refuse alcohol.[7] Process and scope of the guideline This guideline summarizes the definition, assessment, and treatment of cognitive impairment in AUD, as well as the management of long-stay AUD patients. A PubMED search was conducted with relevant search terms to identify studies, including systematic reviews and meta-analyses, randomized controlled trials (RCTs), and observational studies that describe assessment and treatment of cognitive impairment in AUD. Additional hand search of references was performed to identify further relevant studies. Special emphasis was placed on identifying studies from India. Prior guidelines on this topic were also reviewed and included where available. Terminologies Several terminologies have been used to describe cognitive impairments in AUD. They are: Korsakoff syndrome (KS), alcohol-related dementia (ARD), alcohol-related brain damage (ARBD), alcohol-related cognitive impairments (ARCIs), and alcohol use disorder – mild cognitive impairment (AUD-MCI) [Table 1]. DSM-5 recognizes these conditions as alcohol-related neurocognitive disorder (major and minor, nonamnestic and amnestic, confabulatory), while ICD-11 differentiates between dementia and amnestic disorder due to use of alcohol. As there is an overlap between these definitions and it is sometimes difficult to distinguish the direct effects of alcohol from other conditions contributing to cognitive impairment in AUD such as KS, hepatic encephalopathy, or traumatic brain injury, the term ARCI is preferred over others as it encompasses all conditions related to cognitive impairment in AUD.Table 1: Conditions/Terminologies related to cognitive impairment in AUDClinical features of WE include the classic triad of ataxia, ophthalmoplegia, and confusion; however, not all patients present with all three features. Caine et al.[9] criteria for WE include a) presence of dietary deficiencies, b) oculomotor abnormalities, c) cerebellar dysfunction, and d) either an altered mental state or mild memory impairment; two of four features are highly suggestive. KS is characterized by severe anterograde amnesia, along with other inconsistent features such retrograde amnesia, difficulty identifying temporal sequence of events, executive function deficits, and confabulations.[10] Specific criteria for alcohol-related dementia have been suggested by Oslin et al.,[8] which help characterize probable or possible diagnosis [Table 2] and are validated in a longitudinal study.[11] However, there is no criterion for definitive diagnosis. Schmidt et al.[12] modified criteria add “no history of an acute onset of symptoms associated with WE” for diagnosis of ARD.Table 2: Diagnostic criteria for alcohol-related dementia (adapted from Oslin et al.[ 8 ])Prevalence of cognitive impairment in AUD Bruijnen et al.[13] in a cross-sectional multicentric study of outpatients from specialty addiction clinics found that 31% of those with substance use disorder screened positive for cognitive impairment, with 34% of those with AUD. Alcohol users had notably lower cognitive test scores compared to cannabis users. A previous study also found 38% of substance users had cognitive impairment.[14] Both studies suggest the need for early cognitive screening in AUD to improve treatment outcomes. Profile of cognitive impairment in AUD Four cognitive profiles have been identified in AUD: 1) unimpaired cognitive functioning, 2) representative dysexecutive syndrome with preserved memory and intelligence, 3) modified dysexecutive pattern with impaired memory and executive functions but preserved intelligence, and 4) global deterioration in memory, intelligence, and executive functions. The dysexecutive syndrome involves deficits in mental processes such as working memory, set-shifting, divided attention, problem-solving, and decision-making.[15] Episodic memory deficits are more relevant to AUD than semantic or implicit memory deficits.[16] These deficits in AUD typically involve difficulty in new long-term learning. Alcohol primarily impairs the encoding process that converts short-term memories into long-term ones, while short-term encoding is less affected. People with AUD also have trouble retrieving long-term memories, sometimes even after one or two drinks. These memory processes can be so severely affected that, once sober, individuals struggle to recall key details or entire events that occurred while they were intoxicated; this phenomenon is known as blackouts.[17,18] Other features include gaps in visuospatial functioning, including impaired visuospatial processing, greater impairment in visual memory and visual learning compared to verbal learning, and deficits in perceptual-motor tasks and visuospatial organization.[19,20] The domains are summarized in Table 3.Table 3: Cognitive domains impaired in AUDHow may AUD drive cognitive impairment? Several explanations have been proposed to explain the typical cognitive impairments seen in AUD, which can be broadly divided into three hypotheses [Table 4].[18] The first is the right hemisphere hypothesis. This follows from the impaired cognitive functions mentioned earlier, which are mostly served by the right hemisphere (RH). The strongest evidence for RH dysfunction in AUD comes from electrophysiological studies showing significant abnormalities in RH structures.[20] However, not all studies have supported the RH hypothesis.[21]Table 4: Mechanisms of cognitive impairment in AUDThe second hypothesis involves frontal lobe damage, which explains the centrality of executive function deficits seen in alcohol-related cognitive impairment. This is supported by clinical studies showing impairments in prefrontal neurobehavioral functioning,[22,23] structural imaging showing decreased frontal lobe volumes in AUD,[24] functional imaging showing consistently showing reduced frontal lobe circulation,[25] and lower levels of glucose metabolism,[26] all indicating a “hypofrontal” condition. Personality traits linked to frontal lobe involvement, such as disinhibition and impulsivity, may predispose individuals to alcohol dependence, especially early onset.[27] Additionally, the genetic predisposition to AUD may partly be due to genetic predisposition to impairments in frontal lobe circuitry.[28] The third hypothesis is the global brain damage/premature ageing theory.[20] Like the earlier theories, it draws evidence from neuropsychological deficits noted in AUD. This hypothesis tries to reconcile differences in literature: Some researchers have shown a preferential RH vulnerability to chronic alcohol consumption,[29] while others have found that frontal lobe and executive function deficits are most affected and worsen with age.[30] A meta-analysis of neuropsychological functioning in chronic alcohol users after abstinence highlights the diffuse nature of deficits involving the RH, frontal lobes, medial temporal, subcortical, and cerebellar structures.[31] Risk factors for cognitive impairment with alcohol Age As people age, their body water content decreases and their ability to metabolize alcohol reduces. This means that, for the same amount of alcohol consumed, older people will have a higher blood alcohol concentration compared to younger people. Additionally, brain changes in chronic alcohol users and nonalcoholic elderly individuals are similar,[32] including prominent frontal lobe atrophy, widened cerebral sulci, and enlarged ventricles. These observations support the premature ageing hypothesis mentioned earlier. Gender Men seem to be more vulnerable than women to the cognitive adverse effects of moderate to heavy drinking, although there are gender differences in specific cognitive domains [Table 5]. For example, women with AUD often perform better on episodic memory tests, while men tend to do better on visuospatial tasks.[33] Some of these differences continue even after achieving sobriety.[34] Neuroimaging study findings are inconsistent: Some suggest women experience greater reductions in gray and white matter than men,[35] while others do not.[36] A recent review found that women generally perform worse than men on tasks involving divided attention, memory, and decision-making.[37] Additionally, women often experience a faster progression of alcohol-related problems and their consequences, known as “telescoping,” which highlights differences in how alcohol affects cognition and psychological health between the sexes.[38]Table 5: Gender differences in cognitive impairment among patients with alcohol use disorderGeneral health When evaluating the relationship between alcohol and cognitive impairment, it is important to consider physical and mental health conditions that may mediate or moderate this relationship. Relevant physical conditions include liver dysfunction, cardiovascular impairment, and poor nutritional status. For example, thiamine deficiency from poor nutrition can lead to persistent cognitive deficits after chronic alcohol use and can cause persisting amnestic disorder, also known as Korsakoff syndrome.[20] Mental health conditions associated with chronic alcohol use include externalizing disorders such as conduct disorder, depression, anxiety disorders, bipolar disorder, and schizophrenia. Any of these conditions may moderate or mediate the relationship between alcohol and neurobehavioral outcomes. Although it is challenging to determine the exact contribution of each variable, it is important to consider their role when developing management or prevention strategies. Family history Hereditary factors influence vulnerability to AUD. Research from the Collaborative Studies on the Genetics of Alcoholism (COGA) involving multiplex families suggests that several interacting genetic loci, each with modest effects, contribute to AUD vulnerability.[40] Associations between dopamine gene polymorphisms and reward-dependent behaviors that influence AUD vulnerability have also been found.[41] More research is needed to understand the causal variants of these genes, their contribution to medical and psychiatric comorbidity, and their role in brain damage susceptibility in AUD. Indian evidence Prevalence of cognitive impairment in AUD: Community/hospital-based studies Several Indian studies have examined the prevalence of cognitive impairment in AUD. A hospital-based study found that four out of five patients with AUD who completed detoxification showed signs of global cognitive impairment.[42] Another facility-based study reported that the mean score on cognitive impairment screening tools for patients with alcohol dependence was below the cutoff.[43] Two community-based studies on adults[44] and older adults[46] found that over 50% of individuals with AUD had cognitive impairment. Additionally, a hospital-based study on patients with schizophrenia found that nearly three out of four patients had cognitive impairment, with half of the sample having comorbid AUD.[46] Factors influencing the association between AUD and cognitive impairment Alcohol use has been linked to different levels of cognitive impairment in community-dwelling older adults compared to those who never use alcohol.[47,48] However, some studies have found no such association.[49] Factors related to alcohol use—such as drinking patterns, duration of use, type of alcohol consumed, severity of dependence, family history, concurrent smoking, and age of onset of alcohol use—have been consistently correlated with cognitive impairment across these studies.[44,45,50] Follow-up studies Investigators have found that neurocognitive functioning improves in the short term with abstinence from alcohol. This highlights the importance of maintaining sobriety as a goal in AUD management.[4] Impact of cognitive impairment in AUD Cognitive deficits can affect the treatment and outcomes in AUD. They can impact the patient’s understanding of the problem and acceptance of treatment. Motivational enhancement therapy and cognitive behavioral therapy are challenging for these patients, necessitating more behavioral treatment strategies along with pharmacotherapy.[51] Assessing cognitive deficits is important for treatment plans as treatment with a heavy cognitive component may be more effective after cognitive processes relevant to the therapy have recovered.[52] Additionally, cognitive deficits can hinder medication adherence. Assessment of cognitive impairment in AUD Clinical assessment of cognitive impairment in AUD includes gathering information during history taking and bedside cognitive function testing. An approach to management of cognitive impairment in AUD is given in Figure 1.Figure 1: Approach to assessment and treatment of cognitive impairment in AUDBedside cognitive assessment The initial evaluation of cognitive impairment begins during clinical history taking. Patients or family members often report difficulties with attention, memory, planning, and carrying out daily activities. A thorough physical and neurological examination is essential to identify medical conditions that could contribute to cognitive impairment. A mental status examination should be performed to assess the cognitive functions at the bedside [see Table 6].Table 6: Bedside cognitive assessmentScreening for cognitive impairment General screening tools Screening for cognitive deficits in AUD patients is important in alcohol treatment centers as it can help tailor therapeutic programs. A simple, rapid screening test with good sensitivity, specificity, and reproducibility is needed. The Montréal Cognitive Assessment (MoCA),[53] a general cognitive screening tool, is widely used for this purpose. MoCA is adapted to five Indian languages, Hindi, Kannada, Telugu, Malayalam, and Bengali.[54] In AUD patients, the MoCA allows for rapid and confident screening of cognitive deficits[55] and helps evaluate cognitive changes following alcohol withdrawal.[56] The other commonly used tools are Mini Mental State Examination (MMSE)[57] and Addenbrooke’s Cognitive Examination – Revised (ACE-R).[58] Comparing the MoCA, MMSE, and ACE-R suggests that the MoCA and ACE-R are valid and for cognitive impairment in substance use has been found to be in screening for cognitive impairment in AUD is and adapted to Indian including Hindi, Telugu, Kannada, Malayalam, Indian and and for The MoCA is also for changes in cognitive in In the MoCA has been used to evaluate cognitive functions in AUD but scores are by some General cognitive screening tools for AUD patients are in Table General screening tools for cognitive function in screening tools Several specific tools for cognitive impairment in AUD have been [see Table A new screening of cognitive impairment to AUD patients, the of was five cognitive and functions that are impaired in AUD: episodic memory, working memory, executive visuospatial and A Cognitive for Alcohol was from the for of three and for rapid screening of cognitive impairment in AUD. 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