Cerebrospinal Fluid Biomarkers in Patients With Alcohol Use Disorder and Persistent Cognitive Impairment

Abstract

Background The prevalence of cognitive impairment is high among alcohol‐dependent patients. Although the clinical presentation of alcohol‐related cognitive disorder (ARCD) may resemble that of Alzheimer’s disease (AD), the prognosis and treatment of the 2 diseases are different. Cerebrospinal fluid (CSF) biomarkers (tau, phosphorylated tau, and amyloid β) have high diagnostic accuracy in AD and are currently being used to discriminate between psychiatric disorders and AD, but are not used to diagnose ARCD. The aim of this study was to characterize CSF biomarkers in a homogeneous, cognitively impaired alcohol‐dependent population. Methods This single‐center study was conducted in an addiction medicine department of a Parisian Hospital. We selected patients with documented persistent cognitive impairment whose MoCA (Montreal Cognitive Assessment) score was below 24/30 after at least 1 month of documented inpatient abstinence from alcohol. We measured the CSF biomarkers (tau, phosphorylated tau, and amyloid β 1‐42 and 1‐40) in 73 highly impaired alcohol‐dependent patients (Alcohol Use Disorders Identification Test score over 11 for women and 12 for men) with. Results Patients' average age was 60 ± 9.1 years and 45 (61.6%) had a normal CSF profile, 8 (11.0%) had a typical CSF AD profile, and 20 (27.4%) had an intermediate CSF profile. Conclusions This study revealed a high prevalence of AD in alcohol‐dependent patients with persistent cognitive deficits and several anomalies in their CSF profiles. Thus, it is important to consider AD in the differential diagnosis of persistent cognitive deficits in patients with alcohol dependence and to use CSF biomarkers in addition to imaging and neuropsychological testing to evaluate alcohol‐related cognitive impairment.

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

“…In 15 severe ARCI patients, it was not observed a cognitive worsening of memory function at 6.5 months of follow-up, contrarily to AD patients. Moreover, in the very stringent severe ARCI group constituted to reduce clinical heterogeneity by having eliminated the others etiologies for dementia (Azuar et al, 2021) and where alcohol abstinence was documented and where continuous neuropsychological rehabilitation was delivered during a 9 month follow-up on average, it was observed a modest but statistically significant improvement on executive functions, discernible on the TMT-B test. The disease progression was different between severe ARCI and AD patients.…”

“…Malnourishment itself was defined as either weight loss ≥ 10%, with respect to any previously recorded weight from a previous medical record; or weight loss ≥ 5% in 1 month, with respect to a previously recorded weight; or Body Mass Index ≤ 17 kg/ m 2 , or serum albumin < 30 g/l; or serum prealbumin < 110 mg/l. Third, any other documented etiology for dementia (degenerative or vascular) had to be ruled out with the adequate brain imaging and/or cerebrospinal fluid examination (Azuar et al, 2021).…”

“…Regarding the executive functions, the results were discordant and only Fujiwara et al showed a possible improvement in some of the executive functions at follow-up after 2 years, but the patients were abstinent since several years at baseline (Fujiwara et al, 2008). This wide variability may be related to the heterogeneity in patients included as having Wernicke-Korsakoff syndrome, already a difficult classification (Schwarzinger et al, 2018;Azuar et al, 2021), as well as the heterogeneity of assessment in terms of choice in neurocognitive tests, of time since the diagnosis or time between the test and the retest.…”

Alcohol Withdrawal Is an Oxidative Stress Challenge for the Brain: Does It Pave the Way toward Severe Alcohol-Related Cognitive Impairment?

“…The neuroprogression theory applies to AW leading to persistent cognitive deficits. But at the end of the evolution when a severe cognitive disorder is diagnosed in a patient with a past history of severe AUD, despite comprehensive etiological inquiry [ 82 ], it is impossible to differentiate the proper impact of repetitive AW from the neurotoxic effect of alcohol use. The effects of alcohol intake and AW may be cumulative and also interact with other independent pathophysiological processes: the development of neurodegenerative disorders, a vascular dysfunction, events such as seizures or strokes, nutritional depletion, etc., lowering the threshold of significant impairment and advancing the diagnosis.…”

Trimethylamine N-Oxide (TMAO) and Indoxyl Sulfate Concentrations in Patients with Alcohol Use Disorder

“…TMAO is found in the cerebrospinal fluid, and could promote blood–brain barrier disruption, aggregation of Aβ protein and tau-tubulin assembly [ 14 ]. TMAO could also be involved in the perturbation of beta-amyloid and tau homeostasis and thus may play a role in the development of cognitive deficits in AUD patients [ 15 , 16 , 17 ]. Lastly, another recent experimental work showed that TMAO can contribute to brain aging [ 18 ].…”