The Effect of Chronic Alcohol on Cognitive Decline: Do Variations in Methodology Impact Study Outcome? An Overview of Research From the Past 5 Years

Abstract

Excessive alcohol use is often associated with accelerated cognitive decline, and extensive research using animal models of human alcohol consumption has been conducted into potential mechanisms for this relationship. Within this literature there is considerable variability in the types of models used. For example, alcohol administration style (voluntary/forced), length and schedule of exposure and abstinence period are often substantially different between studies. In this review, we evaluate recent research into alcohol-induced cognitive decline according to methodology of alcohol access, as well as cognitive behavioral task employed. Our aim was to query whether the nature and severity of deficits observed may be impacted by the schedule and type of alcohol administration. We furthermore examined whether there is any apparent relationship between the amount of alcohol consumed and the severity of the deficit, as well as the potential impact of abstinence length, and other factors such as age of administration, and sex of subject. Over the past five years, researchers have overwhelmingly used non-voluntary methods of intake, however deficits are still found where intake is voluntary. Magnitude of intake and type of task seem most closely related to the likelihood of producing a deficit, however even this did not follow a consistent pattern. We highlight the importance of using systematic and clear reporting styles to facilitate consistency across the literature in this regard. We hope that this analysis will provide important insights into how experimental protocols might influence findings, and how different patterns of consumption are more or less likely to produce an addiction-vulnerable cognitive phenotype in animal models.

Chronic alcohol-induced long-lasting working memory deficits are associated with altered histone H3K9 dimethylation in the prefrontal cortex

“…In studies using animal models of human alcohol consumption, damages of the medial PFC neurons have been associated with deficits in various spatial WM tasks in both voluntary and non-voluntary models (Charlton and Perry, 2022). Indeed, all spatial WM tasks rely on the functional integrity of the medial PFC working in conjunction with the dHPC and, consistent with this, alcohol-induced damage of prefrontal neurons produced enduring WM impairments in rodents assessed through the spontaneous alternation T-maze or Y-maze tests (Vargas et al, 2014;Ikram et al, 2019).…”

Lipidomic changes of cerebral cortex in aldehyde dehydrogenase-2 knock-in heterozygote mice after chronic alcohol exposure

“…Unfortunately, there was no significant difference in cognitive behavior observed in ALDH2 deficiency mice after chronic alcohol administration in this study. Besides for ALDH2 genotype, the severity of deficits might be impacted by age, sex, schedule, and type of alcohol administration ( Charlton and Perry, 2022 ). However, as the respect of lipid changes, ALDH2*2 mice had not only vital changes in the overall composition of lipids, but also diverse alterations in the length and degree of unsaturation of the acyl chains of glycerophospholipids.…”

Baclofen treatment prevents persistent working memory deficits induced by alcohol withdrawal through restoration of histone H3 methylation in mice

“…In studies using animal models of human alcohol consumption, hypo-functionality of the medial PFC contributes to deficits in spatial WM in both voluntary and non-voluntary models [32]. In mice, prolonged exposure to alcohol impaired spatial memory in the water maze test and reduced spontaneous alternation performance using Y-maze task [33].…”