Alcohol-related amnesia and dementia: Animal models have revealed the contributions of different etiological factors on neuropathology, neurochemical dysfunction and cognitive impairment

Abstract

Chronic alcoholism is associated with impaired cognitive functioning. Over 75% of autopsied chronic alcoholics have significant brain damage and over 50% of detoxified alcoholics display some degree of learning and memory impairment. However, the relative contributions of different etiological factors to the development of alcohol-related neuropathology and cognitive impairment are questioned. One reason for this quandary is that both alcohol toxicity and thiamine deficiency result in brain damage and cognitive problems. Two alcohol-related neurological disorders, alcohol-associated dementia and Wernicke-Korsakoff syndrome have been modeled in rodents. These pre-clinical models have elucidated the relative contributions of ethanol toxicity and thiamine deficiency to the development of dementia and amnesia. What is observed in these models-from repeated and chronic ethanol exposure to thiamine deficiency-is a progression of both neural and cognitive dysregulation. Repeated binge exposure to ethanol leads to changes in neural plasticity by reducing GABAergic inhibition and facilitating glutamatergic excitation, longterm chronic ethanol exposure results in hippocampal and cortical cell loss as well as reduced hippocampal neurotrophin protein content critical for neural survival, and thiamine deficiency results in gross pathological lesions in the diencephalon, reduced neurotrophic protein levels, and neurotransmitters levels in the hippocampus and cortex. Behaviorally, after recovery from repeated or chronic ethanol exposure there is impairment in working or episodic memory that can recover with prolonged abstinence. In contrast, after thiamine deficiency there is severe and persistent spatial memory impairments and increased perseverative behavior. The interaction between ethanol and thiamine deficiency does not produce more behavioral or neural pathology, with the exception of reduction of white matter, than long-term thiamine deficiency alone.

Effects of drugs of abuse on hippocampal plasticity and hippocampus-dependent learning and memory: contributions to development and maintenance of addiction

“…In addition to the overall health problems caused by alcohol abuse, alcoholism is also known to cause cognitive impairments (Ryan and Butters 1983;see Stavro et al 2013 for a meta-analysis) with over 50% of alcoholics reporting memory and cognition problems (Vetreno et al 2011). The results from laboratory animal studies also demonstrate alcohol's impairing effects on cognition.…”

“…Evidence from human studies seems to be in agreement with animal studies showing chronic ethanol-induced cognitive impairments and disrupted hippocampal function. For example, impairments in learning and memory (Ryan and Butters 1983;Vetreno et al 2011), attention and executive function (Loeber et al 2009), and abstraction (Klisz and Parsons 1977; for review, see Bates et al 2002) were reported after chronic alcohol use. These cognitive deficits also persisted during abstinence (Fein et al 1990;Stavro et al 2013).…”

Thiamine diphosphate synthesis and redox state indicator in rat brain during of B(1) hypovitaminosis

“…The literature data show that in neurodegenerative pathologies (Wernicke-Korsakov syndrome, Alzheimer's and Parkinson's disease, etc. ), as well as in TD, changes in different brain regions do not occur synchronously [22][23][24]. Taking into account these observations, we conside red it worthwhile to study changes in ThDP metabolism in different parts of the brain during the Hv-T development.…”

Principales daños sanitarios y sociales relacionados con el consumo de alcohol

“…Aunque la mayoría de las personas alcohólicas tienen trastornos cognitivos (de memoria y aprendizaje) aún se debate el papel de la toxicidad del alcohol y de la deficiencia de tiamina en estos problemas, en particular en la demencia relacionada con alcohol y en el síndrome de Wernicke-Korsakoff. En este sentido, los modelos animales muestran que los problemas relacionados con alcohol pueden ser parcialmente reversibles pero no los debidos a deficiencia de tiamina 72,73 . No hay evidencias de que el consumo ligero o moderado aumente el riesgo de demencia e incluso es posible que lo disminuya [74][75][76][77] .…”