Another hypothesis is that thiamine (vitamin B1) deficiency is primarily responsible for the development of ARD. Individuals with alcohol use disorders are at particularly high risk Carfilzomib mw of thiamine deficiency, not only from poor dietary nutrition but because alcohol directly compromises thiamine metabolism [16]. Thiamine deficiency can lead to Wernicke’s encephalopathy (WE), an acute neurological disorder characterized by the clinical triad of oculomotor abnormalities, cerebellar dysfunction, and altered mental state and by the traditionally defined pathology of neuronal loss and hemorrhagic lesions in the paraventricular and periaqueductal grey matter. Not all individuals with WE show the triad of neurological symptoms, and the severity of signs is likely related to the extent of the underlying pathology [17].

To increase diagnostic accuracy of WE, refined operational criteria specify a minimum of two symptoms for diagnosis, a guideline recently endorsed by the European Federation of Neurological Societies (EFNS) [18,19]. Long-term outcomes of WE can include development of a syndrome of profound memory impairment – Korsakoff syndrome (KS) – that appears to be related to additional disruption to diencephalic and hippocampal circuitry. As KS shares similar pathological substrates and often follows an episode of WE, it is commonly referred to as the Wernicke-Korsakoff syndrome [1]. Increasing evidence suggests that the WKS encompasses a spectrum of pathological, neurological, and cognitive impairments resulting from thiamine deficiency [4].

The heterogeneity in presentation of the WKS, in combination with a lack of distinct pathological evidence for ARD, has led to the suggestion that cases of ARD are variants of the WKS [20]. Other evidence suggests that ARD and WKS are distinct disorders with overlapping clinical symptoms and associations such as peripheral neuropathology and ataxia [21]. The relationship of Wernicke-Korsakoff syndrome to alcohol-related dementia: pathophysiology In cases found to have WKS pathology at autopsy, the syndrome was correctly diagnosed in only around 20% of individuals prior to death [22]. Overlap with ARD has been noted, and it has been hypothesized that inactive (chronic) WE is likely to be the main underlying pathology GSK-3 in both KS and ARD [23,24].

Individuals with diagnosed KS and ARD show greater loss of neurons in the nucleus basalis than individuals selleck screening library with uncomplicated alcoholism, although this needs replication [25,26]. Graded deficits in regional brain volumes, in which ‘uncomplicated alcoholics’ demonstrate similar but less severe lesions than individuals with WKS (mammillary bodies, thalamus, cerebellar hemispheres, and vermis), also suggest that subclinical bouts of thiamine deficiency contribute to mild structural changes in alcohol-related disorders [17].