The diencephalic amnesia characteristic of the Korsakoff's syndrome (KS) has greatly contributed to our understanding of multiple memory systems or processes of the brain. Based on similarities between the neuropsychological decline in KS and aging, there have been suggestions that alcoholism can accelerate natural chronological aging or that older people are particularly susceptible to the cumulative effects of alcoholism (i.e., direct neurotoxicity and thiamine deficiency). The assumption that developmental factors could contribute to an individual susceptibility to the neurotoxic effects of alcohol was highlighted in the 1970's by the studies that indicated abnormalities in the activity of the transketolase enzyme in the KS. However, the hypothesis that a mutation of the transketolase gene could underlie the enzymatic abnormalities has been recently rejected. We will critically review here issues related to the neurochemistry and neuropathology, neuropsychology and neuroimaging of the KS. We will advocate the view that a genetic contribution can only weakly account for a predisposition to the KS, but it cannot be discarded. It seems reasonable to assume that there is a critical age for the neurotoxic action of alcohol, and the effects of alcoholism are simply disproportionately expressed in older alcoholics.
Keywords: Korsakoff's syndrome, amnesia, development