Application of the criteria of Caine et al (1997)
revealed that 16% of the ‘uncomplicated alcoholics' in this sample had signs of WE (ie met two criteria), which is in agreement with the prevalence rates reported postmortem in this population (12–14% Harper et al, 1986
), and indicates a higher than expected potential occult incidence of this neuropsychiatric disorder in alcoholics without apparent complications. Half of the alcoholic group met criteria for dietary deficiency and had lower TDP levels than those without a history of nutritional deficiency even though the two groups did not significantly differ on TDP level. This finding suggests that these two ways of measuring potential dietary deficiency may reflect two different but related phenomena: the nutritional status at the time of the blood test and a history of withholding meals while drinking. The use of biomarkers complements the taking of a comprehensive history, which remains essential because there is currently no established threshold level of TDP above which patients would be safe from developing brain damage (Thomson et al, 2010
). Our preliminary findings indicate that current TDP concentrations are not influenced by the length of sobriety, the severity of alcohol consumption or dependence, or age.
Ataxia was also frequently observed among alcoholics (Sullivan et al, 2010
). That only two alcoholics had nystagmus and none had mild-cognitive impairment may reflect the rarity of certain criteria (Caine et al, 1997
; Harper et al, 1986
; Naidoo et al, 1991
), suboptimal measurements used herein, or the resolution of these signs following only a short period of sobriety. Extending earlier work (Caine et al, 1997
), this study also shows that more than half of the ‘uncomplicated alcoholics' met one criterion and may, therefore, be considered at risk for WE. These findings encourage the use of the Caine et al
criteria in clinical settings for detection, prevention, and treatment of alcoholics at risk for or with signs of alcohol-related neuropsychiatric complications before the development of irreversible and debilitating damage such as KS. These criteria could be used together with the clinical protocols for diagnosis and treatment developed by Thomson and colleagues (Thomson et al, 2002
; Thomson and Marshall, 2006
). Given the high prevalence of preclinical signs of WE in uncomplicated alcoholics and the low reports of anaphylactic reaction with thiamine supplementation (for review, see Thomson et al, 2002
), such treatment could be proposed not only to alcoholics with ostensible clinical signs of WE, but to all alcoholics. The addition of thiamine to food products has been another established method of delivery of thiamine for many years, particularly the enrichment of flour (Harper et al, 1998
Our neuropsychological results comport with previous investigations showing that, when analyzed as a group, alcoholics have lower performance than controls on scores reflecting the average of verbal and performance IQ (Tedstone and Coyle, 2004
), memory (Pitel et al, 2007a
), and processing speed tasks (Pitel et al, 2007b
). However, whole group analyses cannot address the heterogeneity in the profiles of cognitive and motor performance observed within a sample of alcoholics. By conducting subgroup analysis, this study supports previous individual analysis (Pitel et al, 2008
), indicating that in some patients, alcoholism does not affect cognitive and motor functioning, while in others, severe alcohol-related neuropsychological impairments occur.
Heterogeneity in the patterns of neuropsychological performance in the alcoholics examined herein was observed. Comparison between subgroups of alcoholics classified according to the WE criteria of Caine et al
revealed a graded effect in the cognitive and motor performance of the alcoholic subgroups, with those not meeting any criteria performing at control levels, those at risk for WE showing mild-to-moderate deficits on some of the functional domains examined, and those with signs of WE showing the most severe deficits on each of the domains. These graded effects suggest, first, that the presence of signs of WE explains, at least partially, the heterogeneity of alcoholism-related cognitive and motor deficits. Second, because alcoholics at risk for WE performed worse than controls or alcoholics not meeting any WE criteria on tests of IQ, memory, visuoconstruction, and processing speed, these domains may be particularly vulnerable to the effects of alcohol. This study also provides preliminary correlational evidence that memory performance in alcoholics is especially related to levels of the biologically active form of thiamine, indicating that this functional domain of memory may be particularly sensitive to impairments in the levels of thiamine even when in the normal range. Interestingly, we found relationships between neuropsychological performance and TDP concentrations in the group of alcoholics taken as a whole and in those with a history of nutritional deficiency, but not in those without such history. Alcoholics with a history of nutritional deficiency, who present with slightly lower TDP levels than those without such history may be more susceptible to the combined effects of alcohol and thiamine decreases, or lower TDP levels may be an enduring marker for previous bouts of nutritional insufficiencies. Third, because the alcoholic subgroups did not differ with respect to age, sex, lifetime alcohol intake, or length of sobriety, these factors are unlikely to explain why alcoholics differ in the number of criteria met or the extent of functional impairment. Higher education in alcoholics with no WE criteria suggests that education might be considered as protective against alcohol-related neuropsychiatric disorders, similar, perhaps, to what has been described in other disorders such as Alzheimer's disease (Querbes et al, 2009
). However, differences observed between alcoholic subgroups in neuropsychological performance endured after controlling for education, indicating that this factor did not explain the graded effect of cognitive and motor deficits. The analysis of IQ scores comports with these findings because current IQ was not disproportionately different from premorbid IQ in the subgroups of alcoholics. Finally, other factors not investigated in this study, such as the individual genetically determined vulnerability to the combined effects of alcohol and thiamine deficiency, are potential contributors to heterogeneity in the expression of alcoholism-related neuropsychological compromise.
These conclusions are based on a limited sample and require replication with larger and more diverse group including notably more female alcoholics. Nonetheless, this initial study provides promising evidence for the utility of Caine et al criteria in identifying alcoholics at risk for WE. Use of such retrospective criteria combined with current examination and thiamine testing (TDP in whole blood) could be instrumental in overcoming certain challenges of in vivo human study, including questionable reliability of some clinical variables such as the estimation of lifetime alcohol consumption or the nutritional history, especially in alcoholics with neuropsychological deficits.