Neurological, nutritional and alcohol consumption factors underlie cognitive and motor deficits in chronic alcoholism

Abstract

Variations in pattern and extent of cognitive and motor impairment occur in alcoholism (ALC). Causes of such heterogeneity are elusive and inconsistently accounted for by demographic or alcohol consumption differences. We examined neurological and nutritional factors as possible contributors to heterogeneity in impairment. Participants with ALC (n = 96) and a normal comparison group (n = 41) were examined on six cognitive and motor domains. Signs of historically determined subclinical Wernicke's encephalopathy were detected using the Caine et al. criteria, which were based on postmortem examination and chart review of antemortem data of alcoholic cases with postmortem evidence for Wernicke's encephalopathy. Herein, four Caine criteria provided quantification of dietary deficiency, cerebellar dysfunction, low general cognitive functioning and oculomotor abnormalities in 86 of the 96 ALC participants. Subgroups based on Caine criteria yielded a graded effect, where those meeting more criteria exhibited greater impairment than those meeting no to fewer criteria. These results could not be accounted for by history of drug dependence. Multiple regression indicated that compromised performance on ataxia, indicative of cerebellar dysfunction, predicted non-mnemonic and upper motor deficits, whereas low whole blood thiamine level, consistent with limbic circuit dysfunction, predicted mnemonic deficits. This double dissociation indicates biological markers that contribute to heterogeneity in expression of functional impairment in ALC. That non-mnemonic and mnemonic deficits are subserved by the dissociable neural systems of frontocerebellar and limbic circuitry, both commonly disrupted in ALC, suggests neural mechanisms that can differentially affect selective functions, thereby contributing to heterogeneity in pattern and extent of dysfunction in ALC.

Keywords: Caine criteria; Wernicke's encephalopathy; alcohol; ataxia; memory; thiamine.

Figure 1

Bar graphs depicting age- and education-corrected scores on the cognitive and motor composites for the ALC and NC groups. ANOVAs: Attention/Working Memory (Att/WM) t(132)=2.66, p=.0087; Production (Prod) t(131)=2.67, p=.0085; Immediate Memory (ImmMem) t(131)=3.90, p=.0002; Delayed Memory (DelMem) t(131)=3.54, p=.0006; Visuospatial Construction (Visuosp) t(135)=2.32, p=.02; Upper Limb Motor (UppMot) t(131)=1.89, p=.06.

Figure 2

Bar graphs depicting the alcohol Caine-categorized subgroups in comparison with the ALC group as a whole and the NC group. Att/WM - Attention/Working Memory; Prod – Production; ImmMem – Immediate Memory; DelMem – Delayed Memory; Visuosp –Visuospatial Construction; UppMot – Upper Limb Motor.

Figure 3

Bar graphs depicting the ALC group divided into subgroups based on the dietary deficiency and cerebellar dysfunction criteria. Attention/Working Memory: ALCs meeting only the ataxia criterion scored lower than ALCs meeting neither criterion (t=2.24, p=.028) or ALCs who met only the diet criterion (t=2.48, p=.016). Production: ALCs meeting only the ataxia criterion and ALCs meeting both criteria scored lower than ALCs meeting neither criterion (t=2.19, p=.032; t=2.28, p=.025) and ALCs meeting only the diet criterion (t=2.14, p=.035; t=2.25, p=.027). Immediate Memory: ALCs meeting both criteria scored lower than ALCs meeting neither criterion (t=2.75, p=.007) and ALCs meeting only the diet criterion (t=2.29, p=.025). Delayed Memory: ALCs meeting both criteria were impaired compared with ALCs who met neither criteria (t=2.78, p=.007). Upper Limb Motor: ALCs meeting only the ataxia criterion and ALCs meeting both criteria scored lower than ALCs meeting only the diet criterion (t=2.29, p=.025; t=2.45, p=.017).

Figure 4

Bar graphs showing age-corrected scores for the 4 gait and balance tasks for ALC and NC.

Figure 5

Scatterplots showing the relationship between age-corrected ataxia score (average of the 4 balance and gait measures) and the attention/working memory, production, and upper limb composite scores for ALC.

Figure 6

Scatterplots showing the relationship between thiamine levels and total lifetime alcohol consumption and immediate memory and delayed memory scores for ALC.

Figure 7

Model showing a double dissociation between factors predicting mnemonic and nonmnemonic abilities in ALC. Total lifetime alcohol and thiamine level were each independent and unique predictors of episodic memory in ALC, whereas ataxia predicted nonmnemonic functions.

Figure 8