Severity of neuropsychological impairment in cocaine and alcohol addiction: association with metabolism in the prefrontal cortex
Introduction
Despite the growth of the research on the cognitive deficits in cocaine abusers (reviewed in Rogers and Robbins, 2001), the nature of these deficits is uncertain and the study of their putative neuropathological mechanisms is still in its infancy. Variability in research findings comparing cocaine users to non-users contributes to the delay in establishing a consensus on the magnitude and pattern of the neuropsychological (NP) deficits in cocaine addiction. Thus, although significant decrements are revealed in many of the NP studies (e.g., Beatty, Katzung, Moreland, & Nixon, 1995; Gillen et al., 1998; Rosselli & Ardila, 1996), lack of significant differences between cocaine users and non-users are common (e.g., Bolla, Rothman, & Rothman, 1999; Selby & Azrin, 1998) and counterintuitive results, where cocaine users outperform controls, are also frequently reported (e.g., Bolla et al., 1999, Gillen et al., 1998, Hoff et al., 1996, van Gorp et al., 1999).
Characterizing the underlying cognitive domains instead of analyzing multiple single test indices of cognitive functioning, might minimize some of this variability. Factor analytic techniques are ideal for reducing the redundant information contained within multiple single measures into a few separate dimensions. This is important because most tests in common clinical NP use place simultaneous demands on several cognitive functions. Analyzing this smaller set of variables would also increase sample-to-variable ratio, thereby reducing chance findings while preserving the measured content.
The analysis of cognitive domains in drug addiction has been previously undertaken in our laboratory (Hoff et al., 1996) and by others (e.g., Beatty et al., 1995; Di Sclafani, Tolou-Shams, Price, & Fein, 2002; Gillen et al., 1998; Robinson, Heaton, & O’Malley, 1999; Selby & Azrin, 1998). However, factor analytic techniques were not employed and no effort was made to empirically test the a priori assignment of test measures into the predetermined cognitive clusters.
Moreover, the relationship of these cognitive domains with brain function (e.g., Hoff et al., 1996, Holman et al., 1991; Mittenberg & Motta, 1993; Strickland et al., 1993) has not been determined. Associations between cerebral perfusion and neurocognitive performance in drug addicted individuals have been previously deducted from the co-occurrence of perfusion abnormalities and NP impairments in the same individuals (see for example Gottschalk, Beauvais, Hart, & Kosten, 2001; Holman et al., 1991, Strickland et al., 1993). When the analysis of correlations between functional measures of brain and behavior was conducted, sample sizes were limited (Wang et al., 1993), specific cognitive domains were not examined (Woods et al., 1991), or regional brain measures were not used (e.g., Di Sclafani et al., 1998).
In the present study, 20 NP test indices most reliably defining six predetermined cognitive domains in 42 crack/cocaine addicted subjects and 72 comparison subjects were submitted to exploratory factor analysis. A group of 40 alcoholics was additionally included for comparison and to increase statistical power. We then examined the association of the empirically (factor-analytically) derived four cognitive scales with measures of regional cerebral glucose metabolism obtained at resting baseline using positron emission tomography with 2-deoxy-2[]fluoro-d-glucose (PET ). Six regions of interest (ROIs) were selected for these correlation analyses: the orbitofrontal gyrus, anterior cingulate gyrus, dorsolateral prefrontal cortex, hippocampus, thalamus, and basal ganglia. These regions comprise the brain reward circuit most frequently implicated in the neurobiology of drug addiction (see Goldstein & Volkow, 2002; Volkow & Fowler, 2000).
Section snippets
Subjects
A comprehensive battery of NP tests was administered to 42 cocaine addicted subjects, 40 alcoholics, and 72 comparison subjects who participated in PET studies at Brookhaven National Laboratory between 1988 and 1996. The NP functioning of subgroups of the current study’s population was previously described (e.g., Hoff et al., 1996, Wang et al., 1993). The NP battery was administered a mean of 60 days (range −13–1466 days; 90% of the subjects were tested within 6 months and 98% within 1 year of
Demographics, drug use, and PET measures
Means and standard deviations for demographics, drug use variables, and measures of regional absolute and relative metabolism in the reward ROIs for the three study groups are presented in Table 1. There were significant differences between the cocaine addicted subjects and comparison subjects in distribution of sex and handedness, and in age and education. For the alcohol group, there were significant differences from the comparison subjects in distribution of handedness, in education, and in
Discussion
The main objective of this study was to characterize the nature of the NP impairment in crack/cocaine addicted subjects using a group of alcoholics and non-addicted subjects for comparison. The present study: (1) developed a four-dimensional model of neurocognitive functioning from multiple standard NP test indices in 42 crack/cocaine addicted subjects, 40 alcoholics, and 72 comparison subjects participating in PET neuroimaging studies at Brookhaven National Laboratory between 1988 and 1996;
Conclusions
In conclusion, this study documented a relatively mild NP impairment in cocaine addiction which should not be misinterpreted as indicative of the absence of neurocognitive dysfunction in this group. Demonstrating clear associations between cognitive functioning as assessed by NP testing and neuronal functioning as estimated by PET , we furthered the fledgling research on the brain–behavior relationship in drug addiction.
Acknowledgements
This study was supported by grants from the National Institute on Drug Abuse (to NDV: DA06891-06; and to RZG: 1K23 DA15517-01), US Department of Energy (OBER), National Institute on Alcohol Abuse and Alcoholism (AA/ODO9481-04), and ONDCP.
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