Effects of Chronic Alcohol Dependence and Chronic Cigarette Smoking on Cerebral Perfusion: A Preliminary Magnetic Resonance Study

Brain perfusion quantitates blood flow to tissue per unit time and is typically tightly coupled with brain metabolic activity (e.g., Raichle et al., 1976; Silverman et al., 2001). Previous studies of the effects of chronic alcohol dependence on cerebral perfusion employing 133Xe inhalation tomography and 99mTc-HMPAO single photon emission tomography (SPECT) demonstrated perfusion abnormalities in the frontal, parietal, and temporal lobes. Specifically, these studies indicated larger perfusion deficits in the right hemisphere (Berglund et al., 1987; Tutus et al., 1998), left hemisphere (Erbas et al., 1992), or bilateral abnormalities (Demir et al., 2002; Mampunza et al., 1995; Nicolas et al., 1993). Similarly, abnormal glucose metabolism has been shown with 18FDG-positron emission tomography (PET), especially in frontal lobes of alcohol-dependent individuals (Gilman et al., 1990; Volkow et al., 1994). Lower frontal cerebral perfusion among individuals in alcohol treatment was associated with deficits in working memory and executive functions (Demir et al., 2002; Nicolas et al., 1993; Noel et al., 2001, 2002). However, the aforementioned studies did not account for the potential effects of concurrent chronic cigarette smoking on cerebral perfusion and/or metabolism. Tobacco products are the most frequently used substances among alcoholics, with an estimated 80% of alcohol-dependent individuals smoking regularly (Hurt et al., 1994; Pomerleau et al., 1997; Romberger and Grant, 2004) and 50 to 90% demonstrating nicotine dependence (Daeppen et al., 2000; Marks et al., 1997). Active cigarette smoking in alcoholics has been associated with significantly higher quantity and frequency of alcohol consumption (John et al., 2003), particularly compared with nonsmoking or former-smoking alcohol-dependent individuals (York and Hirsch, 1995). Chronic cigarette smoking has been associated with increased risk for arteriosclerosis (e.g., Bolego et al., 2002; Haustein et al., 2004), compromised vasomotor reactivity (Bolego et al., 2002; Terborg et al., 2002), and impaired pulmonary function (Yamashita et al., 1988). After at least 2 hours of abstinence from smoking, chronic nonalcoholic smokers demonstrated 4 to 12% lower global brain perfusion, compared with nonsmokers, as measured by 133Xe inhalation (Rogers et al., 1983; Yamashita et al., 1988). However, another study without any constrains on smoking before an IMP–SPECT scan demonstrated 22% lower global perfusion in smokers (Rourke et al., 1997), with perfusion inversely related to cigarette pack-years. The lower perfusion reported in smokers in the latter study may be partially accounted for by acute effects of smoking, consistent with 7 to 10% global decrease in glucose utilization following acute nicotine administration (Domino et al., 2000; Stapleton et al., 2003). Smoking also elicits different patterns of relative perfusion responses, with increases of the order of 6 to 8% in a number of brain regions including prefrontal and cingulate cortices as well as decreases in cerebellum and occipital lobes that were associated with plasma nicotine levels (Brody, 2005; Domino et al., 2004; Rose et al., 2003). Thus, it is not clear if acute cigarette smoking affects absolute perfusion in prefrontal and cingulate cortices (Brody, 2005). Chronic cigarette smoking, independent of chronic and heavy alcohol consumption, was also linked to compromised memory, cognitive flexibility, executive functions, psychomotor speed, general intellectual abilities, and working memory (see Durazzo et al., 2004, and references therein). Moreover, smoking appears to modulate relationships between brain morphology, metabolites, and neurocognition in recently detoxified and short-term abstinent alcoholics (Durazzo et al., 2004, 2006; Gazdzinski et al., 2005). This possibly reflects a reorganization of neural networks or compensatory increase in the activity of other functional networks (see Desmond et al., 2003; Pfefferbaum et al., 2001) to counter the additional adverse neurobiologic effects of chronic smoking. Perfusion deficits may be related to metabolic and/or structural abnormalities observed in recently detoxified alcoholics (see Sullivan, 2000, for review). Brain perfusion is closely coupled with brain glucose metabolism (Silverman et al., 2001), and we showed that glucose metabolism was positively associated with the concentration of N-acetylaspartate (NAA; putative marker of neuronal viability) measured with magnetic resonance spectroscopy (O'Neill et al., 2000). Some studies also reported associations between cerebral hypoperfusion and atrophy (Nicolas et al., 1993; Oishi et al., 1999; Yamaguchi et al., 1983). Thus, perfusion deficits may be associated with decreased levels of NAA and/or brain shrinkage reported in alcoholics. Via proton magnetic resonance spectroscopic imaging, we demonstrated that cigarette smoking exacerbated alcohol-induced neuronal dysfunction in the frontal lobe of alcohol-dependent individuals and that chronic smoking had independent, detrimental effects on tissue in select subcortical nuclei and the cerebellum (Durazzo et al., 2004). We also showed comorbid chronic cigarette smoking and alcoholism were associated with parietal, temporal, and occipital gray matter (GM) volume reductions that were greater than GM shrinkage induced by alcohol dependence alone (Gazdzinski et al., 2005). Given the high comorbidity between alcohol dependence and chronic cigarette smoking and their adverse effects on cerebral perfusion, it is not clear if the perfusion deficits reported in previous studies of alcohol-dependent individuals are solely attributable to alcohol consumption or if the combination of both chronic alcohol dependence and cigarette smoking produce greater adverse effects on brain perfusion than alcohol dependence alone. Furthermore, it is unclear if smoking affects the relationships between cerebral perfusion and cognitive function in alcohol dependence. In this cross-sectional study, we used magnetic resonance imaging (MRI) to noninvasively measure cerebral perfusion in a group of 1-week-abstinent alcohol-dependent individuals (ALC), who were retrospectively classified into smokers (sALC) and nonsmokers (nsALC), and in an age-matched group of nonsmoking light drinking individuals (nsLD). We compared groups on mean brain perfusion in GM and white matter (WM) of the frontal and parietal lobes, bilaterally, and related regional perfusion to performance on a brief neuropsychological test battery assessing visuospatial learning and memory, working memory, and visuomotor scanning speed and incidental learning. We tested the following hypotheses: Alcohol-dependent participants, as a group, demonstrate lower frontal and parietal GM and WM perfusion than nonsmoking light drinkers. Smoking alcoholics demonstrate lower frontal and parietal perfusion than nonsmoking alcoholics and nonsmoking light drinkers in GM and WM. Nonsmoking alcoholics demonstrate lower frontal and parietal perfusion than nonsmoking light drinkers in the frontal and parietal lobes, bilaterally. Regional perfusion is negatively correlated with measures of drinking and smoking severity. Lower frontal and parietal perfusion are associated with worse performance on measures of visuospatial learning and memory, working memory, and visuomotor scanning speed and incidental learning.