The primary goal of the proposed research is to test two opposing models of why the CNS morbidity due to alcohol abuse is greatest in the elderly alcoholic. The generally accepted age-related vulnerability model postulates a greater vulnerability of the older brain to the toxic effects of alcohol. An alternative model, the cumulative effects model, postulates the duration and amount of abusive drinking (regardless of when in the lifespan it took place) and the aging process as the only factors underlying the greater CNS morbidity in the older alcoholic. In the cumulative effects model, the younger brain is able to compensate for the damage done by alcohol abuse/dependence until cognitive losses associated with normal aging undermine these compensatory mechanisms and the CNS morbidity due to alcohol abuse/dependence (earlier in life) becomes apparent. There is no data in the literature to test the differential predictions of these models (e.g., data on the CNS status of elderly individuals who were alcoholic into late middle age, but who have been abstinent for 10 years or more) because research to date has focused only on recently abstinent individuals. We will test these two opposing models of how age modulates chronic alcohol abuse effects on CNS structure and function using state-of-the-art methods. Structural brain imaging will be used to assess regional morphological brain changes; electrophysiological and neuropsychological testing will assess functional changes in information processing abilities. The study will use a cross-sectional design with five groups, each group consisting of 30 males and 30 females. The secondary goal of this project is to determine whether there are gender differences in the effects of chronic alcohol abuse on CNS function, and the matter in which age modulates these effects. Our final goal in the project is to examine other factors (e.g., brain """"""""functional reserve,"""""""" presence of the APOE-epsilon4 allele) that may modulate the effects of chronic alcohol abuse/dependence and age on brain structure and function.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project (R01)
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Alcohol and Toxicology Subcommittee 4 (ALTX)
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Witt, Ellen
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Neurobehavioral Research, Inc.
United States
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Fein, George; Cardenas, Valerie A (2017) P3b amplitude is not reduced in abstinent alcoholics with a current MDD. Alcohol 63:33-42
Fein, George; Camchong, Jazmin; Cardenas, Valerie A et al. (2017) Resting state synchrony in long-term abstinent alcoholics: Effects of a current major depressive disorder diagnosis. Alcohol 59:17-25
Fein, George (2015) Psychiatric Comorbidity in Alcohol Dependence. Neuropsychol Rev 25:456-75
Fein, George; Cardenas, Valerie A (2015) Neuroplasticity in Human Alcoholism: Studies of Extended Abstinence with Potential Treatment Implications. Alcohol Res 37:125-41
Fein, George; Greenstein, David (2013) Gait and balance deficits in chronic alcoholics: no improvement from 10 weeks through 1 year abstinence. Alcohol Clin Exp Res 37:86-95
Fein, George; Smith, Stan; Greenstein, David (2012) Gait and balance in treatment-naive active alcoholics with and without a lifetime drug codependence. Alcohol Clin Exp Res 36:1550-62
Fein, George; Andrew, Colin (2011) Event-related potentials during visual target detection in treatment-naive active alcoholics. Alcohol Clin Exp Res 35:1171-9
Smith, Stan; Fein, George (2011) Persistent but less severe ataxia in long-term versus short-term abstinent alcoholic men and women: a cross-sectional analysis. Alcohol Clin Exp Res 35:2184-92
Sameti, Mohammad; Smith, Stan; Patenaude, Brian et al. (2011) Subcortical volumes in long-term abstinent alcoholics: associations with psychiatric comorbidity. Alcohol Clin Exp Res 35:1067-80
Fein, George; Shimotsu, Ryan; Barakos, Jerome (2010) Age-related gray matter shrinkage in a treatment naïve actively drinking alcohol-dependent sample. Alcohol Clin Exp Res 34:175-82

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