We have observed increased cerebrospinal fluid (CSF) and reduced grey and white matter volumes in many regions of the brains of chronic alcoholic men shortly after withdrawal. Over the first 4 weeks of abstinence, there is some reversibility of the CSF volume increase, especially ventricular enlargement. The brain shrinkage associated with chronic alcoholism accelerates with advancing age, and it is also associated with some measures of lifetime alcohol exposure, suggesting that the aging brain may be especially susceptible to the neurotoxic effects of alcohol. We have begun a longitudinal magnetic resonance imaging (MRI) study of morphological brain changes associated with chronic alcoholism in men. We will expand this study to include alcoholic and control women. We propose to add additional older male subjects, with early and late onset of alcoholism. We will follow all subjects over more extended periods of time in order to identify factors influencing the appearance, progression, and/or reversibility of neuroanatomic alterations. In addition we will explore the significance of the morphologic brain alterations in terms of neuropsychological (NP) and electrophysiology (ERP) function. The experimental design and subject selection are constructed to allow us to test the """"""""vulnerable aging brain"""""""" vs the """"""""cumulative alcohol toxicity"""""""" hypotheses regarding the aging/alcoholism interaction effect on brain morphology. NP testing will include assessment of neuroanatomically localized cognitive and motor functions. Scalp recorded ERP components, particularly the P3, will be analyzed using a newly developed statistical inverse solution, based on a 4-shell model of the brain. This analysis will allow us to differentiate between abnormalities attributable to changes in potential sources themselves and those attributable to non-brain (i.e., skull and scalp thickness) and brain (i.e., tissue reduction and CSF expansion) factors. Newly developed MRI acquisition sequences and analysis procedures will be used to enable quantitative assessments of specific neuroanatomic structures and production of whole section proton longitudinal relaxation time (T1) maps.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA005965-11
Application #
3109234
Study Section
Biochemistry, Physiology and Medicine Subcommittee (ALCB)
Project Start
1983-07-01
Project End
1996-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
11
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Stanford University
Department
Type
Schools of Medicine
DUNS #
800771545
City
Stanford
State
CA
Country
United States
Zip Code
94305
Sullivan, Edith V; Zahr, Natalie M; Sassoon, Stephanie A et al. (2018) The Role of Aging, Drug Dependence, and Hepatitis C Comorbidity in Alcoholism Cortical Compromise. JAMA Psychiatry 75:474-483
Pfefferbaum, Adolf; Zahr, Natalie M; Sassoon, Stephanie A et al. (2018) Accelerated and Premature Aging Characterizing Regional Cortical Volume Loss in Human Immunodeficiency Virus Infection: Contributions From Alcohol, Substance Use, and Hepatitis C Coinfection. Biol Psychiatry Cogn Neurosci Neuroimaging 3:844-859
Kwon, Dongjin; Pfefferbaum, Adolf; Sullivan, Edith V et al. (2018) Regional growth trajectories of cortical myelination in adolescents and young adults: longitudinal validation and functional correlates. Brain Imaging Behav :
Fama, Rosemary; Le Berre, Anne-Pascale; Hardcastle, Cheshire et al. (2017) Neurological, nutritional and alcohol consumption factors underlie cognitive and motor deficits in chronic alcoholism. Addict Biol :
Zahr, Natalie M; Pfefferbaum, Adolf; Sullivan, Edith V (2017) Perspectives on fronto-fugal circuitry from human imaging of alcohol use disorders. Neuropharmacology 122:189-200
Zahr, Natalie M; Pfefferbaum, Adolf (2017) Alcohol's Effects on the Brain: Neuroimaging Results in Humans and Animal Models. Alcohol Res 38:183-206
Zahr, Natalie M; Sullivan, Edith V; Rohlfing, Torsten et al. (2016) Concomitants of alcoholism: differential effects of thiamine deficiency, liver damage, and food deprivation on the rat brain in vivo. Psychopharmacology (Berl) 233:2675-86
Zahr, Natalie M; Rohlfing, Torsten; Mayer, Dirk et al. (2016) Transient CNS responses to repeated binge ethanol treatment. Addict Biol 21:1199-1216
Zahr, Natalie M; Carr, Rebecca A; Rohlfing, Torsten et al. (2016) Brain metabolite levels in recently sober individuals with alcohol use disorder: Relation to drinking variables and relapse. Psychiatry Res Neuroimaging 250:42-9
Park, Jae Mo; Josan, Sonal; Jang, Taichang et al. (2016) Volumetric spiral chemical shift imaging of hyperpolarized [2-(13) c]pyruvate in a rat c6 glioma model. Magn Reson Med 75:973-84

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