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Neurotoxicity of Alcoholism: Its Effect on Cognitive Function

Neurotoxicity of Alcoholism: Its Effect on Cognitive Function. RSA Education Lecture Series June, 2006 Lecturer: Sara Jo Nixon, Ph.D Section Editor: Marlene Oscar-Berman, Ph.D. What is the prevalence of neurocognitive impairments associated with long-term chronic alcoholism?.

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Neurotoxicity of Alcoholism: Its Effect on Cognitive Function

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  1. Neurotoxicity of Alcoholism: Its Effect on Cognitive Function RSA Education Lecture Series June, 2006 Lecturer: Sara Jo Nixon, Ph.D Section Editor: Marlene Oscar-Berman, Ph.D.

  2. What is the prevalence of neurocognitive impairments associated with long-term chronic alcoholism?

  3. Prevalence of Alcoholic Individuals with and without Cognitive Impairments(~20 Million Nationwide) 90% (18 million) 10% (2 million) with severe impairments: (i) Alcohol-Induced Persisting Amnestic Disorder [Korsakoff’s syndrome], or (ii) Alcohol-Induced Persisting Dementia. Do not meet DSM-IV criteria for amnesia or dementia. Approx. 50% (9 million) Approx. 50% (9 million) Mild to moderate impairments remain after 3 weeks of abstinence. No impairments detectable after 2-3 weeks of abstinence. Approx. 70-90% (6-8 million) Approx. 10-30% (2-3 million) Intermediate-Duration Mild Neurocognitive Disorder Associated with Alcohol Abuse and Alcoholism (improvement after several months of abstinence). Persisting Mild Neurocognitive Disorder Associated with Alcohol Abuse or Alcoholism (with continued deficits despite 1 year of abstinence). Modified from Grant & Adams, 1996

  4. Why are the outcomes so different?

  5. B. Neuropsychiatric Risk Factors: Pre-abuse FAS/FAE Systemic illnesses and general health Head injury Psychiatric comorbidity Use of other drugs D. Alcohol History: Amount per occasion Duration of abusive drinking Pattern over lifetime Recent amount/duration Length of abstinence A. Age Gender Family History Temperament C. SES & Education Brain Structure & Function E.Test Characteristics & Subject Sample F. Motivation & Expectancies Neuropsychological Performance

  6. WAIS-R Subtests Digit Symbol ObjectAssembly Block Design Evert & Oscar-Berman, AHRW 1995

  7. 55 50 Mean Performance Index 45 0 Visual-Spatial Performance Verbal Memory Set-Shifting Flexibility Verbal Skills Performance of alcoholic and nonalcoholic men and women in tests of four types of neuropsychological functioning. Nixon, 1994 AHRW, adapted from Glenn et al., 1993

  8. Alcoholism and Brain Dysfunction Controls (n=61) • Problem solving • Attention • Short-term memory • Visuospatial ability • Balance and postural stability Alcoholics (n=49) 0 -0.5 Age-Corrected Z-Score -1 -1.5 Executive STM & Upper Declarative Visuo- Balance Memory Production spatial Limb Sullivan et al., ACER 2000

  9. impaired judgment • blunted affect • poor insight • social withdrawal • reduced motivation • distractibility • cognitive rigidity • inattention • perseveration Executive Functions FRONTAL LOBE DYSFUNCTION Characteristic Behaviors of Alcoholics

  10. poor sense of direction • impaired constructional ability • impaired spatial placement • impaired drawing ability Visuospatial Abilities Characteristic Behaviors of Alcoholics PARIETAL LOBE DYSFUNCTION

  11. impaired timing • impaired tracking • impaired balance • impaired gait • increased falls Motor Control CEREBELLAR DYSFUNCTION Characteristic Behaviors of Alcoholics

  12. Theoretical/EmpiricalNeuropsychological Assessments: • Mild, diffuse generalized brain dysfunction: • Continuing discussion of aging sensitivity and differential sensitivity of specific brain areas/functions • Characterized by considerable heterogeneity: • 50-85% of those affected • Highly sensitive laboratory tests • Ecologically relevant tests show similar outcome • impersonal problem-solving • interpersonal problem-solving Oscar-Berman, 1987 Parsons & Nixon, 1993

  13. Neurocognitive Tests: • Use techniques from cognitive psychology and behavioral/cognitive neuroscience. • Shifting the focus from a localization approach to a process approach, e.g., attentional processes, executive function as outcome of system processes.

  14. Other Processing ApproachesCognitive Efficiency: Speed/Accuracy Trade-offs LM=Little Men VPA=Visual-Perceptual Analysis BMCST=Bexley-Maudsley Category Sorting Test Glenn & Parsons, 1991

  15. Overall Efficiency Similarly shaded bars denote NS differences. Overall E Ratio CNTRL Etoh/Pot Etoh/All Etoh Etoh/Stim n = (65) (12) (41) (43) (28) Nixon et al., ACER 1998

  16. Summary: Cognitive/Behavioral Effects • Widespread Deficits: by function and/or area • Often Subclinical Levels: statistically significantly inferior to community comparison groups • Observable via either neuropsychological or neurocognitive techniques • Not associated with withdrawal processes • Equivalent impairments for males/females (?)

  17. Electrophysiology:Event-Related Potential Components N1,Nd: Nd amplitude reflecting selection of relevant channel P3: P3b - more typically studied- task relevant stimulus in awareness P3a - rare, deviant or novel stimuli in repetitive unattended train of stimuli N2(MMN): Latency index stimulus evaluation time Amplitude related to degree of stimulus deviance MMN - produced in response to an attended deviant

  18. Average event-related potential (ERP) wave recorded in response to a target stimulus (blue line) and nontarget stimulus (red line). Target stimuli are those that require the subject to respond in some way. Porjesz & Begleiter, AHRW 1995

  19. Illustration of N400 cry drink The pizza was too hot to eat 5V 0 400 msec Bentin, 1989

  20. T3: Temporal 3 (left hemisphere) Alcoholics Controls N400 T4: Temporal 4 (right hemisphere) Nixon et al., 2002

  21. Summary: NeurophysiologicalAlcohol Related Aberrations • Early components associated with attentional processes • Later components associated with stimulus evaluation, target identification • Components associated with semantic processing

  22. Control Alcoholic Y o u n g e r A l c o h o l i c s ( N = 3 3 ) O l d e r A l c o h o l i c s ( N = 2 9 ) 57 yr old men Lifetime consumption of alcohol 1866 kg 60 kg (~600 gal) (~20 gal) 1 Cortical Gray Matter Volumes controls 0 Z-score - 1 - 2 Post Post Ant Prefrontal Frontal Ant Temporal Parietal-Occipital Pfefferbaum et al., 1997

  23. Group Differences: Match to Center vs. Rest Areas 9, 10, 45, 46 Controls > Alcoholics p<.001 Areas 45, 47 p=.05 p<.001 Alcoholics > Controls left right right Pfefferbaum et al., NeuroImage 2001

  24. Recovery of function: When and Where?

  25. Neuropsychological Recoveryin Alcoholic Women Fabian & Parsons, 1983

  26. Efficiency Over Time* *Time 1 includes only those who were in Time 2 (excludes Etoh/Pot due to low n). Group main effect p = .006; Time main effect p = .006.No significant group * time effort Nixon et al., unpublished data

  27. Neurophysiological Recovery • Different aspects associated with differential recovery: • Current data suggest no/limited changes in certain components: • Raises issues about preexisting alterations in neurophysiology and role in risk:

  28. Neurofunctional Recovery Mean differences in regional brain metabolism in 10 alcoholic subjects between 8-15 days and 31-60 days after alcohol withdrawal. Volkow et al., 1994

  29. Symptom Severity (GSI) Abstinence (Years) DeSoto, O’Donnell & DeSoto, 1989

  30. Means (SD) of neuropsychological test performances for Family History Positive alcoholic subjects and Family History Negative alcoholic subjects. Family History:Role in Cognitive Function Group FH + FH - Variable (n = 27) (n = 21) Halstead Impairment Index 0.51(.27) 0.53(.27) Tactual Performance Test 47.3(10.9) 45.6(9.2) (Time/block T-score) Tactual Performance Test 47.0(11.9) 47.4(9.3) (Memory T-score) Tactual Performance Test 47.7(10.1) 50.0(7.9) (Errors T-score) Speech-Sounds Perception Test 39.8(9.9) 42.2(8.9) (Errors T-score) Seashore Rhythm Test 50.0(13.1) 53.6(8.9) (Correct T-score) Halsted Category Test 40.4(10.6) 42.1(10.1) (Errors T-score) Finger Tapping 44.5(12.4) 46.8(17.1) (Dominant T-score) Adams et al., 1998

  31. Behavioral Disorders Confounds Regression Analyses: Behavioral Disorders, Sex, Group, & Cognitive Efficiency Regression Set Cognitive Efficiency Utah-total, child, or adult* Group Sex CBDC-total Group Sex CBDC subscales† ADD, CD, LD ns F(1,170) = 9.73, p = 0.002 ns F(1,158) = 11.08, p = 0.001 ns ns F(1,157) = 9.05, p = 0.001 *None of the Utah scores contributed significantly to the regression. †Of the CBDC subscales, LD contributed significantly, although it entered the equation after Group. Nixon et al., 1995

  32. Overall Summary • Observable long-term cognitive deficits • Differential recovery • Verbal earliest • Frontal lobe/executive function • Abstracting perhaps last • Correlation between performance and underlying physiological processes; further study • Number of factors which must be clarified and considered • Gender: Is there a differential sensitivity? • FH: Associated with both neurocognitive and behavioral risk for “deficits” • Pre-existing behavioral disorders

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