neurotoxicity of alcoholism: its effect on cognitive function rsa education lecture series june,...
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Neurotoxicity of Alcoholism: Its
Effect on Cognitive Function
Neurotoxicity of Alcoholism: Its
Effect on Cognitive Function
RSA Education Lecture SeriesJune, 2006
Lecturer: Sara Jo Nixon, Ph.DSection Editor: Marlene Oscar-Berman,
Ph.D.
RSA Education Lecture SeriesJune, 2006
Lecturer: Sara Jo Nixon, Ph.DSection Editor: Marlene Oscar-Berman,
Ph.D.
What is the prevalence of neurocognitive
impairments associated with long-term chronic
alcoholism?
Prevalence of Alcoholic Individuals with and without Cognitive Impairments
(~20 Million Nationwide)
10% (2 million)with severe impairments:
(i) Alcohol-Induced Persisting Amnestic Disorder [Korsakoff’s syndrome], or(ii) Alcohol-Induced Persisting Dementia.
Mild to moderate impairments remain after 3 weeks of abstinence.
Approx. 10-30% (2-3 million)
Persisting Mild NeurocognitiveDisorder Associated with Alcohol Abuse or Alcoholism (with continued deficits despite 1 year of abstinence).
Modified from Grant & Adams, 1996
Intermediate-Duration Mild Neurocognitive Disorder Associated with Alcohol Abuse and Alcoholism (improvement after several months of abstinence).
No impairments detectable after 2-3 weeks of abstinence.
Approx. 70-90% (6-8 million)
Do not meet DSM-IV criteriafor amnesia or dementia.
90% (18 million)
Approx. 50% (9 million)
Approx. 50% (9 million)
Why are the outcomes so different?
B. Neuropsychiatric Risk Factors:Pre-abuse FAS/FAESystemic illnesses and general healthHead injuryPsychiatric comorbidityUse of other drugs
D. Alcohol History:Amount per occasionDuration of abusive drinkingPattern over lifetimeRecent amount/durationLength of abstinence
BrainStructure &Function
NeuropsychologicalPerformance
C. SES &Education
F. Motivation & Expectancies
A. Age Gender Family History Temperament
E. TestCharacteristics& Subject Sample
Digit SymbolDigit Symbol
Evert & Oscar-Berman, AHRW 1995Evert & Oscar-Berman, AHRW 1995
ObjectAssemblyObjectAssembly
Block DesignBlock Design
WAIS-RSubtestsWAIS-RSubtests
Performance of alcoholic and nonalcoholic men and women in tests of four types of neuropsychological
functioning.
Performance of alcoholic and nonalcoholic men and women in tests of four types of neuropsychological
functioning.
Verbal Skills Visual-SpatialPerformance
Verbal Memory Set-Shifting Flexibility
0
45
50
55
Mean Performance Index
Nixon, 1994 AHRW, adapted from Glenn et al., 1993
Alcoholism and Brain Dysfunction
• Problem solving• Attention• Short-term memory• Visuospatial ability• Balance and postural stability
-1.5-1.5
-1-1
-0.5-0.5
00
Age-C
orr
ect
ed Z
-Sco
reA
ge-C
orr
ect
ed Z
-Sco
re
ExecutiveExecutive STM &STM & UpperUpper DeclarativeDeclarative Visuo-Visuo- BalanceBalance
Alcoholics (n=49)Alcoholics (n=49)
Controls (n=61)Controls (n=61)
ProductionProduction LimbLimb MemoryMemory spatialspatial
Sullivan et al., ACER Sullivan et al., ACER 20002000
Characteristic Behaviors of Alcoholics
• impaired judgment• blunted affect • poor insight• social withdrawal• reduced motivation• distractibility• cognitive rigidity• inattention• perseveration
ExecutiveFunctions
FRONTAL LOBE DYSFUNCTIONFRONTAL LOBE DYSFUNCTION
Characteristic Behaviors of Alcoholics
PARIETAL LOBE DYSFUNCTIONPARIETAL LOBE DYSFUNCTION
• poor sense of direction• impaired constructional ability• impaired spatial placement• impaired drawing ability
VisuospatialAbilities
Characteristic Behaviors of Alcoholics
CEREBELLAR DYSFUNCTIONCEREBELLAR DYSFUNCTION
• impaired timing• impaired tracking• impaired balance• impaired gait• increased falls
MotorControl
Theoretical/Empirical Neuropsychological Assessments:
Theoretical/Empirical Neuropsychological 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
• 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, 1987Parsons & Nixon, 1993
Neurocognitive Tests: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.
• 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.
Other Processing ApproachesCognitive Efficiency:
Speed/Accuracy Trade-offs
Other Processing ApproachesCognitive Efficiency:
Speed/Accuracy Trade-offs
0.85
0.90
0.95
1.00
1.05
1.10
1.15
LM VPA BMCST Sternberg
AlcoholicsControls
LM=Little Men VPA=Visual-Perceptual Analysis BMCST=Bexley-Maudsley Category Sorting TestLM=Little Men VPA=Visual-Perceptual Analysis BMCST=Bexley-Maudsley Category Sorting Test
Glenn & Parsons, 1991Glenn & Parsons, 1991
Overall EfficiencyOverall Efficiency
0.39(0.12)
0.41(0.12)
0.33(0.10) 0.30
(0.10)0.30
(0.09)
.20
.25
.30
.35
.40
.45
Overall E Ratio
Overall E Ratio
Similarly shaded barsdenote NS differences. Similarly shaded barsdenote NS differences.
CNTRCNTRLL
Etoh/PotEtoh/Pot Etoh/AllEtoh/All EtohEtoh Etoh/StimEtoh/Stim
n = (65) (12) (41) (43) (28)
Nixon et al., ACER 1998
Summary: Cognitive/Behavioral EffectsSummary: 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 (?)
• 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 (?)
Electrophysiology:Event-Related Potential Components
Electrophysiology:Event-Related Potential Components
N1,Nd:Nd amplitude reflecting selection of relevant
channelP3:
P3b - more typically studied- task relevant stimulus in awareness
P3a - rare, deviant or novel stimuli in repetitive unattended train of stimuliN2(MMN):
Latency index stimulus evaluation timeAmplitude related to degree of stimulus devianceMMN - produced in response to an attended deviant
N1,Nd:Nd amplitude reflecting selection of relevant
channelP3:
P3b - more typically studied- task relevant stimulus in awareness
P3a - rare, deviant or novel stimuli in repetitive unattended train of stimuliN2(MMN):
Latency index stimulus evaluation timeAmplitude related to degree of stimulus devianceMMN - produced in response to an attended deviant
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.
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
Illustration of N400Illustration of N400
crycry
drinkdrink
eateat
0 400 msec
5V
Bentin, 1989Bentin, 1989
The pizza was too hot toThe pizza was too hot to
N400N400
T3: Temporal 3 (left hemisphere)
T4: Temporal 4 (right hemisphere)
AlcoholicsControls
Nixon et al., 2002Nixon et al., 2002
Summary: NeurophysiologicalAlcohol Related AberrationsSummary: NeurophysiologicalAlcohol Related Aberrations
• Early components associated with attentional processes
• Later components associated with stimulus evaluation, target identification
• Components associated with semantic processing
• Early components associated with attentional processes
• Later components associated with stimulus evaluation, target identification
• Components associated with semantic processing
Cortical Gray Matter Volumes
AlcoholicAlcoholic ControlControl
57 yr old men57 yr old men
Lifetime consumption of alcohol 1866 kg 60 kg (~600 gal) (~20 gal)
Lifetime consumption of alcohol 1866 kg 60 kg (~600 gal) (~20 gal)
Prefrontal
Prefrontal
Frontal Frontal AntAnt PostPost
Parietal-OccipitalParietal-OccipitalTemporalTemporal
-2
-1
0
1
OOllddeerr AAllccoohhoolliiccss ((NN==2299))
YYoouunnggeerr AAllccoohhoolliiccss ((NN==3333))
controls
Z-score
Z-score
AntAnt PostPost
Pfefferbaum et al., 1997
Group Differences: Group Differences: Match to Center Match to Center vsvs. Rest. Rest
Areas 9, 10, 45, Areas 9, 10, 45, 4646
rightrightleftleft
Areas 45, 47Areas 45, 47
rightright
Controls > AlcoholicsControls > Alcoholics
Alcoholics > ControlsAlcoholics > Controls
p=.05p=.05
p<.001p<.001
p<.001p<.001
Pfefferbaum et al., NeuroImage 2001Pfefferbaum et al., NeuroImage 2001
Recovery of function: When and Where?
Neuropsychological Recoveryin Alcoholic WomenNeuropsychological Recoveryin Alcoholic Women
Fabian & Parsons, 1983Fabian & Parsons, 1983
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
Neurophysiological Recovery 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:
• 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:
Mean differences in regional brain metabolism in 10 alcoholic subjects between 8-15 days and 31-60 days after alcohol withdrawal.Mean differences in regional brain metabolism in 10 alcoholic subjects between 8-15 days and 31-60 days after alcohol withdrawal.
Volkow et al., 1994Volkow et al., 1994
Neurofunctional RecoveryNeurofunctional Recovery
Symptom Severity (GSI)
Abstinence (Years) DeSoto, O’Donnell & DeSoto, 1989
Family History: Role in Cognitive FunctionFamily History: Role in Cognitive Function
VariableVariable
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)
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)
FH +FH +GroupGroup
Means (SD) of neuropsychological test performances for Family History Positive alcoholic subjects and Family History Negative alcoholic subjects.
Means (SD) of neuropsychological test performances for Family History Positive alcoholic subjects and Family History Negative alcoholic subjects.
FH - FH -
Adams et al., 1998Adams et al., 1998
(n = 27)(n = 27)
(n = 21)(n = 21)
Behavioral Disorders Confounds
Behavioral Disorders ConfoundsRegression Analyses:
Behavioral Disorders, Sex, Group, & Cognitive Efficiency
Regression Analyses: Behavioral Disorders, Sex, Group, & Cognitive
EfficiencyRegression SetRegression Set
Utah-total, child, or adult*GroupSex
CBDC-totalGroupSex
CBDC subscales†
ADD, CD, LD
Utah-total, child, or adult*GroupSex
CBDC-totalGroupSex
CBDC subscales†
ADD, CD, LD
Cognitive EfficiencyCognitive Efficiency
nsF(1,170) = 9.73, p = 0.002
ns
F(1,158) = 11.08, p = 0.001 ns
nsF(1,157) = 9.05, p = 0.001
nsF(1,170) = 9.73, p = 0.002
ns
F(1,158) = 11.08, p = 0.001 ns
nsF(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.
*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
Overall SummaryOverall 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
• 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