Sara L. Dolan, Ph.D.
Baylor University Department of Psychology and Neuroscience
Baylor Addiction Research Center
Baylor University
One Bear Place #97334
Waco, TX 76798-7334
Sara_Dolan@baylor.edu
(254) 710-2573
TIPSS 6/2010

 DSM-IV Alcohol-Related Disorders
 History and Background
 Review of neuropsychological, neuroimaging, and neuropathological correlates of alcohol related disorders
 Review of evidence-based treatments for alcohol dependence
 Neuropsychological function and treatment

 Alcohol Intoxication Delirium
 Alcohol Withdrawal Delirium (With
Perceptual Disturbances)

 Alcohol-Induced Persisting Dementia
 Learning/memory impairment AND 1 +:
 Aphasia, Apraxia, Agnosia, Executive dysfunction
 Alcohol-Induced Persisting Amnestic
Disorder
 Learning/memory impairment (Wernicke-
Korsakoff’s)

 Beyond thiamine-deficiency (i.e.,
Wernicke – Korsakoff’s), alcoholism researchers have focused on models based on brain systems vulnerabilities
 Three predominant theories on the pattern of consequences of alcoholism on the brain
1.
Premature aging / whole brain
2.
Right brain
3.
Frontal lobes
Parsons, Butters, and Nathan, 1987

Cerebellum

 Alcoholism accelerates brain aging
 Findings only support premature aging in older alcoholics (i.e., age 50 +)
(Oscar-Berman,
2000)
 Alcohol leads to mild generalized dysfunction of the brain
(Parsons, 1996)

 Right hemisphere is more vulnerable to the effects of alcoholism than the left hemisphere
 Impairments in visuospatial functioning and emotional processing
(Oscar-Berman, 2000)
 Emotional processing deficits also may be due to abnormalities in other brain regions
(e.g., limbic system, frontal lobes;
Colson & Dolan,
2010; Oscar-Berman & Schendan, 2000
)

 Frontal lobes show increased susceptibility to alcoholism-related damage
 Evidence from post-mortem neuropathological studies
(Harper, 1998) and neuroimaging of living patients
(Sullivan, 2000)
 Also behavioral and neuropsychological deficits in executive functioning seem to be prominent in both currently-drinking and recently-detoxified alcoholics
(e.g., Bechara et al.,
2001)

Neuropsychological
Impairment in Substance
Abusers
 Approximately 33-75% of patients admitted to VA outpatient substance abuse treatment programs have measurable cognitive impairment
 Mostly in the mild to moderate range
( Eckardt & Martin, 1986; Meek et al., 1989; Parsons & Leber, 1981; Tabakoff & Petersen,
1988 )

Neuropsychological Deficits in Substance Abusers
 Alcoholics have deficits in:
 Memory (anterograde worse than retrograde)
 Visual worse than verbal
 Visuospatial functions
 Executive functions
 Problem-solving, abstraction
 Cognitive efficiency
( Page, 1983; Page, 1987; Parsons et al., 1987;
Ratti et al., 2002; Wilson, 1987 )

 A disruption of processes thought to:
 Monitor
 Direct
 Organize
 Regulate behavior…
…to enable persons effectively to achieve desired goals while minimizing adverse consequences
 Mediated by the prefrontal cortex
( Lezak, 1995 )

Neuropsychological
Functioning
 Early studies suggested that sober alcoholics demonstrate impairment on neuropsychological tests that is similar to that of patients with diagnosed mild-to-moderate brain injury
(Parsons, 1986).

 15 studies examining performance between alcoholic patients and control peers revealed poorer performance on a variety of tests
(Parsons & Farr, 1981)

 Compromised fronto-cortico-cerebellar circuits underlie cognitive deficits
(Scheurich, 2005)
 Patterns of correlations between cortical and subcortical volume deficits
 To compensate for deficient task performance, alcohol-dependent patients require the use of additional and higher-order executive functions
(Scheurich, 2005)

 In recently detoxified alcoholics, CT findings show widened sulci, ventricular dilation, and cerebellar atrophy
(Grant, 1987)
 MRI: Reductions in cortical and subcortical gray and white matter
(Jernigan et al, 1992; Schmidt et al.,
2005)
 Reduction in brain weight and volume associated with reduction in white matter volume
(Harper et al., 2003)
 Reduction in total hippocampus volume
(Arciniegas et al., 2006)

 Functional MRI studies:
 Decreased prefrontal cortical function in chronic substance abusers (for a review, see London et al.,
2000 )
 Additional recruitment of brain areas ( Scheurich,
2005 )
 Cerebral glucose metabolism (PET studies):
Decreased regional cerebral blood flow to frontal regions, ranging from a 75% ( Nicolas et al., 1993 ) to
86% ( Erbas et al., 1992 ) reduction in chronic alcoholics
 SPECT: decreased blood flow in frontal lobes and cerebellum (latter appears to persist even after a period of abstinence)

Etiology of Progressive Cognitive
Decline
 Wernicke’s Encephalopathy (B1 deficiency)
 Characterized by nystagmus, abducens and conjugate gaze palsies, ataxia, and mental disturbance (confusional state)

Etiology of Progressive
Cognitive Decline
 Wernicke-Korsakoff Syndrome (aka
Korsakoff psychosis or Korsakoff amnesic state; DSM-IV=Alcohol-Induced
Persisting Amnestic Disorder)
 Retentive memory impaired out of proportion to other cognitive functions (chronic manifestation of Wernicke disease)
 With treatment, recovery occurs in less than 20% of patients

 Association between alcohol use (especially heavy use or dependence) and the development of dementia
(Oslin et al., 1998)
 Heavy alcohol use contributes to the emergence of dementia in more than 20% of patients diagnosed with dementia (cited in Kapaki et al., 2005)
 May be most apparent among men and those with
ApoE4 allele (Mukamal et al., 2003)
 Cortical and subcortical pathology (Schmidt et al, 2005)

 Recovery of function is supported in the neuropsychological and neuroradiological literature
(Grant, 1987)
 Some studies report only partial recovery
(Oslin & Cary, 2003)

 Cognitive functioning improves with extended abstinence
 Much improvement over first 21-30 days of abstinence
 Can take as long as 1 year
 How does recovery occur?
 Glial regeneration
 Synaptic plasticity

No Impairment Mild Moderate Severe
 Mild (subtle) = may or may not evidence impairment in daily life
 “Social” drinkers (6+ drinks per day;
Parsons, 1998
)
 Moderate = more likely show some impairment in daily life
 Severe = Wernicke’s Encephalopathy (acute),
Korsakoff’s Disease, Alcohol-Induced Persisting
Dementia (chronic)

 33 – 75% of alcoholics entering treatment display neuropsychological deficits, most in the mild to moderate range
 Problem-solving
 Abstract thinking
 Concept shifting
 Learning / Memory
Eckardt & Martin, 1986; Meek et al., 1989; Parsons & Leber, 1981; Tabakoff & Petersen, 1988

 Categories = 50%
 Abstract thinking
 COWA = 50%
 Verbal fluency
 Trails-B = 17%
 Cognitive flexibility
 Stroop = 12%
 Response inhibition
 Shipley Vocabulary = 13%
 Verbal skills
Morgenstern & Bates, 1999

Specific Neuropsychological
Deficits and Substance Abuse
Treatment Process
 Attention / Learning / Memory
 Patients can’t learn or remember new skills taught in treatment (Sanchez-Craig & Walker,
1982)

Specific Neuropsychological
Deficits and Substance Abuse
Treatment Process
 Executive function – patients can’t apply new skills after treatment
(Morgenstern & Bates, 1999)
 Abstract thinking
 Generalizability of skills outside of treatment
 Cognitive flexibility
 Switching tracks
 Verbal Fluency
 Producing alternative strategies
 Response Inhibition
 Inhibiting pre-potent responses

Neuropsychological Deficits and
Substance Abuse Treatment
Process
 Failure to acquire strategies taught during treatment
 The cognitive and behavioral strategies taught in treatment may be less effective in preventing relapse
 Impaired individuals have different change processes than unimpaired individuals
Block, Bates, & Hall, 2003; Morgenstern & Bates, 1999

Neuropsychological Function and Treatment Process /
Outcome
 Clinicians’ misattributions of patients’ behaviors
 Verbal skills (previously learned information) remain relatively preserved, so patients appear unimpaired
 Clinicians fail to identify cognitive impairment in at least 40% of patients
( Fals-
Stewart et al., 1993; 1994 )
 Neuropsychological dysfunction may result in more rule violations in treatment
( Fals-Stewart et al., 1994 )

 Cognitive-Behavioral
 Motivational Enhancement (MI)
 Twelve Step Facilitation
 Community Reinforcement
 CRAFT
 Behavioral Couples Therapy

 Change thoughts, feelings, and behaviors associated with addiction
 Relapse-Prevention Coping Skills
Training
 Communication Skills Training
 Cue Exposure Treatment

 Increase self-directed motivation to change
 Increase self-efficacy for change
 Be non-confrontational

 AA/NA/CA
 Emergency planning
 Sober social support

• Empirically-supported psychosocial treatments for SUDs
(Finney, Willbourne, and Moos,
2007)
:
– Enhance/maintain motivation to change.
– Involve teaching/learning of coping skills.
– Restructure the social environment.
– Can involve conditioning-based interventions.
– Change perceptions of social norms.
– Enhance self-efficacy for robust behavioral change.

 187 Alcohol-Dependent patients in residential treatment
 Clinical trial of naltrexone and coping skills training
 31% female
 39.0 ± 9.4 years of age
 13.4 ± 2.3 years of education
 66.1 ± 28.3 % alcohol use days during the 6 months pre-treatment

 Urge-Specific Strategies (USS; 6 mo.
α = .91; 12 mo. α = .90)
 21 situation-specific strategies taught in cue exposure, communication skills, or relaxation/meditation
 General Strategies for Alcoholics (GSA; 6 mo. α = .92; 12 mo. α = .90)
 21-item lifestyle change strategies taught in communication skills and in the general treatment program

6 and 12 mos post-Tx:
1.USS
2.GSA
3.Measure of substance use
6 months 12 months
Sample size n = 131 n = 117
Relapse rate 55% 70%

Positive consequence
Negative consequence
Mastery messages
Distracting thoughts
Challenge the thoughts
Think about treatment
Months 4-6 Months 7-12 Months 4-6 Months 7-12
Lapse Lapse pr pr
**
**
** ns
* ns
**
**
*
**
*
*
-.47**
-.31*
-.42**
-.26*
-.24*
-.13
-.29*
-.15
-.27*
-.37**
-.32**
-.28*
*p < .01; **p < .001

USS – Cognitive, Behavioral
Alternative behavior
Solve the problem
Think through behavior chain
Refuse the drink
Months 4-6 Months 7-12 Months 4-6 Months 7-12
Lapse Lapse pr pr
** ** -.33** -.33**
*
**
**
**
-.30*
-.21
-.34**
-.37**
** * -.21
-.35**
*p < .01; **p < .001

USS – Behavioral, Other
Escape
Delay, wait it out
Other social support
Spiritual coping
Months 4-6 Months 7-12 Months 4-6 Months 7-12
Lapse Lapse pr pr ns * -.25* -.32* ns
**
*
*
*
*
-.25*
-.21
-.21
-.23
-.31*
-.15
*p < .01; **p < .001

GSA - Cognitive
Positive consequence
Months 4-6 Months 7-12 Months 4-6 Months 7-12
Lapse
**
Lapse
** pr
-.50** pr
-.46**
Remind self sober
Challenge thoughts
**
*
**
**
-.43**
-.34**
-.49**
-.41**
Negative consequence
Think about treatment
Spiritual focus
*
*
* ns
**
*
-.27*
-.25*
-.25*
-.24*
-.30**
-.21
*p < .01; **p < .001

GSA - Behavioral
Sober good time
Work toward future goals
Other social support
Work on problems regularly
Tell others sober
Months 4-6 Months 7-12 Months 4-6 Months 7-12
Lapse
**
**
Lapse
**
** pr
-.47**
-.40** pr
-.49**
-.45**
**
**
**
*
*
*
-.36**
-.30*
-.29*
-.26*
-.18
-.17
*p < .01; **p < .001

Keep busy
Eat, sleep, healthy behavior
Talk over feelings
Avoid tempting situations
Relax or meditate regularly
Months 4-6 Months 7-12 Months 4-6 Months 7-12
Lapse Lapse pr pr ns ns
*
*
-.40**
-.39**
-.39**
-.30**
** ns ns ns
-.31**
-.27*
-.25*
-.32**
* ns -.16
-.26*
*p < .01; **p < .001

 Top 5 situation-specific coping strategies
 Positive consequence thoughts, mastery messages, alternative behaviors, problem solving, think through a behavior chain
 Top 5 general lifestyle coping strategies
 Positive consequence thoughts, remind self that you are sober, challenge thoughts about drinking, sober good time, work toward future goals

 Improve treatment by:
 Teaching situation-specific AND general lifestyle coping skills
 Emphasizing strategies that are more effective
 Eliminating skills that are ineffective
( Dolan et al., in preparation )

 Bill is a 50 year-old male veteran who presents for treatment of his “excessive drinking”
 Self-reported alcohol consumption escalated to a fifth of vodka per night for
7 months, following his divorce

 He has started getting into trouble at work, and his grown children “don’t seem to know who he is anymore” because of his behavior
 He used to be a very organized person and now his apartment is a mess and he isn’t able to get his bills paid correctly

 He successfully completes detox
 On Day 1 of Intensive Outpatient
Treatment, he appears to have some difficulty comprehending the structure of the treatment program, and he asks repetitive questions

 A neuropsychological evaluation reveals that he has memory and executive dysfunction
 Very typical profile for alcohol-related neuropsychological dysfunction
 What do we do to maximize treatment benefit for this patient?

Factors that Might Influence
Treatment Outcome
 Treatment-specific variables
 Length and type of treatment
 Individual differences
 Severity of dependence
 Presence of comorbid psychiatric disorders
 Personality factors
 Anger level
( Project MATCH, 1997 )

 Comorbidity
 Mood, anxiety disorders
 PTSD
 Medical conditions

Factors that May Influence
Treatment Outcome
 What about neuropsychological function?
 Do these patients have the cognitive capacity to participate in treatment aimed at changing thoughts and behaviors related to their substance use disorder?
 I.e., Are their brains intact enough to learn, process, and apply new relapse-prevention skills?

 Participants
 Substance dependent individuals (n=20) from a local state-funded residential treatment program
 Clean for > 21 days
 Procedures
 Diagnostic interview (r/o psychotic disorder)
 Questionnaires
 Neuropsychological battery
 Coping Skills assessment
57

 Baseline IQ
 Verbal learning, memory
 WAIS-III
 Attention, working memory
 Speeded information processing
 Visuospatial functioning
58

59

 Executive functioning
 Wisconsin Card Sorting Test (Set-shifting, working memory, responsiveness to feedback, cognitive flexibility)
 Trailmaking Test A&B (Visual scanning, attention, cognitive flexibility)
 Controlled Oral Word Association (verbal fluency)
 Stroop Color Word Test
60

Trail Making Test Part B

Wisconsin Card Sorting Test

63

64

65

66

67

 More fine-grained analysis of executive functioning
 N=49
 Neuropsychological Battery:
 Verbal Fluency
 Trailmaking Test
 Wisconsin Card Sorting Test
 Color-Word Interference (Stroop)
 Iowa Gambling Task
 Tower of Hanoi
68

69

70

Age
Gender
Education
Daily Alcohol Intake
Mean / Frequency
32.06
46% M
12.17
7.23
Prior Treatment Attempts 2.33
Sobriety Length
Contemplation Ladder
54.53
9.21
SETOT
SOTOT
88.44
87.24
VF 9.4
VF Letter vs. Category 9.3
SD
10.01
2.03
23.97
2.89
53.71
1.75
35.19
32.14
3.4
3.0
71

VF - Letter
VF – Letter vs.
Category
SETOT SOTOT
-.25*
-.33**
-.30**
-.31**
Number of
USC-E skills >4
-.24*
-.23*
GETOT ns
-.25*
GOTOT ns
-.27*
72

 Patient – Treatment Matching
 Pre-treatment neuropsychological assessment
 Target skills to individual patient’s neuropsych profile
 Reduction in number of skills taught in CBT
 Behavioral possibly better than cognitive focus
 Extensive repetition
 Extra role-plays
 Cognitive Rehabilitation
 A la TBI, schizophrenia
73

 Computer-assisted cognitive stimulation exercises may increase speed of cognitive recovery
(Grohman et al., 2003)
 This may then improve treatment process and outcome
 However, time- and cost-intensive

Grant Support
 Baylor University
Research Committee
 NIAAA T32 (Brown
University; mentors:
Damaris Rohsenow,
Ph.D. and Paul Malloy,
Ph.D.)
Students
 Graduate: Robyn
Baldridge, Sarah
Martindale, Laura Sejud,
Sean McGowan, Anthony
Giardina
 Undergraduate: Sanja
Trtanj
75