Journal of Attention Disorders
Medications Do Not Necessarily Normalize
Cognition in ADHD Patients
Lynda G. JohnsonNorth Carolina Neuropsychiatry Clinics, Chapel Hill and Charlotte Objective: Although ADHD medications are effective for the behavioral components of the disorder, little information
exists concerning their effects on cognition, especially in community samples. Method: A cross-sectional study of ADHD
patients treated with three different ADHD drugs was conducted. Patients’ performance on a computerized neurocognitive
screening battery was compared to untreated ADHD patients and normal controls (NML). A total of 177 ADHD patients
aged 10–18, achieved a favorable response to one of the following medications: Adderall XR (AMP), atomoxetine (ATMX),
and Concerta (MPH-OROS) compared to 95 untreated ADHD patients and 101 NML. Results: Significant differences were
detected between normals and untreated ADHD patients. Treated patients performed better than untreated patients but
remained significantly impaired compared to normal subjects. Conclusion: Even with optimal treatment, based on parents’
and teachers’ opinions, subtle and not-so-subtle neurocognitive impairments persisted in the ADHD patients. Some ADHD
patients may require additional educational assistance, even in the face of successful medication treatment. (J. of Att. Dis.
2007; XX(X) XX-XX
ADHD; cognition; amphetamine; methylphenidate; atomoxetine Psychostimulant drugs affect diverse cognitive func- It has been suggested that neurocognitive testing has tions, including executive function, reaction time, predictive value in determining individual differences in fine motor coordination, and various aspects of attention.
drug response (Mehta, Goodyer, & Sahakian, 2004), Neuropsychological studies of ADHD children and although studies have also shown that cognition may adults indicate impairments in many cognitive areas: improve in ADHD patients, excluding behavioral selective attention (Brodeur & Pond, 2001); memory improvement (Gimpel et al., 2005; Vance, Maruff, & (Muir-Broaddus, Rosenstein, Medina, & Soderberg, Barnett, 2003). Conversely, behavior may improve absent 2002; Roth et al., 2004); reaction time (Leth-Steensen, detectable changes in cognition (Everett, Thomas, Cote, Elbaz, & Douglas, 2000) and information processing Levesque, & Michaud, 1991; Lufi, Parish-Plass, & Gai, speed (Weiler, Bernstein, Bellinger, & Waber, 2000); 1997). Computerized tests of attention and vigilance motor speed (Mitchell, Chavez, Baker, Guzman, &Azen, 1990) and visuomotor ability (Kalff et al., 2002); Authors’ Note: Drs Gualtieri and Johnson are two of the developers
and executive control functions, such as set-shifting of the CNS Vital Signs screening battery. Dr Gualtieri has conducted (Cepeda, Cepeda, & Kramer, 2000), inhibitory control clinical trials on behalf of Astra-Zeneca, Bristol-Myers Squibb, (Schachar et al., 2002), and working memory (Barnett Celltech, Cephalon, Eli Lilly, Glaxo-Smith-Kline, Medeva, Organon, et al., 2001). It has never been established, however, that Shire, Wyeth-Ayerst, and UCB. He has been a speaker for and/or con- the cognitive effects of stimulant drugs are central to sultant to Eli Lilly, GSK, Pfizer, Shire, and Wyeth. This research was their therapeutic utility. In ADHD treatment, cognitive supported by North Carolina Neuropsychiatry, PA, in Chapel Hill andCharlotte. No external support was sought or received on behalf of and behavioral improvement are not necessarily dissoci- this research. Address correspondence to Dr C. Thomas Gualtieri, NC ated, but neither are they closely correlated (Konrad, Neuropsychiatry, 400 Franklin Square, 1829 East Franklin Street, Gunther, Hanisch, & Herpertz-Dahlmann, 2004).
Chapel Hill, NC 27514; e-mail: [email protected].
(Continuous Performance Tests [CPTs]), widely used in examining the clinical status of all the ADHD patients in the evaluation and treatment of ADHD, have been criti- a particular locus at a point in time. The question we cized for their low specificity and sensitivity (Lovejoy & posed is, how effective are stimulant (and related) drugs Rasmussen, 1990; Trommer, Hoeppner, Lorber, & as they are used by practitioners in the real world, at least Armstrong, 1988), and the correspondence between impulsive errors on CPTs and behavioral impulsivity hasnot been established (Abikoff & Klein, 1992). When Methods and Materials
used for assessment of medication efficacy, the applica-bility of results to the patient’s natural environment is This was a cross-sectional descriptive study of clinic unproven (Aman & Turbott, 1991; Cohen, Kelly, & attendees, children, and adolescents to evaluate their Atkinson, 1989) or even absent (Elia, Borcherding, neurocognitive performance with respect to medication Rapoport, & Keysor, 1991). CPTs are not consistently treatment. The subjects had responded satisfactorily to sensitive to stimulant effects (Fischer & Newby, 1998).
one of the three most frequently prescribed medications When ADHD studies address the issue of cognition, for ADHD in the United States: Adderall XR (AMP, four the methods employed tend to demonstrate that treated salts of d- and 1-amphetamine in an extended release patients perform better than untreated patients on neu- preparation), atomoxetine (ATMX), and Concerta ropsychological tests or that patients improve on neu- (MPH-OROS, methylphenidate isomers in an osmotic ropsychological measures after they are treated release capsule) compared to NML and to untreated (Aggarwal & Lillystone, 2000; Gimpel et al., 2005). Few studies, however, evaluate posttreatment performance inADHD patients relative to normal controls (NML). In1991, Everett et al. compared untreated ADHD children Subjects
to NML on two tests of executive function, the Stroop All of the ADHD patients at two neuropsychiatry clin- Test (ST) and the Wisconsin Cart Sort. At baseline, the ics (in Chapel Hill and Charlotte, NC) are administered ADHD group was significantly impaired compared to a computerized screening battery of cognitive tests as normals. After a year of treatment, they improved on the part of their initial evaluation and at appropriate intervals Wisconsin but remained impaired on the ST (Everett during follow-up. They are requested to allow the clinics et al., 1991). In 1993, Risser and Bowers compared 10 to store their data in a central research database after it is ADHD children on stimulant medication to normal appropriately deidentified. The database includes basic children on a number of cognitive measures, including demographic data, diagnoses, medication status, and test the Wechsler Developmental Index, the Bender Visual- motor Gestalt Test, and the Benton Visual Retention Test.
The subjects of this investigation were children and In spite of treatment, the ADHD children had persistent adolescents with all types of ADHD. Initial diagnoses neuropsychological deficits (Risser & Bowers, 1993). In were made by treating clinicians on the basis of DSM-IV- another study, stimulant treatment in ADHD children led TR criteria, parent and teacher rating scales. Diagnoses to improvement in simple but not choice reaction time were reviewed by a second senior psychiatrist (T.G.) or neuropsychologist (L.J.) prior to inclusion in the data- We have only found one study that generated contrary base and then again prior to inclusion in this study.
results. Barnett et al., using a computerized test (CogState), Subjects were outpatients who had been treated with one reported that 21 stimulant-treated ADHD children per- of the three medications listed above, and the dose had formed as well as NML on a spatial working memory been titrated to an optimal clinical response. The Ss task, whereas 27 untreated ADHD children performed selected for this investigation had been on a stable dose significantly worse (Barnett et al., 2001). The CogState battery, however, captures data on several other cognitive The patients were not randomly assigned to one drug functions, and these were not reported in the article.
or another; rather, they themselves chose which medica- The question we address here is not whether cognitive tion to use. As a rule, newly diagnosed ADHD patients and behavioral changes are correlated when ADHD are given two prescriptions, one for AMP and one for patients are treated with psychostimulant medications; it MPH-OROS. Patients are instructed to take one drug for is fairly well established that they are not. The question 2 weeks and to titrate to optimal dose, and then to try the we pose is whether, in a community-treated sample of other. The titration schedule for AMP would be 20 or 40 patients, successful treatment normalizes neurocognitive mg qam and for MPH-OROS 18–36–54–72 mg qam.
performance. We employed a cross-sectional approach, After 4 weeks, the patients return to the clinic and a Gualtieri, Johnson / Medications Do Not Necessarily Normalize Cognition and validity of the CNSVS battery have been published Demographic Characteristics of the Five Groups
elsewhere (Gualtieri & Johnson, 2006d).
Verbal memory (VBM) and visual memory (VIM) are adaptations of the Rey Auditory Verbal Learning Test and the Rey Visual Design Learning Test (Rey, 1964; Taylor, 1959). VBM and VIM are recognition tests, how- ever, not tests of recall. Correct responses from VBM and VIM are summed to generate a composite memory The Finger Tapping Test (FTT) is one of the core tests of the Halstead-Reitan Battery, but similar tests were used by 19th century psychologists like Wundt, Galton, and Cattell. Symbol digit coding (SDC) is based on the Symbol Digit Modalities Test (SDMT) (Smith, 1982), which is a variant of the Wechsler digit symbol substitu- tion test (DSST). The total of right and left taps from the FTT and total correct responses on the SDC generates a composite score for psychomotor speed.
The ST in CNSVS has three parts that generate simple Note: NML = normal controls; MPH-OROS = Concerta; ATMX = and complex reaction times. Averaging the two complex reaction time scores from the ST generates a domainscore for reaction time. It might be more precise to refer decision is made on clinical grounds to continue on one to this domain as information processing speed.
drug or another. After another month, they return to the The Shifting Attention Test (SAT) measures the clinic and are tested on what they (and their parents) con- subject’s ability to shift from one instruction set to sider to be the optimal dose of the preferred drug. This another quickly and accurately. Other computerized bat- method accounted for the 81 subjects on AMP and the 51 teries, such as the Neurobehavioral Evaluation System 2 (NES2), CogState, and CANTAB®, have SATs. Color- A group of patients on stable and clinically effective shape tests such as the SAT have been used in cognitive doses of the nonstimulant ADHD drug, ATMX, were imaging studies (Le, Pardo, & Hu, 1998; Nagahama et al., chosen as a comparison group. The 45 patients on 1998). A domain score for cognitive flexibility is gener- ATMX were children and adolescents who were taking ated by taking the number of correct responses on the ATMX because they had experienced side effects on SAT and subtracting the number of errors on the SAT NML (N = 101) were children and adolescents with no The CPT is a measure of vigilance or sustained atten- active psychiatric, neurological, or medical conditions nor tion (Rosvold & Delgado, 1956). A domain score for any history of participating in a normative study for the complex attention is generated by adding the number of CNS Vital Signs (CNSVS) database. ADHD controls (N = errors committed in the CPT, the SAT, and the Stroop.
95) were newly diagnosed patients who had not yet begun The domain score for vigilance attention is the sum of to take any medications. Demographic data on the five A composite score, the Neurocognition Index (NCI), is computed as the average of the z scores of fivedomains (memory, psychomotor speed, reaction time, Cognitive Evaluation
complex attention, and cognitive flexibility).
Patients’ neurocognitive performance was measured The CNSVS battery has been normed in 1,069 normal on a computerized battery of tests. The CNSVS battery volunteers who were in good health without past or pre- contains seven tests that are widely used by neuropsy- sent psychiatric or neurological disorders, head injury, chologists and known to be reliable and valid. The tests learning disabilities, and so on, and free of any centrally embrace an appropriate span of cognitive domains and acting medications. The subjects ranged in age from 7 to are known to be sensitive to most of the causes of mild 90. Peak performance on the tests is achieved during the cognitive dysfunction. Data establishing the reliability third decade of life and declines gradually thereafter.
Clinical Data for Five Groups. Test Scores and Significance
Note: NML = normal controls; MPH-OROS = Concerta; ATMX = atomoxetine; AMP = Adderall XR; MANOVA = multivariate analysis of thevariance.
Test-retest (TRT) reliability of the CNSVS battery and bipolar disorder (Gualtieri & Johnson, 2006a); and was established in a study of 99 Ss, 40 normal volun- malingering (Gualtieri & Johnson, 2006d).
teers, and 59 psychiatric patients who took the entirebattery on two separate occasions, separated on average by 62 days. The TRT interval ranged from 1 to 282 days,with a median interval of 27 days. Reliability coeffi- The CNSVS database contains records from more cients ranged from .65 (Attention) to .87 (Psychomotor than 4,000 patients with neurological and/or psychiatric Speed). The TRT of the CNSVS battery is comparable to disorders. The database was scanned for patients who those reported for similar, traditional tests and to similar met the following criteria: (a) primary diagnosis ADHD; tests in other computerized test batteries (Gualtieri & (b) age, 10–18 years; (c) no comorbid neurological con- ditions, cognitive disorders (e.g., learning disabilities, The concurrent validity of the CNSVS battery was brain injury), or psychiatric disorders (e.g., anxiety, established in a series of studies comparing the perfor- depression, autism); (d) treatment with AMP, ATMX, or mance of subjects on CNSVS to their performance on MPH-OROS, stable doses maintained for at least 4 conventional neuropsychological tests and on another weeks; (e) no concurrent medications.
computerized neurocognitive test, the NES2 (Baker This process identified four groups: Three groups et al., 1985). The conventional tests were the Rey were children and adolescents treated with MPH-OROS, Auditory Verbal Learning Test, Logical Memory and ATMX, or AMP. The charts were reexamined by the Facial Recognition from the Wechsler Memory Test, a authors to establish that parents and treating clinicians mechanical finger tapper, the ST, Trails B, and the Verbal agreed that the patient was a positive responder to the Fluency Test. From the NES2, the comparison tests were medication and that no further treatment recommenda- Finger Tapping, Switching Attention, and the CPT.
tions were contemplated. The fourth group was untreated CNSVS tests were moderately well correlated with tests and newly diagnosed ADHD patients. These were the of psychomotor speed (finger tapping [.41–.52] and cod- ing [.6–.79]) and executive function on the NES2 The NML were selected from the CNSVS normative (.51–.55). Correlations between the CPT in CNSVS and database. These were individuals with no present or past the NES2 were low (.26–.47). The concurrent validity of psychiatric, developmental, or neurological disorder, in the CNSVS battery is comparable to similar conven- good health, in good standing in school, and taking no current medications. All of the patients had been tested The discriminant validity of the CNSVS battery has within a 14-month period (July 2003–August 2004).
been established in studies of patients with mild cogni-tive impairment (MCI) and early dementia (Gualtieri &Johnson, 2006c); Post-Concussion Syndrome (PCS) and severe traumatic brain injury (Gualtieri & Johnson,2005, 2006b); ADHD (Gualtieri & Johnson, 2006a); Subject data, test scores, and results of the multivariate depression (Gualtieri & Johnson, 2006e); schizophrenia analysis are presented in Table 2. There were no significant Gualtieri, Johnson / Medications Do Not Necessarily Normalize Cognition Three-Group Comparison
Note: MANOVA = multivariate analysis of variance.
differences among the groups in terms of race, but there neuropsychiatric disorders, does not necessarily nor- were for age and gender; therefore, the multivariate analy- malize the cognitive performance of ADHD children sis of the variance (MANOVA) incorporate age and gen- and adolescents. Taking the NCI as a benchmark, untreated ADHD patients perform 15% lower than nor- The results in Table 2 indicate highly significant mals. However, treated ADHD patients perform 10% group differences among the five groups, in all six cog- nitive domains and in the summary score, NCI. The next Three alternative conclusions might be drawn from step was to determine the source of the differences.
these data. First, it is possible that the treatment was sub- It did not reside in the between-drug comparisons optimal. Perhaps better practitioners might have achieved (Pillai’s trace, F = 1.053, p > .40). In light of that, the better results. Second, because ADHD is a behavioral dis- results of the three drug groups were combined, and order, cognitive performance is irrelevant to treatment. We analysis was performed comparing three groups, NML, do not accept either of these. We believe that the third pos- medicated ADHD patients, and unmedicated ADHD sible conclusion is the right one: That even with optimal controls. As expected, group differences, controlling for treatment by experienced clinicians, children, and adoles- age and gender, were significantly different for the NCI cents with ADHD, as a group, have persistent cognitive disabilities. Drug treatment may ameliorate the cognitive The data in Table 4 indicate where the significant difficulties of ADHD patients, but it does not necessarily group differences reside. Analysis of variance (ANOVA) normalize cognition. Medication treatment may be neces- with Bonferroni correction measured the significance of sary, therefore, for children and adolescents with ADHD, differences, and effect sizes were measured by Cohen’s d. The most impressive differences were, as expected, This conclusion would be more convincing if we had between NML and untreated ADHD; significant differ- systematic behavioral data to present. The premise on ences and moderate-to-strong effect sizes were observed which the study is based, after all, is that the treated in every domain, save memory, and in the NCI. The subjects were positive responders on clinical grounds. If NML were also significantly superior to treated ADHD we had objective data, from behavioral observations, or patients in every domain, except reaction time and psy- even subjective data from rating scales, which would chomotor speed. Medicated patients differed from lend strength to the assertion that all the subjects were in untreated patients in the domains of reaction time, cog- fact responders. We regret that no such data were avail- nitive flexibility, and vigilance attention, although the able. On the other hand, in the neuropsychiatry clinics, medication response in ADHD children and adolescents The data are presented graphically in Figure 1.
is assessed on the basis of interviews with parents andpatients, reports from teachers and improvement in Discussion
grades, and by comparing different drugs and differentdoses. This is, in fact, the way response is measured in ADHD treatment, conducted by experienced practi- clinical practice, and the point of this study is simply tioners in a clinic specializing in ADHD and other this: Under the usual circumstances of good clinical care, Group Differences by ANOVA With Bonferroni Correction and Effects Size by Cohen’s d
Normals, Medicated Patients, and Untreated Patients
Notes, Figure 1. NML = normal controls. MED = ADHD patients on medication. ADHD = unmedicated ADHD patients. NCI = neurocognition index. MEM = memory domain score. PMS = psychomotor speed. RT = reaction time. CF = cognitive flexibility. ATT = complex attention. AV = vigilance attention. medication treatment does not necessarily resolve all of testing. The degree to which neuropsychological tests the cognitive problems that ADHD patients have.
correlate with real-world performance has been the The patients in this study were treated with medica- subject of a good deal of research and controversy.
tion because they were doing poorly in school. With Overall, the research suggests that many neuropsycho- treatment, their performance in school improved. We logical tests have a moderate level of ecological validity regret that we do not have grades to analyze and report, when predicting everyday cognitive functioning. The and to correlate with improvement in cognition on the strongest relationships are noted when the outcome mea- computerized neurocognitive test battery. That would be sure corresponds to the cognitive domain assessed by the the appropriate subject for a prospective study, and neuropsychological tests (Chaytor & Schmitter- would address the ecological validity of the cognitive Gualtieri, Johnson / Medications Do Not Necessarily Normalize Cognition The relevance of neuropsychological tests to ADHD 30 words is presented. The 15 target words are mixed diagnosis and to treatment assessment has also been the randomly among 15 new words. When the subject rec- subject of some concern. The results of psychological ognizes a word from the original list, he or she presses tests, for example, the freedom from distractibility factor the space bar. After this trial of 30 stimuli, the subject of the Wechsler Intelligence Scale for Children (WISC- goes on to do the next six tests. At the end of the battery, III) is not found to be “a reliable or a valid index of atten- about 20 min later, the 15 target words appear again, tion or a diagnostic screening measure for identifying children with ADHD” (Reinecke, Beebe, & Stein, 1999, The VIM Test is based on the Rey Visual Design p. 322). The correlation between performance on the Learning Test; the latter is in turn, a parallel to the Rey CPT and parent or teacher rating scales is modest at best Auditory Verbal Learning Test, using geometric figures (Forbes, 1998; McGee, Clark, & Symons, 2000; Raggio rather than words, and requiring the subject to draw the & Pierce, 1999; Rielly, Cunningham, Richards, Elbard, figures from memory. In CNSVS, the VIM Test is just & Mahoney, 1999), and computerized CPTs like the tests like the VBM Test. In the VIM Test 15 geometric figures of variables of attention (TOVA) generate unacceptably are presented; the subject has to identify those figures high false positive rates (30%) in NML and children with nested among 15 new figures. Then, after five more tests, other psychiatric disorders (28%) (Forbes, 1998; Schatz, there is a delayed recognition trial.
The VBM draws from a reservoir of 120 words selected If a child’s behavior, then, is improved when he or she from word-frequency tables. The VIM draws from a reser- has been treated with an ADHD medication, and if voir of 120 simple geometric designs. The scoring is cor- grades improve as well, then why should it matter if per- rect hits and correct passes, immediate and delayed.
formance on a battery of neuropsychological tests is 10% Correct responses from VBM and VIM are summed to lower than normal? We believe that this is more than a generate a composite memory or memory domain score.
trivial result, and that it does have clinical relevance.
The highest score one can attain is 120, the lowest is 60.
Even with successful treatment, ADHD children and Scores below 60 suggest willful exaggeration.
adolescents have subtle but clearly demonstrable cogni-tive deficits. Some of these patients may need more than Finger Tapping Test (FTT)
just medication. Furthermore, it is possible that theinsufficiency of ADHD treatment is responsible for the The FTT is one of the most commonly used tests in relatively low adherence rates over time. Recent reports neuropsychology, because of its simplicity and reliabil- indicate that one third of ADHD children are no longer ity, and also generates relevant data about fine motor taking medication after 2 years (Bussing et al., 2005) and control, which is based on motor speed as well as kines- that only about one in five take medication over a longer thetic and visual-motor ability (Mitrushina, Boone, & period (Miller, Lalonde, & McGrail, 2004).
D’Elia, 1999). It was one of the core tests of theHalstead-Reitan Battery, which dates to the 1940s, butsimilar tests were used by 19th century psychologists Appendix
like Wundt, Galton, and Cattell. The FTT is believed tobe one of the most sensitive neuropsychological tests for The CNS Vital Signs (CNSVS) Battery
determining brain impairment (Mitrushina et al., 1999).
Verbal Memory (VBM) Test and Visual
In CNSVS, the FTT is a very simple test. Subjects are asked to press the space bar with their right index finger Memory (VIM) Test
as many times as they can in 10 s. They do this once forpractice, and then there are three test trials. The test is Vital Signs includes parallel tests of verbal memory repeated with the left hand. The score is the average (word list learning) and visual memory (figure learning).
The tests are virtually identical, but one uses words asstimuli, the other geometric shapes.
Symbol digit coding (SDC)
The VBM test is an adaptation of the Rey Auditory Verbal Learning Test (Rey, 1964; Taylor, 1959). It is a The Symbol Digit Modalities Test (SDMT) (Smith, recognition test, however, not a test of recall. In the 1982) is a variant of the Wechsler DSST, but the position CNSVS version, 15 words are presented, one-by-one, on of symbols and digits is reversed. The clinical and psy- the screen. A new word is presented every 2 s. The chometric properties of the SDMT are similar to those of subject is asked to remember these words. Then a list of the DSST. Although the SDMT may be a harder test, and thus more sensitive to neurotoxicity, performance on the generated in part two of the test (range, 78–188 ms) (the SDMT and the DSST are highly correlated (Lezak, Stroop effect). Part three also generates an error score.
1994). Smith maintained that the SDMT was “usually Averaging the two complex reaction time scores from the most sensitive (test) to the presence of acute or the ST generates a domain score for reaction time. It chronic ‘organic’ cerebral dysfunction” (Smith, 1982).
might be more precise to refer to this domain as infor- In the CNSVS SDC, the subject is given a training session to learn how to link numbers to digits. The testitself consists of serial presentations of screens, each of The Shifting Attention Test (SAT)
which contains a bank of eight symbols above and eightempty boxes below. The subject types in the number that The SAT measures the subject’s ability to shift from corresponds to the symbol that is highlighted. Only the one instruction set to another quickly and accurately. In digits from 2 through 9 are used; this is to avoid confu- the SAT, subjects are instructed to match geometric sion between “1” and “I” on the keyboard. The test lasts objects either by shape or by color. Three figures appear for 120 s. The goal is to type in as many correct numbers on the screen, one on top and two on the bottom. The top figure is either a square or a circle. The bottom figures Neither the SDMT nor the DSST are suitable for are a square and a circle. The figures are either red or repeated administration, because subjects are able to blue; the colors are mixed randomly. The subject is asked remember the code and thus accelerate their perfor- to match one of the bottom figures to the top figure. The mance (Hindmarch, 1980). Modifications in the test are rules change at random. For one presentation, the rule is necessary if it is to be used repeatedly; for example, to match the figures by shape, for another, by color. This changing the code in a random way on successive admin- goes on for 90 s. The goal is to make as many correct istrations. The SDC in CNSVS draws from a reservoir of matches as one can in the time allotted. The scores gen- 32 symbols. Each time the test is administered, the pro- erated by the SAT are: correct matches, errors, and gram randomly chooses eight new symbols to match to response time (ms). A domain score for cognitive flexi- bility is generated by taking the number of correct Scoring is the number of correct responses generated responses on the SAT and subtracting the number of in 2 min. The total of right and left taps from the FTT and total correct responses on the SDC generates a com- There is not a precise parallel to the SAT in the com- pendium of conventional neuropsychological tests,although Trails B and the Wisconsin Cart Sort are some- The Stroop Test (ST)
times considered to be tests of shifting attention.
Computerized tests, however, such as the NES2, There have been several versions of the ST over the CogState, and CANTAB, have SATs that are not dissim- years. The modification adopted for CNSVS uses only ilar to the SAT, and color-shape tests like the SAT have four colors/color words (red, green, yellow, blue), and been used in cognitive imaging studies (Le et al., 1998; only one key is in play, the space bar. The test has three parts. In the first, the words RED, YELLOW, BLUE, andGREEN (printed in black) appear at random on the screen, The Continuous Performance Test (CPT)
and the subject presses the space bar as soon as he or shesees the word. This generates a simple reaction time score.
The CPT is a measure of vigilance or sustained atten- In the second part, the words RED, YELLOW, BLUE, tion or attention over time (Rosvold & Delgado, 1956).
and GREEN appear on the screen, printed in color. The It has been a popular test because of its robust relation- subject is asked to press the space bar when the color of ship to psychiatric disorders. Poor performance on the the word matches what the word says. This generates a CPT has been reported in ADHD (Epstein, Johnson, Varia, & Conners, 2001; Sykes, Douglas, Weiss, & In the third part, the words RED, YELLOW, BLUE, Minde, 1971), learning disabilities (Lindsay, Tomazic, and GREEN appear on the screen, printed in color. The Levine, & Accardo, 2001; McGee et al., 2000), patients subject is asked to press the space bar when the color of with epilepsy (Mirksy & van Buren, 1965), and schizo- the word does not match what the word says. This part phrenics (Vadhan, Serper, Harvey, Chou, & Cancro, also generates a complex reaction time score, called the 2001; Wohlberg & Kornetsky, 1973). It is sensitive to color-word reaction time. The color-word reaction time is CNS dysfunction in general, and is not specific to any on average 120 ms longer than the complex reaction time particular condition (Riccio & Reynolds, 2001).
Gualtieri, Johnson / Medications Do Not Necessarily Normalize Cognition The CPT is also sensitive, for better or worse, to the Benedict, K. B., & Benson, J. (2004). The use of CNSVS in college effects of various drugs. In ADHD children, performance students with primary attention and/or learning disorders. 16th Annual on the CPT is reliably improved by stimulant medica- Postsecondary Disability Training Institute (PTI), Mount Snow, VT.
Bird, C. M., Papadopoulou, K., Ricciardelli, P., Rossor, M. N., & tions (Barkley, 1977; Riccio, Waldrop, Reynolds, & Cipolotti, L. (2003). Test-retest reliability, practice effects and Lowe, 2001). Alcohol consumption (Dougherty, Marsh, reliable change indices for the recognition memory test. British Moeller, Chokshi, & Rosen, 2000) adversely affects per- Journal of Clinical Psychology, 42, 407-425.
formance on the CPT, but nicotine tends to improve per- Bornstein, R. A., Miller, H. B., & Van Schoor, J. T. (1989).
formance on the test (Levin, Conners, Silva, Canu, & Neuropsychological deficit and emotional disturbance in head-injured patients. Journal of Neurosurgery, 70, 509-513.
March, 2001). Certain anticonvulsant medications impair Brodeur, D. A., & Pond, M. (2001). The development of selective performance on the CPT (Hutt, Jackson, Belsham, & attention in children with attention deficit hyperactivity disorder.
Journal of Abnormal Child Psychology, 29, 229-239.
The CPT in Vital Signs is a conventional version of Bussing, R., Zima, B., Mason, D., Hou, W., Garvan, C., & Forness, S.
the test, although it is shorter than some other versions.
(2005). Use and persistence of pharmacotherapy for elementary In the Vital Signs CPT, the subject is asked to respond to school students with attention-deficit/hyperactivity disorder.
Journal of Child and Adolescent Psychopharmacology, 15, 78-87.
target stimulus “B” but not to any other letter. In 5 min, Cepeda, N. J., Cepeda, M. L., & Kramer, A. F. (2000). Task switch- the test presents 200 letters; 40 of the stimuli are targets ing and attention deficit hyperactivity disorder. Journal of (the letter “B”) and 160 are nontargets (other letters).
Abnormal Child Psychology, 28, 213-226.
The stimuli are presented at random, although the target Chaytor, N., & Schmitter-Edgecombe, M. (2003). The ecological stimulus is blocked so it appears 8 times during each validity of neuropsychological tests: A review of the literature oneveryday cognitive skills. Neuropsychology Review, 13, 181-197.
Cohen, M. L., Kelly, P. C., & Atkinson, A. W. (1989). Parent, teacher, Scoring is correct responses, commission errors child. A trilateral approach to attention deficit disorder. American (impulsive responding), and omission errors (inatten- Journal of Diseases of Children, 143, 1229-1233.
tion). The CPT also reports subjects’ choice reaction Collie, A., Maruff, P., Darby, D. G., & McStephen, M. (2003). The time for each variable. A domain score for complex effects of practice on the cognitive test performance of neurologi- attention is generated by adding the number of errors cally normal individuals assessed at brief test-retest intervals.
Journal of the International Neuropsychological Society, 9, 419-428.
committed in the CPT, the SAT, and the Stroop.
Coughlan, A. K., & Hollows, S. E. (1984). Use of memory tests in differentiating organic disorder from depression. British Journal References
Dikmen, S. S., Heaton, R. K., Grant, I., & Temkin, N. R. (1999). Test- Abikoff, H., & Klein, R. G. (1992). Attention-deficit hyperactivity retest reliability and practice effects of expanded Halstead-Reitan and conduct disorder: Comorbidity and implications for treatment.
Neuropsychological Test Battery. Journal of International Journal of Consulting and Clinical Psychology, 60, 881-892.
Neuropsychological Society, 5, 346-356.
Adams, W. (1982). Effect of methylphenidate on thought processing Dikmen, S. S., Temkin, N. R., Miller, B., Machamer, J., & Winn, H. R.
time in children. Journal of Developmental & Behavioral (1991). Neurobehavioral effects of phenytoin prophylaxis of post- traumatic seizures. Journal of the American Medical Association, Aggarwal, A., & Lillystone, D. (2000). A follow-up pilot study of objective measures in children with attention deficit hyperactivity Dodrill, C. B., & Troupin, A. S. (1975). Effects of repeated adminis- disorder. Journal of Paediatrics and Child Health, 36, 134-138.
trations of a comprehensive neuropsychological battery among Aman, M. G., & Turbott, S. H. (1991). Prediction of clinical response chronic epileptics. The Journal of Nervous and Mental Disease, in children taking methylphenidate. Journal of Autism and Developmental Disorders, 21, 211-228.
Dougherty, D. M., Marsh, D. M., Moeller, F. G., Chokshi, R. V., & Baker, E. L., Letz, R. E., Fidler, A. T., Shalat, S., Plantamura, D., & Rosen, V. C. (2000). Effects of moderate and high doses of alco- Lyndon, M. (1985). A computer-based neurobehavioral evaluation hol on attention, impulsivity, discriminability, and response bias in system for occupational and environmental epidemiology: immediate and delayed memory task performance. Alcohol and Methodology and validation studies. Neurobehavioral Toxicology Clinical Experimental Research, 24, 1702-1711.
& Teratology, 7, 369-377.
Dulcan, M., & Popper, C. (1991). Concise Guide to Child and Barkley, R. A. (1977). A review of stimulant drug research with Adolescent Psychiatry. Washington, DC.
hyperactive children. Journal of Child Psychology and Psychiatry, Elia, J., Borcherding, B. G., Rapoport, J. L., & Keysor, C. S. (1991).
Methylphenidate and dextroamphetamine treatments of hyperactiv- Barnett, R., Maruff, P., Vance, A., Luk, E. S., Costin, J., Wood, C., et al.
ity: Are there true nonresponders? Psychiatry Research, 36, 141-155.
(2001). Abnormal executive function in attention deficit hyperac- Elwood, R. W. (2001). MicroCog: Assessment of cognitive function- tivity disorder: The effect of stimulant medication and age on ing. Neuropsychology Review, 11, 89-100.
spatial working memory. Psychological Medicine, 31, 1107-1115.
Epstein, J. N., Johnson, D. E., Varia, I. M., & Conners, C. K. (2001).
Barr, W. B. (2003). Neuropsychological testing of high school ath- Neuropsychological assessment of response inhibition in adults letes. Preliminary norms and test-retest indices. Archives of with ADHD. Journal of Clinical & Experimental Neuropsychology, Clinical Neuropsychology, 18, 91-101.
Erlanger, D., Feldman, D., Kutner, K., Kaushik, T., Kroger, H., Festa, J., Hindmarch, I. (1980). Psychomotor function and psychoactive drugs.
et al. (2003). Development and validation of a web-based neuro- British Journal of Clinical Pharmacology, 10, 189-209.
psychological test protocol for sports-related return-to-play Hutt, S. J., Jackson, P. M., Belsham, A., & Higgins, G. (1968).
decision-making. Archives of Clinical Neuropsychology, 18, 316.
Perceptual-motor behaviour in relation to blood phenobarbitone Everett, J., Thomas, J., Cote, F., Levesque, J., & Michaud, D. (1991).
level: A preliminary report. Developmental Medicine and Child Cognitive effects of psychostimulant medication in hyperactive children. Child Psychiatry and Human Development, 22, 79-87.
Kalff, A. C., Hendriksen, J. G., Kroes, M., Vles, J. S., Steyaert, J., Fischer, M., & Newby, R. F. (1998). Use of the restricted academic Feron, F. J., et al. (2002). Neurocognitive performance of 5- task in ADHD dose-response relationships. Journal of Learning and 6-year-old children who met criteria for attention deficit/ hyperactivity disorder at 18 months follow-up: Results from a Forbes, G. B. (1998). Clinical utility of the Test of Variables of prospective population study. Journal of Abnormal Child Attention (TOVA) in the diagnosis of attention-deficit/hyperactiv- ity disorder. Journal of Clinical Psychology, 54, 461-476.
Konrad, K., Gunther, T., Hanisch, C., & Herpertz-Dahlmann, B.
Franzen, M. D., Tishelman, A. C., Sharp, B. H., & Friedman, A. G.
(2004). Differential effects of methylphenidate on attentional (1987). An investigation of the test-retest reliability of the Stroop functions in children with attention-deficit/hyperactivity disorder.
Color-Word Test across two intervals. Archives of Clinical Journal of the American Academy of Child and Adolescent Psychiatry, Gill, D. M., Reddon, J. R., Stefanyk, W. O., & Hans, H. S. (1986).
Le, T. H., Pardo, J. V., & Hu, X. (1998). 4 T-fMRI study of nonspa- Finger tapping: Effects of trials and sessions. Perceptual and tial shifting of selective attention: Cerebellar and parietal contri- butions. Journal of Neurophysiology, 79, 1535-1548.
Gimpel, G., Collett, B., Veeder, M., Gifford, J., Sneddon, P., Leth-Steensen, C., Elbaz, Z. K., & Douglas, V. I. (2000). Mean Bushman, B., et al. (2005). Effects of stimulant medication on response times, variability, and skew in the responding of ADHD cognitive performance of children with ADHD. Clinical children: A response time distributional approach. Acta Pediatrics (Phila), 44, 405-411.
Psychologica (Amsterdam), 104, 167-190.
Golden, C. J. (1978). Stroop Color and Word Test: A manual for clin- Levin, E. D., Conners, C. K., Silva, D., Canu, W., & March, J. (2001).
ical and experimental uses. Chicago: Stoelting Company.
Effects of chronic nicotine and methylphenidate in adults with Goldstein, G., & Watson, J. (1989). Test-retest reliability of the attention deficit/hyperactivity disorder. Experimental and Clinical Halstead-Reitan Battery and the WAIS in a neuropsychiatric pop- Psychopharmacology, 9, 83-90.
ulation. Clinical Neuropsychologist, 3, 265-272.
Lezak, M. D. (1994). Domains of behavior from a neuropsycho- Gonzalez, H., Mungas, D., & Haan, M. (2002). A verbal learning and logical perspective: The whole story. Nebraska Symposium on memory test for English- and Spanish-speaking older Mexican- American adults. Clinical Neuropsychology, 16, 439-451.
Lindsay, R. L., Tomazic, T., Levine, M. D., & Accardo, P. J. (2001).
Green, R. C., Green, J., Harrison, J. M., & Kutner, M. H. (1994).
Attentional function as measured by a continuous performance Screening for cognitive impairment in older individuals. Validation task in children with dyscalculia. Journal of Developmental & study of a computer-based test. Archives of Neurology, 51, 779-786.
Behavioral Pediatrics, 22, 287-292.
Gualtieri, C., & Johnson, L. (2005). Allocation of attentional Lovejoy, M. C., & Rasmussen, N. H. (1990). The validity of vigilance tasks resources in patients with ADHD: Maturational changes from age in differential diagnosis of children referred for attention and learning 10 to 29. Journal of Attention Disorders, 9, 534-542.
problems. Journal of Abnormal Child Psychology, 18, 671-681.
Gualtieri, C. T., & Johnson, L. G. (2006a). A computerized neu- Lufi, D., Parish-Plass, J., & Gai, E. (1997). The effect of methylphenidate rocogntive test battery for studies of schizophrenic and bipolar on the cognitive and personality functioning of ADHD children.
The Israel Journal of Psychiatry and Related Sciences, 34, 200-209.
Schizophrenia Research, Davos, Switzerland, 2006. Schizophrenia McGee, R. A., Clark, S. E., & Symons, D. K. (2000). Does the Conners’ Continuous Performance Test aid in ADHD diagnosis? Gualtieri, C. T., & Johnson, L. G. (2006b). A computerized test sen- Journal of Abnormal Child Psychology, 28, 415-424.
sitive to mild and severe brain injury. Manuscript submitted for Mehta, M. A., Goodyer, I. M., & Sahakian, B. J. (2004).
Methylphenidate improves working memory and set-shifting in Gualtieri, C. T., & Johnson, L. G. (2006c). Neurocognitive testing AD/HD: Relationships to baseline memory capacity. Journal of supports a broader concept of mild cognitive impairment. Journal Child Psychology and Psychiatry, 45, 293-305.
of Alzheimers Related Dementia, 20, 359-366.
Miller, A., Lalonde, C., & McGrail, K. (2004). Children’s persistence Gualtieri, C. T., & Johnson, L. G. (2006d). Reliability and validity of with methylphenidate therapy: A population based study.
a computerized neurocognitive test battery, CNS Vital Signs.
Canadian Journal of Psychiatry, 49, 761-768.
Archives of Clinical Neuropsychology, 21, 623-643.
Mirksy, A. F., & van Buren, J. M. (1965). On the nature of the Gualtieri, C. T., & Johnson, L. G. (2006e, June). Reliability and valid- “absence” in centrencephalic epilepsy: A study of some behavioral, ity of a computerized neurocognitive test for research in schizo- electroencephalographic and autonomic factors. Electroencephalo- phrenia and bipolar disorder. Presentation at the New Clinical graphy and Clinical Neurophysiology, 18, 348.
Drug Evaluation Unit (NCDEU), Boca Raton, Florida.
Mitchell, W. G., Chavez, J. M., Baker, S. A., Guzman, B. L., & Azen, Gualtieri, C. T., Johnson, L. G., & Benedict, K. B. (2004a). A com- S. P. (1990). Reaction time, impulsivity, and attention in hyperac- puterized cognitive screening battery for psychiatrists. APA tive children and controls: A video game technique. Journal of Gualtieri, C. T., Johnson, L. G., & Benedict, K. B. (2004b).
Mitrushina, M., Boone, K. B., & D’Elia, L. F. (1999). Handbook of Reliability and validity of a brief computerized neurocognitive normative data for neuropsychological assessment. New York: screening battery. INS Annual Meeting, Baltimore.
Gualtieri, Johnson / Medications Do Not Necessarily Normalize Cognition Muir-Broaddus, J. E., Rosenstein, L. D., Medina, D. E., & Soderberg, Schachar, R., Jadad, A. R., Gauld, M., Boyle, M., Booker, L., Snider, A., C. (2002). Neuropsychological test performance of children with et al. (2002). Attention-deficit hyperactivity disorder: Critical ADHD relative to test norms and parent behavioral ratings.
appraisal of extended treatment studies. Canadian Journal of Archives of Clinical Neuropsychology, 17, 671-689.
Nagahama, Y., Sadato, N., Yamauchi, H., Katsumi, Y., Hayashi, T., Schatz, A. M., Ballantyne, A. O., & Trauner, D. A. (2001). Sensitivity Fukuyama, H., et al. (1998). Neural activity during attention shifts and specificity of a computerized test of attention in the diagnosis between object features. Neuroreport, 9, 2633-2638.
of Attention-Deficit/Hyperactivity Disorder. Assessment, 8, 357-365.
Raggio, D. J., & Pierce, J. (1999). Use of the school Performance Smith, A. (1982). Symbol digit modalities test (SDMT) manual Rating Scale with children treated for attention deficit hyperactiv- (revised). Los Angeles: Western Psychological Services.
ity disorder. Perceptual and Motor Skills, 88, 957-960.
Sykes, D. H., Douglas, V. I., Weiss, G., & Minde, K. K. (1971).
Reinecke, M. A., Beebe, D. W., & Stein, M. A. (1999). The third Attention in hyperactive children and the effect of methylphenidate factor of the WISC-III: It’s (probably) not freedom from dis- (ritalin). Journal of Child Psychology and Psychiatry, 12, 129-139.
tractibility. Journal of the American Academy of Child and Taylor, E. M. (1959). The appraisal of children with cerebral deficits. Adolescent Psychiatry, 38, 322-328.
Cambridge, MA: Harvard University Press.
Rey, A. (1964). L’examen clinique en psychologie. Paris: Presses Trommer, B. L., Hoeppner, J. B., Lorber, R., & Armstrong, K. (1988).
Pitfalls in the use of a continuous performance test as a diagnos- Riccio, C. A., & Reynolds, C. R. (2001). Continuous performance tic tool in attention deficit disorder. Journal of Developmental & tests are sensitive to ADHD in adults but lack specificity. A review Behavioral Pediatrics, 9, 339-345.
and critique for differential diagnosis. Annals of the New York Vadhan, N. P., Serper, M. R., Harvey, P. D., Chou, J. C., & Cancro, R.
Academy of Science, 931, 113-139.
(2001). Convergent validity and neuropsychological correlates of Riccio, C. A., Waldrop, J. J., Reynolds, C. R., & Lowe, P. (2001).
the schedule for the assessment of negative symptoms (SANS) Effects of stimulants on the continuous performance test (CPT): attention subscale. Journal of Nervous and Mental Disease, 189, Implications for CPT use and interpretation. Journal of Neuropsychiatry and Clinical Neuroscience, 13, 326-335.
Vance, A. L., Maruff, P., & Barnett, R. (2003). Attention deficit Rielly, N. E., Cunningham, C. E., Richards, J. E., Elbard, H. J., & hyperactivity disorder, combined type: Better executive function Mahoney, W. J. (1999). Detecting Attention Deficit Hyperactivity performance with longer-term psychostimulant medication.
Disorder in a communications clinic: Diagnostic utility of the Australian and New Zealand Journal of Psychiatry, 37, 570-576.
Gordon Diagnostic System. Journal of Clinical and Experimental Weiler, M. D., Bernstein, J. H., Bellinger, D. C., & Waber, D. P. (2000).
Neuropsychology, 21, 685-700.
Processing speed in children with attention deficit/hyperactivity Risser, M. G., & Bowers, T. G. (1993). Cognitive and neuropsycho- disorder, inattentive type. Child Neuropsychology (Neuropsychology, logical characteristics of attention deficit hyperactivity disorder Development and Cognition: Section C), 6, 218-234.
children receiving stimulant medications. Perceptual and Motor Wohlberg, G. W., & Kornetsky, C. (1973). Sustained attention in remitted schizophrenics. Archives in General Psychiatry, 28, 533-537.
Rosvold, H. E., & Delgado, J. M. (1956). The effect on delayed- alternation test performance of stimulating or destroying elec- C. Thomas Gualtieri, MD, is medical director at the North
trically structures within the frontal lobes of the monkey’s Carolina Neuropsychiatry Clinics, Chapel Hill and Charlotte.
brain. Journal of Comparative & Physiological Psychology, 49,365-372.
Roth, R. M., Wishart, H. A., Flashman, L. A., Riordan, H. J., Huey, L., Lynda G. Johnson, PhD, is director of neuropsychology at
& Saykin, A. J. (2004). Contribution of organizational strategy the North Carolina Neuropsychiatry Clinics. Drs Gualtieri and to verbal learning and memory in adults with attention-deficit/ Johnson are two of the developers of the CNS Vital Signs hyperactivity disorder. Neuropsychology, 18, 78-84.

Source: http://www.ncneuropsych.com/research/add-normalize.pdf

Die wechselwirkungen zwischen antiepileptika und anderen medikamenten

B e h a n d l u n g Die Wechselwirkungen zwischen Anti-epileptika und anderen Medikamenten Zugabe der so genannten enzyminduzierenden Medikamente (be-schleunigen den Abbau von Medikamenten in der Leber) unterein Unter Wechselwirkungen zwischen Medikamenten (so genannte Interaktionen) versteht man eine gegenseitige Beeinflussung ihrer ander zu einer Wirkungsabschwächung. Bei diesen

Bb_ist brain-doping tatsächlich doping

Ist Brain-Doping tatsächlich Doping? Zur medialen Definition pharmazeutischer leistungssteigernder Maßnahmen im Beruf und Alltag der Konzentration, Provigil® zur Erhöhung undVerlängerung der Wachsamkeit); Medikamente,»Forget sports doping. The next frontier iswelche die körperliche Leistungsfähigkeit erhö-brain doping.« So schreibt Karen Kaplan in ei-hen (z.B. Steroide). Viagr

Copyright © 2010-2014 Drug Shortages pdf