ADHD Atten Def Hyp Disord (2014) 6:241–248 DOI 10.1007/s12402-014-0132-3
REVIEW ARTICLE
Utility of cognitive neuropsychological assessment in attention-deficit/hyperactivity disorder Klaus W. Lange • Joachim Hauser • Katharina M. Lange Ewelina Makulska-Gertruda • Tomoyuki Takano • Yoshihiro Takeuchi • Lara Tucha • Oliver Tucha
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Received: 4 September 2013 / Accepted: 4 March 2014 / Published online: 18 March 2014 Ó Springer-Verlag Wien 2014
Abstract The present review addresses the question of whether and how neuropsychological tests assessing cognition in attention-deficit/hyperactivity disorder (ADHD) can contribute to clinical and scientific issues concerning ADHD. Neuropsychological studies have shown various though inconsistent cognitive deficits in patients with ADHD. While patients with ADHD, at group level, may differ from healthy participants in regard to cognitive functioning, there is no distinct psychometric cognitive test or profile allowing an individual diagnosis of ADHD or the identification of subtypes according to DSM. Psychometric neuropsychological tests may provide a precise description of the cognitive problems in individual patients and offer specific information for individualized treatment planning. In addition, neuropsychological assessment may contribute to neuroscientific research by providing endophenotypes or biological markers of ADHD. Cognitive neuropsychological assessment appears to be at present of limited clinical use and confined to individual descriptions. Keywords Attention-deficit/hyperactivity disorder (ADHD) Cognition Neuropsychology Psychometry Review K. W. Lange (&) J. Hauser K. M. Lange E. Makulska-Gertruda Department of Experimental Psychology, University of Regensburg, 93040 Regensburg, Germany e-mail: [email protected]; [email protected] T. Takano Y. Takeuchi Department of Pediatrics, Shiga University of Medical Science, ¯ tsu, Japan O L. Tucha O. Tucha Department of Clinical and Developmental Neuropsychology, University of Groningen, Groningen, The Netherlands
Introduction Attention-deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in childhood and adolescence. The cardinal symptoms of ADHD are excessive motor activity, inattention and impulsiveness (e.g. Barkley 2006; Lange et al. 2010a). ADHD affects approximately 2–7 % of children and adolescents and persists into adulthood in about 50 % of cases (Barkley 2006; Clements et al. 2003; Paule et al. 2000). A metaanalysis of follow-up studies showed that the persistence of ADHD is approximately 15 % at age 25 years when individuals meeting full criteria for ADHD are included, while this rate is 65 % in cases consistent with DSM-IV’s definition of ADHD in partial remission (Faraone et al. 2006). Environmental, social, genetic and neurobiological factors appear to be relevant in the aetiology of ADHD (Barkley 2006; Biederman and Faraone 2005; Vancassel et al. 2007; Wankerl et al. 2014). The diagnosis of ADHD is made clinically and includes a physical examination as well as an evaluation of the patients’ developmental history and current behaviour. ADHD is a descriptive diagnosis and does not take aetiology into account. The behavioural checklists commonly used are measures dependent on subjective opinions and therefore have their limitations. In addition, the ratings of school children with ADHD by parents and teachers are frequently discrepant and do not appear to provide an objective diagnostic basis (e.g. Furman 2005). The current diagnostic structure of ADHD according to the criteria set in the fourth and fifth editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR and DSM-5) (American Psychiatric Association 2000, 2013) is behaviourally based and does not require psychometric testing to make the diagnosis.
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Neuropsychological tests are designed to provide a valid, reliable and objective description of relationships between behaviour and brain activity. These tests assume that behaviour is directly affected by brain activity and primarily assess dysfunctions related to various cognitive domains. The majority of studies investigating cognitive impairment in patients with ADHD use standardized neuropsychological tests in order to describe the functional domains affected and to make predictions regarding underlying pathophysiological or pathological alterations in the brain. The present review addresses the question of whether and how neuropsychological tests assessing cognition can contribute to clinical and scientific issues concerning ADHD.
Neuropsychological assessment in ADHD Numerous studies have reported cognitive impairments in ADHD related to the domains of attention, memory, executive functions, spatial abilities and language skills. Attention can be considered the basis on which most other cognitive functions develop (White et al. 2009). It can be defined as a multidimensional concept with several distinct functions (Cohen 1993). For example, the multidimensional model of attention by van Zomeren and Brouwer (1994) distinguishes between alertness, sustained attention/vigilance, selective attention, divided attention and shifting. An inappropriate level of attention is of particular importance in ADHD according to the diagnostic criteria. Several studies have demonstrated that both children and adults with ADHD may show deficits of alertness (Cao et al. 2008), vigilance/sustained attention (Corkum and Siegel 1993; Losier et al. 1996; Manly et al. 2001; Tucha et al. 2009; Weyandt et al. 1998), selective attention (Jonkman et al. 1999; Lovejoy et al. 1999; Seidman et al. 1998; Tucha et al. 2008), divided attention (Lange et al. 2007; Jenkins et al. 1998; Tucha et al. 2006a) and shifting (Hollingsworth et al. 2001; Tucha et al. 2006b). Executive functions describe the ability to respond in an adaptive manner to novel situations and comprise concept formation, fluency, working memory, planning, problem solving and cognitive flexibility as well as goal-directed initiation, monitoring and inhibition of actions (Lezak et al. 2004). Neuropsychological investigations have shown that both children and adults with ADHD have behavioural problems similar to those of patients with acquired frontal lobe lesions (Benson 1991; Boucugnani and Jones 1989). The findings of neuroimaging studies (Casey et al. 1997; Castellanos et al. 1996; Filipek et al. 1997; Hynd et al. 1993; Vaidya et al. 1998), genetic investigations (Cook et al. 1995; LaHoste et al. 1996) and neurochemical
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analyses (Barkley 2006) support the notion of executive dysfunctioning in ADHD. Psychometric neuropsychological tests in children and adults with ADHD have shown executive deficits including impaired concept formation (Antshel et al. 2010; Lawrence et al. 2004), verbal fluency (Tucha et al. 2005), working memory (Klingberg et al. 2005; Schweitzer et al. 2000; Westerberg et al. 2004), planning (Willcutt et al. 2005; Sergeant et al. 2002), problem solving (Tucha et al. 2011), cognitive flexibility (Shue and Douglas 1992) and impulsivity (Willcutt et al. 2005). Although neuropsychological studies have repeatedly demonstrated various deficits of executive functions in patients with ADHD, these research findings remain inconsistent. While some studies found clear differences in measures of executive functioning, others failed to find evidence of a reduced performance of patients with ADHD in these measures (Homack and Riccio 2004; van Mourik et al. 2005; Sergeant et al. 2002). Memory functions in children and adults with ADHD have been demonstrated to be impaired regarding shortterm memory (Quinlan and Brown 2003; Barnett et al. 2005; Lorch et al. 2010) and long-term memory (MuirBroaddus et al. 2002). However, these findings were not found to be consistent (Horton 1996; Kovner et al. 1998). In addition, thorough analysis taking into account the amount of originally encoded information showed no differences between healthy individuals and patients with ADHD (Kaplan et al. 1998). Therefore, reduced memory performance of patients with ADHD has been related to attention deficits and impaired executive functioning (Kaplan et al. 1998; Pollak et al. 2008; Seidman et al. 1998), which is also supported by recent findings on prospective and source memory of adults with ADHD (Fuermaier et al. 2013a, b). Spatial abilities such as spatial orientation, perception of spatial relations, mental spatial manipulation and visuoconstructive abilities have been reported to be impaired in both children and adults with ADHD (Aman et al. 1998; Biederman et al. 1993, Rolfe et al. 2008; Sheppard et al. 1999; Schreiber et al. 1999; Tucha and Lange 2001). However, other studies found impairments regarding different aspects of spatial functioning or were unable to present any evidence of impaired spatial abilities. For example, while Biederman et al. (1993) observed a difference in visuo-constructive abilities between healthy adults and adults with ADHD, several studies failed to find such an impairment although the same tests were applied (e.g. Biederman et al. 1994; Gansler et al. 1998; Kovner et al. 1998; Seidman et al. 1998). Patients’ performance in spatial ability tasks, in particular in visuo-constructive tasks, has been shown to be adversely influenced by executive dysfunctioning (Sami et al. 2003; Schreiber et al. 1999).
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Language deficits affecting expressive language, language comprehension, communication, and private speech have been reported in patients with ADHD (Barkley 2006; Berk and Landau 1993; Bruce et al. 2006; Hartsough and Lambert 1985; Wassenberg et al. 2010). These deficits are, however, not very common (10–30 % of patients, Barkley 2006). Comprehensive neuropsychological test batteries including standardized and norm-referenced assessment instruments have been developed in the last decades and are nowadays routinely used in clinical neuropsychology and neuropsychiatry. The question arises of whether the diagnosis of ADHD may be improved using neuropsychological tests. In theory, standardized psychometric tests could allow the quantification of ADHD symptoms. One might also be able to establish cut-off values in order to distinguish between disturbed and undisturbed behaviour. Neuropsychological measures might therefore eventually play a decisive role in the diagnosis of ADHD. Several attempts have been made to diagnose ADHD using neuropsychological tests. These approaches include, for example, the use of single neuropsychological tests (for review see Castellanos et al. 2006), the application of neuropsychological tests with some degree of sensitivity for ADHD in adulthood (Kaplan and Stevens 2002), or the description of neurocognitive profiles associated with ADHD in adults (McLean et al. 2004). In comparison to healthy individuals, neuropsychological tests used in patients with ADHD can show more or less impairment in certain cognitive domains than in others. These comparisons demonstrate statistically significant differences between patients and controls on group level. This does not suffice to make a diagnosis according to DSM in an individual patient. Psychometric neuropsychological tests do, however, allow a precise description of cognitive deficits in single patients, and this may support the search for individual treatment options. Koziol and Budding (2012) make a strong case in favour of neuropsychological evaluation in order to establish specific brain–behaviour relationships that drive symptom presentations. This approach may in the future be able to replace the monolithic category of ADHD and provide more insight into the spectrum of possibly distinct and neurobiologically defined entities. This requires, however, far more detailed and reliable knowledge than is currently available as to the neuroanatomical substrates of disorders associated with inattention and other symptoms of ADHD.
Ecological validity of neuropsychological tests An important issue regarding neuropsychological assessment of cognitive functions is the relevance of
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psychometric test results in real life. The focus of neuropsychology has recently been shifting towards a greater emphasis on understanding the relationship between test results and performance of everyday tasks (ecological validity) (Spooner and Pachana 2006). Ecological validity describes the ability of a neuropsychological test to reflect or predict the behaviour in daily life or to allow a prognosis in regard to behavioural outcomes of therapeutic interventions. A major concern regarding the usefulness of neuropsychological assessment in neurology and psychiatry relates to the ecological test validity. Neuropsychological tests are often used to make predictions regarding ‘real-world’ functioning (e.g. activities of daily living, vocational function, etc.) in younger adults. However, most neuropsychological instruments were not designed to address real-world outcomes and attempts to interpret these tests in such a manner have been of limited use. A certain functional and predictive relationship between a patient’s performance on a set of neuropsychological tests and their behaviour in a variety of real-world settings can be noted when the outcome measures correspond to the cognitive domain assessed by the neuropsychological tests (for review see Chaytor and Schmitter-Edgecombe 2003). Overall, however, the research suggests that many neuropsychological tests have only a moderate level of ecological validity when predicting everyday cognitive functioning (Chaytor and Schmitter-Edgecombe 2003; Lange et al. 2010b). In children and adolescents with ADHD, the ecological validity of the commonly used tasks and analogue behavioural observation procedures are also an important topic regarding the generalization of neuropsychological findings to clinical issues concerning their diagnosis, outcome and treatment response (e.g. Barkley 1991). The ecological validity of most methods assessing inattention, hyperactivity and impulsivity and measures of these constructs in natural settings in children with ADHD is of a low-tomoderate degree, with some traditional laboratory tasks including those assessing executive functions proving unsatisfactory (Barkley 1991, 2012). Several factors may moderate the degree of ecological validity of neuropsychological tests and are in need of further exploration. These factors include the effects of the population being tested, the person completing the outcome measure (e.g. parent or teacher vs. clinician) and severity of disorder. In addition, it is necessary to have a standard measurement of outcome for each cognitive domain if one wants to perform comparisons across studies (Chaytor and Schmitter-Edgecombe 2003). Future advances regarding ecological validity are likely to come from a greater reliance on multilevel assessments of the target behaviours grounded in the natural environment.
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Neuropsychological assessment and subtypes of ADHD Various subtypes of ADHD have been proposed on the basis of phenomenology, pervasiveness of symptoms, or presence of comorbid disorders. DSM-IV-TR (American psychiatric Association 2000) distinguishes between the predominantly hyperactive-impulsive type (ADHD-HI), the predominantly inattentive type (ADHD-I) and the combined (hyperactive-impulsive and inattentive) type (ADHD-C). Most propositions regarding cognitive measures assumed to be associated with DSM subtypes of ADHD could not be confirmed by significant between-group comparisons. Most attention deficits associated with the inattentive subtype (DSM-III ADD without hyperactivity) have been shown to be artefacts of reduced IQ. When IQ was controlled, the differences in attention between children with ADD and healthy controls disappeared (Taylor et al. 1991). Barkley (1997, 2012) proposed that among ADHD subtypes, inattention is qualitatively different, with ADHD-C representing impaired goal-directed persistence arising from poor inhibition and ADHD-I reflecting impaired speed of processing. This suggestion needs to be confirmed and will require tests that are not solely able to detect quantitative differences regarding attention functions but rather qualitative differences related to distinct brain systems. It has, for example, been shown that children with ADHD-C compared with those with ADHD-I have more difficulties inhibiting inadequate responses (Geurts et al. 2005; Huang-Pollock et al. 2005; Klorman et al. 1999) Children with ADHD-I display a slower tempo for information processing than children with ADHD-C (Nigg et al. 2002). The neuropsychological differences between ADHD subtypes were revealed by comparisons on group level and do not provide a basis for individual classification. Neuropsychological test results have generally not been helpful in identifying ADHD subtypes according to DSM (Doyle et al. 2000; Hinshaw et al. 2002). Neuropsychological studies on ADHD and ADHD subtypes rely on the assumption that the DSM categories represent homogeneous syndromes. An attempt has been made in order to determine whether data-driven neuropsychological subtypes can be discerned in children with and without ADHD using graph theory and community detection (Fair et al. 2012). In this study, typically developing children could be classified into distinct neuropsychological subgroups, while some of the heterogeneity in children with ADHD might be ‘nested’ in this normal variation. Further studies need to assess if this approach can be translated into clinical use.
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Neuropsychological measures as biological markers or endophenotypes of ADHD Neuropsychological measures are, in the strict sense, no biological markers. However, they fulfil some of the criteria of classical biomarkers such as the objective measurement of processes that may indicate the presence of physiological alterations, functional deficits, or pathological conditions. In addition, neuropsychological measures are the most frequently considered behavioural correlates of classical biological markers (for review see Thome et al. 2012). Deficits in all domains of cognitive functioning have been observed in children and adults with ADHD. However, these findings are inconsistent across studies. Impairments in sustained attention, vigilance and working memory are the most common and robust findings. One would therefore expect deficits of these functions to be reliable neuropsychological markers of ADHD. A considerable number of investigations was, however, unable to find differences between patients with ADHD and controls (sustained attention/vigilance: 23–39 % of studies depending on outcome measures; working memory: 25–46 % of studies; see meta-analytical studies by Frazier et al. 2004; Martinussen et al. 2005; Willcutt et al. 2005). In addition, effect sizes indicated only small-to-moderate differences between patients and controls (sustained attention/vigilance: d = 0.51–0.64; working memory: d = 0.43–0.75). No sensitive or specific profile based on neuropsychological tests assessing cognition in ADHD has as yet been found. Cognitive test results may distinguish between groups of patients with ADHD and healthy controls. However, a neuropsychological marker allowing the diagnosis of ADHD in individuals is not available and unlikely to be found in the future. It has been suggested that heritability research in ADHD may be facilitated by neuropsychological measures of cognitive functions. For example, several studies, in which cognitive and motor neuropsychological tasks were administered to children from ADHD and control families, showed that various of these measures appeared useful for genetic research in ADHD by forming candidate endophenotypes, i.e. underlying, heritable and vulnerability traits that indicate an enhanced liability for developing ADHD (for overview see Rommelse et al. 2008). It could also be shown that some neuropsychological measures correlate more strongly between siblings than an ADHD composite, suggesting these measures may have a larger heritability than ADHD itself (Rommelse et al. 2008). Significant sibling cross-correlations also suggested that these neuropsychological measures are related to similar
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familial (and heritable) factors as ADHD, suggesting that these measures may be useful for ADHD genetic research. Further research is needed in order to establish the usefulness of neuropsychological endophenotyping based on psychometric assessments of cognition in ADHD.
Conclusion Although numerous neuropsychological studies have shown various deficits of cognitive functions in patients with ADHD, these findings are inconsistent. While some studies found significant impairments in measures of cognition in ADHD, others failed to confirm these findings. Individuals with ADHD appear to have unique profiles of neuropsychological functioning, with some patients showing impairments in one function and other patients displaying deficits in another function. The wide range of behavioural presentations may reflect the fact that ADHD can be characterized by multiple aetiologies and frequent comorbidity. In addition, statistical comparisons on group level may reveal differences between patients with ADHD and healthy controls or between participants with different subtypes of ADHD regarding various measures of cognition. However, there exists no psychometric cognitive test or test profile that allows the individual diagnosis of ADHD or a subtype of ADHD. In the future, it might be useful to investigate whether or not more complex approaches assessing the interrelationship between attention, memory, executive functions and other cognitive domains may further the utility of cognitive neuropsychological assessment in ADHD. The DSM focusing on behavioural observation and cognitive neuropsychology emphasizing brain–behaviour relationships represent two different approaches to the diagnosis of ADHD. Advocates of DSM rely on symptom rating scales and refuse to acknowledge a contribution of neuropsychological assessment to the (differential) diagnosis of ADHD (e.g. Barkley 2006). Proponents of neuropsychological assessment criticize the heterogeneity inherent in the DSM diagnosis of ADHD and underline the specificity in identifying and treating individual ADHD presentations (e.g. Koziol and Budding 2012). There is no statistically based correspondence between an observation according to DSM and a particular psychometric test result. Neuropsychological tests are therefore unlikely to contribute to the diagnosis as long as the DSM remains the cornerstone of the diagnosis of ADHD. The ecological validity of psychometric tests employed in the assessment of ADHD is at best moderate and neuropsychological test results may therefore not always generalize to real-world environments. However, psychometric tests are the only way to objectively assess the
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patient’s actual cognitive abilities outside of grades on academic tests. Behavioural checklists are measures dependent on subjective opinions and therefore have their limitations. It may therefore be worthwhile developing and evaluating ecologically valid tests including instruments assessing complex cognitive abilities. In patients with ADHD, neuropsychological tests are currently able to demonstrate more or less impairment in certain cognitive domains than in others. This provides statistically significant differences between conditions at group level but does not suffice to make an individual diagnosis according to DSM. It remains to be established whether or not big data and multivariate pattern analysis can provide distinct neuropsychological subgroups, which may eventually allow individual classification. Psychometric neuropsychological assessment is, however, able to quantitatively characterize the cognitive problems in a single patient, and this may support the search for individual treatment options. Another major problem to tackle in the future remains that of establishing a unique association between a certain neuropsychological test and certain brain systems specifically related to a certain behaviourally defined disorder. Cognitive neuropsychological assessment appears to be at present of limited clinical use and confined to individual descriptions. Individual classification on the basis of psychometric testing of cognition is hampered mainly by the fact that ADHD is a disorder with multiple aetiologies, no distinct biomarkers and a high rate of comorbidity.
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247 Paule M, Rowland A, Ferguson S, Chelonis J, Tannock R, Swanson J, Castellanos F (2000) Attention deficit/hyperactivity disorder: characteristics, interventions, and models. Neurotoxicol Teratol 22:631–651 Pollak Y, Kahana-Vax G, Hoofien D (2008) Retrieval processes in adults with ADHD: a RAVLT study. Dev Neuropsychol 33:62–73 Quinlan DM, Brown TE (2003) Assessment of short-term verbal memory impairments in adolescents and adults with ADHD. J Attent Disord 6:143–152 Rolfe MH, Hamm JP, Waldie KE (2008) Differences in paper and pencil versus computerized line bisection according to ADHD subtype and hand-use. Brain Cogn 66:188–195 Rommelse NN, Altink ME, Martin NC, Buschgens CJ, Buitelaar JK, Sergeant JA, Oosterlaan J (2008) Neuropsychological measures probably facilitate heritability research of ADHD. Arch Clin Neuropsychol 23:579–591 Sami N, Carte ET, Hinshaw SP, Zupan BA (2003) Performance of girls with ADHD and comparison girls on the Rey-Osterrieth Complex Figure: evidence for executive processing deficits. Child Neuropsychol 9:237–254 Schreiber HE, Javorsky DJ, Robinson JE, Stern RA (1999) ReyOsterrieth Complex Figure performance in adults with attention deficit hyperactivity disorder: a validation study of the Boston Qualitative Scoring System. Clin Neuropsychol 13:509–520 Schweitzer JB, Faber TL, Grafton ST, Tune LE, Hoffman JM, Kilts CD (2000) Alterations in the functional anatomy of working memory in adult attention deficit hyperactivity disorder. Am J Psychiatry 157:278–280 Seidman LJ, Biederman J, Weber W, Hatch M, Faraone SV (1998) Neuropsychological function in adults with attention-deficit hyperactivity disorder. Biol Psychiatry 44:260–268 Sergeant JA, Geurts H, Oosterlaan J (2002) How specific is a deficit of executive functioning for attention-deficit/hyperactivity disorder? Behav Brain Res 130:3–28 Sheppard DM, Bradshaw JL, Mattingley JB, Lee P (1999) Effects of stimulant medication on the lateralisation of line bisection judgements of children with attention deficit hyperactivity disorder. J Neurol Neurosurg Psychiatry 66:57–63 Shue KL, Douglas VI (1992) Attention deficit hyperactivity disorder and the frontal lobe syndrome. Brain Cogn 20:104–124 Sonuga-Barke EJS (2005) Causal models of attention-deficit/hyperactivity disorder: from common simple deficits to multiple developmental pathways. Biol Psychiatry 57:1231–1238 Spooner DM, Pachana NA (2006) Ecological validity in neuropsychological assessment: a case for greater consideration in research with neurologically intact populations. Arch Clin Neuropsychol 21:327–337 Taylor EA, Sandberg S, Thorley G, Giles S (1991) The epidemiology of childhood hyperactivity. Oxford University Press, London Thome J, Ehlis AC, Fallgatter AJ, Krauel K, Lange KW, Riederer P, Romanos M, Taurines R, Tucha O, Uzbekov M, Gerlach M (2012) Biomarkers for attention-deficit/hyperactivity disorder (ADHD). A consensus report of the WFSBP task force on biological markers and the World Federation of ADHD. World J Biol Psychiatry 13:379–400 Tucha O, Lange KW (2001) Effects of methylphenidate on kinematic aspects of handwriting in hyperactive boys. J Abnorm Child Psychol 29:351–356 Tucha O, Mecklinger L, Laufko¨tter R, Kaunzinger I, Paul GM, Klein HE, Lange KW (2005) Clustering and switching on verbal and figural fluency functions in adults with attention deficit hyperactivity disorder. Cogn Neuropsychiatr 10:231–248 Tucha O, Prell S, Mecklinger L, Bormann-Kischkel C, Ku¨bber S, Linder M, Walitza S, Lange KW (2006a) Effects of methylphenidate on multiple components of attention in children with
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248 attention deficit hyperactivity disorder. Psychopharmacology 185:315–326 Tucha O, Walitza S, Mecklinger L, Sontag TA, Ku¨bber S, Linder M, Lange KW (2006b) Attentional functioning in children with ADHD—predominantly hyperactive-impulsive type and children with ADHD—combined type. J Neural Transm 113:1943–1953 Tucha L, Tucha O, Laufko¨tter R, Walitza S, Klein HE, Lange KW (2008) Neuropsychological assessment of attention in adults with different subtypes of attention deficit/hyperactivity disorder. J Neural Transm 115:269–278 Tucha L, Tucha O, Walitza S, Sontag TA, Laufko¨tter R, Linder M, Lange KW (2009) Vigilance and sustained attention in children and adults with ADHD. J Atten Disord 12:410–421 Tucha L, Tucha O, Sontag TA, Stasik D, Laufko¨tter R, Lange KW (2011) Differential effects of methylphenidate on problem solving in adults with ADHD. J Atten Disord 15:161–173 Vaidya CJ, Austin G, Kirkorian G, Ridlehuber HW, Desmond JE, Glover GH, Gabrieli JD (1998) Selective effects of methylphenidate in attention deficit hyperactivity disorder: a functional magnetic resonance study. Proc Natl Acad Sci USA 95:14494–14499 van Mourik R, Oosterlaan J, Sergeant JA (2005) The Stroop revisited: a meta-analysis of interference control in AD/HD. J Child Psychol Psychiatry 46:150–165 van Zomeren AH, Brouwer WH (1994) Clinical neuropsychology of attention. Oxford University Press, New York
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REVIEW ARTICLE
Utility of cognitive neuropsychological assessment in attention-deficit/hyperactivity disorder Klaus W. Lange • Joachim Hauser • Katharina M. Lange Ewelina Makulska-Gertruda • Tomoyuki Takano • Yoshihiro Takeuchi • Lara Tucha • Oliver Tucha
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Received: 4 September 2013 / Accepted: 4 March 2014 / Published online: 18 March 2014 Ó Springer-Verlag Wien 2014
Abstract The present review addresses the question of whether and how neuropsychological tests assessing cognition in attention-deficit/hyperactivity disorder (ADHD) can contribute to clinical and scientific issues concerning ADHD. Neuropsychological studies have shown various though inconsistent cognitive deficits in patients with ADHD. While patients with ADHD, at group level, may differ from healthy participants in regard to cognitive functioning, there is no distinct psychometric cognitive test or profile allowing an individual diagnosis of ADHD or the identification of subtypes according to DSM. Psychometric neuropsychological tests may provide a precise description of the cognitive problems in individual patients and offer specific information for individualized treatment planning. In addition, neuropsychological assessment may contribute to neuroscientific research by providing endophenotypes or biological markers of ADHD. Cognitive neuropsychological assessment appears to be at present of limited clinical use and confined to individual descriptions. Keywords Attention-deficit/hyperactivity disorder (ADHD) Cognition Neuropsychology Psychometry Review K. W. Lange (&) J. Hauser K. M. Lange E. Makulska-Gertruda Department of Experimental Psychology, University of Regensburg, 93040 Regensburg, Germany e-mail: [email protected]; [email protected] T. Takano Y. Takeuchi Department of Pediatrics, Shiga University of Medical Science, ¯ tsu, Japan O L. Tucha O. Tucha Department of Clinical and Developmental Neuropsychology, University of Groningen, Groningen, The Netherlands
Introduction Attention-deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in childhood and adolescence. The cardinal symptoms of ADHD are excessive motor activity, inattention and impulsiveness (e.g. Barkley 2006; Lange et al. 2010a). ADHD affects approximately 2–7 % of children and adolescents and persists into adulthood in about 50 % of cases (Barkley 2006; Clements et al. 2003; Paule et al. 2000). A metaanalysis of follow-up studies showed that the persistence of ADHD is approximately 15 % at age 25 years when individuals meeting full criteria for ADHD are included, while this rate is 65 % in cases consistent with DSM-IV’s definition of ADHD in partial remission (Faraone et al. 2006). Environmental, social, genetic and neurobiological factors appear to be relevant in the aetiology of ADHD (Barkley 2006; Biederman and Faraone 2005; Vancassel et al. 2007; Wankerl et al. 2014). The diagnosis of ADHD is made clinically and includes a physical examination as well as an evaluation of the patients’ developmental history and current behaviour. ADHD is a descriptive diagnosis and does not take aetiology into account. The behavioural checklists commonly used are measures dependent on subjective opinions and therefore have their limitations. In addition, the ratings of school children with ADHD by parents and teachers are frequently discrepant and do not appear to provide an objective diagnostic basis (e.g. Furman 2005). The current diagnostic structure of ADHD according to the criteria set in the fourth and fifth editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR and DSM-5) (American Psychiatric Association 2000, 2013) is behaviourally based and does not require psychometric testing to make the diagnosis.
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Neuropsychological tests are designed to provide a valid, reliable and objective description of relationships between behaviour and brain activity. These tests assume that behaviour is directly affected by brain activity and primarily assess dysfunctions related to various cognitive domains. The majority of studies investigating cognitive impairment in patients with ADHD use standardized neuropsychological tests in order to describe the functional domains affected and to make predictions regarding underlying pathophysiological or pathological alterations in the brain. The present review addresses the question of whether and how neuropsychological tests assessing cognition can contribute to clinical and scientific issues concerning ADHD.
Neuropsychological assessment in ADHD Numerous studies have reported cognitive impairments in ADHD related to the domains of attention, memory, executive functions, spatial abilities and language skills. Attention can be considered the basis on which most other cognitive functions develop (White et al. 2009). It can be defined as a multidimensional concept with several distinct functions (Cohen 1993). For example, the multidimensional model of attention by van Zomeren and Brouwer (1994) distinguishes between alertness, sustained attention/vigilance, selective attention, divided attention and shifting. An inappropriate level of attention is of particular importance in ADHD according to the diagnostic criteria. Several studies have demonstrated that both children and adults with ADHD may show deficits of alertness (Cao et al. 2008), vigilance/sustained attention (Corkum and Siegel 1993; Losier et al. 1996; Manly et al. 2001; Tucha et al. 2009; Weyandt et al. 1998), selective attention (Jonkman et al. 1999; Lovejoy et al. 1999; Seidman et al. 1998; Tucha et al. 2008), divided attention (Lange et al. 2007; Jenkins et al. 1998; Tucha et al. 2006a) and shifting (Hollingsworth et al. 2001; Tucha et al. 2006b). Executive functions describe the ability to respond in an adaptive manner to novel situations and comprise concept formation, fluency, working memory, planning, problem solving and cognitive flexibility as well as goal-directed initiation, monitoring and inhibition of actions (Lezak et al. 2004). Neuropsychological investigations have shown that both children and adults with ADHD have behavioural problems similar to those of patients with acquired frontal lobe lesions (Benson 1991; Boucugnani and Jones 1989). The findings of neuroimaging studies (Casey et al. 1997; Castellanos et al. 1996; Filipek et al. 1997; Hynd et al. 1993; Vaidya et al. 1998), genetic investigations (Cook et al. 1995; LaHoste et al. 1996) and neurochemical
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analyses (Barkley 2006) support the notion of executive dysfunctioning in ADHD. Psychometric neuropsychological tests in children and adults with ADHD have shown executive deficits including impaired concept formation (Antshel et al. 2010; Lawrence et al. 2004), verbal fluency (Tucha et al. 2005), working memory (Klingberg et al. 2005; Schweitzer et al. 2000; Westerberg et al. 2004), planning (Willcutt et al. 2005; Sergeant et al. 2002), problem solving (Tucha et al. 2011), cognitive flexibility (Shue and Douglas 1992) and impulsivity (Willcutt et al. 2005). Although neuropsychological studies have repeatedly demonstrated various deficits of executive functions in patients with ADHD, these research findings remain inconsistent. While some studies found clear differences in measures of executive functioning, others failed to find evidence of a reduced performance of patients with ADHD in these measures (Homack and Riccio 2004; van Mourik et al. 2005; Sergeant et al. 2002). Memory functions in children and adults with ADHD have been demonstrated to be impaired regarding shortterm memory (Quinlan and Brown 2003; Barnett et al. 2005; Lorch et al. 2010) and long-term memory (MuirBroaddus et al. 2002). However, these findings were not found to be consistent (Horton 1996; Kovner et al. 1998). In addition, thorough analysis taking into account the amount of originally encoded information showed no differences between healthy individuals and patients with ADHD (Kaplan et al. 1998). Therefore, reduced memory performance of patients with ADHD has been related to attention deficits and impaired executive functioning (Kaplan et al. 1998; Pollak et al. 2008; Seidman et al. 1998), which is also supported by recent findings on prospective and source memory of adults with ADHD (Fuermaier et al. 2013a, b). Spatial abilities such as spatial orientation, perception of spatial relations, mental spatial manipulation and visuoconstructive abilities have been reported to be impaired in both children and adults with ADHD (Aman et al. 1998; Biederman et al. 1993, Rolfe et al. 2008; Sheppard et al. 1999; Schreiber et al. 1999; Tucha and Lange 2001). However, other studies found impairments regarding different aspects of spatial functioning or were unable to present any evidence of impaired spatial abilities. For example, while Biederman et al. (1993) observed a difference in visuo-constructive abilities between healthy adults and adults with ADHD, several studies failed to find such an impairment although the same tests were applied (e.g. Biederman et al. 1994; Gansler et al. 1998; Kovner et al. 1998; Seidman et al. 1998). Patients’ performance in spatial ability tasks, in particular in visuo-constructive tasks, has been shown to be adversely influenced by executive dysfunctioning (Sami et al. 2003; Schreiber et al. 1999).
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Language deficits affecting expressive language, language comprehension, communication, and private speech have been reported in patients with ADHD (Barkley 2006; Berk and Landau 1993; Bruce et al. 2006; Hartsough and Lambert 1985; Wassenberg et al. 2010). These deficits are, however, not very common (10–30 % of patients, Barkley 2006). Comprehensive neuropsychological test batteries including standardized and norm-referenced assessment instruments have been developed in the last decades and are nowadays routinely used in clinical neuropsychology and neuropsychiatry. The question arises of whether the diagnosis of ADHD may be improved using neuropsychological tests. In theory, standardized psychometric tests could allow the quantification of ADHD symptoms. One might also be able to establish cut-off values in order to distinguish between disturbed and undisturbed behaviour. Neuropsychological measures might therefore eventually play a decisive role in the diagnosis of ADHD. Several attempts have been made to diagnose ADHD using neuropsychological tests. These approaches include, for example, the use of single neuropsychological tests (for review see Castellanos et al. 2006), the application of neuropsychological tests with some degree of sensitivity for ADHD in adulthood (Kaplan and Stevens 2002), or the description of neurocognitive profiles associated with ADHD in adults (McLean et al. 2004). In comparison to healthy individuals, neuropsychological tests used in patients with ADHD can show more or less impairment in certain cognitive domains than in others. These comparisons demonstrate statistically significant differences between patients and controls on group level. This does not suffice to make a diagnosis according to DSM in an individual patient. Psychometric neuropsychological tests do, however, allow a precise description of cognitive deficits in single patients, and this may support the search for individual treatment options. Koziol and Budding (2012) make a strong case in favour of neuropsychological evaluation in order to establish specific brain–behaviour relationships that drive symptom presentations. This approach may in the future be able to replace the monolithic category of ADHD and provide more insight into the spectrum of possibly distinct and neurobiologically defined entities. This requires, however, far more detailed and reliable knowledge than is currently available as to the neuroanatomical substrates of disorders associated with inattention and other symptoms of ADHD.
Ecological validity of neuropsychological tests An important issue regarding neuropsychological assessment of cognitive functions is the relevance of
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psychometric test results in real life. The focus of neuropsychology has recently been shifting towards a greater emphasis on understanding the relationship between test results and performance of everyday tasks (ecological validity) (Spooner and Pachana 2006). Ecological validity describes the ability of a neuropsychological test to reflect or predict the behaviour in daily life or to allow a prognosis in regard to behavioural outcomes of therapeutic interventions. A major concern regarding the usefulness of neuropsychological assessment in neurology and psychiatry relates to the ecological test validity. Neuropsychological tests are often used to make predictions regarding ‘real-world’ functioning (e.g. activities of daily living, vocational function, etc.) in younger adults. However, most neuropsychological instruments were not designed to address real-world outcomes and attempts to interpret these tests in such a manner have been of limited use. A certain functional and predictive relationship between a patient’s performance on a set of neuropsychological tests and their behaviour in a variety of real-world settings can be noted when the outcome measures correspond to the cognitive domain assessed by the neuropsychological tests (for review see Chaytor and Schmitter-Edgecombe 2003). Overall, however, the research suggests that many neuropsychological tests have only a moderate level of ecological validity when predicting everyday cognitive functioning (Chaytor and Schmitter-Edgecombe 2003; Lange et al. 2010b). In children and adolescents with ADHD, the ecological validity of the commonly used tasks and analogue behavioural observation procedures are also an important topic regarding the generalization of neuropsychological findings to clinical issues concerning their diagnosis, outcome and treatment response (e.g. Barkley 1991). The ecological validity of most methods assessing inattention, hyperactivity and impulsivity and measures of these constructs in natural settings in children with ADHD is of a low-tomoderate degree, with some traditional laboratory tasks including those assessing executive functions proving unsatisfactory (Barkley 1991, 2012). Several factors may moderate the degree of ecological validity of neuropsychological tests and are in need of further exploration. These factors include the effects of the population being tested, the person completing the outcome measure (e.g. parent or teacher vs. clinician) and severity of disorder. In addition, it is necessary to have a standard measurement of outcome for each cognitive domain if one wants to perform comparisons across studies (Chaytor and Schmitter-Edgecombe 2003). Future advances regarding ecological validity are likely to come from a greater reliance on multilevel assessments of the target behaviours grounded in the natural environment.
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Neuropsychological assessment and subtypes of ADHD Various subtypes of ADHD have been proposed on the basis of phenomenology, pervasiveness of symptoms, or presence of comorbid disorders. DSM-IV-TR (American psychiatric Association 2000) distinguishes between the predominantly hyperactive-impulsive type (ADHD-HI), the predominantly inattentive type (ADHD-I) and the combined (hyperactive-impulsive and inattentive) type (ADHD-C). Most propositions regarding cognitive measures assumed to be associated with DSM subtypes of ADHD could not be confirmed by significant between-group comparisons. Most attention deficits associated with the inattentive subtype (DSM-III ADD without hyperactivity) have been shown to be artefacts of reduced IQ. When IQ was controlled, the differences in attention between children with ADD and healthy controls disappeared (Taylor et al. 1991). Barkley (1997, 2012) proposed that among ADHD subtypes, inattention is qualitatively different, with ADHD-C representing impaired goal-directed persistence arising from poor inhibition and ADHD-I reflecting impaired speed of processing. This suggestion needs to be confirmed and will require tests that are not solely able to detect quantitative differences regarding attention functions but rather qualitative differences related to distinct brain systems. It has, for example, been shown that children with ADHD-C compared with those with ADHD-I have more difficulties inhibiting inadequate responses (Geurts et al. 2005; Huang-Pollock et al. 2005; Klorman et al. 1999) Children with ADHD-I display a slower tempo for information processing than children with ADHD-C (Nigg et al. 2002). The neuropsychological differences between ADHD subtypes were revealed by comparisons on group level and do not provide a basis for individual classification. Neuropsychological test results have generally not been helpful in identifying ADHD subtypes according to DSM (Doyle et al. 2000; Hinshaw et al. 2002). Neuropsychological studies on ADHD and ADHD subtypes rely on the assumption that the DSM categories represent homogeneous syndromes. An attempt has been made in order to determine whether data-driven neuropsychological subtypes can be discerned in children with and without ADHD using graph theory and community detection (Fair et al. 2012). In this study, typically developing children could be classified into distinct neuropsychological subgroups, while some of the heterogeneity in children with ADHD might be ‘nested’ in this normal variation. Further studies need to assess if this approach can be translated into clinical use.
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Neuropsychological measures as biological markers or endophenotypes of ADHD Neuropsychological measures are, in the strict sense, no biological markers. However, they fulfil some of the criteria of classical biomarkers such as the objective measurement of processes that may indicate the presence of physiological alterations, functional deficits, or pathological conditions. In addition, neuropsychological measures are the most frequently considered behavioural correlates of classical biological markers (for review see Thome et al. 2012). Deficits in all domains of cognitive functioning have been observed in children and adults with ADHD. However, these findings are inconsistent across studies. Impairments in sustained attention, vigilance and working memory are the most common and robust findings. One would therefore expect deficits of these functions to be reliable neuropsychological markers of ADHD. A considerable number of investigations was, however, unable to find differences between patients with ADHD and controls (sustained attention/vigilance: 23–39 % of studies depending on outcome measures; working memory: 25–46 % of studies; see meta-analytical studies by Frazier et al. 2004; Martinussen et al. 2005; Willcutt et al. 2005). In addition, effect sizes indicated only small-to-moderate differences between patients and controls (sustained attention/vigilance: d = 0.51–0.64; working memory: d = 0.43–0.75). No sensitive or specific profile based on neuropsychological tests assessing cognition in ADHD has as yet been found. Cognitive test results may distinguish between groups of patients with ADHD and healthy controls. However, a neuropsychological marker allowing the diagnosis of ADHD in individuals is not available and unlikely to be found in the future. It has been suggested that heritability research in ADHD may be facilitated by neuropsychological measures of cognitive functions. For example, several studies, in which cognitive and motor neuropsychological tasks were administered to children from ADHD and control families, showed that various of these measures appeared useful for genetic research in ADHD by forming candidate endophenotypes, i.e. underlying, heritable and vulnerability traits that indicate an enhanced liability for developing ADHD (for overview see Rommelse et al. 2008). It could also be shown that some neuropsychological measures correlate more strongly between siblings than an ADHD composite, suggesting these measures may have a larger heritability than ADHD itself (Rommelse et al. 2008). Significant sibling cross-correlations also suggested that these neuropsychological measures are related to similar
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familial (and heritable) factors as ADHD, suggesting that these measures may be useful for ADHD genetic research. Further research is needed in order to establish the usefulness of neuropsychological endophenotyping based on psychometric assessments of cognition in ADHD.
Conclusion Although numerous neuropsychological studies have shown various deficits of cognitive functions in patients with ADHD, these findings are inconsistent. While some studies found significant impairments in measures of cognition in ADHD, others failed to confirm these findings. Individuals with ADHD appear to have unique profiles of neuropsychological functioning, with some patients showing impairments in one function and other patients displaying deficits in another function. The wide range of behavioural presentations may reflect the fact that ADHD can be characterized by multiple aetiologies and frequent comorbidity. In addition, statistical comparisons on group level may reveal differences between patients with ADHD and healthy controls or between participants with different subtypes of ADHD regarding various measures of cognition. However, there exists no psychometric cognitive test or test profile that allows the individual diagnosis of ADHD or a subtype of ADHD. In the future, it might be useful to investigate whether or not more complex approaches assessing the interrelationship between attention, memory, executive functions and other cognitive domains may further the utility of cognitive neuropsychological assessment in ADHD. The DSM focusing on behavioural observation and cognitive neuropsychology emphasizing brain–behaviour relationships represent two different approaches to the diagnosis of ADHD. Advocates of DSM rely on symptom rating scales and refuse to acknowledge a contribution of neuropsychological assessment to the (differential) diagnosis of ADHD (e.g. Barkley 2006). Proponents of neuropsychological assessment criticize the heterogeneity inherent in the DSM diagnosis of ADHD and underline the specificity in identifying and treating individual ADHD presentations (e.g. Koziol and Budding 2012). There is no statistically based correspondence between an observation according to DSM and a particular psychometric test result. Neuropsychological tests are therefore unlikely to contribute to the diagnosis as long as the DSM remains the cornerstone of the diagnosis of ADHD. The ecological validity of psychometric tests employed in the assessment of ADHD is at best moderate and neuropsychological test results may therefore not always generalize to real-world environments. However, psychometric tests are the only way to objectively assess the
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patient’s actual cognitive abilities outside of grades on academic tests. Behavioural checklists are measures dependent on subjective opinions and therefore have their limitations. It may therefore be worthwhile developing and evaluating ecologically valid tests including instruments assessing complex cognitive abilities. In patients with ADHD, neuropsychological tests are currently able to demonstrate more or less impairment in certain cognitive domains than in others. This provides statistically significant differences between conditions at group level but does not suffice to make an individual diagnosis according to DSM. It remains to be established whether or not big data and multivariate pattern analysis can provide distinct neuropsychological subgroups, which may eventually allow individual classification. Psychometric neuropsychological assessment is, however, able to quantitatively characterize the cognitive problems in a single patient, and this may support the search for individual treatment options. Another major problem to tackle in the future remains that of establishing a unique association between a certain neuropsychological test and certain brain systems specifically related to a certain behaviourally defined disorder. Cognitive neuropsychological assessment appears to be at present of limited clinical use and confined to individual descriptions. Individual classification on the basis of psychometric testing of cognition is hampered mainly by the fact that ADHD is a disorder with multiple aetiologies, no distinct biomarkers and a high rate of comorbidity.
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