MENTAL RETARDATION AND DEVELOPMENTAL DISABILITIES RESEARCH REVIEWS 13: 228 236 (2007)

DOWN SYNDROME: COGNITIVE PHENOTYPE

Wayne Silverman1,2*
1 2

Department of Behavioral Psychology, Kennedy Krieger Institute, Baltimore, Maryland

Department of Psychiatry and Behavioral Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland

Down syndrome is the most prevalent cause of intellectual impairment associated with a genetic anomaly, in this case, trisomy of chromosome 21. It affects both physical and cognitive development and produces a characteristic phenotype, although affected individuals vary considerably with respect to severity of specific impairments. Studies focusing on the cognitive characteristics of Down syndrome were reviewed, and while performance in most areas could be predicted based upon overall intellectual disability, relative weaknesses were consistently found to be associated with expressive language, syntactic/morphosyntactic processing, and verbal working memory. This profile of uneven deficits could result from a failure to develop typically automatic processing for speech perception and production, and this possibility is discussed along with its implications for intervention. ' 2007 Wiley-Liss, Inc.
MRDD Research Reviews 2007;13:228236.

Korenberg, 1991], potentially narrowing the search for critical genetic mechanisms. However, recent studies have indicated that presence of the Down syndrome critical region is necessary but not sufficient to produce the phenotype [Olson et al., in press], reemphasizing the complexity of the mechanisms involved. Recent evidence has also showed that gene overexpression in Down syndrome can be specific to tissue type [Li et al., 2006], and it seems likely that the synchronization of overexpression of specific genes with brain development could account for the nature of the cognitive impairments and variation in their severity that characterize affected individuals. COGNITION Neisser [1967, p. 4] defined cognition in his classic text as the processes by which a perceived, remembered, and thought about world is brought into being in response to the energy impinging upon our sensory receptors, encompassing all the processes by which the sensory input is transformed, reduced, elaborated, stored, recovered, and used. By the third edition of Andersons [1990] text, the statement of this definition had been condensed essentially into intelligence and thought, but the scope was not less impressive. As defined in the field and in common usage, cognition includes those mental processes, both conscious and unconscious, that control virtually everything we do or think, and no single review could hope to discuss the entire breadth of relevant research. Therefore, the focus herein will be restricted primarily to areas of cognition that seem to differentiate Down syndrome from other conditions resulting in intellectual disability. Although this consideration of cognition is highly constrained, substantial complexity is an inherent characteristic associated with the concept of cognitive phenotype. Establishing its presence requires description of a specific profile of capabilities, and therefore measures of performance cannot simply reflect the presence of specific or general impairment,

Key Words: Down syndrome; cognition; cognitive phenotype; language; working memory

own syndrome is among the most prevalent causes of intellectual disability, currently affecting approximately one in every 730 babies born in the United States [Centers for Disease Control and Prevention, 2006]. It occurs when an extra copy of chromosome 21 (or critical regions of chromosome 21) is present [Lejeune et al., 1958], producing a well-recognized phenotype that includes characteristic facial and musculoskeletal features, increased risk for a number of health concerns (e.g., congenital heart defects, childhood leukemia, Alzheimers disease in old age), and intellectual impairment [e.g., Epstein, 1989], although there is considerable variability in these features among affected individuals. The impact of Down syndrome on performance capabilities is in most respects comparable to that of other conditions causing intellectual disability. However, relative weaknesses in some aspects of language and verbal memory are specific to this etiology, and there is a compelling need to understand the underlying basis for this profile. The presence of an extra chromosome 21 makes Down syndrome a biologically complex disorder. Mapping of human chromosome 21 has been completed and almost 300 genes have been identified [Ensembl, 2007]. Overexpression of any one of these genes could influence development in itself, but these gene products can also interact with each other and with those of genes on other chromosomes to affect development in important ways. It seemed until very recently that genes within a constrained region of chromosome 21 were responsible for determining the phenotpype [Epstein et al., 1991;

Grant sponsor: Mental Retardation/Developmental Disabilities Branch, National Institute on Child Health and Human Development; Grant number: P30 HD024061. *Correspondence to: Wayne Silverman, Department of Behavioral Psychology, Kennedy Krieger Institute, 707 North Broadway, Suite 222S, Baltimore, MD 21205. E-mail: silvermanw@kennedykrieger.org Received 24 July 2007; Accepted 26 July 2007 Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/mrdd.20156

' 2007 Wiley -Liss, Inc.

but must contain sufficient variation among tasks to permit inferences of distinctive relative strengths and weaknesses. Performance has to be examined across multiple domains employing multiple tasks that systematically tax the capacity of specific underlying processes, and this entails sophisticated approaches to task selection and design, as well as the critical consideration of the processes underlying successful task performance. As Waugh and Norman [1965] emphasized, there is an imperfect correspondence between experimenter-defined task demands and the actual cognitive processes that are engaged in performing successfully, and great care is needed in drawing inferences about any specific process. These types of inferences should always be based on multiple and converging sources of evidence. Once a profile for a genotype is described, its distinctiveness needs to be established. This entails comparisons with other populations with respect to multiple rather than individual measures of performance, and informative results will be in the form of Measure by Population interactions. This introduces needs for more complex study designs, recruitment of larger samples (to provide adequate statistical power to detect these interactions), careful consideration of appropriate comparison groups, and selection of analytical models for dealing with the intricacies of complex data sets. The task of determining a cognitive phenotype for Down syndrome is complicated by other factors, including the complexity of the genotype, the presence of individual differences within this population, and the extended duration of brain development in humans. Specific neural systems mature at different rates over time, and overexpression of genes on chromosome 21 could interact in complex ways with other influences on development. Thus, specific cognitive profiles of Down syndrome could change with development and later-life aging, and the dynamic nature of the processes involved must be taken into consideration. (Zigman and Lott [2007] discuss aging-related issues, and these are not addressed herein, nor are studies focused on development in infancy and early childhood.) This has practical consequences. Performance will be influenced by biological development on the one hand, and experiences and training on the other. Learning not only affects cogni-

tive processes, but also brain function and structure [c.f., Crosier et al., 2004; Praag et al., 2004], and comparisons among populations must address this reality. This could be done by following individuals longitudinally and assessing them at key points in time, but this has not been done over any appreciable span of development because of several considerations that complicate such an effort. Processes of relevance will tend to be changing with development and maturation as more complex competencies emerge [Gibson, 1978; Miller, 1999], and Group by Task interactions at any point in time may reflect quantitative differences in relative biological age rather than persistent processing strengths or weaknesses. (This could also be contributing to the instability in intelligence quotient (IQ) attributed to Down syndrome over the years, as Dykens et al. [2000] and Gibson [1978] discuss.) In addition, repeated testing itself provides opportunities for practice and learning, the effects of which can influence performance and complicate interpretation of findings. Alternatives to longitudinal designs include studies focused on a narrow period of development, and that has been the most prevalent approach. Results of these studies can then be integrated to provide a fuller picture of development [c.f., Gibson, 1978], but most of the issues discussed earlier would remain. In addition, as in any cross-sectional strategy employed to examine individuals at different ages, potential birth cohort effects represent a major concern. Children with Down syndrome born recently encounter family and community attitudes as well as health care practices that are far more positive than they were 20 years ago (even more so compared to 50 years ago), and this is likely to have substantial effects on development [e.g., Buckley et al., 2006]. The issue in the present context is whether these influences affect some cognitive processes more than others, and if they operate in similar ways for people with Down syndrome and intellectual disability due to other causes. Whatever the reality, these are concerns that demand attention. Cross-sequential designs address many of the disadvantages of longitudinal and cross-sectional studies by adopting the most advantageous features of each. In these studies, groups of participants are followed over time, but coverage of a broad span of development is provided by enrolling individuals within groups varying in age such that eventual


overlap occurs, permitting explicit examination of cohort and practice effects. However, cross-sequential studies have apparently not been employed to examine the Down syndrome phenotype, except for studies of aging during adulthood [e.g., Zigman et al., 2002]. Selection of comparison groups can also have substantial impacts on studies of cognitive phenotype [c.f., Chapman and Hesketh, 2000]. Differences between people with Down syndrome and their typically developing peers at similar chronological ages will reflect the substantial effects of intellectual disability, per se, and adjustments of task difficulty to address this concern might have unpredictable consequences for underlying processing. Norms for broadly used assessment instruments were standardized on samples that included only a small number of people with intellectual disability at any given age (even fewer with Down syndrome), and these instruments were never intended to make fine distinctions among individuals performing at lower ranges of their scales. The dominant strategy for addressing these concerns has been to employ a comparison group of typically developing children having comparable levels of cognitive development, but this strategy of mental-age matching may be particularly problematic for studies of cognitive phenotypes, as will be discussed following overviews of specific studies. Many investigators have recognized the difficulties associated with basing inferences about behavioral phenotype in contrasts with typically developing individuals however they are matched, and a comparison group consisting of individuals at comparable chronological age and severity of intellectual disability but with a different etiology is an attractive option. This is a direction in which the field now seems to be moving, and these types of studies take one of two general forms. The first involves comparisons among genetically well-defined groups, and individuals with Down syndrome have been compared to peers with Fragile X syndrome [Abbeduto et al., 2001] or Williams syndrome [e.g., Wang and Bellugi, 1994] with clear distinctions noted. These designs have the advantage of providing maximal genetic homogeneity within groups, but findings can be difficult to interpret because the appearance of selective weaknesses in one group might also reflect relative strengths in the other. The second simply conducts comparisons with individuals having


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other etiologies. Of course, this comparison group would be genetically heterogeneous, and the extent to which various causal conditions produce different profiles of cognitive strengths and weaknesses will add to unsystematic variation. Many individuals within groups having intellectual disability due to unknown causes also seem to have relative weaknesses associated with language processes [Abbeduto, 1991], and this should justify additional caution as inclusion criteria are considered. In summary, the concept of a Down syndrome cognitive phenotype suggests inherent variation in efficiency and/or capacity among specific processes, the pattern of which is distinct from that of other populations. Because cognition focuses on capacities and competencies that can only be inferred from measures of overt performance, and successful completion of any task necessarily requires the engagement of many processes in addition to those of immediate interest, great care has to be exercised in selection of procedures and methods of analysis. No single option is without inherent concerns, and discovery of the true nature of the Down syndrome cognitive phenotype will depend upon the accumulation of evidence from multiple sources employing complementary research strategies. COMPREHENSIVE APPROACHES TO ASSESSMENT Multiple studies have employed broad batteries of assessments to examine strengths and weaknesses in performance associated with etiology of intellectual disability, and Down syndrome has been of particular interest because of its relatively high prevalence and well-defined phenotype. Meyers et al. [1961] were well ahead of their time in employing this strategy in a rigorous way. They examined four broad areas of fine motor control, perceptual speed, language and reasoning in several groups of teenage individuals defined loosely by etiology (compared to todays practice), as well as a comparison group of typically developing children of similar mental age. Overall, their descriptive data seemed to identify five measures reflecting specific areas of weakness in their group with Down syndrome and no area of relative strength. These included receptive vocabulary, one measure of perceptual speed, two measures of nonverbal reasoning (Ravens matrices and a figure reproduction task), and forward digit span, although only receptive vocabulary and digit span differed sig230

nificantly from the other etiologically defined groups. Clausen [1966] conducted an ambitious study employing a battery of 33 tests to examine the impact on performance of etiology in people 824 years of age, and he explicitly addressed profiles of individuals with Down syndrome [Clausen, 1968]. Of 50 measures of performance, only six revealed significant group differences. A single advantage associated with Down syndrome involved the ability to move one arm to match the position of the other while blindfolded (left arm movement showing a statistically significant advantage but only a trend for right arm movement), while weaknesses included threshold for speech discrimination (unrelated to abnormal audiometry), visual acuity, one measure of perceptual threshold, brightness discrimination, and one measure of reaction time. (With respect to perceptual/motor speed, inspection of the descriptive findings shows that individuals with Down syndrome performed consistently more poorly than their peers, although only two of eight measures reached significance.) Considering the general pattern of his findings, Clausen [1968] continued to endorse his 1966 position that differences among subpopulations with intellectual disability are relatively small compared to the effects of overall degree of intellectual impairment, but he identified sensory and discrimination functions, as well as perceptual speed as possible areas of weakness specifically associated with Down syndrome. Pueschel et al. [1987] compared children with Down syndrome (812 years of age) and a mental age-matched group of typically developing 5-yearolds using the Peabody Picture Vocabulary Test [Dunn and Dunn, 1981] and the Kaufman Assessment Battery for Children [Kaufman and Kaufman, 1983]. Results suggested relative weakness associated with Down syndrome in the processing of verbal compared to visual information. However, Kessler et al. [1988] also included measures of verbal processing (memory) in a broader battery and failed to find weaknesses in this area specific to Down syndrome. In two studies focused on cognitive decline in older adulthood, Das et al. employed a broad battery to compare people with Down syndrome to individuals with intellectual disability due to other causes [Das and Mishra, 1995; Das et al., 1995]. For the purpose of this review, it was fortuitous that they included groups of younger adults,


and findings suggested selective weaknesses associated with immediate memory for verbal and nonverbal material, receptive vocabulary, speech rate, and various measures placing speed demands on performance. (Interestingly, a matrix analogies test [Naglieri, 1985] showed superior performance for the young adult group with Down syndrome, but interpretation of this finding is unclear.) In an additional study, Snart et al. [1982] examined the performance of adolescents employing a battery of six tasks emphasizing memory and planning, as well as simultaneous and successive coding. They found weaknesses in both simultaneous and successive processing, but not in planning for individuals with Down syndrome, who also performed more slowly than peers with intellectual disability due to other causes. Pennington et al. [2003] employed another battery of tasks to examine prefrontal- and hippocampal-dependent processing associated with Down syndrome in adolescence. Overall, no evidence of prefrontal dysfunction was found compared to typically developing children matched for mental age, while there was a clear evidence of deficits associated with hippocampal function indicating a relative weakness associated with consolidation of information in longterm memory. Other relative weaknesses were present in expressive and receptive syntax, as well as immediate verbal memory. Abbeduto et al. [2003] also examined performance characteristics of teenagers with Down syndrome and found that, relative to performance on tasks reflecting nonverbal processing capabilities, the area of receptive language is a relative weakness, especially with respect to the processing of syntax. Vicari et al. [2004a] employed a similar strategy to examine areas of processing strengths and weaknesses, and found that, while receptive language was generally consistent with overall severity of intellectual disability, expressive language was impaired, especially with respect to syntax. PROCESSING SPEED Findings reviewed in the previous section suggest that Down syndrome is associated with slower rates of responding, and that has been a consistent finding over many studies [c.f., Gibson, 1978]. Because cognitive processing operates in real time, speed of responding should reflect capacity or efficiency, and therefore these findings suggest the presence of either general or specific


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limitations associated with Down syndrome. Processing speed can be measured by restricting stimulus duration and observing the effects on performance or measuring the amount of time needed for successful task completion, and both methods have been employed to study the effects of intellectual disability on cognition [c.f., Nettelbeck and Wilson, 1997; Tomporowski and Tinsley, 1997]. Studies of processing speed and Down syndrome have relied predominantly on measures of reaction time, and Gibsons [1978] thorough review of studies up to that time concluded that interpretation of overall findings was unclear. Berkson [1960] is representative of earlier reaction time studies, and he found that Down syndrome was associated with substantially slower responding in four different tasks. However, implications of these findings seem unclear. Variability within groups was substantial, a typical characteristic of individuals with lower IQs, but in this instance the mean IQ 5 31 for the group with Down syndrome was quite low relative to other studies of reaction time and intellectual disability [e.g., Nettlebeck and Brewer, 1976]. Further, responding in these relatively simple tasks seemed to be extremely slow, suggesting that some individuals may have failed to appreciate the need to respond as rapidly as they possibly could. In a more recent study, Silverman and Kim [1997] employed four different choice reaction time tasks to compare older adults with Down syndrome (without dementia) to their peers with intellectual disability due to other causes. All four tasks allowed overall reaction times to be partitioned into components representing overall speed and rate of taskspecific cognitive processing, and results consistently showed no evidence of reduced processing speed explicitly associated with Down syndrome. Lincoln et al. [1985] described another approach to the study of processing speed. They examined performance in a relatively simple reaction time task that required responding to an infrequent verbal stimulus together with event-related potentials (ERPs) obtained by synchronizing electroencephalographic (EEG) recordings with stimulus onset. This procedure generates task-specific waveforms, and the latencies and amplitudes of its components can be systematically related to underlying processing. Responses for 12-year-old children with Down syndrome were appreciably slower than both mental age (MA) and

chronological age (CA) matched typically developing groups. Analyses of ERP waveforms showed four components with longer latencies for the children with Down syndrome plus a distinct pattern suggesting underlying neural mechanisms that were qualitatively distinct, and Karrer et al. [1998] described other ERP findings suggesting that these effects might originate during early development. Lincoln et al. concluded that Down syndrome causes impairments in the speed of orienting to and processing of verbal information, immediate auditory memory, and organization of motor responding. However, they did not examine performance in other tasks, nor did they make comparisons with children having intellectual disability due to other causes, and therefore the specificity of these findings is uncertain. Further, some ERP components had shorter latencies for the group with Down syndrome compared to the MA-matched children, and no convincing explanation was provided for exceptionally slow-responding ones. Interestingly, Lalo et al. [2005] also found evidence for increased ERP component latencies in their comparison between young adults with and without (CA matched) Down syndrome but only slightly slower response readiness (based upon EMG recording). These results again suggest that very slow response, when it is found, may be reflecting misinterpretation of the speeded nature of task demands rather than severe limitations in underlying cognitive capabilities. Overall, then, the evidence of a differential impact of Down syndrome on reaction time remains as inconclusive as it was almost 30 years ago [Gibson, 1978], but should any effects be present over and above those associated with intellectual disability, per se, they would appear to be reflecting inefficiencies within motor control subsystems. LANGUAGE Abbeduto et al. [2007] and Rondal [2004] have recently reviewed the profile of language strengths and weaknesses associated with Down syndrome, and space does not permit a thorough consideration here. However, language is so integrally related to cognition that some discussion is necessary. Overall, there is convincing evidence of selective impairment from childhood onward in expressive compared to receptive language [e.g., Gibson, 1978; Rondal and Edwards, 1997; Miller, 1999; Abbeduto et al., 2001; Rondal,


2004], while prelinguistic articulations appear to develop typically during infancy [Smith and Oller, 1981; Oller and Seibert, 1988; Steffens et al., 1992], as does the intentional use of communication during the preschool years [Owens and MacDonald, 1982; Coggins et al., 1983]. However, Sigman [1999] suggested that qualitatively atypical patterns of communication are associated with Down syndrome from an early age, indicating that chromosome 21 gene overexpression is likely to have developmental consequences for cognition although the ability to quantify these effects may be limited until performance capabilities expand. While the impact of Down syndrome on very early language development remains a topic of debate, there is broad agreement on the fact that impairments from age 56 onward are quite evident [e.g., Guralnick, 2002; c.f., Rondal, 2006]. There is substantial variation among individuals in the relative severity of these impairments however, and only some domains of language appear to be affected to a degree greater than would be expected based upon overall level of functioning. Many studies have even suggested a relative strength in the area of receptive vocabulary, but recent findings by Miolo et al. [2005], Chapman [2006], and Price et al. [2007] have implied that this impression may have been created by an idiosyncracy of the Peabody Picture Vocabulary Test [Dunn and Dunn, 1981, 1997] or its British equivalent [Dunn et al., 1982]. Whether this proves to be the case or not, the preponderance of evidence indicates that receptive vocabulary (and lexical development by implication) is not an area of relative weakness. Pragmatics and conversational style are also areas that seem to function as expected based upon severity of intellectual disability [Beeghly et al., 1990; Rondal, 1994; Rondal and Edwards, 1997], although Abbeduto et al. [2006] suggested that some aspects of referential communication important for effective conversational exchanges may be a relative weakness among adolescents and young adults. Syntactic development and morphosyntactic processing, on the other hand, are affected particularly severely by Down syndrome [Beeghly et al., 1990; Rondal, 1994; Kernan and Sabsay, 1996; Rondal and Edwards, 1997; Abbeduto et al., 2001; Vicari et al., 2002]. While studies examining syntactic and morphosyntactic skills have consistently identified these areas as relative


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weaknesses [e.g., Marcell et al., 1995], Miller [1999] was careful to note that language profiles change with age, and syntactic weakness emerges during late childhood and the early teens. Miles and Chapman [2002], as well as Thordardottir et al. [2002] demonstrated competence for understanding some aspects of complex syntax in teenagers with Down syndrome while reemphasizing expressive language as a relative weakness, but Miolo et al. [2005] also found clear evidence for problems with sentence comprehension. Thus, the evidence of specific weaknesses in expressive language and syntactic/morphosyntactic processing associated with Down syndrome is convincing. Developmental difficulties with articulation seem a reasonable explanation in the former case, but syntactic processing weakness implies the involvement of additional higher order mechanisms. MEMORY Intellectual disability of any type is associated with impairments in memory [c.f., Bray et al., 1997], and Down syndrome is no exception. While Ohr and Fagan [1991] concluded that memory may be unaffected during infancy, inspection of their results suggests that Down syndrome performance may have been affected even at very young ages. As for language, the developmental onset of memory deficits associated with Down syndrome may be somewhat uncertain, but their presence from adolescence onward is not, nor is the distinctiveness of the cognitive profile. Memory is a complex construct that has been described in many different ways over the years [c.f., Devenny, 2006], but Baddeley and his colleagues have described a model that seems particularly conducive to discussing memory impairments associated with Down syndrome [Baddeley and Hitch, 1974; Baddeley, 2001]. They defined working memory as the system responsible for the temporary storage and manipulation of information that underlies performance in a wide range of activities. Originally, Baddeley and Hitch [1974] proposed that working memory consists of three subsystems, a resource/capacity limited central executive that controls processing, and two subordinate systems for storing and actively processing either verbal/acoustic (the phonological loop) or visuospatial information (the visuospatial sketchpad). More recently, they recognized the need for an additional mechanism to facilitate interactions with 232

long-term storage systems, and a multidimensional episodic buffer has been added [Baddeley, 2000]. Down syndrome is associated with selective weaknesses in remembering verbal but not visuospatial information for relatively short periods of time [Jarrold and Baddeley, 1997; Jarrold et al., 2000, 2002; Numminen et al., 2001; Seung and Chapman, 2004; Vicari et al., 2004b; Rowe et al., 2006]. Further, visuospatial and verbal memory spans are similar for individuals with Down syndrome while verbal span has been found to be greater for most other populations [Craik, 1969; c.f., Marcell and Armstrong, 1982], providing converging evidence for a relative weakness in verbal memory processes. Substantial effort has been devoted to discovering the root causes of this specific weakness in verbal working memory, with major emphasis placed on studies of the phonological loop. A major function of the phonological loop is to keep information available via active rehearsal, and therefore the slow articulation/speech rate associated with Down syndrome could be an important contributor [Seung and Chapman, 2004]. However, relative deficits persist in the absence of active rehearsal [e.g., Jarrold et al., 2000; Vicari et al., 2004b] or when articulation rate is controlled. Other findings showed that the selective weakness is also unrelated to mode of presentation [Varnhagen et al., 1987] or the presence of mild hearing loss [Seung and Chapman, 2004; Chapman, 2006]. Thus, while there seems to be little disagreement that Down syndrome causes a selective weakness in performance on tasks dependent upon verbal working memory, the specific processing responsible for this robust phenomenon remains unclear. Vicari et al. recently concluded that they saw no evidence of dysfunction in the phonological loop associated with Down syndrome. However, Jarrold et al. [2002] suggested that a reduced storage capacity for phonological information, a subprocess within the phonological loop distinct from active rehearsal, may be differentially impaired for individuals with Down syndrome. They also left open the possibility that some other impairment in the processing or storage of information may be present. Interrelationships among verbal working memory, speech, and language deficits characteristic of Down syndrome have been examined. These studies underscore a potential interdependency among processes ranging from


discrimination of speech sounds to sentence imitation and recall [c.f., Miolo et al., 2005]. Chapman and Hesketh [2001], Miolo et al. [2006], Chapman [2006], Laws [2004], Laws and Gunn [2004], and Fidler et al. [2005] have all examined relationships between language and memory deficits of individuals with Down syndrome, and all have concluded that clear connections are present. Several other studies have shown that abnormal function of tympanic membranes can be associated with poorer processing of verbal material within this population [Libb et al., 1985; Marcell, 1995; Marcell et al., 1995], suggesting that reduced auditory acuity can have impacts on higher-order processes. However, no consensus has emerged regarding the underlying nature of these relationships. Additional difficulty associated with hippocampal function and consolidation of information within long-term memory has already been mentioned [Pennington et al., 2003; c.f., Nadel, 2003]. Carlesimo et al. [1997], however, found no suggestion of deficits specifically associated with weakness in this area when adolescents with Down syndrome were compared to peers with similar levels of intellectual disability, although they did find evidence suggesting poor encoding and retrieval. Jarrold et al. [2007] also found no differential deficits related to long-term memory for verbal information associated with Down syndrome, although they did report evidence of difficulty in recalling (but not recognizing) visual information, again suggesting selective deficit associated with retrieval. GENERAL THOUGHTS This review summarizes the impressive progress that has been made in expanding our understanding of the phenotypic characteristics of Down syndrome; but even more rapid advances should be possible if consensus can be reached regarding several issues. As Chapman and Hesketh [2000] noted, criteria defining comparison groups can have substantial influences on results, yet studies continue to vary considerably in this regard. The employment of comparison participants matched on mental age is a prevalent approach, but mental age can be defined with respect to language, nonlanguage, or composite performance. Because findings from studies of the Down syndrome cognitive phenotype are likely to be affected by which of these options is selected, investigators should be encouraged to


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characterize typically developing comparison groups in sufficient detail to permit multiple-matching procedures, and these variations should be examined in analyses [c.f., Jarrold et al., 2007]. More generally, the strategy of employing individuals developing typically at comparable cognitive ages as the primary comparison group implicitly accepts developmental rather than difference theories of intellectual disability [c.f., Zigler, 1969; Hodapp and Zigler, 1997] while the very concept of cognitive phenotypes seems to be based on differences in development and profiles of capabilities. Intuitively, it seems imprudent to assume that an 18-year-old person with Down syndrome should be qualitatively indistinct from a typically developing 8-year-old, or that 6- and 20-year-old persons with Down syndrome are comparable if their performance is similar on an assessment of intelligence or language. Factors related to brain maturation, physical development, life experiences, overall level of intellectual impairment, opportunities for learning, and the like would seem to be better controlled when comparisons are made among individuals of comparable ages and levels of intellectual disability. These comparison groups would also permit matching on language or nonlanguage abilities, as well as the presence of secondary diagnosis (e.g., sensory impairment), permitting insights into the specificity of performance profiles. Chapman and Hesketh [2000] discussed the use of a comparison group of individuals with intellectual disability due to unknown causes, and correctly noted that modern diagnostic technologies are resulting in constant reductions in the size of this subpopulation. However, as Dykens et al. [2000] noted, comparison groups made up of individuals with mixed etiologies permit identification of the specific phenotypic characteristics of any one population of interest. Returning to an issue discussed in the introduction of this review, cognition refers to mental capabilities, and these can only be inferred from measures of performance. Unfortunately, determination of the relationship between performance and competence is always complex, and in the case of Down syndrome the evidence is clear that individuals do not always demonstrate their true capabilities [Wishart and Duffy, 1990; Wishart, 1995; also see discussion in Jarrold et al., 2007]. Investigators interested in cognition, therefore, need to recognize that overall

performance is influenced both by the cognitive processes of interest and an abundance of other factors, some within the cognitive domain and some without (e.g., health status, motivation, idiosyncratic interpretation of task demands). In the case of working memory, for example, tasks also place demands on attention, perception and response generation, and poor overt performance could reflect a breakdown in any of these subsystems. Typically, this complication can be accommodated by manipulating task structure systematically to vary demands on only one process, working memory in this case, and systematic influences of increasing complexity can be taken as a reflection of subsystem capacity/efficiency. A major assumption inherent in this approach is that individuals understand the task and perform as best they can, but the reasons for any individual failing to demonstrate some minimal level of proficiency are uncertain. Those individuals, therefore, must be considered qualitatively distinct from their performing peers, but that has been the exception to the rule. Investigators have been overly accepting of performance that, if taken literally, would suggest profound real world dysfunction (e.g., working memory spans that would preclude long-term learning; simple reaction times that imply inability to navigate within the environment), and a more critical attitude seems prudent. (Note that low levels of absolute performance can be extremely difficult to notice following some data transformations, and it would be extremely beneficial to report findings in their original format more consistently.) Another not uncommon practice is to interpret results based solely on patterns of statistical significance among individual measures. While it seems obvious, failure to find significant effects is not the same as their absence, and profiles of performance rather than individual measures should be contrasted in analyses. Viable options include examination of interactions or appropriate statistical adjustment (e.g., analysis of covariance including the insignificant variable as a covariate). CONCLUSIONS Substantial investments have been made in studies of cognition and Down syndrome, and results to date have shown that the major factors influencing individual profiles of performance are severity of overall intellectual disability and age [Gibson, 1978]. This is


also true among populations with intellectual disability due to other causes, and in general, the parallels in performance among etiologically defined subpopulations seem far more apparent than the differences. There is a clear need to understand how such a diversity of impacts on brain development can have such similar consequences for cognition. That being said, Down syndrome does appear to have a distinct cognitive phenotype [Nadel, 2006], although other groups with similar profiles of relative strengths and weaknesses may be identified as studies of other populations progress. Key characteristics include relative weakness in expressive language, syntactics, and verbal working memory, and considerable effort has been invested in discovering the processes responsible for this profile. Unfortunately, the intuitively most attractive candidates have been found wanting. Imprecise or slow articulation is not sufficient, nor is auditory impairment, given that relatively poor performance of individuals with Down syndrome specific to selected areas is still found when these factors are taken into consideration. Further, weaknesses in verbal working memory do not appear to be caused directly by limitations in short-term storage or executive processing systems over and above those associated with intellectual disability [Jarrold et al., 2002]. What then can explain this profile? As emphasized earlier, performance in any task engages many component processes, all of which place demands on the overall system to one degree or another. These demands are influenced by task configuration, the structure of the processing system, the capacities of constituent subprocesses, and the interactions among all these factors. Simple tasks (or components of tasks) place little or no demand on cognitive systems and can be processed automatically and effortlessly, virtually without explicit attention [Schneider and Shiffrin, 1977]. Examples include simple orienting toward a salient stimulus (e.g., loud noise or bright light), or engaging in a highly overlearned activity like riding a bicycle or understanding your native language [Shiffrin and Schneider, 1977]. In contrast to these easy tasks, successful performance under more demanding circumstances requires the engagement of controlled processing, and this entails explicit effort and attention. All other things being equal, the extent to which automatic and controlled processes need to be engaged, distributed over all cognitive


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subsystems involved in task completion, will be a major determinant of performance efficiency and success. This is particularly germane in the case of language. Coherent conversational exchanges require the decoding of an extremely complex stream of auditory stimulation into a meaningful representation [e.g., Liberman et al., 1967; Liberman, 1998], connecting these percepts to information stored in longterm memory to determine semantic meaning, and interpreting the structure inherent in sequences of words to generate an accurate understanding of the discourse. All of this must be accomplished while information is maintained in a limited capacity working memory system. Intended responses also have to be produced, reengaging semantic, syntactic, articulatory, and memory processes, and so the conversation goes, momentto-moment, with ongoing generation of representations within long-term memory. Considerable automaticity is normally involved in efficient speech production and perception, and there is convincing evidence that these activities recruit common underlying processes [Pulvermuller et al., 2006; Vigneau et al., 2006] and have linkages to auditory short-term memory [Grossberg and Myers, 2000; Wagner et al., 2004]. In everyday conversation, therefore, controlled processes are free to engage in effectively structuring meaningful sentences and establishing accurate memory representations. However, should the automatic nature of articulation fail to develop, or should representations of phonemic sequences fail to be adequately established in long-term semantic memory, then lexical access might not occur automatically [c.f., Grossberg and Myers, 2000]. Processing resources would then need to be redirected from higher-order language processing, and this could result in precisely the higher-order weaknesses associated with Down syndrome. Chapman and her colleagues have discussed mechanisms contributing to the Down syndrome cognitive phenotype that seem consistent with this line of reasoning [Chapman and Hesketh, 2000; Chapman et al., 2000; Miolo et al., 2005], as have others [Carlisimo et al., 1997; Jarrold et al., 2002]. Interestingly, recent neuroimaging studies of verbal working memory have shown that cerebellar as well as cortical regions are involved in phonological loop processes, and cerebellar connections seem to be particularly important for fluid articulation, rehearsal, and 234

effective maintenance of subspan information loads [c.f., Wagner et al., 2004]. Thus, the striking impact of Down syndrome on cerebellar development seems likely to contribute directly to the cognitive phenotype. IMPLICATIONS There are clear implications for intervention if incomplete automatization of speech-related processes truly contributes to the relative weaknesses in language and verbal working memory characteristic of Down syndrome. However, it seems prudent to investigate this idea further, given its speculative nature, and the presence of considerable heterogeneity within the population with Down syndrome should make this possible. All other things being equal, individuals able to speak clearly and effortlessly should be less likely to have relative weaknesses in language and verbal memory. Correctly and effortlessly would have to be thoughtfully operationalized, however, given that clear speech can be produced via both automatic and controlled processing. This should be feasible, though. For example, when a simple articulation task is added to another procedure (e.g., an effortful visual search task), automatic articulators should be unaffected (or nearly so) by the additional demand while controlled articulators should show clear declines in performance. Should empirical findings support the model, then intensive early intervention emphasizing expressive language enhancement should produce a cascade of benefits. As Shiffrin and Schneider [1977] discussed, automaticity can be acquired with experience, and everyone who has achieved proficiency in playing a musical instrument or learned to read is clearly familiar with the phenomenon. However, automaticity in any skill area can only be achieved through considerable effort and discipline, and speech proficiency for individuals with Down syndrome will be no exception. As with any analogous situation, substantial investments in both time and energy will be necessary, and efforts will need to be integrated into early intervention programs structured to promote cognitive and physical development more generally. Although the specifics of the programs would be very different, the intensity of current efforts targeting autism might serve as a useful model, and there is every reason to believe that the benefits could be as significant.


ACKNOWLEDGMENTS Thanks to Ms. Anita Camper for her assistance throughout the process of preparing this review.

REFERENCES
Abbeduto L. 1991. Development of verbal communication in persons with moderate to mild mental retardation. In: Bray N, editor. International review of research in mental retardation. New York: Academic Press. p 91 115. Abbeduto L, Murphy MM, Cawthon SW, et al. 2003. Receptive language skills of adolescents and young adults with Down or fragile X syndrome. Am J Ment Retard 108: 149160. Abbeduto L, Murphy M, Richmond E, et al. 2006. Collaboration in referential communication: comparison of youth with Down syndrome or Fragile X syndrome. Am J Ment Retard 111:170183. Abbeduto L, Pavetto M, Kesin E, et al. 2001. The linquistic and cognitive profile of Down syndrome: evidence from a comparison with fragile X syndrome. Down Syndr Res Pract 7:915. Abbeduto L, Warren S, Conners F. 2007. Language development in Down syndrome: from the prelinguistic period to the acquisition of literacy. Ment Retard Dev Disabil Res Rev 13:247261. Anderson J. 1990. Cognitive psychology and its implications, 3rd ed. New York: W.H. Freeman. p 12. Baddeley A. 2001. Is working memory still working? Am Psychol 56:851864. Baddeley A. 2000. The epdisodic buffer: a new component of working memory? Trends Cognit Sci 4:417423. Baddeley A, Hitch F. 1974. Working memory. In: Bower G, editor. The psychology of learning and motivation. New York: Academic Press. p 4790. Beeghly M, Weiss-Perry B, Cicchetti D. 1990. Beyond sensorimotor functioning: early communicative and play development of children with Down syndrome. In: Ciccichetti D, Beeghley M, editors. Children with Down syndrome: a developmental perspective. New York: Cambridge University Press. p 329368. Berkson G. 1960. An analysis of reaction time in normal and mentally deficient young men. J Ment Defic Res 4:6977. Bray NW, Fletcher KL, Turner LA. 1997.Cognitive competencies and strategy use in individuals with mental retardation. In:MacLean W, editor. Ellis handbook of mental deficiency, psychological theory and research, 3rd ed. Mahway, NJ: Erlbaum Associates. p 197217. Buckley S, Bird G, Sacks B, et al. 2006. A comparison of mainstream and special education for teenagers with Down syndrome: implications for parents and teachers. Down Syndr Res Pract 9:5467. Carlesimo GA, Marotta L, Vicari S. 1997. Longterm memory in mental retardation: evidence for a specific impairment in subjects with Downs syndrome. Neuropsychologia 35: 7179. Centers for Disease Control and Prevention. 2006. Improved national prevalence estimates for 18 selected major birth defects


MRDD Research Reviews DOI 10.1002/mrdd

Down Syndrome: Cognitive Phenotype

Silverman

United States, 19992001. Morb Mortal Wkly Rep 54:13011305. Chapman RS. 2006. Language learning in Down syndrome: the speech and language profile compared to adolescents with cognitive impairment of unknown origin. Down Syndr Res Pract 10:6166. Chapman R, Hesketh LJ. 2000. Behavioral phenotype of individuals with Down syndrome. Ment Retard Dev Disabil 6:8495. Chapman RS, Seung H-K, Schwartz SE, et al. 2000. Predicting language production in children and adolescents with Down syndrome: the role of comprehension. J Speech Lang Hear Res 43:340350. Clausen J. 1966. Ability structure and subgroups in Mental Retardation. Washington, DC: Spartan Books. Clausen J. 1968. Behavioral characteristics of Down syndrome subjects. Am J Ment Defic 73:118126. Coggins TE, Carpenter RL, Owings NO. 1983. Examining early intentional communication in Downs syndrome and nonretarded children. Br J Disord Commun 18:98107. Craik F. 1969. Modality effects in short-term storage. J of Verbal Learn Verbal Behav 8: 658664. Crosier R, Philpot B, Sawtell N, et al. 2004. Long-term plasticity of glutametergic synaptic transmission in the cerebral cortex. In: Gazzaniga MS, editor. The cognitive neurosciences III. Cambridge, MA: MIT Press. p 109126. Das JP, Mishra RK. 1995. Assessment of cognitive decline associated with aging: a comparison of individuals with Down syndrome and other etiologies. Res Dev Disabil 16:1125. Das JP, Divis B, Alexander J, et al. 1995. Cognitive decline due to aging among persons with Down syndrome. Res Dev Disabil 16: 461478. Devenny DA. 2006. The contribution of memory to the behavioural phenotype of Down syndrome. In: Rondal JA, Perera J, editors. Down syndrome, neurobehavioural specificity. West Sussex, England: Wiley. p 85100. Dunn L, Dunn L. 1981. The Peabody picture vocabulary test (revised). Circle Pines, MN: American Guidance Service (AGS). Dunn L, Dunn L. 1987. The peabody picture vocabulary test, 3rd ed. Circle Pines, MN: American Guidance Service (AGS). Dunn L, Dunn L, Whetten C, et al. 1982. British picture vocabulary scale. Windsor, UK: NFER-Nelson. Dykens RM, Hodapp R, Finucane BM, editors. Genetics and mental retardation syndromes. Baltimore, MD: Brookes. Ensembl. 2007. E! release 44: Chromosome 21. Available at www.ensembl.org. Epstein C. 1989.Down syndrome: trisomy 21. In: Scriver C, Beandet A, Sly W, Valle D, editors. Metabolic basis of inherited disease. New York: McGraw-Hill. p 291326. Epstein C, Korenberg J, Anneren G, et al. 1991. Protocols to establish genotype-phenotype correlations in Down syndrome. Am J Hum Gen 49:207235. Fidler D, Most D, Guiberson M. 2005. Neuropsychological correlates of word identification in Down syndrome. Res Dev Disabil 26: 487501. Gibson D. 1978. Down syndrome: the psychology of mongolism. Cambridge, England: Cambridge University Press. Grossberg S, Myers CW. 2000. The resonant dynamics of speech perception: interword inte-

gration and duration-dependent backward effects. Psychol Rev 107:735767. Guralnick MJ. 2002. Involvement with peers: comparisons between young children with and without Downs syndrome. J Intellect Disabil Res 46:379393. Hodapp R, Zigler E. 1997. New issues in the developmental approach to mental retardation. In: MacLean W, editor. Ellis handbook of mental deficiency, psychological theory and research, 3rd ed. Mahwah, NJ: Erlbaum. p 115136. Jarrold C, Baddeley AD. 1997. Short-term memory for verbal and visuospatial information in Downs syndrome. Cogn Neuropsychiatry 2:101122. Jarrold C, Baddeley AD, Hewes AK. 2000. Verbal short-term memory deficits in Down syndrome: a consequence of problems in rehearsal? J Child Psychiatry 40:233244. Jarrold C, Baddeley AD, Phillips CE. 2002. Verbal short-term memory in Down syndrome: a problem of memory, audio, or speech? J Speech Lang Hear Res 45:531544. Jarrold C, Baddeley A, Phillips C. 2007. Longterm memory for verbal and visual information in Down syndrome and Williams syndrome: performance on the doors and people test. Cortex 43:233247. Karrer JH, Karrer R, Bloom D, et al. 1998. Event-related brain potentials during an extended visual recognition memory task depict delayed development of cerebral inhibitory processes among 6-month-old infants with Down syndrome. Int J Psychopsysiol 29:167200. Kaufman A, Kaufman N. 1983. K-ABC kaufman assessment battery for children administration and scoring manual. Circle Pine, MN: American Guidance Service (AGS). Kernan KT, Sabsay S. 1996. Linguistic and cognitive ability of adults with Down syndrome and mental retardation of unknown etiology. J Commun Disord 29:401422. Kessler J, Markowitsch HJ, Denzler P, et al. 1988. Cognitive function of juveniles with Down syndrome and other forms of mental retardation. Int J Neurosci 38:19. Korenberg J. 1991. Down syndrome phenotypic mapping. Prog Clin Biol Res 373:4352. Lalo E, Vercueil L, Bougerol T, et al. 2005. Late event-related potentials for movement complexity in young adults with Down syndrome. Neurophysiol Clin 35:8191. Laws G. 2004. Contributions of phonological memory, language comprehension and hearing to the expressive language of adolescents and young adults with Down syndrome. J Child Psychol Psychiatry 45:10851095. Laws G, Gunn D. 2004. Phonological memory as a predictor of language comprehension in Down syndrome: a five-year follow-up study. J Child Psychol Psychiatry 45: 326337. Lejeune J, Gautier M, Turpin R. 1958. Etudes des chromosomes somatiques de neuf enfants mongolieus [Studies of somatic chromosomes of nine mongoloid children]. Competes Renders de lAcademie des Sciences Serie III 248:17211722. Li C, Guo M, Sales N, et al. 2006. Cell type specific over-expression of chromosome 21 genes in fibroblasts and fetal hearts with trisomy 21. BMC Med Genet 7:24. Libb JW, Dahle A, Smith K, et al. 1985. Hearing disorder and cognitive function of individuals with Down syndrome. Am J Ment Defic 90:353356.


Liberman AM. 1998. When theories of speech meet the real world. Psycholinquist Res 27:111122. Liberman A, Cooper F, Shankweiler D, et al. 1967. Perception of the speech code. Psychol Rev 74:431461. Lincoln AJ, Courchesne E, Kilman BA, et al. 1985. Neuropsychological correlates of information-processing by children with Down syndrome. Am J Ment Defic 89: 403414. Marcell MM. 1995. Relationships between hearing and auditory cognition in Downs syndrome youth. Down Syndr Res Pract 3: 7591. Marcell MM, Armstrong V. 1982. Auditory and visual sequential memory of Down syndrome and nonretarded children. Am J Ment Defic 87:8695. Marcell MM, Ridgeway MM, Sewell DH, et al. 1995. Sentence imitation by adolescents and young adults with Downs syndrome and other intellectual disabilities. J Intellect Disabil Res 39:215232. Meyers CE, Dingman HF, Attwell AA, et al. 1961. Comparative abilities of normals and retardates of MA 6 years on a factor-type test battery. Am J Ment Defic 66:250258. Miles S, Chapman R. 2002. Narrative content as described by individuals with Down syndrome and typically developing children. J Speech Lang Hear Res 45:175189. Miller JF. 1999.Profiles of language development in children with Down syndrome. In: Miller J, Leddy M, Leavitt L, editors. Improving the communication of people with down syndrome. Baltimore, MD: Brookes. p 11 39. Miolo G, Chapman RS, Sindberg HA. 2005. Sentence comprehension in adolescents with Down syndrome and typically developing children: role of sentence voice, visual context, and auditory-verbal short-term memory. J Speech Lang Hear Res 48:172188. Nadel L. 2003. Downs syndrome: a genetic disorder in biobehavioral perspective. Genes Brain Behav 2:156166. Nadel L. 2006.Neuropsychological aspects of Down syndrome. In: Rondal J, Perera J, editors. Down syndrome: neurobehavioral specificity. West Sussex, England: Wiley. p 6785. Naglieri JA. 1985. Matrix analogies testexpanded form. New York: The Psychological Corporation. Neisser U. 1967. Cognitive psychology. New York: Appleton Century Crofts. p 311. Nettlebeck T, Brewer N. 1976. Effects of stimulus-response variables on the choice reaction time of mildly retarded adults. Am J Ment Defic 81:8592. Nettlebeck T, Wilson C. 1997. Speed of information processing and cognition. In: MacLean W, editor. Ellis handbook of mental deficiency, psychological theory and research, 3rd ed. Mahwah, NJ: Erlbaum Associates. p 245274. Numminem H, Service E, Honen T, et al. 2001. Working memory and everyday cognition in adults with Down syndrome. J Intellect Disabil Res 34:157168. Ohr PS, Fagen JW. 1991. Conditioning and longterm memory in three-month-old infants with Down syndrome. Am J Ment Retard 96:151162. Oller DK, Silbert JF. 1988. Babbling of prelinquistic mentally retarded children. Am J Ment Retard 92:369375.


MRDD Research Reviews DOI 10.1002/mrdd

Down Syndrome: Cognitive Phenotype

Silverman

235

Olson LE, Roper RJ, Sengstaken CL, et al. 2007. Trisomy for the Down syndrome critical region is necessary but not sufficient for brain phenotypes of trisomic mice. Hum Mol Genet 16:774782. Owens RE, MacDonald JD. 1982. Communicative uses of the early speech of nondelayed and Dwn syndrome children. Am J Ment Defic 86:503510. Pennington BF, Moon J, Edgin J, et al. 2003. The neuropsychology of Down syndrome: evidence for hippocampal dysfunction. Child Dev 74:7593. Praag H, Zhao X, Gage F. 2004. Neurogenesis in the adult mammalian brain. In: Gazzaniga MS, editor. The cognitive neurosciences, III. Cambridge, MA: MIT Press. p 127137. Price J, Roberts N, Vandergrift N, et al. 2007. Language comprehension in boys with fragile X syndrome and boys with Down syndrome. J Intellect Disabil Res 51: 318326. Pueschel SM, Gallagher PL, Zartler AS, et al. 1987. Cognitive and learning processes in children with Down syndrome. Res Dev Disabil 8:2137. Pulvermuller F, Huss M, Kherif F, et al. 2006. Motor cortex maps articulatory features of speech sounds. Proc Natl Acad Sci USA 103:78657870. Rondal JA. 1994. Exceptional cases of language development in mental retardation: the relative autonomy of language as a cognitive system. In: Tager-Flusberg H, editor. Constraints on language acquisition: studies of atypical children. Hillsdale, NJ: Erlbaum. p 155 174. Rondal JA. 2004. Intersyndrome and intrasyndrome. In: Rondal JA, Hodapp RM, Soresi S, Dykens EM, Nola L, editors. Intellectual disabilities: genetics, behaviour and inclusion. London: Whurr. p 49113. Rondal JA. 2006. Specific language profiles in Down syndrome and other genetic syndromes of mental retardation. In: Rondal J, Perera J, editors. Down syndrome: neurobehavioral specificity. West Sussex, England: Wiley. p 101123. Rondal JA, Edwards S. 1997. Language in mental retardation. London: Whurr.

Rowe J, Lavender A, Turk V. 2006. Cognitive executive function in Downs syndrome. Br J Clin Psychol 45:517. Schneider W, Shiffrin R. 1977. Controlled and automatic human information processing. I. Detection, search and attention. Psychol Rev 84:166. Seung H-K, Chapman R. 2004. Sentence memory of individuals with Downs syndrome and typically developing children. J Intellect Disabil Res 48:106171. Shiffrin R, Schneider W. 1977. Controlled and automatic human information processing. II. Perceptual learning, automatic attending and a general theory. Psychol Rev 84: 127190. Sigman M. 1999. Developmental deficits in children with Down syndrome. In: Tager-Flusberg H, editor. Neurodevelopmental disorders. Cambridge, MA: MIT Press. p 179196. Silverman W, Kim H. 1997. Reaction times verify nondemented status of adults with Down syndrome. Down Syndr Q 2:110. Smith BL, Oller DK. 1981. A comparative study of pre-meaningful vocalizations produced by normally developing and Downs syndrome infants. J Speech Hear Disord 46:4651. Snart F, OGrady M, Das JP. 1982. Cognitive processing by subgroups of moderately mentally retarded children. Am J Ment Defic 86:465472. Steffens ML, Oller DK, Lynch M, et al. 1992. Vocal development in infants with Down syndrome and infants who are developing normally. Am J Ment Retard 97:235246. Thordardottir ET, Chapman RS, Wagner L. 2002. Complex sentence production by adolescents with Down syndrome. Appl Psycholinquistics 23:163183. Tomporowski P, Tinsley V. 1997. Attention in mentally retarded persons. In: MacLean W, editor. Ellis handbook of mental deficiency, psychological theory and research, 3rd ed. Mahway, NJ: Erlbaum Associates. p 219 244. Varnhagen CK, Das JP, Varnhagen S. 1987. Auditory and visual memory span: cognitive processing by TMR individuals with Down syndrome or other etiologies. Am J Ment Defic 91:398405.

Vicari S, Bates E, Caselli MC, et al. 2004a. Neuropsychological profile of Italians with Williams syndrome: an example of a dissociation between language and cognition? J Int Neuropsychol Soc 10:862876. Vicari S, Caselli MC, Gagliardi G, et al. 2002. Language acquisition in special populations: a comparison between Down and Williams syndromes. Neuropsychologia 40:24612470. Vicari S, Marotta L, Carlesimo GA. 2004b. Verbal short-term memory in Downs syndrome: an articulatory loop deficit? J Intellect Disabil Res 48:8092. Vigneau M, Beaucousin V, Herve PY, et al. 2006. Meta-analyzing left hemisphere language areas: phonology, semantics, and sentence processing. Neuroimaging 30:14141432. Wagner AD, Bunge SA, Badre D. 2004. Cognitive control, semantic memory, and priming: contributions from prefrontal cortex. In: Gazzaniga MS, editor. The cognitive neurosciences III. Cambridge, MA: MIT Press. p 709725. Wang PP, Bellugi U. 1994. Evidence from two genetic syndromes for a dissociation between and visual-spatial short-term memory. J Clin Exp Neuropsychol 16:317322. Waugh N, Norman D. 1965. Primary memory. Psychol Rev 72:89104. Wishart JG. 1995. Cognitive abilities in children with Down syndrome: developmental instability and motivational deficits. Prog Clin Biol Res 393:5791. Wishart JG, Duffy L. 1990. Instability of performance on cognitive tests in infants and young children with Downs syndrome. Br J Educ Psychol 60:1022. Zigler E. 1969. Developmental versus difference theories of mental retardation and the problem of motivation. Am J Ment Defic 73: 536556. Zigman WB, Lott IT. 2007. Alzheimers disease in Down syndrome: neurobiology and risk. Ment Retard Dev Disabil Res Rev 13: 237246. Zigman WB, Schupf N, Urv T, et al. 2002. Incidence and temporal patterns of adaptive behavior change in adults with mental retardation. Am J Ment Retard 107:161 174.

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