This study re-examined the language and social skills of four females with language impairment who were initially studied eight years ago (Brinton, Fujiki, Montague, & Hanton, 2000; Fujiki, Brinton, Isaacson, & Summers, 2001). Language measures included the Clinical Evaluation of Language Fundamentals-Fourth Edition (Semel, Wiig, & Secord, 2003) and a thirty minute language sample. Social measures included the UCLA Loneliness Scale-Version 3 (Russell, 1996), parent, teacher and student forms of the Social Skills Rating System (Gresham & Elliott, 1990), and an interview with each participant's teacher or speech-language pathologist. Results of the current assessment were compared to results from the original assessment. In terms of social ability, the two girls who were classified as having the best social skills initially, Jean and Kristine, still appeared to be the most successful in the current study. Despite their social strengths, Jean's teacher indicated that she was socially immature and had difficulty reading the social cues of teachers and peers. Kristine reported that she prefers isolation. Her teacher reported that Kristine may be at risk for self-harm. Amy was still enrolled in resource and speech-language services. Though she had found acceptance in a cultural peer group, her communication style often appeared rude and disrespectful to adults. Marie was dismissed from speech-language intervention, but was still enrolled in resource and received extra academic support from Sylvan Learning Center to be moderately successful. Socially, she demonstrated a high level of problem behaviors and mood swings. According to the UCLA Loneliness Scale, she experienced the most loneliness and isolation of the four subjects. Similar to what has been observed in group studies of children with language impairment, the results from this study found social deficits in these individuals persisted into young-adulthood.

Recently researchers have identified a group of children with language impairment (LI) whose IQ scores are below the typical IQ cutoff of 85 for specific language impairment (SLI) but above the IQ cutoff of 70 for intellectual disability (Weismer et al., 2000). This group is referred to as having nonspecific language impairment (NLI). Eleven children with NLI, eleven same-age peers with SLI, and eleven same-age typical peers were compared on withdrawn and sociable behaviors demonstrated in the classroom setting using the Teacher Behavior Rating Scale (Hart & Robinson, 1996). Three subtypes of withdrawal (solitary-active, solitary-passive, reticent) and two subtypes of sociable behavior (impulse control/likability and prosocial) were examined. The children were compared on the severity of their ratings as well as the pattern of item responses for each behavioral subtype. Teachers rated the group with NLI significantly more poorly than the typical group on the reticence, impulse control/likability, and prosocial subtypes. Teachers rated the group with SLI significantly more poorly than the typical group on the impulse control/likability subtype. Participants were added to the typical group and the group with SLI to increase statistical power. With additional participants, the children with SLI were also rated significantly more poorly than the typical children on the reticence, likability, and prosocial subtypes. The group with NLI was consistently rated more poorly than the group with SLI except on the solitary-active subtype. However, there were no significant differences between the groups with LI, even with additional participants. The pattern of item responses was similar between the groups with NLI and SLI on all behavioral subtypes. In addition, the pattern of item responses for the groups with LI also matched the pattern of the typical group on the solitary-active withdrawal, impulse control/likability, and prosocial subtypes. These data indicate that the differences between the groups with NLI and SLI may be quantitative but not qualitative.

The purpose of this study was to determine whether children with specific language impairment (SLI) are more or less variable than children with typically developing language. In addition, the within child variability for children with SLI was analyzed to consider how heterogeneity influenced identification of areas of linguistic strengths and weaknesses in this population. Fifty seven children with SLI, 7:0–11:0, and fifty seven of their peers with typically developing language were assessed using five subtests and a composite language score from the Comprehensive Assessment of Spoken Language (CASL) (Carrow-Woolfolk, 1999). The children with typically developing language were significantly more variable as a group than the children with SLI. The heterogeneity of the children with SLI did not allow for the creation of subgroups based on language strengths and weaknesses.

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Background: Drug use among the driving population is a major hazard to road safety and has been the subject of widespread research worldwide. In an attempt to detect and appropriately prosecute “drug-drivers”, the UK has made legislative changes and has introduced Field Impairment Tests (FIT) in the Railway and Transport Safety Act 2003. These FIT, which are identical to the Standardised Field Sobriety Tests (SFST), were devised in the USA in the 1970s to identify clinical signs of impairment due to alcohol intoxication, but were not designed or intended to identify drug-related driving impairment. Concerns have been expressed that FIT are too difficult for their stated function, and are also inappropriate tests, since although they have been validated for alcohol effects they have never been validated for the effects of drugs. This thesis has sought to clarify matters and has questioned the validity of FIT by testing two opposing hypotheses – 1) FIT are reliable and valid tests of drug-related impairment to drive - and drug-free individuals perform well on all tests. 2) FIT are not reliable and valid tests of drug-related impairment to drive - and are too difficult for some groups of drug-free individuals to perform. Methods: A questionnaire was designed and a postal survey was undertaken of 960 Forensic Medical Examiners (FMEs) who were asked to give their opinion on the Field Impairment Tests (FIT). The responses of the FMEs were analysed in detail (chapter 3). FIT were then carried out on three separate groups of 100 subjects in police custody who were all known to have used no drugs for a period of at least 8 hours prior to the testing process (chapter 4). Group A subjects were opiate dependent; Group B were subjects who received legally prescribed methadone; Group C individuals denied any form of drug use. All study groups were simultaneously examined using conventional psychomotor tests, and the results were compared using detailed statistical analysis with logistic regression and summative scores. Results: Returned FME questionnaires showed 63% of FMEs considered the tests “about right” but a significant number (p<0.0001) of 33% of FMEs stated FIT were “too difficult”. The studies on subjects in custody clearly showed 82% of group A; 44% of group B; and 19% of group C were unable to complete FIT satisfactorily, although only 12% of group A; 2% of group B; and 3% of group C were unable to successfully perform conventional psychomotor and cognitive tests. These findings clearly supported the assertions held by 33% of FMEs surveyed that FIT were too difficult for their stated purpose and that poor performance in FIT could not be regarded as definitive evidence of drug-related impairment in driving ability. VII Conclusions: The results of the research studies conducted have provided very strong support in favour of hypothesis 2) FIT are not reliable and valid tests of drug-related impairment to drive - and are too difficult for some groups of drug-free individuals to perform. In an attempt to overcome the problems in respect of FIT, specific proposals have been offered including the introduction of a new battery of more relevant clinical tests of impairment (CTI); a change in the method and manner in which the proposed new tests are applied; and possible legislative and administrative measures which might be introduced to more appropriately and effectively tackle this on-going hazard to road safety.

The search for reliable early indicators of age-related cognitive decline represents an important avenue in aging research. Most research on late-life development charts cognitive change as a function of chronological age (CA), however, although CA is a commonly used developmental index, it offers little insight into the mechanisms underlying cognitive decline. In contrast, biological age (BioAge), reflecting the vitality of essential biological processes, represents a promising operationalization of developmental time. My overall programmatic doctoral research interests involve the identification of biological risk factors that predict age-related cognitive decline, impairment and dementia. In this dissertation document, I present: an overview of my empirical contributions to the BioAge and cognitive aging literature throughout my doctoral training; the dissertation project which uses preliminary data from the PREVENT study and provides evidence that elevated plasma pro-inflammatory proteins are associated with cognitive status (healthy controls (HC) vs Alzheimer’s disease dementia (AD)), cognitive performance and are related to poorer cognitive performance in amnestic mild cognitive impairment (a-MCI); and a discussion on the broad implications of the project results and future directions in BioAge research. / Graduate

With advancing age, many cognitive faculties deteriorate, and navigation abilities may be among those most affected. The majority of previous work investigating navigation impairments in ageing has focused on allocentric processing, attributing deficits to hippocampal dysfunction. However, real-world navigation is dependent upon numerous different strategies, as well as the ability to flexibly switch between them. Outside the context of navigation, it has been demonstrated that strategy switching, thought to be coordinated by regions of prefrontal cortex and the locus coeruleus-noradrenergic system, is also susceptible to the effects of ageing. Deficits in navigational strategy switching, and prefrontal or noradrenergic dysfunction, are therefore also likely to contribute to age-related navigation impairments. The work presented in this thesis aimed to explore age-related impairments in strategy switching within the context of navigation, and the underlying neural mechanisms in terms of a prefrontal-noradrenergic model of switching. The studies presented in Chapter Three assessed the use of allocentric and egocentric navigational strategies by young and older people. Older participants tended to use an egocentric strategy where an allocentric strategy was required, possibly due to a difficulty in switching to the appropriate allocentric strategy. In Chapter Four, I provide an account of two studies directly assessing navigational strategy switching, using two different tasks based in virtual reality. The first study utilised a virtual adaptation of the plus maze task, involving switching between an allocentric place strategy and an egocentric response strategy, and demonstrated that older participants were specifically impaired at switching to the place strategy. The second study used a more realistic task set in a virtual town environment, which involved switching from an egocentric route-following strategy to an allocentric wayfinding strategy, and also demonstrated an age-related deficit in switching to an allocentric strategy. In Chapter Five, I begin to explore the mechanisms underlying impaired navigational strategy switching in ageing. Firstly, I describe a further behavioural study that used variants of the virtual plus maze and a navigational gambling task to demonstrate a contribution of impaired decision making to the deficit in switching to an allocentric strategy. This indicates that the deficit can be attributed, at least in part, to prefrontal dysfunction. A second study presented in the same chapter demonstrated that practising orienteering does not protect against decline in navigational strategy switching ability with ageing. Chapter Six provides an account of my direct assessment of the neural bases of navigational strategy switching using functional magnetic resonance imaging. In young subjects, I found some evidence in support of the roles of prefrontal regions in navigational strategy switching. However, I was unable to complete development of a task suitable for assessing age differences in functional activation of brain regions involved in navigational strategy switching. The final experimental study, included in Chapter Seven, assessed pupil size and heart rate as physiological correlates of noradrenergic activity during performance of the virtual plus maze. Both young and old participants demonstrated a noradrenergic response to all strategy changes, suggesting that impairments are more likely attributable to dysfunction of prefrontal cortex than of the locus coeruleus, although some subtle effects suggested that noradrenergic dysfunction does have some effect on navigational strategy switching deficits. In the same chapter, I report the results of a meta-analysis of data from five of the preceding studies, suggesting that deficits in both strategy switching and allocentric processing combine to produce a greater impairment in switching to an allocentric strategy. The main finding of this series of studies is that navigational strategy switching is impaired in ageing, which may contribute to the more widely reported difficulties that older people have with navigation. My work also provides evidence in support of a prefrontal-noradrenergic model of navigational strategy switching, and suggests that dysfunction of prefrontal cortex and, to a lesser extent, the locus coeruleus-noradrenergic system is responsible for decline in navigational strategy switching ability with ageing. In conclusion, this thesis draws attention to the important role of deficient executive processing and dysfunction of extra-hippocampal brain regions in age-related navigation impairments.

The relationship between cerebrovascular disease (CVD) risk factors and cognitive impairment or dementia has been widely studied with significant variability in findings between groups. We hypothesized that chronic small vessel injury in the form of arteriolar sclerosis, measured quantitatively using MRI to measure total white matter hyperintensity (WMH) volumes, would identify specific association of CVD risk factors and patterns of cognitive decline, associated with mild cognitive impairment of the cerebrovascular type, that represent the core features of vascular cognitive impairment in our cohort. A Cross-sectional analysis of clinical and quantitative MRI data on 114 subjects with normal cognitive function (n=52) and mild cognitive impairment (MCI; n=62) was performed. Quantitative total WMH volumes were examined in relation to potentially causative CVD risk factors and resultant test scores across cognitive domains using linear regression models adjusted for age, gender, and education. Among CVD risk factors analyzed, age (p< 0.001), education (p= 0.003), hypertension (p= 0.012), and hyperlipidemia (p= 0.008) demonstrated the strongest associations with WMH volumes. Conversely, diabetes, smoking, history of heart attacks, atrial fibrillation, and history of stroke that have shown associations with CVD pathology on imaging in other studies were not statistically associated with increased WMH in this cohort. WMH volumes were associated with decrease performance on the Trial Making Test type A & B and long delayed free recall on the California Verbal Learning Test. Our findings suggest similarities and yet differences in comparison to other studies. Hypertension and hyperlipidemia appear to represent common shared risks across geographically disparate groups. Our findings, like others, suggest CVD pathology impact processing speed and executive function and provide further evidence for CVD effects on short-term memory in those at risk for cognitive decline and the future development of dementia in our cohort.

Dementia is a common cause of disability in the elderly and, in the absence of a successful long-term treatment, it is important to investigate possible lifestyle interventions to help reduce an individual s risk of developing the condition. This thesis investigated the relationship between physical activity and dementia risk, finding that not all research supports the link. The literature review presented in this thesis (Chapter 2) highlighted several possible mediating factors, specifically the type of physical activity performed, the cognitive domains being studied and participant characteristics. Women seemed most susceptible to the effect of physical activity and some other forms of midlife interventions, possible mechanisms for which were discussed in another review (Appendix A). The cognitive test battery to be used in later studies was evaluated for its relevance to dementia and treatment during a 6-month study of Alzheimer's disease patients and their carers (Chapter 3). Memory tasks were found to be especially sensitive to clinical outcomes of dementia treatment (Chapter 4). An observational study of Indonesian elderly found a positive relationship between physical activity and memory performance on the same tests. This effect was strongest in women and in those with no pre-existing cognitive impairment (Chapter 5). However, the relationship could be further modified by other demographic factors, such as education. Health was independently affected in this model by exercise and its association with engaging in physical activity in this cohort was further investigated in Chapter 6. A randomised controlled trial (Chapter 7) was conducted to assess the effect of a 12-week programme of non-aerobic physical activity in sedentary middle-aged adults. Results indicated that resistance training, but not flexibility exercises, influenced memory but not executive function. Overall, this thesis suggests that several types of physical activity may be effective at slowing cognitive decline in elderly groups who are at increased risk of dementia, such as those in middle age and elderly women (Chapter 8). These findings should be expanded with the aim to improve healthcare advice and influence policy-making.

Over the past decade, there have been diverse theoretical perspectives and increasing empirical literature on bilingualism and specific language impairment (SLI), some of which highlighted the complex nature of accurately diagnosing SLI in bilingual populations. The goal of the current study is to enhance our understanding of morphosyntax development in an understudied bilingual population - Mandarin-English children who are growing up in an L2-dominant environment (English) in the United States. The study included a total of 55 bilingual Mandarin-English children between the ages of four and seven years, including 53 typically developing (TD) children and 2 children diagnosed with SLI. Using a newly developed screening test - the Bilingual English-Mandarin Oral Screener (BEMOS), we compared Mandarin performance in both TD and SLI children on 7 morphosyntax tasks which respectively measure passive -bei, possessive -de, prepositional phrases, noun classifiers, quantifier and scope, aspects (imperfective “-zai” and perfective “-le”), and sentence repetition. Our analysis of TD bilingual children revealed a trend towards a significant age effect in the total score and a near-significant effect in the preposition and the aspect sub-sections of the screener. When age was considered, perceived Mandarin proficiency by parents was associated with TD bilingual children’s performance. All students performed poorly on the classifier section, but our error analysis showed a predominant response pattern of imitation, suggesting bilingual children have growing sensitivity and are attentive to semantic similarity of nouns. Overgeneralized use of the general classifier “ge” was also observed in the errors. Both children with SLI scored lower overall compared to their age- and gender-matched TD peers, especially in the classifier and quantifier & scope sections. Reliable clinical markers were not identified due to the two SLI children’s distinct performance. Clinical implications and future research needs were also discussed. / text