Reduced Hemispheric Asymmetry of Brain Anatomical Networks Is Linked to Schizophrenia: A Connectome Study.

Despite convergent evidence indicating a variety of regional abnormalities of hemispheric asymmetry in schizophrenia, patterns of wider neural network asymmetry remain to be determined. In this study, we investigated alterations in hemispheric white matter topology in schizophrenia and their association with clinical manifestations of the illness. Weighted hemispheric brain anatomical networks were constructed for each of 116 right-handed patients with schizophrenia and 66 matched healthy participants. Graph theoretical approaches were then employed to estimate the hemispheric topological properties. We found that although small-world properties were preserved in the hemispheric network, a significant hemispheric-independent deficit of global integration was found in schizophrenia. Furthermore, a significant group-by-hemisphere interaction was revealed in the characteristic path length and global efficiency, attributing to significantly reduced hemispheric asymmetry of global integration in patients compared with healthy controls. Specifically, we found reduced asymmetric nodal efficiency in several frontal regions and the hippocampus. Finally, the abnormal hemispheric asymmetry of brain anatomical network topology was associated with clinical features (duration of illness and psychotic psychopathology) in patients. Our findings provide new insights into lateralized nature of hemispheric dysconnectivity and highlight the potential for using brain network measures of hemispheric asymmetry as neural biomarkers for schizophrenia and its clinical features.

Modular-level alterations of structure-function coupling in schizophrenia connectome.

Convergent evidences have revealed that schizophrenia is associated with brain dysconnectivity, which leads to abnormal network organization. However, discrepancies were apparent between the structural connectivity (SC) and functional connectivity (FC) studies, and the relationship between structural and functional deficits in schizophrenia remains largely unknown. In this study, resting-state functional magnetic resonance imaging and structural diffusion tensor imaging were performed in 20 patients with schizophrenia and 20 matched healthy volunteers (patients/controls = 19/17 after head motion rejection). Functional and structural brain networks were obtained for each participant. Graph theoretical approaches were employed to parcellate the FC networks into functional modules. The relationships between the entries of SC and FC were estimated within each module to identify group differences and their correlations with clinical symptoms. Although five common functional modules (including the default mode, occipital, subcortical, frontoparietal, and central modules) were identified in both groups, the patients showed a significantly reduced modularity in comparison with healthy participants. Furthermore, we found that schizophrenia-related aberrations of SC-FC coupling exhibited complex patterns among modules. Compared with controls, patients showed an increased SC-FC coupling in the default mode and the central modules. Moreover, significant SC-FC decoupling was demonstrated in the occipital and the subcortical modules, which was associated with longer duration of illness and more severe clinical manifestations of schizophrenia. Taken together, these findings demonstrated that altered module-dependent SC-FC coupling may underlie abnormal brain function and clinical symptoms observed in schizophrenia and highlighted the potential for using new multimodal neuroimaging biomarkers for diagnosis and severity evaluation of schizophrenia. Hum Brain Mapp 38:2008-2025, 2017. © 2017 Wiley Periodicals, Inc.

Association of Magnetic Resonance Imaging Markers of Cerebrovascular Disease Burden and Cognition.

BACKGROUND AND PURPOSE: The present study sought to examine the association between the burden of cerebrovascular disease (CeVD) as assessed by multimodal magnetic resonance imaging and neurocognitive function. METHODS: Cognitively impaired patients and controls were tested on an extensive neuropsychological battery and underwent multimodal brain magnetic resonance imaging. CeVD markers determined from magnetic resonance imaging included the presence of multiple lacunes, multiple cerebral microbleeds, and moderate or severe white matter hyperintensities as markers for small-vessel disease and cortical stroke and intracranial stenosis as markers for large-vessel disease. A weighted CeVD burden score was constructed, and its association with global and domain-specific cognitive performance was investigated. RESULTS: A total of 305 cases and 94 controls were included in the analysis. A graded association of CeVD burden with neurocognitive function was found. Moreover, a clear threshold of CeVD burden was associated with severe impairment. White matter hyperintensities was associated with global neurocognitive deficits, whereas microbleeds were associated with domain-specific impairments. CONCLUSIONS: The weighted CeVD burden score comprising markers of both small- and large-vessel diseases were associated with deficits in both global and domain-specific neurocognitive function. Additional studies are needed to validate the use of this CeVD burden score for the prediction of dementia.

Corpus callosum morphology in first-episode and chronic schizophrenia: combined magnetic resonance and diffusion tensor imaging study of Chinese Singaporean patients.

BACKGROUND: Abnormalities in the corpus callosum have been reported in patients with schizophrenia for over 30 years but the influence of inter-individual differences and illness characteristics remains to be fully elucidated. AIMS: To examine the influence of individual and illness characteristics on the corpus callosum in Chinese Singaporean patients with schizophrenia. METHOD: Using magnetic resonance and diffusion tensor imaging, mean corpus callosum area, volume and fractional anisotropy were investigated in 120 Chinese Singaporean patients (52 with chronic and 68 with first-episode schizophrenia) and compared with data from 75 matched healthy controls. RESULTS: Both area and volume were significantly reduced in patients relative to controls but no significant differences in corpus callosum existed between genders in either patients or controls. Differences in area and volume of the corpus callosum were greatest in patients whose condition was chronic relative to patients with a first episode and controls. Anterior callosum in patients, regardless of chronicity, was no different to that of controls. CONCLUSIONS: Morphological abnormalities in the corpus callosum may increase with illness progression.

Midlife metabolic syndrome and neurocognitive function in a mixed Asian sample.

BACKGROUND: An association between metabolic syndrome (MetS) and disturbances in neurocognitive function has been identified in Caucasians but the nature and extent of impaired cognition in Asian MetS patients, who may be at greater risk of degenerative cognitive decline, remains unspecified. METHODS: A cross-sectional study was conducted at the National University Hospital of Singapore. Participants were recruited from a diabetes clinic at the National University Hospital. Fifty-three patients who met MetS criteria and 44 clinical controls were recruited. All participants were 55 years and above and community ambulant. Neurocognitive function was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB). CANTAB performances between MetS and control groups were examined with analysis of variance (ANOVA) and the relative contributions of vascular risk, and intrademographic factors on CANTAB scores were dilineated with stepwise regression analyses. RESULTS: Participants with MetS consistently performed significantly worse than controls across all CANTAB subtests. Education and Chinese race were found to be potential protective factors. CONCLUSIONS: Executive and memory impairment is present in Asian patients with midlife MetS who may be particularly vulnerable to the detrimental impact of MetS in midlife.

Paracingulate sulcus asymmetry; sex difference, correlation with semantic fluency and change over time in adolescent onset psychosis.

The left paracingulate sulcus (PCS) is longer than the right and the adjacent cortex is activated by the generation of words. In adult patients with chronic schizophrenia the anatomical asymmetry is reduced. In 35 controls and 38 adolescents with schizophrenia or schizoaffective disorder (mean age = 16 years) we found that semantic verbal fluency correlated with leftward PCS asymmetry in controls but not in patients. At intake, PCS length did not differ between patients and controls, but at follow-up (13 controls, 10 patients, mean age = 18 years) PCS asymmetry (comprising both increasing left and decreasing right length) increased significantly, the increase was greater in males than in females, and there was a trend for a diagnosis * sex * side * time interaction such that in controls leftward PCS asymmetry increased, while in patients of both sexes there was convergence toward symmetry. Thus sulcal anatomy develops differentially in the two sexes during adolescence, and the pattern of asymmetric sex-dependent change over time may distinguish patients with psychosis from controls. Greater change in asymmetry during adolescence may explain earlier age of onset in males and greater deficits in verbal fluency.

Super-cognition in aging: Cognitive profiles and associated lifestyle factors.

Previous research on older adults with superior cognitive abilities (super-cognition) has typically examined cognition using a single domain approach, which may not adequately capture the multidimensional nature of successful cognitive aging. Furthermore, the lifestyle factors associated with super-cognition have not been studied adequately. The current study examined the cognitive profiles and lifestyle factors associated with super-cognition. Community-dwelling older adults (N = 693) were administered neuropsychological tests and self-reported measures of lifestyle factors at midlife (retrospectively recalled). Then, using an a priori set of criteria, we classified them as super-cognition or normal. A latent class analysis was conducted to examine the different cognitive profiles of super-cognition, and both groups were compared on their lifestyle-related outcomes. A total of 64 and 263 participants met the criteria for super-cognition and normal participants respectively. A three-class solution best described super-cognition among our participants. Approximately half of them had superior immediate memory; two other smaller groups of participants with super-cognition had superior attention, language, and visuospatial abilities. Participants with super-cognition reported less participation in social activities and, frequently, working more than 9 hours/day and feeling stressed, at midlife. Super-cognition among the elderly is associated with having a busier, more socially-isolated and stressful midlife.

Injury and recovery: severe amnestic syndrome following traumatic brain injury.

PRIMARY OBJECTIVE: To illustrate the clinical course of a patient with a marked amnestic syndrome resulting from a closed head injury that had significant effects on frontal and thalamic memory structures. METHODS AND PROCEDURES: The patient underwent a series of brain imaging investigations (CT and MRI) and neuropsychological investigations to determine the severity and course of behavioural and cognitive impairments. RESULTS: Three months post-injury, the patient demonstrated dense retrograde and anterograde amnesia for auditory-verbal and visuo-spatial information, disorientation and confabulation. In contrast, memory for faces appeared unimpaired. One month later the patient's behaviour, orientation and spatial memory had improved with no concomitant improvement in auditory-verbal memory. CONCLUSIONS: The findings indicate that injury to the diencephalon manifests in a verbal amnesic syndrome that is anterograde in nature if localized in the region of the anterior left thalamus, but leaves a relatively intact visual memory. Furthermore, injuries to the frontal and temporal lobes and their projections to the diencephalon may be more important in the emergence and resolution of retrograde amnesia and disturbances in autobiographical recall than previously appreciated.

Dynamic Reorganization of Functional Connectivity Reveals Abnormal Temporal Efficiency in Schizophrenia.

Emerging evidence suggests that schizophrenia is associated with brain dysconnectivity. Nonetheless, the implicit assumption of stationary functional connectivity (FC) adopted in most previous resting-state functional magnetic resonance imaging (fMRI) studies raises an open question of schizophrenia-related aberrations in dynamic properties of resting-state FC. This study introduces an empirical method to examine the dynamic functional dysconnectivity in patients with schizophrenia. Temporal brain networks were estimated from resting-state fMRI of 2 independent datasets (patients/controls = 18/19 and 53/57 for self-recorded dataset and a publicly available replication dataset, respectively) by the correlation of sliding time-windowed time courses among regions of a predefined atlas. Through the newly introduced temporal efficiency approach and temporal random network models, we examined, for the first time, the 3D spatiotemporal architecture of the temporal brain network. We found that although prominent temporal small-world properties were revealed in both groups, temporal brain networks of patients with schizophrenia in both datasets showed a significantly higher temporal global efficiency, which cannot be simply attributable to head motion and sampling error. Specifically, we found localized changes of temporal nodal properties in the left frontal, right medial parietal, and subcortical areas that were associated with clinical features of schizophrenia. Our findings demonstrate that altered dynamic FC may underlie abnormal brain function and clinical symptoms observed in schizophrenia. Moreover, we provide new evidence to extend the dysconnectivity hypothesis in schizophrenia from static to dynamic brain network and highlight the potential of aberrant brain dynamic FC in unraveling the pathophysiologic mechanisms of the disease.

Additive effect of cerebral atrophy on cognition in dementia-free elderly with cerebrovascular disease.

Objective: To explore the additive effect of neurodegenerative diseases, measured by atrophy, on neurocognitive function in Asian dementia-free elderly with cerebrovascular disease (CeVD). Methods: The present study employed a cross-sectional design and was conducted between 2010 and 2015 among community-dwelling elderly participants recruited into the study. Eligible participants were evaluated with an extensive neuropsychological battery and neuroimaging. The weighted CeVD burden scale comprising markers of both small- and large-vessel diseases was applied, with a score of ≥2, indicating significant CeVD burden. Cortical atrophy (CA) and medial temporal atrophy (MTA) were graded using the global cortical atrophy scale and Schelten's scale, respectively. Global and domain-specific (attention, executive function, language, visuomotor speed, visuoconstruction, visual memory, and verbal memory) neurocognitive performance was measured using a locally validated neuropsychological battery (Vascular Dementia Battery, VDB). Results: A total of 819 dementia-free participants were included in the analysis. Among none-mild CeVD subjects, there was no significant difference in the global cognitive performance across atrophy groups (no atrophy, CA, and CA+MTA). However, in moderate-severe CeVD subjects, CA+MTA showed significantly worse global cognitive performance compared with those with CA alone (mean difference=-0.35, 95% CI -0.60 to -0.11, p=0.002) and those without atrophy (mean difference=-0.46, 95% CI -0.74 to -0.19, p<0.001, p<0.001). In domain-specific cognitive performance, subjects with CA+MTA performed worse than other groups in visual memory (p=0.005), executive function (p=0.001) and visuomotor speed (p<0.001) in moderate-severe CeVD but not in none-mild CeVD. Conclusions and relevance: Atrophy and moderate-severe CeVD burden showed an additive effect on global and domain-specific cognitive performance. This study highlights the importance of investigating the mechanisms of clinico-pathological interactions between neurodegenerative processes and vascular damage, particularly in the pre-dementia stage.

Mild Cognitive Impairment Reversion and Progression: Rates and Predictors in Community-Living Older Persons in the Singapore Longitudinal Ageing Studies Cohort.

BACKGROUND: Studies report varying rates and predictors of mild cognitive impairment (MCI) progression and reversion. METHODS: We determined MCI reversion and progression among 473 community-living adults aged ≥55 years in the Singapore Longitudinal Ageing Study with an average of 6 years of follow-up and estimated association with baseline variables. RESULTS: A total of 208 MCI participants reverted to normal cognition (44.0%) and 19 progressed to dementia (4.0%). In a model adjusted for age, gender, education, ethnicity, cardiovascular risk factors/diseases, APOE ε4 status, depressive symptoms, leisure-time activities (LTA), and baseline Mini-Mental State Examination (MMSE), we found that LTA score (OR = 1.07, 95% CI 1.02-1.13), MMSE score (OR = 1.21, 95% CI 1.11-1.31), and subjective memory complaint (OR = 1.83, 95% CI 1.16-2.90) significantly predicted MCI reversion. Controlling for all variables, age (OR = 1.09, 95% CI 1.02-1.17), lower education (OR = 3.26, 95% CI 1.01-10.49), and the metabolic syndrome (OR = 3.13, 95% CI 1.12-8.77) significantly predicted MCI progression. Controlling for age, sex, ethnicity, and education, diabetes significantly predicted MCI progression (OR = 3.19, 95% CI 1.23-8.26), but the presence of other cardiometabolic factors reduced this association to an OR of 2.18 (95% CI 0.72-6.60). CONCLUSION: In this relatively younger population, there were higher rates of MCI reversion and lower rates of MCI progression which were predicted by the positive effects of LTA and a higher MMSE score as well as by the deleterious effect of the metabolic syndrome and diabetes.

Depressive symptoms moderate the relationship between sleep quality and cognitive functions among the elderly.

OBJECTIVE: The co-occurrence of sleep problems, cognitive impairment, and depression among the elderly suggests that these three conditions are likely to be interrelated. Recent findings suggest that depressive symptoms moderate the relationship between sleep problems and cognitive impairment in elderly people but methodological problems have led to inconsistent conclusions. The present study aims to better understand the relationship between sleep quality, depressive symptoms, and cognitive function. METHOD: We administered the Repeatable Battery for the Assessment of Neuropsychological Status and self-report measures of sleep quality and depression to 380 elderly participants (Mage = 68 years, SD= 5.7). Bootstrapped moderation analyses were conducted to examine the role of depressive symptoms in the relationship between sleep and various aspects of cognitive function. RESULTS: This moderation effect was significant in the domains of delayed memory (ΔR(2) = .01, F = 4.5, p = .04), language (ΔR(2) = .01, F = 4.6, p = .035), and general cognitive status (ΔR(2) = .01, F = 5.3, p = .02). However, unlike previous studies, higher sleep quality corresponded to better outcomes in delayed memory, language abilities, and general cognitive status in participants with low levels of depressive symptoms. No significant relationship between sleep quality and any cognitive function was observed among participants with high levels of depressive symptoms. CONCLUSIONS: Among individuals who reported low levels of depressive symptoms, sleep quality was positively related to cognitive performance in the domains of delayed recall, language, and general cognitive status. However, sleep quality was not significantly associated with cognitive abilities in these domains among participants with elevated levels of depressive symptoms; participants had relatively poor outcomes in these cognitive domains regardless of their sleep quality.

Insomnia and daytime neuropsychological test performance in older adults.

OBJECTIVES/BACKGROUND: There is good documentation of the impact of insomnia on daytime cognitive function based on self-reports, but not on neuropsychological test performance. The study investigated the association of difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS), and early morning awakening (EMA) complaints with daytime domain-specific neuropsychological performance in older adults. PARTICIPANTS/METHODS: Participants were 859 older adults (mean 71.9 years) in the Singapore Longitudinal Ageing Studies. They were interviewed and assessed at community-based eldercare activity centres and completed a sleep survey questionnaire and a battery of neuropsychological tests (Digit span, Rey Auditory Verbal Learning Test, Story memory, Brief Visuospatial Memory Test-Revised, Color Trails Test (1 and 2), Block design, and Verbal fluency). RESULTS: Insomnia complaints were present in 18.0% (n = 155) of participants. Controlling for the presence of other insomnia complaints, psychosocial and medical variables, and depression, EMA was independently and significantly associated with worse executive functioning (p = 0.031). DIS and DMS were not independently associated with poorer performance on any cognitive domain. CONCLUSION: The association of EMA among older adults with decreased executive functioning and underlying mechanistic factors should be further investigated.

Disruption of brain anatomical networks in schizophrenia: A longitudinal, diffusion tensor imaging based study.

Despite convergent neuroimaging evidence indicating a wide range of brain abnormalities in schizophrenia, our understanding of alterations in the topological architecture of brain anatomical networks and how they are modulated over time, is still rudimentary. Here, we employed graph theoretical analysis of longitudinal diffusion tensor imaging data (DTI) over a 5-year period to investigate brain network topology in schizophrenia and its relationship with clinical manifestations of the illness. Using deterministic tractography, weighted brain anatomical networks were constructed from 31 patients experiencing schizophrenia and 28 age- and gender-matched healthy control subjects. Although the overall small-world characteristics were observed at both baseline and follow-up, a scan-point independent significant deficit of global integration was found in patients compared to controls, suggesting dysfunctional integration of the brain and supporting the notion of schizophrenia as a disconnection syndrome. Specifically, several brain regions (e.g., the inferior frontal gyrus and the bilateral insula) that are crucial for cognitive and emotional integration were aberrant. Furthermore, a significant group-by-longitudinal scan interaction was revealed in the characteristic path length and global efficiency, attributing to a progressive aberration of global integration in patients compared to healthy controls. Moreover, the progressive disruptions of the brain anatomical network topology were associated with the clinical symptoms of the patients. Together, our findings provide insights into the substrates of anatomical dysconnectivity patterns for schizophrenia and highlight the potential for connectome-based metrics as neural markers of illness progression and clinical change with treatment.

The Diagnostic Utility of the NINDS-CSN Neuropsychological Battery in Memory Clinics.

AIMS: To examine the diagnostic utility of the National Institute of Neurological Disorders and Stroke and the Canadian Stroke Network (NINDS-CSN) neuropsychological battery in memory clinics comparing controls with patients with no cognitive impairment (NCI), patients with cognitive impairment-no dementia (CIND) at varying severity levels (mild/moderate), and patients with dementia. METHODS: A total of 405 participants with NCI, CIND or dementia were assessed with the NINDS-CSN battery. The discriminatory properties of all three protocols (5, 30 and 60 min) before and after education stratification (none/primary vs. secondary/above) were examined by receiver operating characteristic curves. RESULTS: Overall, the shorter protocols are equivalent to the longer protocol in diagnosing dementia, regardless of education. To discriminate between nondementia groups, before education stratification, the 5-min protocol showed varied discriminatory properties between different diagnostic/severity groups. After stratification, the 5-min protocol was broadly equivalent to the longer protocols in lower-education groups [area under the curve (AUC) range: 0.77-0.87] but was less accurate in the higher-education groups (AUC range: 0.68-0.78). The 30- and 60-min protocol constantly showed moderate-to-excellent differentiating capacities regardless of education (AUC range: 0.80-0.90). CONCLUSION: The NINDS-CSN neuropsychological battery can be applied in memory clinics and effectively discriminate between cognitively intact individuals and those with cognitive impairments of varying severity. Furthermore, level of education should be taken into consideration when choosing protocols with different lengths for cognitive assessment.

Disrupted latent inhibition in individuals at ultra high-risk for developing psychosis.

The addition of off-the-shelf cognitive measures to established prodromal criteria has resulted in limited improvement in the prediction of conversion to psychosis. Tests that assess cognitive processes central to schizophrenia might better identify those at highest risk. The latent inhibition paradigm assesses a subject's tendency to ignore irrelevant stimuli, a process integral to healthy perceptual and cognitive function that has been hypothesized to be a key deficit underlying the development of schizophrenia. In this study, 142 young people at ultra high-risk for developing psychosis and 105 controls were tested on a within-subject latent inhibition paradigm. Additionally, we later inquired about the strategy that each subject employed to complete the test, and further investigated the relationship between reported strategy and the extent of latent inhibition exhibited. Unlike controls, ultra high-risk subjects did not demonstrate a significant latent inhibition effect. This difference between groups became greater when controlling for strategy. The lack of latent inhibition effect in our ultra high-risk sample suggests that individuals at ultra high-risk for psychosis are impaired in their allocation of attentional resources based on past predictive value of repeated stimuli. This fundamental deficit in the allocation of attention may contribute to the broader array of cognitive impairments and clinical symptoms displayed by individuals at ultra high-risk for psychosis.

Validation of the Total Cerebrovascular Disease Burden Scale in a Community Sample.

BACKGROUND: A total cerebrovascular disease (CeVD) burden scale was previously constructed and an inverse association of CeVD burden and cognition was found. However, the generalizability of the CeVD scale has not been examined. OBJECTIVE: The objective was to validate the previously constructed total CeVD burden scale by establishing its association with cognitive function and dementia diagnosis in a community sample. METHODS: Eligible participants were assessed on an extensive neuropsychological battery and underwent MRI scans. The total CeVD scale, comprising markers of both small- and large-vessel diseases, was derived according to previously described criteria. Association of total CeVD burden with global and domain-based cognitive performance and dementia diagnostic utility of the scale was established. RESULTS: A total of 863 participants were included in the analysis. A stepwise association of CeVD burden score with global and domain-specific cognitive function was found. Per score increase on the total CeVD burden scale was associated with 3.6 (95% CI = 2.1-6.4) times higher odds of dementia compared to dementia-free. DISCUSSION: The total CeVD burden scale is associated with cognition and dementia in a community sample. Longitudinal studies are required to establish the predictive ability of this scale.

Metabolic Syndrome and the Risk of Mild Cognitive Impairment and Progression to Dementia: Follow-up of the Singapore Longitudinal Ageing Study Cohort.

IMPORTANCE: The association of the metabolic syndrome (MetS) and component cardiovascular risk factors with the risk of developing mild cognitive impairment (MCI) and MCI progression to dementia is not well established. OBJECTIVE: To investigate the association of the MetS and its component cardiovascular risk factors with the incidence of MCI and its progression to dementia. DESIGN, SETTING, AND PARTICIPANTS: Prospective longitudinal study from September 1, 2003, through December 31, 2009, in communities in 5 districts in the South East region of Singapore. Study participants were a population-based sample of 1519 cognitively normal adults 55 years and older. MAIN OUTCOMES AND MEASURES: Prespecified outcomes were incident MCI and MCI progression to dementia. RESULTS: The study cohort comprised 1519 participants. Their mean (SD) age was 64.9 (6.8) years, and 64.8% (n = 984) were female. Baseline characteristics associated with an increased risk of incident MCI were MetS (hazard ratio [HR], 1.46; 95% CI, 1.02-2.09), central obesity (HR, 1.41; 95% CI, 1.01-1.98), diabetes mellitus (HR, 2.84; 95% CI, 1.92-4.19), dyslipidemia (HR, 1.48; 95% CI, 1.01-2.15), and 3 or more component cardiovascular risk factors (HR, 1.58; 95% CI, 1.13-2.33). Baseline characteristics associated with an increased risk of MCI progression to dementia were MetS (HR, 4.25; 95% CI, 1.29-14.00), diabetes mellitus (HR, 2.47; 95% CI, 1.92-4.19), and 3 or more component cardiovascular risk factors (HR, 4.92; 95% CI, 1.39-17.4). CONCLUSIONS AND RELEVANCE: The MetS was associated with an increased incidence of MCI and progression to dementia. Identifying individuals with diabetes mellitus or the MetS with or without MCI is a promising approach in early interventions to prevent or slow progression to dementia.

Semantic fluency is impaired but phonemic and design fluency are preserved in early-onset schizophrenia.

Impairments of verbal fluency are recognised in adult-onset schizophrenia but their presence in early-onset schizophrenia is not well established. This study investigated the extent and character of verbal fluency disturbance in young patients close to illness onset. Thirty-three adolescents with DSM-IV schizophrenia and 33 controls completed phonemic and semantic fluency tests and a free design fluency test. Patients had significantly impaired semantic fluency compared to controls but no impairment on phonemic or design fluency. The difference between patients and controls for semantic fluency remained significant when corrected for age and IQ. These results lend support to the hypothesis that impaired semantic fluency may be an early trait marker of schizophrenia that is potentially related to a failure of lateralisation of language.

Is lateral bias anomalous in early-onset schizophrenia? Selected comparisons with normal populations.

The aim of this study was to investigate lateral bias in patients with early-onset schizophrenia. Hand, eye, and foot preferences and relative hand skill were examined in early-onset patients (n=44) and matched controls (n=39), and were compared with population estimates. Patients demonstrated a significant excess in mixed handedness (20.5% vs. 8.5%) relative to population estimates and reduced relative hand skill on a pegboard task compared with controls. Left eye preference was significantly less common in schizophrenic patients relative to population estimates. Crossed eye-hand and eye-foot preferences were not significantly increased in the patient group as a whole but were present, respectively, in four of nine and five of nine mixed-handed patients but in none of five mixed-handed controls. These findings are consistent with the view that lateralisation is anomalous in schizophrenia early in the course of illness.