Psychometric properties of the AIR Self-Determination Scale: the Chinese version (AIR SDS-C) for Chinese people with intellectual disabilities.

BACKGROUND: The construct of self-determination has received considerable attention in the international field of intellectual disabilities (ID). Recently, there has been a rapid development of this construct in Chinese societies including Hong Kong. However, there is no locally validated instrument to measure self-determination in people with ID. This article explains the validation process of the AIR Self-Determination Scale - Chinese version (AIR SDS-C) adapted from the 24-item AIR Self-Determination Scale, developed by Wolman and his colleagues, which is used in school setting. METHODS: People with mild/moderate ID aged 15 years or above were recruited from special schools and social services units in different regions of Hong Kong. Factor analysis and reliability tests were conducted. RESULTS: Data for a total of 356 participants were used for the analysis. A confirmatory factor analysis was performed to test the factorial construct, and Mplus 7.0 was used for the analysis. The factor structure proposed in the original English version was supported by the data, and all factor loadings were between 0.42 and 0.76. The whole scale achieved good reliability (Cronbach's α = 0.88 and ω = 0.90). CONCLUSIONS: The AIR SDS-C appears to be a valid and reliable scale. This study examined adult groups as well as student groups. The application of the scale can thus be extended to a wider population. The implications for theory building and practice are discussed.

Midlife adiposity predicts earlier onset of Alzheimer's dementia, neuropathology and presymptomatic cerebral amyloid accumulation.

Understanding how midlife risk factors influence age at onset (AAO) of Alzheimer's disease (AD) may provide clues to delay disease expression. Although midlife adiposity predicts increased incidence of AD, it is unclear whether it affects AAO and severity of Alzheimer's neuropathology. Using a prospective population-based cohort, Baltimore Longitudinal Study of Aging (BLSA), this study aims to examine the relationships between midlife body mass index (BMI) and (1) AAO of AD (2) severity of Alzheimer's neuropathology and (3) fibrillar brain amyloid deposition during aging. We analyzed data on 1394 cognitively normal individuals at baseline (8643 visits; average follow-up interval 13.9 years), among whom 142 participants developed incident AD. In two subsamples of BLSA, 191 participants underwent autopsy and neuropathological assessment, and 75 non-demented individuals underwent brain amyloid imaging. Midlife adiposity was derived from BMI data at 50 years of age. We find that each unit increase in midlife BMI predicts earlier onset of AD by 6.7 months (P=0.013). Higher midlife BMI was associated with greater Braak neurofibrillary but not CERAD (Consortium to Establish a Registry for Alzheimer's Disease) neuritic plaque scores at autopsy overall. Associations between midlife BMI and brain amyloid burden approached statistical significance. Thus, higher midlife BMI was also associated with greater fibrillar amyloid measured by global mean cortical distribution volume ratio (P=0.075) and within the precuneus (left, P=0.061; right, P=0.079). In conclusion, midlife overweight predicts earlier onset of AD and greater burden of Alzheimer's neuropathology. A healthy BMI at midlife may delay the onset of AD.

Neurocognitive dysfunction and pharmacological intervention using guanfacine in a rhesus macaque model of self-injurious behavior.

Self-injurious behavior (SIB) is a common comorbidity of psychiatric disorders but there is a dearth of information about neurological mechanisms underlying the behavior, and few animal models exist. SIB in humans is characterized by any intentional self-directed behavior that leads to wounds, whereas in macaques it is not always accompanied by wounds. We describe a cohort of rhesus macaques displaying SIB as adults, in which changes within the central nervous system were associated with the SIB. In these macaques, increases in central nervous system striatal dopamine (DA) receptor binding (BPND) measured by positron emission tomography (PET) [11C]raclopride imaging correlated with severity of wounding (rs=0.662, P=0.014). Furthermore, utilizing standardized cognitive function tests, we showed that impulsivity (stop signal reaction time, SSRT) and deficits in attentional set shifting (intra-/extradimensional shift) were correlated with increased severity of SIB (rs=0.563, P=0.045 and rs=0.692, P=0.009, respectively). We also tested the efficacy of guanfacine, an α2A adrenergic agonist that acts to improve postsynaptic transmission of neuronal impulses, in reducing SIB. A subset of these animals were enrolled in a randomized experimenter-blinded study that demonstrated guanfacine decreased the severity of wounding in treated animals compared with vehicle-only-treated controls (P=0.043), with residual beneficial effects seen for several weeks after cessation of therapy. Animals with the highest severity of SIB that received guanfacine also showed the most significant improvement (rs=-0.761, P=0.009). The elevated PET BPND was likely due to low intrasynaptic DA, which in turn may have been improved by guanfacine. With underlying physiology potentially representative of the human condition and the ability to affect outcome measures of disease using pharmacotherapy, this model represents a unique opportunity to further our understanding of the biology and treatment of SIB in both animals and humans.

Marital satisfaction of Chinese mothers of children with autism and intellectual disabilities in Hong Kong.

BACKGROUND: Previous research showed an association among perceived stigma, perceived caregiving burden and marital satisfaction of mothers. However, little is known about their relationship among mothers of young children with disabilities in the Chinese context. The mediating role of perceived caregiving burden between perceived stigma and marital satisfaction was seldom explored. Hence, the present study aims to investigate the relationship between perceived stigma, perceived caregiving burden and marital satisfaction of Chinese mothers of children with intellectual disabilities or autism spectrum disorders in Hong Kong. METHODS: A cross-sectional survey using convenience sampling was conducted with mothers of pre-school children with disabilities aged from 2 to 6. A total of 160 completed questionnaires were collected from five special child care centres in Hong Kong. RESULTS: The findings in the hierarchical regression analyses showed that perceived stigma and perceived caregiving burden were significant predictors of mothers' marital satisfaction. Perceived burden, including perceived social burden, emotional burden and developmental burden but excluding time-dependence and physical burden, were found to be significant mediators between perceived stigma and marital satisfaction. CONCLUSION: To address the negative consequences brought on by stigma, measures can be taken to prevent stigmatisation and minimise the harmful effects. To alleviate mothers' perceived burden, Acceptance and Commitment Therapy, mutual support groups and psycho-educational and skills training programmes can be conducted for the mothers.

Cognition and amyloid load in Alzheimer disease imaged with florbetapir F 18(AV-45) positron emission tomography.

OBJECTIVE: To examine the association between regional brain uptake of a novel amyloid positron emission tomography (PET) tracer florbetapir F 18 ([(18)F]-AV-45) and cognitive performance in a pilot study. DESIGN: Cross-sectional comparison of [(18)F]-AV-45 in AD patients versus controls. SETTING: Three specialty memory clinics. PARTICIPANTS: Eleven participants with probable Alzheimer disease (AD) by NINDS/ADRDA criteria and 15 healthy comparison (HC) participants. MEASUREMENTS: Participants underwent PET imaging following a 370 MBq (10 mCi) intravenous administration of [(18)F]-AV-45. Regional/cerebellar standardized uptake value ratios (SUVRs) were calculated. Cognition was assessed using Mini-Mental State Examination, Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog), Wechsler Logical Memory IA (immediate recall) test (LMIA), and verbal category fluency. RESULTS: Greater [(18)F]-AV-45 SUVR was associated with poorer performance on all cognitive tests. In the HC group, occipital, parietal, precuneus, temporal, and cortical average SUVR was associated with greater ADAS-Cog, and greater anterior cingulate SUVR was associated with lower LMIA. Two HC participants had [(18)F]-AV-45 cortical/cerebellar SUVR greater than 1.5, one of whom had deficits in episodic recall and on follow-up met criteria for amnestic mild cognitive impairment. CONCLUSION: [(18)F]-AV-45 SUVR in several brain regions was associated with worse global cognitive performance particularly in HC, suggesting its potential as a marker of preclinical AD.

The maintenance effect of cognitive-behavioural treatment groups for the Chinese parents of children with intellectual disabilities in Melbourne, Australia: a 6-month follow-up study.

BACKGROUND: Caring for a child with intellectual disability can be stressful. No data on the longer-term effects of cognitive-behavioural treatment (CBT) on parents from a Chinese-speaking background who have children with intellectual disabilities are available in the literature. This study attempted to fill this research gap by examining the maintenance effect of CBT among the Chinese parents of such children in Melbourne, Australia. METHOD: Thirty-nine participants took part in our CBT groups and attended follow-up meetings. A questionnaire comprising four instruments, the Parenting Stress Index (PS) - Parent Domain, General Health Questionnaire-12 (GHQ-12), Abbreviated Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q-18) and Dysfunctional Attitude Scale (DAS), was administered to the participants at the pre- and post-test stage and at the 6-month follow-up. RESULTS: One-way repeated-measures analyses of variance revealed significant time and group effects in the PS (F(2,27) = 16.93, P < 0.001), Q-LES-Q-18 (F(2,27) = 15.98, P < 0.001), GHQ-12 (F(2,27) = 81.93, P < 0.001) and DAS (F(2,27) = 15.50, P < 0.001) scores at the three measurement times. The participants continued to maintain significant improvements in mental health and quality of life and declines in the severity of parenting stress and dysfunctional attitudes at the 6-month follow-up. Effect size analyses revealed mostly large differences in the foregoing measurements (Cohen's d = 0.76-2.18) between the pre-test and 6-month follow-up. Employing a cut-off score of 3/4 in the GHQ-12 to identify at-risk and not-at-risk cases, approximately 90.5% of the participants could be classified as not-at-risk at the follow-up. Lastly, regression analyses showed that changes in DAS scores significantly predicted changes in the GHQ-12 and Q-LES-Q-18 scores at the follow-up. CONCLUSIONS: This study provides preliminary evidence of the 6-month maintenance effect of CBT groups for the Melbourne-resident Chinese parents of children with intellectual disabilities.

Initial validation of the Chinese Quality of Life Questionnaire-Intellectual Disabilities (CQOL-ID): a cultural perspective.

BACKGROUND: In the field of intellectual disabilities (ID), the quality of life concept has been developing rapidly in Chinese societies including Hong Kong, mainland China and Taiwan. However, there is a lack of locally validated instruments to measure the quality of life of people with ID. The study reported in this paper attempted to validate the Chinese Quality of Life Questionnaire - Intellectual Disabilities adapted from the Quality of Life Questionnaire developed by Schalock & Keith. METHODS: People with mild/moderate ID aged 15 years or above were recruited from special schools, skills centres, community service units and residential units in different regions of Hong Kong. A number of procedures were followed including reliability tests, factor analysis, content validity and construct validity. RESULTS: A total of 359 participants were recruited for the study. Factor analysis was conducted according to the rotated component matrix method, in which 23 items were extracted from the original 40-item version of the Quality of Life Questionnaire and three domains (renamed satisfaction, competence and daily choice making/interpersonal relations) were observed. The items in each domain were shown to have factor loadings ranging from 0.42 to 0.90. Construct validity tests indicated the positive nature of the relationship between earnings, and that self-determination and social interaction increase with more independent living environments and less segregated work environments achieving higher scores (P<0.000, P<0.01 and P<0.05 respectively). The scale also achieved a good degree of reliability (Cronbach's α=0.79). CONCLUSIONS: Initial validity tests indicated that the Chinese Quality of Life Questionnaire - Intellectual Disabilities may be a useful instrument for measuring the quality of life of Chinese people with ID. Cultural issues are discussed and recommendations for future research and service development are made.

Longitudinal cognitive decline is associated with fibrillar amyloid-beta measured by [11C]PiB.

OBJECTIVE: To investigate whether longitudinal declines in cognition are associated with higher fibrillar amyloid-beta (Abeta) deposition in vivo in individuals without dementia. METHOD: [(11)C]PiB images were obtained to measure fibrillar Abeta burden in 57 participants without dementia from the Baltimore Longitudinal Study of Aging. Participants (33 men, 24 women) had a mean (SD) age of 78.7 (6.2) years. Six participants (4 men, 2 women) had mild cognitive impairment defined as Clinical Dementia Rating = 0.5. To measure [(11)C]PiB retention, distribution volume ratios (DVR) for 15 regions of interest were estimated by fitting a simplified reference tissue model to the measured time activity curves. Mixed effects regression was used to predict cognitive trajectories over time using data before and including time of PiB (mean follow-up 10.8 years), with mean cortical DVR, age at baseline, sex, and education as independent predictors. Voxel-based analysis identified local associations. RESULTS: [(11)C]PiB retention was higher in older individuals. Greater declines over time in mental status and verbal learning and memory, but not visual memory, were associated significantly with higher PiB retention. Voxel-based analysis showed significant associations in frontal and lateral temporal regions. CONCLUSIONS: Higher Abeta deposition is associated with greater longitudinal decline in mental status and verbal memory in the preceding years. The differential association for verbal but not visual memory may reflect the greater reliance of verbal word list learning on prefrontal regions, which show early Abeta deposition. Prospective imaging may help distinguish between individuals with evolving neuropathology who develop accelerated cognitive decline vs those with normal aging.

Bayesian hierarchical modeling of receptor occupancy in PET trials.

Receptor occupancy (RO) PET is a non-invasive way to determine drug on target. Given the complexity of procedures, long acquisition times, and high cost, ligand displacement imaging trials often have a limited size and produce sparse RO results over the time course of the blocking drug. To take the best advantage of the available data, we propose a Bayesian hierarchical model to analyze RO as a function of the displacing drug. The model has three components: the first estimates RO using brain regional time-radioactivity concentrations, the second shapes the pharmacokinetic profile of the blocking drug, and the last relates PK to RO. Compared to standard 2-steps RO estimation methods, our Bayesian approach quantifies the variability of the individual RO measures. The model has also useful prediction capabilities: to quantify brain RO for dosage regimens of the drug that were not tested in the experiment. This permits the optimal dose selection of neuroscience drugs at a limited cost. We illustrate the method in the prediction of RO after multiple dosing from a single-dose trial.

Enhancing staff attitudes, knowledge and skills in supporting the self-determination of adults with intellectual disability in residential settings in Hong Kong: a pretest-posttest comparison group design.

BACKGROUND: The ecological perspective recognizes the critical role that is played by rehabilitation personnel in helping people with intellectual disability (ID) to exercise self-determination, particularly in residential settings. In Hong Kong, the authors developed the first staff training programme of its kind to strengthen the competence of personnel in this area. The purpose of this study was to examine the effectiveness of staff training in enhancing residential staff's attitudes, knowledge and facilitation skills in assisting residents with ID to exercise self-determination. METHODS: A pretest-posttest comparison group design was adopted. Thirty-two participants in an experimental group attended a six-session staff training programme. A 34-item self-constructed scale was designed and used for measuring the effectiveness of the staff training. RESULTS: The results showed that the experimental group achieved statistically significant positive changes in all domains, whereas no significant changes were found in the comparison group. CONCLUSIONS: The findings provided initial evidence of the effectiveness of staff training that uses an interactional attitude-knowledge-skills model for Chinese rehabilitation personnel. The factors that contributed to its effectiveness were discussed and recommendations for future research were made.

[The next generation of "atypical" antipsychotics: the role of positron emission tomography]. / Die nächste Generation "atypischer" Antipsychotika: Der Beitrag der Positronenemissionstomographie.

Almost fifteen years of research with Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) have led to a profound understanding of the relationships between antipsychotic doses and plasma levels on the one hand and occupancy of (striatal) D2 -like dopamine receptors on the other hand as well as with the associated clinical effects and side effects. Furthermore, with the development of clinically "atypical" antipsychotics PET studies helped to generate hypotheses regarding the essential pharmacological properties of this heterogeneous class of drugs. Possible mechanisms of action include combined D2 -/5-HT2 antagonism, preferential mesolimbic binding, and fast dissociation from the D2 -receptor. Our recently published PET study on the in vivo characterization of the partial dopamine receptor agonist, aripiprazole, suggests a novel mechanism of action, which leads to clinically "atypical" properties of an antipsychotic. Aripiprazole, of which the antipsychotic efficacy has been proven in various multicenter clinical trials, leads to almost complete saturation of D2 -like dopamine receptors at clinically used doses; however, the incidence of extrapyramidal side effects under aripiprazole is not higher than under placebo. PET like no other method is suitable to display in vivo a novel mechanism of "atypicality" of a new class of antipsychotics.

Neuroimaging studies in Rett syndrome.

Neuroimaging is a key instrument for determining structural and in vivo functional status of the brain, non-invasively. Multiple approaches can now determine aspects of anatomic and neurochemical changes in brain, and have been utilized effectively in Rett Syndrome patients to understand the biological basis of this neurodevelopmental disorder. Studies performed at our institute include volumetric analyses of MRI, magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), cerebral blood flow measurements with MRI, and positron emission tomography scans (PET). These studies have provided considerable insight into mechanisms underlying the clinical features of this disease. Volumetric analyses suggest that decreased brain volume in RS results from global reductions in both gray and white matter of the brain. A selective vulnerability of the frontal lobes is evidenced by the preferential reduction of blood flow, increased choline and reduced n-acetyl aspartate (NAA) by MRS, and increased glucose uptake in these same regions as shown by ((18)F)-fluorodeoxyglucose (FDG) PET scans. We hypothesize that the increased glucose uptake relates to increased glutamate cycling in synapses. The resulting neuroexcitotoxic injury to the developing brain contributes to the seizures, behavioral disturbance and respiratory irregularities commonly seen in phases 1 and 2 of this disorder.

[125/123I] 5-Iodo-3-pyridyl ethers. syntheses and binding to neuronal nicotinic acetylcholine receptors.

Three 3-pyridyl ether nicotinic ligands-(S)-5-Iodo-3-[(2-pyrrolidinyl)-methoxy]pyridine (5-iodo-A-85865), (S)-5-Iodo-3-[1-(methyl)-2-pyrrolidinyl-methoxy]pyridine (5-Iodo-A-84543), and (S)-5-iodo-3-[1-methyl-(2-azetidinyl)-methoxy]pyridine (5-iodo-N-Me-A-85380) were labeled with I-125/I-123, and their ability to label high-affinity brain nicotinic acetylcholine receptors (nAChRs) was evaluated. The most promising ligand, [123/125I] 5-iodo-A-85865, showed approximately 65% inhibition of radioactivity uptake in thalamus in mice pretreated with cytisine. Preliminary SPECT imaging studies with [123I] 5-iodo-A-85865 revealed a distribution profile consistent with nAChRs (thalamus > frontal cortex > cerebellum) and a more rapid pharmacokinetic profile relative to azetidinyl 3-pyridyl ether based ligands.

Quantification of neuroreceptors in living human brain. v. endogenous neurotransmitter inhibition of haloperidol binding in psychosis.

The half-inhibition concentration (IC50) of a drug indicates its ability to inhibit the binding of other ligands of a receptor. The authors used positron emission tomography to test the hypothesis that haloperidol's IC50 toward the binding of tracer N-[11C]methylspiperone ([11C]NMSP) in brain must be increased in patients in whom more dopamine is bound to receptors than in healthy volunteers. The IC50 of haloperidol was significantly elevated from 1.5 nmol/L in healthy volunteers and patients with bipolar disease without psychosis to 4.5 nmol/L in patients with schizophrenia or bipolar disease with psychosis. The higher IC50 values in psychosis are consistent with an 8-fold increased binding of dopamine and a 16-fold elevated concentration of synaptic dopamine in psychosis. At the 80% haloperidol blockade of the receptors, the calculated amount of neurotransmitter bound in the patients with psychosis declined to twice the value estimated in the nonpsychotic subjects, that is, 5 pmol cm(-3).

In vivo imaging of nicotinic receptor upregulation following chronic (-)-nicotine treatment in baboon using SPECT.

To quantify changes in neuronal nAChR binding in vivo, quantitative dynamic SPECT studies were performed with 5-[(123)I]-iodo-A-85380 in baboons pre and post chronic treatment with (-)-nicotine or saline control. Infusion of (-)-nicotine at a dose of 2.0 mg/kg/24h for 14 days resulted in plasma (-)-nicotine levels of 27.3 ng/mL. This is equivalent to that found in an average human smoker (20 cigarettes a day). In the baboon brain the regional distribution of 5-[(123)I]-iodo-A-85380 was consistent with the known densities of nAChRs (thalamus > frontal cortex > cerebellum). Changes in nAChR binding were estimated from the volume of distribution (V(d) ) and binding potential (BP) derived from 3-compartment model fits. In the (-)-nicotine treated animal V(d) was significantly increased in the thalamus (52%) and cerebellum (50%) seven days post cessation of (-)-nicotine treatment, suggesting upregulation of nAChRs. The observed 33% increase in the frontal cortex failed to reach significance. A significant increase in BP was seen in the thalamus. In the saline control animal no changes were observed in V(d) or BP under any experimental conditions. In this preliminary study, we have demonstrated for the first time in vivo upregulation of neuronal nAChR binding following chronic (-)-nicotine treatment.

Self-injurious behavior: gene-brain-behavior relationships.

This paper summarizes a conference held at the National Institute of Child Health and Human Development on December 6-7, 1999, on self-injurious behavior [SIB] in developmental disabilities. Twenty-six of the top researchers in the U.S. from this field representing 13 different disciplines discussed environmental mechanisms, epidemiology, behavioral and pharmacological intervention strategies, neurochemical substrates, genetic syndromes in which SIB is a prominent behavioral phenotype, neurobiological and neurodevelopmental factors affecting SIB in humans as well as a variety of animal models of SIB. Findings over the last decade, especially new discoveries since 1995, were emphasized. SIB is a rapidly growing area of scientific interest to both basic and applied researchers. In many respects it is a model for the study of gene-brain-behavior relationships in developmental disabilities.

Comparison of myocardial oxygen consumption using 11C acetate positron emission tomography scanning in a working and non-working heart transplant model.

OBJECTIVE: In acute cardiac rejection, changes in myocardial oxygen consumption occur; non-invasive detection of these metabolic changes would have obvious clinical utility. In the classic cervical, heterotopic, canine, transplant model, the heart is non-working. It has a low myocardial oxygen consumption. Creation of a working model with normal myocardial oxygen consumption would enhance validity of non-human studies. METHODS: Clearance of 11C acetate was determined by positron emission tomography (PET) scanning and compared with myocardial oxygen consumption in normal and transplanted canine hearts. Donor hearts from mongrel dogs (2.5-3 kg; n=4) were transplanted into the neck of adult beagles (12-15 kg; n=4), no immunosuppression was given. Two non-working hearts were modified to eject only coronary flow via the right ventricle. In two hearts, a novel working model was created with aortic regurgitation to load the left ventricle. Working and non-working hearts underwent PET scanning on post-operative days 2 and 4. Normal dog hearts (n=2) and native hearts of transplanted dogs (n=3) were used to validate the scanning technique. Coronary sinus and aortic oxygen saturation data along with myocardial blood flow (radiolabeled microspheres) confirmed that clearance of 11C acetate in normal and transplanted hearts followed a bi-exponential model. RESULTS: Myocardial oxygen consumption was correlated with the rate constant of 11C acetate rapid phase clearance (r=0.91) in normal and transplanted hearts. The working hearts had increased myocardial oxygen consumption compared to non-working hearts. CONCLUSIONS: This study (1) introduces a model of a working heterotopic cardiac transplantation with near-normal oxygen consumption; and (2) demonstrates that regional myocardial oxygen consumption in transplanted hearts can be detected by 11C acetate PET.

Differential impacts of coping strategies on trati the mental health of Chinese nurses in hospitals in Hong Kong.

This study examined the types of coping strategies used by hospital nurses in Hong Kong. The impacts of these coping strategies on the mental health of nurses were also investigated. Results showed that coping strategies were both situation-specific and culture-specific, with direct action coping, acceptance and positive thinking used more frequently than avoidance and alcohol. It was found that more than one-third of the nurses were considered to be at risk of developing poor mental health, and the most frequent symptomatic complaints included anxieties and feelings of inadequacy in handling daily activities. Nurses who were mentally healthy used more direct action coping and positive thinking, and fewer avoidance strategies and drinking than did nurses who were at risk of developing poor mental health. Contrary to our hypothesis, nurses who adopted more acceptance strategies had poorer mental health. Implications of the study are discussed.