Adaptive behavior in autism: Minimal clinically important differences on the Vineland-II.

Autism Spectrum Disorder (ASD) is associated with persistent impairments in adaptive abilities across multiple domains. These social, personal, and communicative impairments become increasingly pronounced with development, and are present regardless of IQ. The Vineland Adaptive Behavior Scales, Second Edition (Vineland-II) is the most commonly used instrument for quantifying these impairments, but minimal clinically important differences (MCIDs) on Vineland-II scores have not been rigorously established in ASD. We pooled data from several consortia/registries (EU-AIMS LEAP study, ABIDE-I, ABIDE-II, INFOR, Simons Simplex Collection and Autism Treatment Network [ATN]) and clinical investigations and trials (Stanford, Yale, Roche) resulting in a data set of over 9,000 individuals with ASD. Two approaches were used to estimate MCIDs: distribution-based methods and anchor-based methods. Distribution-based MCID [d-MCID] estimates included the standard error of the measurement, as well as one-fifth and one-half of the covariate-adjusted standard deviation (both cross-sectionally and longitudinally). Anchor-based MCID [a-MCID] estimates include the slope of linear regression of clinician ratings of severity on the Vineland-II score, the slope of linear regression of clinician ratings of longitudinal improvement category on Vineland-II change, the Vineland-II change score maximally differentiating clinical impressions of minimal versus no improvement, and equipercentile equating. Across strata, the Vineland-II Adaptive Behavior Composite standardized score MCID estimates range from 2.01 to 3.2 for distribution-based methods, and from 2.42 to 3.75 for sample-size-weighted anchor-based methods. Lower Vineland-II standardized score MCID estimates were observed for younger and more cognitively impaired populations. These MCID estimates enable users of Vineland-II to assess both the statistical and clinical significance of any observed change. Autism Res 2018, 11: 270-283. © 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: The Vineland Adaptive Behavior Scales (2nd edition; Vineland-II) is the most widely used scale for assessing day-to-day "adaptive" skills. Yet, it is unknown how much Vineland-II scores must change for those changes to be regarded as clinically significant. We pooled data from over 9,000 individuals with ASD to show that changes of 2-3.75 points on the Vineland-II Composite score represent the "minimal clinically-important difference." These estimates will help evaluate the benefits of potential new treatments for ASD.

Conceptual structure: Towards an integrated neuro-cognitive account.

How are the meanings of concepts represented and processed? We present a cognitive model of conceptual representations and processing - the Conceptual Structure Account (CSA; Tyler & Moss, 2001) - as an example of a distributed, feature-based approach. In a first section, we describe the CSA and evaluate relevant neuropsychological and experimental behavioral data. We discuss studies using linguistic and non-linguistic stimuli, which are both presumed to access the same conceptual system. We then take the CSA as a framework for hypothesising how conceptual knowledge is represented and processed in the brain. This neuro-cognitive approach attempts to integrate the distributed feature-based characteristics of the CSA with a distributed and feature-based model of sensory object processing. Based on a review of relevant functional imaging and neuropsychological data, we argue that distributed accounts of feature-based representations have considerable explanatory power, and that a cognitive model of conceptual representations is needed to understand their neural bases.

Complementary hemispheric asymmetries in object naming and recognition: a voxel-based correlational study.

Cognitive neuroscientific research proposes complementary hemispheric asymmetries in naming and recognising visual objects, with a left temporal lobe advantage for object naming and a right temporal lobe advantage for object recognition. Specifically, it has been proposed that the left inferior temporal lobe plays a mediational role linking conceptual information with word forms and vice versa, while the right inferior temporal lobe supports the retrieval of conceptual knowledge from visual input. To test these hypotheses, we administered four behavioural tasks to fifteen patients with temporal lobe brain damage, and correlated their behavioural scores with voxel-based measures of neuronal integrity (signal intensities) in whole-brain analyses. The behavioural paradigms included four tasks. Two were verbal tasks: (a) picture naming requiring the mapping of conceptual knowledge to word forms, (b) semantic categorisation of words requiring the reverse mapping of word forms to conceptual knowledge, and two were visual object tasks with no verbal component, both of which required the retrieval of conceptual information from visual objects, i.e., (c) visual object categorisation and (d) normal and chimera object decisions. Performance on the verbal tasks correlated with the neural integrity of partially overlapping left inferior and anterior temporal lobe regions, while performance on the object tasks correlated with the neural integrity of overlapping regions in right inferior and anterior temporal lobe. These findings support the notion of complementary hemispheric advantages for object naming and recognition, and further suggest that the classical language model emphasising posterior regions in the mapping between word forms and conceptual knowledge should be extended to include left inferior temporal lobe.

The validity of clinical diagnoses of dementia in a group of consecutively autopsied memory clinic patients.

BACKGROUND: Epidemiological studies show that up to 10% of individuals aged 65 years and older suffer from dementia, most commonly from dementia of the Alzheimer Type (DAT) (1). Clinicopathological studies are critical to our understanding of this disease and improving the accuracy of clinical diagnoses. OBJECTIVES: Our objectives were to examine the validity of clinical diagnoses of DAT, to determine the prevalence of different forms of dementia in this sample, and to investigate the relationship between age at death and polymorbidity. SUBJECTS AND METHOD: Clinical data were available from 221 patients who had been examined at the Basel Memory Clinic between 1986 and 1996. From this population, 34% (75 patients) were autopsied in the Department of Pathology, University Hospital Basel, and neuropathological examinations were additionally performed on 62 (83%) of these patients. Clinical and neuropathological data were retrospectively compared. RESULTS: 67.8% of the neuropathologically examined patients received a definitive diagnosis of AD (Alzheimer's disease), vascular dementia (VaD) or mixed dementia (AD and VaD). AD alone or with other histopathological hallmarks of dementia was the most prevalent neuropathological diagnosis (63%). VaD was deemed the only cause of dementia in only 4.8% of patients. The sensitivity for DAT was 75.9%, the specificity 60.6%. Increasing age was associated with an increasing number of clinical and neuropathological diagnoses. CONCLUSION: The sensitivity and specificity of the clinical diagnoses of DAT found in our study are similar to previous reports (2-5). Older patients had more etiologies of their dementia than younger patients. This study reaffirms the need for internationally accepted criteria for clinical and neuropathological diagnoses, as well as further clinical-neuropathological investigations to further refine the clinical diagnostic process.

Changes in management of diabetic retinopathy by Australian ophthalmologists as a result of the NHMRC clinical guidelines.

PURPOSE: To document changes in management of diabetic retinopathy by Australian ophthalmologists after release of the National Health and Medical Research Council (NHMRC) clinical guidelines. METHODS: Self-administered questionnaires were mailed to Australian ophthalmologists prior to release of the NHMRC guidelines for the management of diabetic retinopathy, and at one and 2.5 years after release of the guidelines. The questionnaires elicited information about current management practices in relation to diabetic retinopathy RESULTS: The response rate for the baseline and two follow-up surveys was 82%, 81%, and 80%, respectively. More than 85% of the ophthalmologists responded that the guidelines were useful in improving management, were easy to understand, and were already part of their routine clinical practice. A relatively small percentage (12%) felt that the guidelines made recommendations that were not practical or feasible. Contrary to the NHMRC guidelines, at the second follow-up survey, only 50% of the ophthalmologists said that they would almost never perform fluorescein angiography in eyes with mild non-proliferative diabetic retinopathy. The change from baseline to the second follow-up in the percentage of ophthalmologists who would perform cataract surgery after treating clinically significant macular oedema (as advised by the NHMRC guidelines) was statistically significant (baseline = 83.7%, 95% confidence limit = 80.4, 87.0; second follow up = 90.4, 95% confidence limit = 87.3, 93.5). CONCLUSIONS: Distribution of the printed NHMRC Clinical Practice Guidelines: Management of Diabetic Retinopathy and full colour Retinopathy Chart resulted in a significant change in the recommended order of treatment of clinically significant macular oedema. However no significant change in the use of fluorescein angiography was documented.

Changes in attitudes and practices of optometrists in their management of diabetic retinopathy after the release of NHMRC guidelines. National Health and Medical Research Council.

The purpose of this study was to document attitudes and practices of Australian optometrists in their management of diabetic retinopathy prior to the release of the National Health and Medical Research Council (NHMRC) Clinical Practice Guidelines for the Management of Diabetic Retinopathy and at two time points following their release. A self-administered questionnaire was mailed to a stratified random sample of 500 Australian optometrists at the three time points. The same sample was used for the first two surveys and a new random sample was drawn for the second follow-up survey. The response to the three questionnaires was 86%, 80% and 84%, respectively. More than 90% of optometrists reported receiving a copy of the guidelines and 82% reported receiving the supplementary Retinopathy Chart. Fifty-seven per cent reported having read the guidelines at least once in entirety and 65% reported that they refer to the Retinopathy Chart at least monthly in their clinical practice. There was a significant decrease in the number of optometrists who reported that patient unwillingness to be dilated and their fear of precipitating angle closure glaucoma were moderate or major barriers to performing dilated ophthalmoscopy. Concomitantly, the percentage of optometrists who reported that they often or always perform dilated ophthalmoscopy on new patients with diabetes increased significantly from 74.5% (95% confidence limit = 70.2, 78.8) to 81.5% (95% confidence limit = 77.5, 85.5). There have been some significant changes in the self-reported management practices of optometrists in relation to diabetic retinopathy since the release of the NHMRC guidelines and Retinopathy Chart.

Diabetic retinopathy: effects of national guidelines on the referral, examination and treatment practices of ophthalmologists and optometrists.

OBJECTIVE: To investigate the changes in referral, examination and treatment practices for diabetic retinopathy by ophthalmologists and optometrists following the release of national guidelines. METHODS: A two-page self-administered questionnaire was mailed to all Australian ophthalmologists and a random sample of 500 Australian optometrists prior to and 1 year after release of the National Health and Medical Research Council of Australia (NHMRC) clinical practice guidelines for the management of diabetic retinopathy. The questionnaires elicited information about current practice related to the management of patients with diabetic retinopathy. RESULTS: Of the 464 contactable ophthalmologists who responded to the baseline survey, 374 (80.6% response) completed the follow-up survey The response rate for the contactable optometrists was 80.1% (310 of 384). There were almost no significant changes in management practices from baseline to follow up. For example, the percentage of ophthalmologists who reported that they were often or almost always confident in detecting moderate retinal thickening near the macula remained nearly identical from baseline to follow up (80.2% vs 79.1 %). The rate was also similar from baseline to follow up for optometrists (31.1% vs 28.8%). The one area in which ophthalmologists reported significant changes in management towards agreement with the NHMRC guidelines was use of angiography; they were less likely to manage their patients this way (20.4% vs 14.2% with laser and 48.9% vs 38.4% without laser for increasing level of severity in clinical signs; both P < 0.05). CONCLUSIONS: The NHMRC guidelines for diabetic retinopathy have been successfully distributed to ophthalmologists and optometrists in Australia. However, the mere provision of the guidelines has had little impact on management practices. It will be important to determine if ongoing dissemination and implementation strategies not only increase awareness of health-care practitioners to the guidelines, but also change behaviours.

Management of diabetic retinopathy by general practitioners in Victoria.

PURPOSE: To compare the self-reported management of diabetic retinopathy by general practitioners to the National Health and Medical Research Council of Australia (NHMRC) Guidelines for the Management of Diabetic Retinopathy. METHODS: In 1994, a stratified (by urban/rural practice location) sample of 500 general practitioners in Victoria was surveyed in regard to their management of diabetic retinopathy. Following the release of the NHMRC Guidelines for the Management of Diabetic Retinopathy in 1997, these same general practitioners were sent a two-page questionnaire related to their management of diabetic retinopathy. RESULTS: Completed questionnaires were received from 228 general practitioners (59% of original participants). Only 37% (79/216) of the general practitioners reported that they had received a copy of the guidelines. Of the general practitioners who had received the guidelines, 18% (14/79) said that they had not read them at all, while 65% (51/79) had read them partially and 18% (14/79) had read them in their entirety. At follow up, less than half (98/214) of general practitioners reported examining 50% or more of their patients for diabetic retinopathy, compared with 104/214 at baseline. General practitioners who had read the guidelines were more likely to report that not being sure what to do when changes were detected was a minor barrier or was not a barrier to them performing dilated ophthalmoscopy (93% vs 83%, chi2(1) = 3.67, P = 0.055). Nearly all of the general practitioners reported that they refer their patients with diabetes to an ophthalmologist or optometrist at least every 2 years as recommended. Seventy-six per cent (170/224) of the general practitioners felt that 70% or more of their patients complied with their instructions to visit an ophthalmologist or optometrist. CONCLUSION: The NHMRC guidelines for diabetic retinopathy appear to have had a positive effect on some of the attitudes of general practitioners who have read them, but more effort is needed to disseminate the guidelines to all general practitioners and to increase their uptake.

Qualitative hemispheric differences in semantic category matching.

A unilateral category matching task with words as stimuli was employed to investigate semantic processing in the right and left hemispheres (RH, LH). An overall right visual field (RVF)/LH dominance was observed and performances were better than chance, also in the left visual field (LVF)/RH. A qualitative analysis of reaction times with individual differences multidimensional scaling (INDSCAL) revealed that LVF/RH INDSCAL solutions were significantly more differentiated in structure than RVF/LH solutions in terms of number and size of dimensions. These findings support a depth of activation hypothesis of hemispheric processing, with the LH rapidly and focally and the RH slowly and diffusely activating the semantic network.

Category fluency is also predominantly affected in Swiss Alzheimer's disease patients.

OBJECTIVES: To establish the comparative efficacy to differentiate between Swiss patients with dementia of the Alzheimer type (DAT) and elderly normal control subjects (NC) on two different verbal fluency tasks: category fluency and letter fluency. MATERIAL AND METHODS: Fifty Swiss German DAT patients in the early stages of the disease and 50 matched normal control subjects were compared on letter and category fluency tasks. RESULTS: DAT patients exhibited an overproportional impairment on category fluency as compared with letter fluency. Receiver operating characteristic curves (ROC) showed that category fluency correctly classified a significantly higher number of DAT patients and NC subjects (84%) than letter fluency (70%). CONCLUSION: As similar findings have been described for English-speaking DAT patients, we conclude that deficiencies in category fluency are a general phenomenon, reflecting impaired structures of semantic knowledge occurring early in the course of Alzheimer's disease.

Longitudinal examination of American National Adult Reading Test (AMNART) performance in dementia of the Alzheimer type (DAT): validation and correction based on degree of cognitive decline.

The American National Adult Reading Test (AMNART) was constructed to provide a valid and stable estimate of premorbid verbal IQ (VIQ) in dementing individuals. However, recent studies have brought into question its validity in patients with dementia of the Alzheimer type (DAT). The present study was designed to longitudinally assess the validity of the AMNART in 40 DAT patients and 40 demographically matched normal control (NC) subjects. The results showed that VIQ estimates for patients with DAT were significantly lower than those of NC subjects and declined significantly over time with increasing dementia severity as measured by the Mini-Mental State Examination (MMSE) and the Dementia Rating Scale (DRS). An MMSE-based correction factor was derived for the DAT group which allows for the effective estimation of premorbid VIQ in these patients.

Chronic meningitis due to herpes simplex virus in an immunocompetent host.

Herpes simplex virus (HSV) typically causes mucocutaneous disease, encephalitis, and acute men ingitis. There have been no previous reports of chronic meningitis due to this virus. A case of chronic meningitis due to herpes simplex virus type 2 (HSV-2) in a previously healthy 35-year-old woman whose predominant symptoms were headache and meningism without fever is described. Analysis of cerebrospinal fluid (CSF) revealed a lymphocytic pleocytosis, elevated protein, and hypoglycorrhachia. The diagnosis of herpes simplex meningitis was supported by the detection of HSV-2 DNA in CSF by polymerase chain reaction and by intrathecal production of HSV-specific antibody. The patient recovered after treatment with intravenous acyclovir and glucocorticoids.

Neuropsychological assessment of severely demeted elderly: the severe cognitive impairment profile.

BACKGROUND: Although the assessment of cognitive functioning in the late stages of Alzheimer's Disease (AD) is important for identifying abilities that may improve communication and interactions with severely impaired patients in clinical and institutional settings and for assessing the efficacy of pharmacologic agents and behavioral interventions for the treatment of AD, few adequate instruments exist for measuring the cognitive capacities of these severely demented individuals. OBJECTIVES: To evaluate the reliability and validity of the Severe Cognitive Impairment Profile (SCIP), a measure of neuropsychological functioning in severely demented patients, and compare it with other available instruments. DESIGN AND METHODS: We administered the Mattis Dementia Rating Scale (DRS), Mini-Mental State Examination (MMSE), SCIP, and Severe Impairment Battery (SIB) to 41 severely demented patients with AD participating in an AD research center. We used (1) Spearman rank correlation coefficients to assess interrater and test-retest reliability and construct validity of the SCIP; (2) one-way analysis of variance with post hoc comparisons to examine performance on the SCIP and the SIB at different levels of dementia severity; and (3) descriptive statistics to establish the sensitivity of the SCIP to cognitive functioning in a subgroup of very severely demented patients. RESULTS: Interrater and test-retest reliability correlation coefficients were highly significant for total SCIP score (r=0.99 and r=0.96, respectively) as well as for all SCIP subscales. High correlations were also found between SCIP scores and two widely used tests of global cognitive functioning, the DRS (r=0.91) and the MMSE (r=0.84), suggesting good construct validity. The SCIP was able to significantly differentiate between four groups of severely impaired patients divided by level of dementia severity, while the SIB was unable to differentiate between the less severely demented groups. A subgroup of 16 very severely demented patients (DRS score, <50 points) obtained an average of 45% of total possible points on the SCIP, compared with an average of 1% and 21% of total possible points on the MMSE and DRS, respectively. After approximately 1 year of decline, 12 severely demented patients with AD were able to correctly answer an average of more than 58% of the items on the SCIP, compared with only 30% on the DRS and 20% on the MMSE. CONCLUSIONS: The SCIP is a reliable, valid measure of neuropsychological functioning in severely demented patients with AD with the ability to avoid both floor and ceiling effects and to evaluate a wider range of cognitive abilities than other tests used with severely impaired individuals.

Improving the diagnostic accuracy of the Mini-Mental State Examination.

INTRODUCTION: We determined the diagnostic accuracy of the Mini-Mental State Examination (MMSE) for dementia of the Alzheimer type (DAT) in an outpatient geriatric referral center in Switzerland. MATERIAL & METHODS: DAT patients and elderly controls were assigned to two groups: a validation sample (70 DAT patients; 50 controls) and a cross-validation sample (133 DAT patients; 43 controls). A Receiver Operating Characteristic curve was generated to derive the optimal MMSE cut-off score in the validation sample. RESULTS: The optimal MMSE cut-off was < 26/30 (sensitivity of 74%, specificity of 100%). Adjustments for age and education were necessary. The cross-validation confirmed these findings. CONCLUSION: iN A clinical setting the MMSE cut-off should be increased to < 26/30. A thorough neurobehavioral assessment is still necessary for a complete evaluation.

Functional hemispheric asymmetry and belief in ESP: towards a "neuropsychology of belief".

30 right-handed subjects were given a lateralized tachistoscopic lexical-decision task. Subjects' belief in extrasensory perception (ESP) was assessed with a single six-point scale; 16 subjects were designated as believers in ESP and 14 subjects as nonbelievers. Believers in ESP did not exhibit a hemispheric asymmetry for the task while nonbelievers exhibited the expected right visual-field/left-hemisphere dominance documented in the literature. Believers' lack of asymmetry was not caused by an impaired left-hemisphere performance but rather by a significantly enhanced lexical-decision accuracy in the left visual field/right hemisphere compared to nonbelievers. These results are compatible with previous studies indicating a correlation between belief in ESP and a bias for right-hemisphere processing. Moreover, the results are relevant for a discussion of an association between paranormal beliefs and schizotypy: highly schizotypal individuals are not only particularly prone to believe in ESP but are also known to show an attenuation of hemispheric asymmetries in lateralized verbal tasks due to an enhanced contribution of the right hemisphere. We suggest that the neurological basis of delusion-like beliefs may involve a release of right-hemisphere function from left-hemisphere control and sketch the focus of research for a future "neuropsychology of belief."

A new method for documenting lens opacities.

We tested an anterior segment camera and digital analyzer on 32 eyes of 22 patients to determine whether its measurement of lens opacities correlated with measurements obtained by a standardized clinical grading system. The lenses were graded clinically for nuclear opacity, nuclear color, cortical opacity, and posterior subcapsular opacity. The lenses were then photographed and analyzed with this new device, and the results were compared. The camera system showed good reproducibility. Its results correlated well with the clinical gradings for nuclear capacity (P = .001) and cortical opacity (P = .001) but less well with posterior subcapsular opacity (P = .3), although there were only seven eyes with posterior subcapsular opacities. This camera system could help document and follow up lens opacity with more accuracy and reproducibility than has been previously possible.