The protocol for an observational Australian cohort study of CADASIL: The AusCADASIL study.

Introduction: Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare genetic condition with a broad phenotypic presentation. This study aims to establish the first Australian cohort of individuals affected by CADASIL (AusCADASIL) and examine its clinical features and longitudinal course, and to investigate neuroimaging and blood biomarkers to assist in early diagnosis and identify disease progression. Methods: Participants will be recruited from six study centres across Australia for an observational study of CADASIL. We aim to recruit 150 participants with diagnosed CADASIL, family history of CADASIL or suspected CADASIL symptoms, and 150 cognitively normal NOTCH3 negative individuals as controls. Participants will complete: 1) online questionnaires on medical and family history, mental health, and wellbeing; 2) neuropsychological evaluation; 3) neurological examination and brain MRI; 4) ocular examination and 5) blood sample donation. Participants will have annual follow-up for 4 years to assess their progression and will be asked to invite a study partner to corroborate their self-reported cognitive and functional abilities.Primary outcomes include cognitive function and neuroimaging abnormalities. Secondary outcomes include investigation of genetics and blood and ocular biomarkers. Data from the cohort will contribute to an international consortium, and cohort participants will be invited to access future treatment/health intervention trials. Discussion: AusCADASIL will be the first study of an Australian cohort of individuals with CADASIL. The study will identify common pathogenic variants in this cohort, and characterise the pattern of clinical presentation and longitudinal progression, including imaging features, blood and ocular biomarkers and cognitive profile.

Hear Me Out: A Meta-Analysis of Third-Party Disability Due to Presbycusis.

OBJECTIVES: Hearing-related third-party disability is the transferrable impact of presbycusis on an affected individual's surrounding social network. Previous research suggests that interventions to overcome hearing-related communication challenges benefit both the individual with presbycusis and their communication partner. However, there have been no comparisons of the effects of different interventions on third-party disability. We conducted meta-analyses of hearing aid or communication-based longitudinal interventions to determine if: both kinds of interventions significantly benefit communication partners across three categories of third-party disability (communication, emotional health and lifestyle outcomes), hearing aid and communication interventions differ in the size of treatment effects, and demographic variables moderate intervention efficacy. DESIGN: Four databases were systematically searched for studies published after 1990 that included preintervention and postintervention data for communication partners of individuals receiving a hearing aid or communication-based intervention. Studies were included if participants had presbycusis, were aged 45 or over, with no known physical or mental disorders, and had a willing study partner over 18 years old. Databases were last comprehensively and hand-searched in January 2023. One researcher applied the inclusion and exclusion criteria to select studies and complete data extraction. Depending on study design, risk of bias was assessed using the "Quality Assessment Tool for Before-After (Pre-Post) Studies with No Control Group" or the "Risk of Bias 2." Random effects models were run for effect sizes for both intervention types (together and separately) for each third-party disability category. Meta-regressions were run to inspect the effect of demographic variables on intervention efficacy. RESULTS: Six studies satisfied inclusion criteria and showed that for both hearing and communication interventions, communication partners experienced significant improvements in all three outcomes. Communication interventions showed greater benefits for lifestyle outcomes, but hearing aid and communication interventions did not differ for communication and emotional health outcomes. Meta-regressions revealed previously undetected relationships between demographic variables and intervention efficacy. CONCLUSIONS: The results of this meta-analysis and meta-regressions may have clinical and real-world implications in terms of highlighting the widespread benefits of these interventions, and the need to build in greater consideration of an individual's wider network when designing and implementing interventions. Noted limitations included certain combinations of intervention type and third-party disability category that were underrepresented (in absolute and/or relative terms), a lack of combined intervention (hearing aids and communication training) studies, and variation in the types of questionnaires used between studies. The current study discusses possible ways to unite the current literature for more consistent research practices.

Examining the validity of the Mini-Mental State Examination (MMSE) and its domains using network analysis.

BACKGROUND: The Mini-Mental State Examination (MMSE) is the most widely used standardised screener for impairments across a range of cognitive domains. However, the degree to which its domains (orientation, registration, attention, recall, language, and visuospatial) capture cognitive functioning measured using standardised neuropsychological tests is unclear. METHOD: A longitudinal research design with four biannual assessments over a 6-year period was used with an initial sample of 1037 older adults (aged above 70 years). Participants completed MMSE and neuropsychological tests at each assessment. Network analysis was utilised to investigate unique associations among the MMSE and its domains and neuropsychological test performance at each time point. RESULTS: The total MMSE and two of its domains, language and recall, were associated with neuropsychological memory performance. The MMSE orientation, registration and visuospatial domains did not have any unique associations with neuropsychological performance. No stable internal interconnections between MMSE domains were found over time. The association of total MMSE as well as its recall domain with neuropsychological memory performance remained very similar over the 6-year period. CONCLUSIONS: The present study adds evidence to the validity of the MMSE and supports the clinical usage of the MMSE, whereby the total score is used for screening patients with or without cognitive impairments, with repeated administration to monitor cognitive changes over time, to inform intervention. However, the tool is not able to diagnose the cases for changes in specific cognitive domains and as such, should not replace a complete neuropsychological assessment.

Enhancing precision of the Telephone Interview for Cognitive Status-Modified (TICS-M) using the Rasch model.

The Telephone Interview for Cognitive Status-modified (TICS-M) is a well-established and widely used screening instrument for dementia and assessment of global cognitive function in older people. This study aimed to evaluate the psychometric properties of the TICS-M and to enhance the accuracy of the instrument using Rasch methodology. Partial Credit Rasch model was applied to the TICS-M scores. The sample selected for Rasch analysis consisted of 432 participants aged 70-90 years (M = 78.85, SD = 4.73) including 195 males (237 females), and 132 (30.56%) of whom were diagnosed with dementia after the baseline assessment. Initial analysis indicated good reliability of the TICS-M assessment scores, but there were three misfitting items and local dependency issues. Combining locally dependent and misfitting items into super-items achieved the best Rasch model fit for the TICS-M. This modification improved reliability of the assessment scores and resulted in no misfitting items, no local dependency, strict unidimensionality, and invariance across individual factors such as participants age, sex, diagnosis, and in-person neuropsychological assessment scores. Satisfying Rasch model expectations allowed for creation of a transformation table to convert raw TICS-M scores into interval-level data, which improves precision of the instrument. In summary, the TICS-M assessment scores demonstrated excellent reliability as reflected by Person Separation Index (PSI = 0.86) and met expectations of the unidimensional Rasch model after minor adjustments. The ordinal-to-interval transformation table can be used to increase accuracy of the TICS-M without altering its current format. These findings contribute to more accurate assessments of cognitive decline in older people and screening for conditions such as dementia. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Using network analysis to validate domains of the modified telephone interview for cognitive status.

BACKGROUND: The modified Telephone Interview for Cognitive Status (TICS-M) is a widely used tool for assessing global cognitive functions and screening for cognitive impairments. The tool was conceptualised to capture various cognitive domains, but the validity of such domains has not been investigated against comprehensive neuropsychological assessments tools. Therefore, this study aimed to explore the associations between the TICS-M domains and neuropsychological domains to evaluate the validity of the TICS-M domains using network analysis. MATERIALS AND METHODS: A longitudinal research design was used with a large sample of older adults (aged above 70 years; n = 1037 at the baseline assessment) who completed the TICS-M and comprehensive neuropsychological assessments biennially. We applied network analysis to identify unique links between the TICS-M domains and neuropsychological test scores. RESULTS: At baseline, there were weak internal links between the TICS-M domains. The TICS-M memory and language domains were significantly related to their corresponding neuropsychological domains. The TICS-M attention domain had significant associations with executive function and visuospatial abilities. The TICS-M orientation domain was not significantly associated with any of the five neuropsychological domains. Despite an attrition of almost 50% at wave four, weak internal links between the TICS-M domains and most associations between TICS-M and neuropsychological domains that were found initially, remained stable at least over two waves within the 6-year period. CONCLUSIONS: This study supports the overall structural validity of the TICS-M screener in assessing enduring global cognitive function. However, separate TICS-M cognitive domains should not be considered equivalent to the analogous neuropsychological domains.

Establishing conversion of the 16-item Informant Questionnaire on Cognitive Decline in the Elderly scores into interval-level data across multiple samples using Rasch methodology.

BACKGROUND: The 16-item Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE-16) is a well-validated and widely-used measure of cognitive changes (CCs) among older adults. This study aimed to use Rasch methodology to establish psychometric properties of the IQCODE-16 and validate the existing ordinal-to-interval transformation algorithms across multiple large samples. METHODS: A Partial Credit Rasch model was employed to examine psychometric properties of the IQCODE-16 using data (n = 918) from two longitudinal studies of participants aged 57-99 years: the Older Australian Twins Study (n = 450) and the Canberra Longitudinal Study (n = 468), and reusing the Sydney Memory and Ageing Study (MAS) sample (n = 400). RESULTS: Initial analyses indicated good reliability for the IQCODE-16 (Person Separation Index range: 0.82-0.90). However, local dependency was identified between items, with several items showing misfit to the model. Replicating the existing Rasch solution could not reproduce the best Rasch model fit for all samples. Combining locally dependent items into three testlets resolved all misfit and local dependency issues and resulted in the best Rasch model fit for all samples with evidence of unidimensionality, strong reliability, and invariance across person factors. Accordingly, new ordinal-to-interval transformation algorithms were produced to convert the IQCODE-16 ordinal scores into interval data to improve the accuracy of its scores. CONCLUSIONS: The findings of this study support the reliability and validity of the IQCODE-16 in measuring CCs among older adults. New ordinal-to-interval conversion tables generated using samples from multiple independent datasets are more generalizable and can be used to enhance the precision of the IQCODE-16 without changing its original format. An easy-to-use converter has been made available for clinical and research use.

The Impact of Right Temporal Lobe Epilepsy On Nonverbal Memory: Meta-regression of Stimulus- and Task-related Moderators.

Nonverbal memory tests have great potential value for detecting the impact of lateralized pathology and predicting the risk of memory loss following right temporal lobe resection (TLR) for temporal lobe epilepsy (TLE) patients, but this potential has not been realized. Previous reviews suggest that stimulus type moderates the capacity of nonverbal memory tests to detect right-lateralized pathology (i.e., faces > designs), but the roles of other task-related factors have not been systematically explored. We address these limitations using mixed model meta-regression (k = 158) of right-lateralization effects (right worse than left TLE) testing the moderating effects of: 1) stimulus type (designs, faces, spatial), 2) learning format (single trial, repeated trials), 3) testing delay (immediate or long delay), and 4) testing format (recall, recognition) for three patient scenarios: 1) presurgical, 2) postsurgical, and 3) postsurgical change. For presurgical patients the size of the right-lateralization effect was significantly moderated by stimulus type (faces > designs), testing format (recall > recognition) and its interaction with the learning format (repeated trials more affected by format effect than single trials) of the nonverbal memory tests. For postsurgical patients and presurgical-postsurgical change, test format moderated the size of the right-lateralization effect (recognition > recall) and this explained and overshadowed effects of stimulus type (i.e., faces > designs). This comprehensive review reveals the value of recognition testing in gauging the risk of nonverbal memory decline.

Validation and Normative Data for the Modified Telephone Interview for Cognitive Status: The Sydney Memory and Ageing Study.

OBJECTIVES: Telephone-based cognitive screens, such as the Telephone Interview for Cognitive Status (TICS), can potentially reduce the barriers and costs of assessing older adults. However, validation of clinically relevant psychometric properties is lacking in a large and comprehensively assessed sample of older adults. Furthermore, published normative data may lack sensitivity as they have not used regression-based demographic corrections or accounted for cases with subsequent dementia. We address these gaps using the modified TICS (TICS-M; a modified, 13-item, 39-point version) and provide an online norms calculator for clinicians and researchers. DESIGN: Prospective longitudinal study. SETTING: Sydney, Australia. PARTICIPANTS: A total of 617 community-living older adults, aged from 71 to 91 years. MEASUREMENTS: The measures used included the TICS-M, the Mini-Mental State Examination (MMSE), Addenbrooke's Cognitive Examination-Revised (ACE-R), and a comprehensive neuropsychological test battery. Descriptive statistics, correlations, area under the curve, and regression analyses were used to determine the validity and normative properties of the TICS-M. RESULTS: TICS-M total scores (mean = 24.20; SD = 3.76) correlated well with the MMSE (0.70) and ACE-R (0.80) and moderately with neuropsychological tests tested noncontemporaneously. A cutoff score of 21 or lower reliably distinguished between those with and without incident dementia after 1 year (sensitivity = 77%; specificity = 88%) but was less reliable at distinguishing mild cognitive impairment from normal cognition. TICS-M scores decreased with age and increased with higher education levels. The robust normative sample, which excluded incident dementia cases, scored higher on the TICS-M and with less variability than the whole sample. An online calculator is provided to compute regression-based norms and reliable change statistics. CONCLUSIONS: In a large sample of community-dwelling older adults, the TICS-M performed well in terms of construct validity against typical screening tools and neuropsychological measures and diagnostic validity for incident dementia. The comprehensive, regression-based, and robust normative data provided will help improve the sensitivity, accessibility, and cost-effectiveness of cognitive testing with older adults. J Am Geriatr Soc 67:2108-2115, 2019.

A Comprehensive Review of the Quality and Feasibility of Dementia Assessment Measures: The Dementia Outcomes Measurement Suite.

The diagnosis of dementia and the management of its associated symptoms are aided by high-quality assessment tools. However, there is disagreement on the optimal tools among abundant alternatives and lack of consistent quality standards across the different domains of dementia-related change (ie, cognition, severity, function, behavioral and psychological symptoms, delirium, quality of life). Standardization is difficult because the relevance of a measurement tool for health professionals may depend on the clinical setting and on the dementia type and severity. To address this need, we conducted a comprehensive and clinically relevant evidence-based review of dementia-related tools and present a set of recommended tools, the Dementia Outcomes Measurement Suite. The review revealed that considerable development has occurred in terms of assessment of persons with mild cognitive impairment, executive dysfunction, cognitively mediated functional change, and apathy. More research is needed to develop and validate tools to assess health-related quality of life and specific symptoms of dementia including anxiety, wandering, and repetitive vocalizations. This extensive overview of the quality of different measures may serve as a guide for health professionals clinically and for researchers developing new or improved dementia assessment tools.

An evaluation of a paediatric radiation oncology teaching programme incorporating a SCORPIO teaching model.

INTRODUCTION: Many radiation oncology registrars have no exposure to paediatrics during their training. To address this, the Paediatric Special Interest Group of the Royal Australian and New Zealand College of Radiologists has convened a biennial teaching course since 1997. The 2009 course incorporated the use of a Structured, Clinical, Objective-Referenced, Problem-orientated, Integrated and Organized (SCORPIO) teaching model for small group tutorials. This study evaluates whether the paediatric radiation oncology curriculum can be adapted to the SCORPIO teaching model and to evaluate the revised course from the registrars' perspective. METHODS: Teaching and learning resources included a pre-course reading list, a lecture series programme and a SCORPIO workshop. Three evaluation instruments were developed: an overall Course Evaluation Survey for all participants, a SCORPIO Workshop Survey for registrars and a Teacher's SCORPIO Workshop Survey. RESULTS: Forty-five radiation oncology registrars, 14 radiation therapists and five paediatric oncology registrars attended. Seventy-three per cent (47/64) of all participants completed the Course Evaluation Survey and 95% (38/40) of registrars completed the SCORPIO Workshop Survey. All teachers completed the Teacher's SCORPIO Survey (10/10). The overall educational experience was rated as good or excellent by 93% (43/47) of respondents. Ratings of satisfaction with lecture sessions were predominantly good or excellent. Registrars gave the SCORPIO workshop high ratings on each of 10 aspects of quality, with 82% allocating an excellent rating overall for the SCORPIO activity. Both registrars and teachers recommended more time for the SCORPIO stations. CONCLUSIONS: The 2009 course met the educational needs of the radiation oncology registrars and the SCORPIO workshop was a highly valued educational component.

Discriminating audiovisual speed: optimal integration of speed defaults to probability summation when component reliabilities diverge.

We investigated audiovisual speed perception to test the maximum-likelihood-estimation (MLE) model of multisensory integration. According to MLE, audiovisual speed perception will be based on a weighted average of visual and auditory speed estimates, with each component weighted by its inverse variance, a statistically optimal combination that produces a fused estimate with minimised variance and thereby affords maximal discrimination. We use virtual auditory space to create ecologically valid auditory motion, together with visual apparent motion around an array of 63 LEDs. To degrade the usual dominance of vision over audition, we added positional jitter to the motion sequences, and also measured peripheral trajectories. Both factors degraded visual speed discrimination, while auditory speed perception was unaffected by trajectory location. In the bimodal conditions, a speed conflict was introduced (48 degrees versus 60 degrees s(-1)) and two measures were taken: perceived audiovisual speed, and the precision (variability) of audiovisual speed discrimination. These measures showed only a weak tendency to follow MLE predictions. However, splitting the data into two groups based on whether the unimodal component weights were similar or disparate revealed interesting findings: similarly weighted components were integrated in a manner closely matching MLE predictions, while dissimilarity weighted components (greater than 3 : 1 difference) were integrated according to probability-summation predictions. These results suggest that different multisensory integration strategies may be implemented depending on relative component reliabilities, with MLE integration vetoed when component weights are highly disparate.