Demographic Corrections Research Articles

The brief repeatable battery of neuropsychological tests (BRB-N) version a: update of Italian normative data from the Italian Neuroimaging Network Initiative (INNI).

Cognitive impairment is a common clinical manifestation in people with multiple sclerosis (PwMS) and significantly impacts patients' quality life. Cognitive assessment is crucial for treatment decisions and understanding disease progression. Several neuropsychological batteries are used in MS, including the Brief Repeatable Battery of Neuropsychological Tests (BRB-N), Minimal Assessment of Cognitive Function in MS (MACFIMS), and Brief International Cognitive Assessment for MS (BICAMS). However, normative data for BRB-N version A in Italy are outdated. To revise and update normative data for the BRB-N version A in the Italian population. From the Italian Neuroimaging Network Initiative (INNI) database, we retrospectively selected 342 healthy subjects (172 males and 170 females) evaluated at four Italian INNI-affiliated sites (Milan, Siena, Rome, Naples). The subjects underwent neuropsychological assessment using the BRB-N version A. Regression-based method relying on scaled scores was used to calculate demographic correction procedures. No significant differences were found in age, education, and sex distribution among the four sites (p ≥ 0.055). Regression analysis provided normative data to calculate demographically adjusted z-scores for each BRB-N version A test. This study provides updated normative data for the BRB-N version A in the Italian population. The use of a regression-based method and scaled scores ensures consistency with other neuropsychological batteries commonly used in Italy, namely MACFIMS and BICAMS. The availability of updated normative data increases reliability of neuropsychological assessment of cognitive function in Italian PwMS and other clinical populations using BRB-N version A, providing valuable insights for both clinical and research applications.

4 Norm Selection and Application in Socially Responsible Neuropsychological Practice

Objective:In the wake of the national controversy over demographically corrected normative comparisons used in neuropsychological assessment, the field finds itself in need of adopting better practices and providing stronger instruction in norm selection and application when assessing underrepresented populations. Neuropsychologists must employ critical thinking within their clinical decision-making that takes into account patient demographics, analysis of the measures themselves, normative samples, and statistical adjustments employed in normative studies. Not doing so may result in erroneous diagnostic conclusions, exposing underserved patient populations to poor or harmful clinical care and even misdiagnosis. The following case series presents several demographic considerations illustrating how selection and application of different (at times, ill-fitting) normative reference groups can affect treatment outcomes in the Latinx community. We examined the performance of various published norms when applied to monolingual and bilingual Spanish speakers.Participants and Methods:This study samples three demographically diverse (i.e., education, age, and sex) clinical cases and applies regression-based and stratified norms to raw scores to demonstrate the possible differential outcomes when using different reference groups. One example is Ms. Congeniality, a 69-year-old, Spanish and English bilingual woman with 12 years of education who presented for a third revaluation at our clinic due to progressive memory loss. Her prior Spanish language profiles demonstrated impaired confrontation naming and steadily decreasing letter fluency over the past 10 years.Results:Her performance on semantic fluency (i.e., animal naming) showed relative stability based on her raw scores (10 in 2012, 11 in 2016, and 12 in 2022). Using the Neuropsi A&M norms, which stratify performance across nine age ranges between ages 6-85 and three education ranges between 0-10+ years, her performance over the past 10 years ranged between the less than 1st percentile to the 9th percentile (1%, 1%, and 9%, respectively). However, using the NP-NUMBRS norms, which use regression-based continuous age (19-60) and education (0-20) predictors of test performance, her scores corresponded to steadily improved performance (8%, 28%, and 86%). Thus, this qualitative comparison demonstrates a likely overcorrection for individuals of advanced age when using norms based on samples that are a poor fit because they lack representation of older adults, as in NP-NUMBRS, and a possible undercorrection when using norms with overly broad education stratifications (e.g., 10-22 years, as in Neuropsi).Conclusions:Application of ill-fitting normative standards can have far-reaching implications for interpretation of neuropsychological test results. Moreover, this case series exemplifies the need for higher-order instruction in norm selection, specifically for underserved communities who run the risk of being misdiagnosed. Through case examples, this study underscores the importance of understanding the unique effects of different demographic corrections in the context of limited available normative reference groups. This abstract is the first illustration in a series of papers aimed at facilitating the decision-making process within the framework of socially responsible neuropsychological practice.

24 Demographic Adjustment Is Not Demographic Correction: A Simulation Study

Objective:Prior studies have presented demographic adjustment as beneficial because it helps equalize, across demographic groups, the percentage of participants (recruited from the general population without prior diagnosis) who fell beneath the test impairment cutoff (e.g., Smith, et al., 2008). This methodology ignores the possibility that group differences in those falling beneath an impairment cutoff could reflect cognitive impairment prevalence differences between demographic groups in the undiagnosed general population. Demographic group differences in cognitive test scores reflect a mixture of two categories of influences: measurement bias (item/test/examiner bias, language/cultural bias, stereotype threat, etc.) and factors which differentially increase the number of low scores in one group by increasing relative risk (RR) for cognitive impairment (biological aging processes, cognitive reserve, social determinants of health [SDoH], etc.). The current simulation study examined how the effect of demographic adjustment on the diagnostic accuracy of a hypothetical test (operationalized as the area under the curve [AUC] in an ROC analysis) varied as the mixture of influences which caused demographic differences in scores were varied.Participants and Methods:215,040 samples were randomly generated. Each sample consisted of two demographic groups, with Group 0 always representing the lower scoring group. Across samples, Group 1's baseline risk of impairment and Group 0's relative risk were varied, and these determined the prevalence of cognitive impairment in the groups. Three facets of measurement bias were varied in the simulation: how much lower Group 0's average score was than Group 1's, the degree of non-homogeneity of variance between groups, and how much less reliable the measure was for Group 0. Additional parameters were included and varied to ensure the robustness of findings across a variety of situations. Samples reflected all possible combinations of all varied parameters. For each sample, a baseline AUC was calculated when impairment was regressed on the unadjusted test score. Then, test scores were adjusted for demographic group and difference in adjusted and unadjusted AUC was calculated. This adjusted/unadjusted AUC difference was then regressed on the simulation parameters to quantify their relative influence.Results:The more Group 0's average score was reduced by measurement bias, the more improvement in AUC was seen after adjustment (ß = 1.76). Trivial but significant main effects of variance non-homogeneity (ß = .09), increased relative risk (ß = -.08), and reduced reliability (ß = .02) were also found, but more importantly, each of these predictors significantly interacted with Group 0 mean score reduction, such that higher relative risks (ß = -1.22), lower reliability (ß = .36), and higher variance (ß = -.15) in Group 0 compared to Group 1 each reduced the association between Group 0 mean score reduction and improvement in AUC.Conclusions:Demographic adjustment only improves AUC when the mean reduction in scores due to measurement bias is sufficiently high while risk for impairment, test reliability and test score variances are sufficiently equivalent among the demographic groups. When this is not the case, demographic adjustment can be counter-productive, reducing the AUC of the test. We conclude by proposing a novel method for adjusting test scores.

The relationship between learning slopes and Alzheimer’s Disease biomarkers in cognitively unimpaired participants with and without subjective memory concerns

ABSTRACT Objective: Learning slopes represent serial acquisition of information during list-learning tasks. Although several calculations for learning slopes exist, the Learning Ratio (LR) has recently demonstrated the highest sensitivity toward changes in cognition and Alzheimer’s disease (AD) biomarkers. However, investigation of learning slopes in cognitively unimpaired individuals with subjective memory concerns (SMC) has been limited. The current study examines the association of learning slopes to SMC, and the role of SMC in the relationship between learning slopes and AD biomarkers in cognitively unimpaired individuals. Method: Data from 950 cognitively unimpaired participants from the Alzheimer’s Disease Neuroimaging Initiative (aged 55 to 89) were used to calculate learning slope metrics. Learning slopes among those with and without SMC were compared with demographic correction, and the relationships of learning slopes with AD biomarkers of bilateral hippocampal volume and β-amyloid pathology were determined. Results: Learning slopes were consistently predictive of hippocampal atrophy and β-amyloid deposition. Results were heightened for LR relative to the other learning slopes. Additionally, interaction analyses revealed different associations between learning slopes and hippocampal volume as a function of SMC status. Conclusions: Learning slopes appear to be sensitive to SMC and AD biomarkers, with SMC status influencing the relationship in cognitively unimpaired participants. These findings advance our knowledge of SMC, and suggest that LR – in particular – can be an important tool for the detection of AD pathology in both SMC and in AD clinical trials.

Cleveland Clinic Cognitive Battery (C3B): Normative, Reliability, and Validation Studies of a Self-Administered Computerized Tool for Screening Cognitive Dysfunction in Primary Care.

The self-administered iPad-based Cleveland Clinic Cognitive Battery (C3B) was designed specifically for the efficient screening of cognitive functioning of older adults in a primary care setting. 1) Generate regression-based norms from healthy participants to enable demographic corrections to facilitate clinical interpretation; 2) estimate test-retest reliability and practice effects; 3) examine ability to discriminate mild cognitive impairment (MCI) from healthy aging; 4) d etermine validity of screening in a distracting clinical environment; and 5) determine completion rates and patient satisfaction in a primary care setting. Study 1 (S1) recruited a stratified sample of 428 healthy adults, ages 18-89, to generate regression-based equations. S2 assessed 2-week test-retest reliability and practice effects in 30 healthy elders. S3 recruited 30 MCI patients and 30 demographically-matched healthy controls. In S4, 30 healthy elders self-administered the C3B in a distracting environment and in a quiet private room in counterbalanced order. In a demonstration project, 470 consecutive primary care patients were administered the C3B as part of routine clinical care (S5). C3B performance was primarily influenced by age, education, and race (S1), had acceptably high test-retest reliability and minimal practice effects (S2), discriminated MCI from healthy controls (S3), was not negatively impacted by a distracting clinical environment (S4), had high completion rates (>92%) and positive ratings from primary care patients (S5). The C3B is a computerized cognitive screening tool that is reliable, validated, self-administered, and is conducive to integration into a busy primary care clinical workflow for detecting MCI, early Alzheimer's disease, and other related dementias.

A-145 Much Ado About Norming: Ethnic Differences Across Three Normative Systems for COWAT/FAS Performance

Abstract Objective: Demographic correction of cognitive data is being increasingly scrutinized. We compared phonemic fluency for African Americans and Caucasians using three normative systems. Methods: Controlled Oral Word Association Test (COWAT)/FAS raw scores for 321 African Americans (56.4% female, mean age 50 years, mean education 13 years) and a matched sample of 330 Caucasians (53.6% female, mean age 47, mean education 13.5 years) were converted to T-scores using three normative systems (Heaton et al., 2004; Mitrushina et al., 1999; Schretlen et al., 2010). ANOVA was used to compare differences for the overall sample as well as for education level (15 years) and age range (18-35, 36-50, 51-65, and >65 years old). Results: Normative outcomes were significantly different between African American and Caucasian participants [Heaton (F (1,516) = 6.77, p=.01; Mitrushina F (1,509) = 10.32, p=.001; Shretlen F (1,516) = 14.15, p=.001]. Heaton norms were significantly different for ethnicity for all education levels except >15 years of education. Mitrushina meta-norms and CNNS (Schretlen et al., 2010) were significantly different for ethnicity on FAS scores only for >15 years of education. Heaton norms were significantly different for ethnicity for the ranges of 18-35 years old and 51-65 years old. Mitrushina meta-norms and CNNS were significantly different for ethnicity only for the 36-50 years range. None of the norming systems were significantly different for >65 years. Conclusions: The interpretation of FAS performance for African Americans and Caucasians differed by the normative system utilized with different effects for age and education noted between normative approaches.

The 5-factor modified frailty index (mFI-5) is predictive of 30-day postoperative complications and readmission in patients with adult spinal deformity (ASD)

BackgroundThere is limited research regarding the association between the mFI-5 and postoperative complications among adult spinal deformity (ASD) patients. MethodsUsing the National Surgical Quality Improvement Project (NSQIP) database, patients with Current Procedural Terminology (CPT) codes for > 7-level fusion or < 7-level fusion with International Classification of Diseases, Ninth Revision (ICD-9) codes for ASD were identified between 2008 and 2016. Univariate analyses with post-hoc Bonferroni correction for demographics and preoperative factors were performed. Logistic regression assessed associations between mFI-5 scores and 30-day post-operative outcomes. Results2,120 patients met criteria. Patients with an mFI-5 score of 4 or 5 were excluded, given there were<20 patients with those scores. Patients with mFI-5 scores of 1 and 2 had increased 30-day rates of pneumonia (3.5 % and 4.3 % vs 1.6 %), unplanned postoperative ventilation for > 48 h (3.1 % and 4.3 % vs 0.9 %), and UTIs (4.4 % and 7.4 % vs 2.0 %) than patients with a score of 0 (all, p < 0.05). Logistic regression revealed that compared to an mFI-5 of 0, a score of 1 was an independent predictor of 30-day reoperations (OR = 1.4; 95 % CI 1.1–18). A score of 2 was an independent predictor of overall (OR = 2.4; 95 % CI 1.4–4.1) and related (OR = 2.2; 95 % CI 1.2–4.1) 30-day readmissions. A score of 3 was not predictive of any adverse outcome. ConclusionThe mFI-5 score predicted complications and postoperative events in the ASD population. The mFI-5 may effectively predict 30-day readmissions. Further research is needed to identify the benefits and predictive value of mFI-5 as a risk assessment tool.

Demographic correction—A tool for inference from individuals to populations

Abstract Estimation of responses of organisms to their environment using experimental manipulations, and comparison of such responses across sets of species, is one of the primary tools in ecology research. The most common approach is to compare the response of a single life stage of species to an environmental factor and use this information to draw conclusions about population dynamics of these species. Such approach ignores the fact that interspecific fitness differences measured at a single life stage are not directly comparable and cannot be extrapolated to lifetime fitness of individuals and thus species’ population dynamics. Comparison of one life stage only while omitting demographic information can strongly bias conclusions, both in experimental studies with a few species and in large comparative studies. We illustrate the effect of this omission using both an exaggerated fictitious example and biological data on congeneric species differing in their demography. We are showing, taking simple assumptions, that different demography can completely revert conclusions reached by a comparison based on an experiment focusing on a single life stage. We show that a ‘demographic correction’, namely translating observed effects into differences in outcomes of demographic models, is a solution to this problem. It requires turning the detected effects from the experiment into changes of transition probabilities of projection matrix models. Although such solution is limited by the low number of species with demographic data available, we believe that existing data (and data likely to be collected in the near future) permit at least approximate handling of this problem. Read the free Plain Language Summary for this article on the Journal blog.

Global seroprevalence of SARS-CoV-2 antibodies: A systematic review and meta-analysis.

Many studies report the seroprevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies. We aimed to synthesize seroprevalence data to better estimate the level and distribution of SARS-CoV-2 infection, identify high-risk groups, and inform public health decision making. In this systematic review and meta-analysis, we searched publication databases, preprint servers, and grey literature sources for seroepidemiological study reports, from January 1, 2020 to December 31, 2020. We included studies that reported a sample size, study date, location, and seroprevalence estimate. We corrected estimates for imperfect test accuracy with Bayesian measurement error models, conducted meta-analysis to identify demographic differences in the prevalence of SARS-CoV-2 antibodies, and meta-regression to identify study-level factors associated with seroprevalence. We compared region-specific seroprevalence data to confirmed cumulative incidence. PROSPERO: CRD42020183634. We identified 968 seroprevalence studies including 9.3 million participants in 74 countries. There were 472 studies (49%) at low or moderate risk of bias. Seroprevalence was low in the general population (median 4.5%, IQR 2.4-8.4%); however, it varied widely in specific populations from low (0.6% perinatal) to high (59% persons in assisted living and long-term care facilities). Median seroprevalence also varied by Global Burden of Disease region, from 0.6% in Southeast Asia, East Asia and Oceania to 19.5% in Sub-Saharan Africa (p<0.001). National studies had lower seroprevalence estimates than regional and local studies (p<0.001). Compared to Caucasian persons, Black persons (prevalence ratio [RR] 3.37, 95% CI 2.64-4.29), Asian persons (RR 2.47, 95% CI 1.96-3.11), Indigenous persons (RR 5.47, 95% CI 1.01-32.6), and multi-racial persons (RR 1.89, 95% CI 1.60-2.24) were more likely to be seropositive. Seroprevalence was higher among people ages 18-64 compared to 65 and over (RR 1.27, 95% CI 1.11-1.45). Health care workers in contact with infected persons had a 2.10 times (95% CI 1.28-3.44) higher risk compared to health care workers without known contact. There was no difference in seroprevalence between sex groups. Seroprevalence estimates from national studies were a median 18.1 times (IQR 5.9-38.7) higher than the corresponding SARS-CoV-2 cumulative incidence, but there was large variation between Global Burden of Disease regions from 6.7 in South Asia to 602.5 in Sub-Saharan Africa. Notable methodological limitations of serosurveys included absent reporting of test information, no statistical correction for demographics or test sensitivity and specificity, use of non-probability sampling and use of non-representative sample frames. Most of the population remains susceptible to SARS-CoV-2 infection. Public health measures must be improved to protect disproportionately affected groups, including racial and ethnic minorities, until vaccine-derived herd immunity is achieved. Improvements in serosurvey design and reporting are needed for ongoing monitoring of infection prevalence and the pandemic response.

Guided growth in the correction of knee deformity in patients with congenital insensitivity to pain

BackgroundOrthopedic manifestations of congenital insensitivity to pain (CIP) can be devastating if left untreated. Knee deformities are common in patients with CIP and might lead to joint destruction and loss of walking ability. The purpose of the present study was to report the results and complications of guided growth procedures around the knee in patients with CIP.MethodsIn a retrospective review, all patients with CIP who underwent guided growth procedures around the knee from 2009 to 2017 at a tertiary referral hospital were evaluated. Patients with secondary insensitivity to pain (e.g., syringomyelia), as well as patients with incomplete records, were excluded. Demographic data, clinical findings, correction rate, and complications were recorded.ResultsTen knees in six patients fulfilled the inclusion criteria. The median age was 10 (range, 5–12), with a mean follow-up of 31 months (range, 16–56). Distal femoral tension-band hemiepiphysiodesis was the most common procedure, followed by proximal tibial hemiepiphysiodesis. The mean correction rate was 0.28°/month for femoral deformity. Staples were removed prematurely in one patient due to extrusion. No cases of infection or skin dehiscence were observed. None of the patients needed a reconstructive knee procedure during the study period.ConclusionsThe findings of this study suggest that guided growth procedures might have a role in the correction of knee deformities in patients with CIP. However, the correction rate is lower than that of typically developing children, patients should be closely followed to prevent complications, and stringent patient selection criteria should be followed to ensure success.

Influence of age and education on a performance-based measure of everyday functioning

Sociodemographic variables, such as age and education, influence the determination of impairment on neuropsychological tests, but their influence on impairment determinations for tests of everyday functioning is less well defined. Existing studies suggest that older age and lower education levels are associated with worse everyday functioning when assessed by self- or collateral-report. This relationship, however, has not been thoroughly investigated with performance-based methods of everyday functioning. This study aimed to determine the influence of sociodemographic factors on the Functional Impact Assessment (FIA), a performance-based measure of everyday functioning that includes measures of both accuracy and speed. Seventy-three healthy individuals, ages 42 − 88 years, completed the FIA and an additional everyday functioning self-report questionnaire (Functional Activities Questionnaire). Using a multiple regression statistical approach, age and education predicted overall FIA accuracy, while age alone predicted FIA speed. Sociodemographic variables continued to predict FIA performance when controlling for overall cognitive functioning. Sociodemographic variables were unrelated to FAQ scores. These findings indicate that age and education are associated with scores on a performance-based test of everyday functioning. Demographic corrections may improve accuracy in determining functional impairment, but more research is needed given the complex relationships among demographic factors, healthy aging, and dementia risk.

How to Correct for Computer Experience in Online Cognitive Testing?

Objective: Since computerized cognitive test performance may be influenced by computer experience, correction for this measure might be needed. This study examined how to correct for computer experience by examining its influence on online and traditional tests. Method: 248 healthy adults completed an online neuropsychological test battery and 70 adults completed traditional equivalents of the tests. Computer experience was assessed by a performance-based and a self-report measure. Regression analyses were applied to examine their influence on the online and traditional tests. Results: After correction for demographics, the performance-based measure was associated with online and traditional, predominantly speed-based, tests. The self-report measure was also associated with speed-based online tests but not with most traditional tests. Conclusions: Correcting computerized neuropsychological tests using a performance-based measure of computer experience would be unwise, because this measure also seems to tap into cognitive functions. A correction using a self-report measure might be better and is appropriate.

The Uniform Dataset 3.0 Neuropsychological Battery: Factor Structure, Invariance Testing, and Demographically Adjusted Factor Score Calculation.

The goals of this study were to (1) specify the factor structure of the Uniform Dataset 3.0 neuropsychological battery (UDS3NB) in cognitively unimpaired older adults, (2) establish measurement invariance for this model, and (3) create a normative calculator for factor scores. Data from 2520 cognitively intact older adults were submitted to confirmatory factor analyses and invariance testing across sex, age, and education. Additionally, a subsample of this dataset was used to examine invariance over time using 1-year follow-up data (n = 1061). With the establishment of metric invariance of the UDS3NB measures, factor scores could be extracted uniformly for the entire normative sample. Finally, a calculator was created for deriving demographically adjusted factor scores. A higher order model of cognition yielded the best fit to the data χ2(47) = 385.18, p < .001, comparative fit index = .962, Tucker-Lewis Index = .947, root mean square error of approximation = .054, and standardized root mean residual = .036. This model included a higher order general cognitive abilities factor, as well as lower order processing speed/executive, visual, attention, language, and memory factors. Age, sex, and education were significantly associated with factor score performance, evidencing a need for demographic correction when interpreting factor scores. A user-friendly Excel calculator was created to accomplish this goal and is available in the online supplementary materials. The UDS3NB is best characterized by a higher order factor structure. Factor scores demonstrate at least metric invariance across time and demographic groups. Methods for calculating these factors scores are provided.

Normative Data for Wisconsin Card Sorting Test-64 Item in a Spanish Speaking Adult Population Living in the US/Mexico Border Region

Abstract Objective The Wisconsin Card Sorting Test (WCST) is a commonly used test of executive functioning. We aimed to generate norms on the WCST-64 item version for Spanish-speakers living in the US. Participants and Method Healthy Spanish-speakers (N=189) were recruited (Age M = 38.2, SD = 10.3, range 19-60; Education M = 10.9, SD = 4.5, range 0-20; 59.3% female) from the US-Mexico border region. Participants completed the WCST-64 as part of a larger neuropsychological battery. Spearman correlations and Wilcoxon Rank-sum tests were used to assess associations between demographic variables and raw scores. T-scores enabling demographic corrections for various WCST-64 measures (Total Errors, Perseverative Responses, Perseverative Errors, and Number of Categories Completed) were obtained using fractional polynomial equations with corrections for age, education, and gender. Uncorrected percentile scores were reported for Failures to Maintain Set. Rates of neurocognitive impairment (NCI; T &amp;lt; 40) were calculated by applying the newly developed norms along with published norms for non-Hispanic (NH) White and African American English-speakers. Results Older age was significantly associated with worse performance, and higher education was linked to better performance on most WCST-64 raw scores. Current norms resulted in expected rates of NCI (14-16% across measures). Applying norms for NH-Whites overestimated NCI (38-52% across measures). Applying norms for African Americans yielded NCI rates closer to what would be expected, with milder misclassifications (NCI: Total Errors = 14%, Perseverative Responses = 19%, Perseverative Errors = 10%). Conclusions Regional normative data will improve interpretation of test performance on the WCST-64 for Spanish-speakers of Mexican origin living in the US and will facilitate a more valid analysis of neuropsychological profile patterns in this population. Future research will need to explore the generalizability of these norms to other groups.

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

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. Prospective longitudinal study. Sydney, Australia. A total of 617 community-living older adults, aged from 71 to 91 years. 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. 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. 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.

Effect of short-term fasting on electrocardiographic parameters.

IntroductionDuring early drug development trials, electrocardiograms (ECGs) in healthy volunteers who are in a fasting state are evaluated to screen for possible adverse cardiac effects. However, the effect of the duration of fasting on electrocardiographic parameters is largely unknown. We compared the effects of fasting on standard 12‐lead electrocardiographic recordings.MethodsElectrocardiograms were available for 432 healthy subjects (mean age 28.5 ± 12.5; 88.9% male) who participated in early drug development studies after 4‐ and 10‐hr fasting. All ECGs were automatically analyzed for conduction intervals and wave amplitudes with the Marquette 12SL algorithm and compared among fasting duration. Mixed model analyses were used to identify confounding variables.ResultsAfter 10 hr of fasting, compared to after 4 hr of fasting, mean P‐wave duration and amplitude were reduced by 1.95 ± 1.48 ms and 2.18 ± 2.75 μV, mean R wave and S wave amplitude were decreased by 25.83 ± 31.16 μV and 55.39 ± 78.72 μV, mean QRS duration was decreased by 1.84 ± 6.61 ms, and mean T‐wave duration and amplitude were decreased by 2.06 ± 0.72 ms and 9.36 ± 17.21 μV (lead II). The mean PR interval was prolonged by 4.26 ± 17.67 ms, the ventricular rate was reduced by 3.64 ± 8.61 min, and QTcF was reduced by 3.87 ± 14.50 ms. These observations persisted after correction for demographics, electrolytes, blood pressure, heart rate variability, and diurnal variation.ConclusionThe present analysis showed that 10‐hr fasting compared to 4‐hr fasting resulted in changes to the surface ECG, consisting of a reduced wave amplitude and duration and increased isoelectric interval duration.

The Chinese Australian Neuropsychological Normative Study sample performance on Western and Chinese norms: Caveats for cross‐cultural neuropsychology

ObjectiveThe use of neuropsychological tests and norms developed for use with dominant culture English‐speaking Westerners when assessing persons from culturally and linguistically diverse (CALD) backgrounds has been appropriately questioned. Some authors have argued, however, that demographic corrections reduce or eliminate cross‐cultural differences. The primary purpose of the current study was to determine the suitability of using existing demographically adjusted Chinese and Western norms with Chinese Australians.MethodChinese Australian Neuropsychological Normative Study (CANNS) test data (based on N = 145 community dwelling Chinese Australians aged 55–87-years) were converted to demographically adjusted standard scores on the basis of comparison normative samples to examine whether the results were comparable across the CANNS and other Western and Chinese normative datasets.ResultsThe CANNS sample performed poorer than Westerners on the learning trials of the Rey Auditory Verbal Learning Test (RAVLT) but better than both Westerners and Chinese from China/Hong Kong on Trial 7. Performance on non‐verbal tests including the Rey‐Osterrieth Complex Figure Test (ROCFT) Copy, Wechsler Adult Intelligence Scale—Third Edition (WAIS‐III) Digit Symbol Coding (DSC) and Matrix Reasoning (MR), the Five‐Point Test, and the Clock Drawing Test was poorer than that of Westerners despite controlling for age and education. Use of Western norms resulted in significant false positive rates for all non‐verbal tests except MR.ConclusionThe findings of the current study caution against the use of Western tests for which CALD‐specific norms are not available, particularly non‐verbal tests.

General Educational Development (GED) and Educational Attainment Equivalency for Demographically Adjusted Norms†.

To investigate whether the General Educational Development (GED) certificate should be considered equivalent to a standard 12-year high school education when performing demographic corrections on neuropsychological performance levels. If the GED certificate and high school diploma reflect comparable levels of educational achievement, then performance on the Test of Premorbid Function (TOPF) and selected WAIS-IV indices should not differ between groups. Archival neuropsychology data were reviewed to identify patients who either (1) did not complete high school and did not subsequently obtain a GED, (2) did not complete high school but subsequently obtained a GED, or (3) completed high school and did not obtain any further formal education. Most patients were programmatic referrals for epilepsy surgery evaluation, although referrals from the general neurology clinic were also included. The primary dependent measures were the TOPF and WAIS-IV Full Scale IQ (FSIQ). High school graduates obtained higher scores on the TOPF (p < .01, partial η2 = 0.16) and FSIQ (p < .01, partial η2 = 0.14) as compared to both GED subjects and subjects withdrawing from high school with no GED. The non-GED group and the GED group did not differ from each other. These findings demonstrate that the GED is not equivalent to a standard 12-year high school education when characterizing educational background. Although these data do not address what the appropriate year equivalent should be for the GED when adjusting performance for educational background, using 12 years will likely identify more areas of neuropsychological weakness simply by suggesting higher levels of premorbid ability.

Factor V Has Anticoagulant Activity in Plasma in the Presence of TFPIα: Difference between FV1 and FV2.

Activated factor V (FVa) is a potent procoagulant cofactor in the prothrombinase complex, whereas its precursor factor V (FV) stimulates the inhibition of factor Xa (FXa) by tissue factor pathway inhibitor-α (TFPIα), presumably by promoting TFPIα binding to phospholipids. Plasma FV comprises two glycosylation isoforms (FV1 and FV2) with low and high phospholipid-binding affinity, respectively. The FV1/FV2 ratio is increased in carriers of the FV R2 haplotype. This article demonstrates the TFPIα-cofactor function of FV in plasma and compares FV1 and FV2. Thrombin generation at low TF concentration was measured in FV-depleted plasma reconstituted with 0 to 100% FV, FV1 or FV2, and in 122 individuals genotyped for the R2 haplotype. The TFPIα-cofactor activities of FV1 and FV2 were also investigated in a model system of TFPIα-mediated FXa inhibition. In the FV titration, thrombin generation first increased (up to 5% FV) and then progressively decreased at higher FV concentrations. This anticoagulant effect of FV, which was also observed with FV2 but not with FV1, was largely abolished by anti-TFPIα antibodies, suggesting that it reflects TFPIα-cofactor activity of FV. In the model system of TFPIα-mediated FXa inhibition, FV2 was a more potent TFPIα-cofactor than FV1, in line with their respective phospholipid affinities. Accordingly, FV R2 carriers had higher thrombin generation than non-carriers, even after correction for demographics and plasma levels of coagulation factors and inhibitors. FV (and particularly its FV2 isoform) contributes to the TFPIα-dependent down-regulation of thrombin generation in plasma triggered with low TF.

Developing a regression equation for predicting premorbid functioning in an Australian sample using the National Adult Reading Test

ObjectiveIn neuropsychological assessment, predicting the level of premorbid functioning is useful in ascertaining the presence or absence of cognitive decline post‐injury. This study set out to develop regression equations using the National Adult Reading Test (NART) in association with demographic factors to predict the Wechsler Adult Intelligence Scale—Fourth Edition (WAIS‐IV) full‐scale intelligence quotient (FSIQ) and its index scores in a cognitively healthy Australian sample, and to compare the accuracy of these regression equation with the Test of Premorbid Functioning (TOPF) in a clinical sample.MethodThe 111 cognitively healthy male and female participants aged 18–65-years completed a battery of tests, including the WAIS‐IV, NART, and TOPF. The accuracy of the premorbid IQ estimates was then examined on 22 neurologically impaired participants.ResultsThe regression equation using NART errors explained 39.1% of the variance in WAIS‐IV FSIQ. When age, sex, and education were added to the model, the variance increased to 46.6%. Both the regression equations using NART errors and the TOPF significantly over‐estimated IQ in the clinical sample (p < .001), whereas the regression equation combining errors and demographics, and the TOPF with demographic correction, did not.ConclusionEstimating premorbid functioning is an important aspect of neuropsychological assessment. This paper developed a series of regression equations using the NART which are suitable for the Australian context.