Digital Neuropsychology beyond Computerized Cognitive Assessment: Applications of Novel Digital Technologies.

Compared with other health disciplines, there is a stagnation in technological innovation in the field of clinical neuropsychology. Traditional paper-and-pencil tests have a number of shortcomings, such as low-frequency data collection and limitations in ecological validity. While computerized cognitive assessment may help overcome some of these issues, current computerized paradigms do not address the majority of these limitations. In this paper, we review recent literature on the applications of novel digital health approaches, including ecological momentary assessment, smartphone-based assessment and sensors, wearable devices, passive driving sensors, smart homes, voice biomarkers, and electronic health record mining, in neurological populations. We describe how each digital tool may be applied to neurologic care and overcome limitations of traditional neuropsychological assessment. Ethical considerations, limitations of current research, as well as our proposed future of neuropsychological practice are also discussed.

Estudios normativos españoles (Proyecto NEURONORMA Plus): normas para las pruebas Delis Kaplan-Design Fluency Test (DK-DFT), Color Trails Tests (CTT) y Dual Task (DT) / Spanish normative studies (NEURONORMA-Plus project): norms for the Delis Kaplan-Design Fluency Test, Color Trails Test, and Dual Task

Introducción Las tareas de atención compleja y fluencia no verbal se utilizan en las valoraciones neuropsicológicas con el objetivo de explorar subdominios de las funciones ejecutivas. El objetivo de este estudio es proporcionar datos normativos ajustados por edad, escolaridad y género de las pruebas Delis Kaplan-Design Fluency Test (DK-DFT), Color Trails Tests (CTT) y Dual Task (DT) como parte del Proyecto NEURONORMA-Plus. Método Se incluyeron 308 individuos sin deterioro cognitivo de entre 18 y 92 años de edad. Se convirtieron las puntuaciones brutas en puntuaciones escalares ajustadas por edad y se realizaron ajustes por escolaridad y género aplicando regresiones lineales estratificando en dos grupos de edad (< 50 y ≥ 50 años). Resultados Globalmente la edad tuvo un impacto negativo en el DK-DFT y el CTT. La escolaridad mostró un efecto positivo en las puntuaciones del DK-DFT sólo en el grupo de mayor edad (≥ 50 años) y se halló un rendimiento discretamente superior en los hombres más jóvenes en la condición básica de esta prueba. La escolaridad se asoció positivamente con todas las puntuaciones de CTT en ambos grupos de edad, excepto en la subprueba CTT-1 en el grupo de adultos jóvenes. La edad y la escolaridad no mostraron influencia sobre el rendimiento en el DT, a diferencia del género, ya que las mujeres jóvenes tuvieron un rendimiento ligeramente superior. Conclusión Estos datos normativos pueden resultar útiles para la interpretación de las evaluaciones neuropsicológicas en población española. (AU)

Introduction Complex attention and non-verbal fluency tasks are used in neuropsychological assessments with the aim of exploring subdomains of executive function. The purpose of this study is to provide norms and age-, education-, and sex-adjusted data for the Delis Kaplan-Design Fluency Test (DK-DFT), Color Trails Test (CTT), and Dual Task (DT) as part of the NEURONORMA-Plus project. Methods The sample included 308 cognitively healthy individuals aged between 18 and 92 years. Raw scores were converted to age-adjusted scaled scores. These were further converted into education- and sex-adjusted scaled scores by applying linear regression, with 2 age groups (< 50 and ≥ 50 years). Results Overall, age had a negative impact on DK-DFT and CTT performance. We observed a positive effect of education on DK-DFT scores only in the older group (≥ 50 years). Moreover, younger men performed slightly better in the basic condition of this test. Education was positively associated with all CTT scores in both age groups, with the exception of the CTT-1 subtest in the younger group. Age and education did not influence DT performance, whereas sex did, with young women performing slightly better. Conclusions These normative data may be useful in the interpretation of neuropsychological assessments in the Spanish population. (AU)

Improving preclinical to clinical translation of cognitive function for aging-related disorders: the utility of comprehensive touchscreen testing batteries in common marmosets.

Concerns about poor animal to human translation have come increasingly to the fore, in particular with regards to cognitive improvements in rodent models, which have failed to translate to meaningful clinical benefit in humans. This problem has been widely acknowledged, most recently in the field of Alzheimer's disease, although this issue pervades the spectrum of central nervous system (CNS) disorders, including neurodevelopmental, neuropsychiatric, and neurodegenerative diseases. Consequently, recent efforts have focused on improving preclinical to clinical translation by incorporating more clinically analogous outcome measures of cognition, such as touchscreen-based assays, which can be employed across species, and have great potential to minimize the translational gap. For aging-related research, it also is important to incorporate model systems that facilitate the study of the long prodromal phase in which cognitive decline begins to emerge and which is a major limitation of short-lived species, such as laboratory rodents. We posit that to improve translation of cognitive function and dysfunction, nonhuman primate models, which have conserved anatomical and functional organization of the primate brain, are necessary to move the field of translational research forward and to bridge the translational gaps. The present studies describe the establishment of a comprehensive battery of touchscreen-based tasks that capture a spectrum of domains sensitive to detecting aging-related cognitive decline, which will provide the greatest benefit through longitudinal evaluation throughout the prolonged lifespan of the marmoset.

Test of Practical Judgment (TOP-J): Construct, Criterion, and Incremental Validity in a Community Sample of Older Adults.

OBJECTIVE: The Test of Practical Judgment (TOP-J) is a stand-alone judgment measure that is considered to tap into aspects of executive functioning (EF) and inform clinical predictions of daily functioning in older adults. Past validation research is variable and has some limitations. The present study sought to examine the reliability and construct, criterion, and incremental validities of scores on TOP-J 9-item version (TOP-J/9). METHOD: Participants were 95 community-dwelling older adults aged 60 to 85. Participants completed TOP-J/9, measures of EF and global cognition, and three different modalities of instrumental activities of daily living (IADLs) (self-report, performance-based tasks conducted in the laboratory, and performance-based tasks completed at home over 3 weeks). RESULTS: TOP-J/9 scores showed adequate internal consistency (α = 0.73) after correcting for the low number of items. TOP-J/9 was correlated with global cognition and EF, although EF did not survive correction for lower-order processes. Finally, although TOP-J/9 scores were associated with home-based IADL tasks (but not with self-report and laboratory-based IADLs), providing some evidence of criterion validity, they did not incrementally contribute to home-based IADL performance beyond other cognitive measures. However, when two items pertaining to social/ethical judgment were removed, this modified version of TOP-J did relate to EF beyond lower-order processes and contributed uniquely to prediction of home-based IADLs beyond other measures. CONCLUSION: Results suggest that TOP-J/9 taps into global cognitive status (but not necessarily EF) and predicts "real-world" functioning (but not above and beyond other cognitive measures). TOP-J psychometrics may be improved by removing two social/ethical items.

The Dual Mechanisms of Cognitive Control (DMCC) project: Validation of an online behavioural task battery.

Cognitive control serves a crucial role in human higher mental functions. The Dual Mechanisms of Control theoretical framework provides a unifying account that decomposes cognitive control into two qualitatively distinct mechanisms-proactive control and reactive control. Here, we describe the Dual Mechanisms of Cognitive Control (DMCC) task battery, which was developed to probe cognitive control modes in a theoretically targeted manner, along with detailed descriptions of the experimental manipulations used to encourage shifts to proactive or reactive mode in each of four prototypical domains of cognition: selective attention, context processing, multitasking, and working memory. We present results from this task battery, conducted from a large (N > 100), online sample that rigorously evaluates the group effects of these manipulations in primary indices of proactive and reactive control, establishing the validity of the battery in providing dissociable yet convergent measures of the two cognitive control modes. The DMCC battery may be a useful tool for the research community to examine cognitive control in a theoretically targeted manner across different individuals and groups.

Spatial neglect in the digital age: Influence of presentation format on patients' test behavior.

OBJECTIVE: Computerized neglect tests could significantly deepen our disorder-specific knowledge by effortlessly providing additional behavioral markers that are hardly or not extractable from existing paper-and-pencil versions. This study investigated how testing format (paper versus digital), and screen size (small, medium, large) affect the Center of cancelation (CoC) in right-hemispheric stroke patients in the Letters and the Bells cancelation task. Our second objective was to determine whether a machine learning approach could reliably classify patients with and without neglect based on their search speed, search distance, and search strategy. METHOD: We compared the CoC measure of right hemisphere stroke patients with neglect in two cancelation tasks across different formats and display sizes. In addition, we evaluated whether three additional parameters of search behavior that became available through digitization are neglect-specific behavioral markers. RESULTS: Patients' CoC was not affected by test format or screen size. Additional search parameters demonstrated lower search speed, increased search distance, and a more strategic search for neglect patients than for control patients without neglect. CONCLUSION: The CoC seems robust to both test digitization and display size adaptations. Machine learning classification based on the additional variables derived from computerized tests succeeded in distinguishing stroke patients with spatial neglect from those without. The investigated additional variables have the potential to aid in neglect diagnosis, in particular when the CoC cannot be validly assessed (e.g., when the test is not performed to completion).

Regression-based norms for the FAS phonemic fluency test for ages 40-84 based on a Norwegian sample.

The FAS phonemic fluency test is a commonly used neuropsychological test of executive function and processing speed. Although Norwegian discrete norms have been developed for the FAS test, American regression-based norms are frequently used by clinicians in Norway.However, language and cultural differences impact performance on the FAS test, and using foreign norms may not be appropriate. Moreover, while discrete norming relies on stratified subgroups of demographics, regression-based norming uses the entire sample to estimate the influence of demographics on performance and may thus improve normative estimates. Here we develop regression-based norms for the FAS phonemic fluency test based on n = 204 healthy Norwegian controls between the ages 40-84 from the Norwegian Dementia Disease Initiation cohort (DDI). We compare the proposed regression norms to published Norwegian discrete norms and American regression-based norms in an independent sample of n = 182 cognitively healthy adults reporting subjective cognitive decline (SCD). We found that years of education was the only significant predictor of FAS performance in our normative sample, accounting for 14.9% of the variance. Both the proposed regression-based norms and previously published discrete norms adequately adjusted for demographics in the independent sample. In contrast, the American norms underestimated the effect of education and overestimated the effect of age. While both the proposed Norwegian regression norms and the previously published discrete norms are suitable for use in Norway, the proposed regression norms may be less vulnerable to sub-stratification sample characteristics posed by discrete norming procedures, and thereby improve normative estimation.

Case study of invalid to valid shift in cognitive performance following successful treatment of psychogenic nonepileptic seizure events.

Patients with psychogenic nonepileptic seizure (PNES) who fail performance validity testing (PVT) may appear to produce non-valid cognitive profiles. Consequently, they may not get referred to treatment and events persist, with worsening disability and high resource utilization. As a result, we report pre- and post-treatment neuropsychological evaluation findings in a 59-year-old woman with a confirmed diagnosis of PNES established using video-EEG monitoring. At pre-treatment baseline neuropsychological evaluation, PNES events occurred weekly to daily. Performance was impaired across PVTs and across multiple cognitive domains. After behavioral intervention specific to PNES, these events substantially reduced in frequency to rare stress-induced flares. Post-treatment neuropsychological evaluation revealed marked improvement of most cognitive and behavioral scores from baseline, and valid PVT scores. We review predisposing, precipitating, and perpetuating factors for PNES and cognitive impairment in this case and discuss the patient's outcome from treatment. Effectively managing PNES events and dissociative tendencies while reducing unnecessary pharmacological interventions appears to have allowed this patient to function closer to her optimal state. This case illustrates the complexity of Functional Neurologic Disorder (FND) clinical presentation and challenges the assumption that suboptimal neuropsychological performance predicts poor treatment engagement and outcome. We showcase the reversibility of PNES and cognitive manifestations of FND using targeted psychotherapeutic interventions, which resulted in reduced disability and associated healthcare costs, as well as re-engagement in life.

Factores de riesgo neuropsicológico y de personalidad asociados en la poliaccidentalidad laboral / Associated neuropsychological and personality risk factors in occupational polyaccidentality

Introducción: El bienestar y la salud de cada uno de los trabajadores son primordiales en el Departamento de Salud Ocupacional de la Fundación Hospital Universitario Metropolitano. Es importante que el personal goce de un nivel de vida saludable para cumplir satisfactoriamente con todas sus obligaciones y las metas planeadas de la organización. Objetivo: Analizar los factores neuropsicológicos y de personalidad asociados en un grupo de personas que se han accidentado dos o más veces (poliaccidentados). Métodos: Se desarrolló un diseño metodológico de casos y controles. Se tomó como población las bases de datos del departamento de seguridad y salud en el trabajo, con 50 trabajadores accidentados en dos o más ocasiones (poliaccidentados). Se aplicaron como técnicas de recolección de datos la escala abreviada de inteligencia Reynolds (Rist) para apreciar el coeficiente de inteligencia de los sujetos y el cuestionario de personalidad de Cattell (16 Pf), que midió 16 factores primarios y cuatro secundarios. Se utilizó la Batería Neuropsicológica de Funciones Ejecutivas y Lóbulos Frontales (BANFE) para evaluar los factores neuropsicológicos. Resultados: fue procesados mediante el paquete estadístico Statistical package Social Science (Spss) versión 21.0 que permitió realizar la prueba de hipótesis para las variables estudiadas, se utilizó la prueba U de Mann Whitney, con un criterio alfa de 0,05 y un nivel de confianza del 95 por ciento. Conclusiones: El grupo de poliaccidentados presentó alteraciones en las áreas orbito-medial, ventromedial y dorso-laterales lo que los predispone a una mayor posibilidad de realizar actividades riesgosas y presentar menor consciencia del riesgo(AU)

Introduction: The well-being and health of each of the workers are paramount in the Department of Occupational Health at Fundación Hospital Universitario Metropolitano. It is important that the staff enjoy a healthy standard of living in order to satisfactorily fulfil all their obligations and the planned goals of the organization. Objective: To look at the neuropsychological and personality factors associated in a group of individuals who have been injured two or more times (poly-accidented). Methods: A case-control methodological design was developed. The databases of the Department of Labor Safety and Health were taken as the population, with 50 workers injured on two or more occasions (poly-accidents). The abbreviated Reynolds Intelligence Scale (Rist) was applied as data collection techniques to assess the intelligence coefficient of the subjects and Cattell personality questionnaire (16 Pf), to measured 16 primary factors and four secondary factors. The Neuropsychological Battery of Executive Functions and Frontal Lobes (BANFE) was used to evaluate neuropsychological factors. Results: They were processed using the Statistical Package Social Science (Spss) version 21.0 that allowed the hypothesis test to be carried out for the variables studied, Mann Whitney U test was used, with 0.05 alpha criterion and 95 percent level of confidence. Conclusions: The group of poly-accidented patients showed alterations in the orbito-medial, ventromedial and dorso-lateral areas, which predisposes them to greater possibility of carrying out risky activities and presenting less risk awareness(AU)

Development of stimulus-driven attention test for unilateral spatial neglect - Accuracy, reliability, and validity.

We developed a simple method to assess stimulus-evoked attention function in unilateral spatial neglect (USN), and examined its accuracy, reliability, and validity. Thirty-one patients with USN and sixteen patients with right hemisphere damage without USN were given a task of reading Japanese characters that suddenly appeared on a display, and a reading or touching task of red Japanese characters that are arranged on the display. The sensitivity and specificity were calculated from the measurement results, and the cutoff value was calculated using the receiver operating characteristic curve. Area under the curve was used to evaluate the discriminatory ability. Reliability was calculated by the intraclass correlation coefficient using the test-retest method. Validity was assessed by correlating the scores of the new method with the scores of the traditional assessment, the behavioral inattention test, and the Catherine Bergego Scale. This new method was able to detect left USN with the same level of accuracy as the conventional assessment and showed moderate or better reliability. In addition, a moderate correlation was found with the conventional assessment, and a higher correlation was observed with items related to perception and cognition in daily life.

Harmonizing neuropsychological assessment for mild neurocognitive disorders in Europe.

INTRODUCTION: Harmonized neuropsychological assessment for neurocognitive disorders, an international priority for valid and reliable diagnostic procedures, has been achieved only in specific countries or research contexts. METHODS: To harmonize the assessment of mild cognitive impairment in Europe, a workshop (Geneva, May 2018) convened stakeholders, methodologists, academic, and non-academic clinicians and experts from European, US, and Australian harmonization initiatives. RESULTS: With formal presentations and thematic working-groups we defined a standard battery consistent with the U.S. Uniform DataSet, version 3, and homogeneous methodology to obtain consistent normative data across tests and languages. Adaptations consist of including two tests specific to typical Alzheimer's disease and behavioral variant frontotemporal dementia. The methodology for harmonized normative data includes consensus definition of cognitively normal controls, classification of confounding factors (age, sex, and education), and calculation of minimum sample sizes. DISCUSSION: This expert consensus allows harmonizing the diagnosis of neurocognitive disorders across European countries and possibly beyond.

Development of an interactive tool of early social responsiveness to track autism risk in infants and toddlers.

AIM: To evaluate the psychometric properties of a 4-minute assessment designed to identify early autism spectrum disorder (ASD) status through evaluation of early social responsiveness (ESR). METHOD: This retrospective, preliminary study included children between 13 and 24 months (78 males, 79 females mean age 19.4mo, SD 3.1) from two independent data sets (an experimental/training sample [n=120] and a validation/test sample [n=37]). The ESR assessment examined social behaviors (e.g. eye contact, smiling, ease-of-social-engagement) across five common play activities (e.g. rolling a ball, looking at a book). Data analyses examined reliability and accuracy of the assessment in identifying ESR abilities and in discriminating children with and without ASD. RESULTS: Results indicated adequate internal consistency and test-retest reliability of the ESR assessment. Receiver operator curve analysis identified a cutoff score that discriminated infants with ASD-risk from peers in the training sample. This score yielded moderate sensitivity and high specificity for best-estimate ASD diagnosis in the validation sample. INTERPRETATION: Preliminary findings indicated that brief, systematic observation of ESR may assist in discriminating infants with and without ASD, providing concrete evidence to validate or supplement parents', pediatricians', or clinicians' concerns. Future studies could examine the utility of ESR 'growth curves'.

Accuracy of a Self-Administered Online Cognitive Assessment in Detecting Amnestic Mild Cognitive Impairment.

OBJECTIVES: Our aim was to validate the online Brain Health Assessment (BHA) for detection of amnestic mild cognitive impairment (aMCI) compared to gold-standard neuropsychological assessment. We compared the diagnostic accuracy of the BHA to the Montreal Cognitive Assessment (MoCA). METHODS: Using a cross-sectional design, community-dwelling older adults completed a neuropsychological assessment, were diagnosed as normal cognition (NC) or aMCI, and completed the BHA and MoCA. Both logistic regression (LR) and penalized logistic regression (PLR) analyses determined BHA and demographic variables predicting aMCI; MoCA variables were similarly modeled. Diagnostic accuracy was compared using area under the receiver operating characteristic curve (ROC AUC) analyses. RESULTS: Ninety-one participants met inclusion criteria (51 aMCI, 40 NC). PLR modeling for the BHA indicated Face-Name Association, Spatial Working Memory, and age-predicted aMCI (ROC AUC = 0.76; 95% confidence interval [CI]: 0.66-0.86). Optimal cut-points resulted in 21% classified as aMCI (positive), 23% negative, and 56% inconclusive. For the MoCA, digits, abstraction, delayed recall, orientation, and age predicted aMCI (ROC AUC = 0.71; 95% CI: 0.61-0.82). Optimal cut-points resulted in 22% classified positive, 8% negative, and 70% inconclusive (LR results presented within). The BHA model classified fewer participants into the inconclusive category and more as negative for aMCI, compared to the MoCA model (Stuart-Maxwell p = .004). DISCUSSION: The self-administered BHA provides similar detection of aMCI as a clinician-administered screener (MoCA), with fewer participants classified inconclusively. The BHA has the potential to save practitioners time and decrease unnecessary referrals for a comprehensive assessment to determine the presence of aMCI.

The utility of the Structured Inventory of Malingered Symptomatology for distinguishing individuals with Dissociative Identity Disorder (DID) from DID simulators and healthy controls.

Background: Individuals with dissociative identity disorder (DID) have complex symptoms consistent with severe traumatic reactions. Clinicians and forensic assessors are challenged by distinguishing symptom exaggeration and feigning from genuine symptoms among these individuals. This task may be aided by administering validity measures. Objective: This study aimed to document how individuals with DID score on the Structured Inventory of Malingered Symptomatology (SIMS). The second objective was to compare coached DID simulators and healthy controls to DID patients on the SIMS's total score and subscales. The third objective was to examine the utility rates of the SIMS in distinguishing simulated DID from clinically diagnosed DID. Method: We compared SIMS data gathered from participants from two Dutch sites, one Swiss site and one U.S. site. Sixty-three DID patients were compared to 77 coached DID simulators and 64 healthy controls on the SIMS. A multivariate analysis compared the groups on the SIMS total scores and subscales, and post-hoc Games Howell tests and univariate ANOVAs examined differences between the groups. Utility statistics assessed the accuracy of the SIMS in distinguishing clinical from simulated DID. Results: DID simulators scored significantly higher than DID individuals and healthy controls on every SIMS subscale as well as the total score. The majority (85.7%) of the individuals with DID scored above the cut-off, which is typically interpreted as indicative of possible symptom exaggeration. DID individuals scored higher than the healthy controls on every subscale except Low Intelligence, even after controlling for dissociation. The subscales and items most frequently endorsed by the DID group are consistent with symptoms associated with complex trauma exposure and dissociative reactions. The SIMS total score had a sensitivity of 96% but an unacceptably low specificity of 14%. Conclusions: The findings indicate that the instrument is not accurate in assessing potential symptom exaggeration or feigning in DID.

Antecedentes: Los individuos con trastorno de identidad disociativo (TID) tienen síntomas complejos consistentes con reacciones traumáticas severas. Los clínicos y evaluadores forenses se enfrentan al reto de distinguir la exageración de los síntomas y la simulación de los síntomas genuinos entre estos individuos. Esta tarea puede verse facilitada por la administración de medidas de validez.Objetivo: Este estudio tuvo como objetivo documentar la puntuación de los individuos con TID en el Inventario Estructurado de Sintomatología Simulada (SIMS). El segundo objetivo era comparar los simuladores de TID entrenados y los controles sanos con los pacientes de TID en la puntuación total y las subescalas del SIMS. El tercer objetivo fue examinar los índices de utilidad del SIMS para distinguir el TID simulado del TID diagnosticado clínicamente.Método: Se compararon los datos de la SIMS obtenidos de participantes de dos centros holandeses, un centro suizo y un centro estadounidense. Se compararon 63 pacientes de TID con 77 simuladores de TID entrenados y 64 controles sanos en el SIMS. Un análisis multivariante comparó los grupos en las puntuaciones totales y subescalas de la SIMS, y las pruebas post-hoc de Games Howell y los ANOVAs univariantes examinaron las diferencias entre los grupos. Las estadísticas de utilidad evaluaron la precisión de la SIMS para distinguir el TID clínico del simulado.Resultados: Los simuladores de TID obtuvieron puntuaciones significativamente más altas que los individuos con TID y los controles sanos en cada subescala del SIMS, así como en la puntuación total. La mayoría (85,7%) de los individuos con TID puntuaron por encima del punto de corte, que suele interpretarse como indicativo de una posible exageración de los síntomas. Los individuos con TID puntuaron más alto que los controles sanos en todas las subescalas excepto en Inteligencia baja, incluso después de controlar la disociación. Las subescalas y los ítems más frecuentemente respaldados por el grupo de TID son consistentes con los síntomas asociados con la exposición al trauma complejo y las reacciones disociativas. La puntuación total del SIMS tuvo una sensibilidad del 96% pero una especificidad inaceptablemente baja del 14%.Conclusiones: Los resultados indican que el instrumento no es preciso para evaluar la potencial exageración o simulación de los síntomas en el TID.

Development of a cognitive composite for measuring change in progressive supranuclear palsy.

INTRODUCTION: Individuals with progressive supranuclear palsy (PSP) experience cognitive changes that are challenging to follow without a validated neuropsychological test battery to measure progression. This study describes a composite measure to evaluate cognition in individuals with PSP. METHODS: Baseline cognitive test data from 486 participants with PSP in the PASSPORT (NCT03068468) study included the Repeatable Battery for Assessment of Neuropsychological Status (RBANS), Color Trails Test (CTT) parts 1 and 2, letter-number sequencing, and letter fluency. Data were analyzed using summary statistics and a matrix of Pearson correlations. A hypothetical factor structure was constructed and validated. RESULTS: Observed correlations were highest for scores between story memory and story recall (correlation coefficient = 0.78) and lowest for scores between letter fluency and picture naming (correlation coefficient = 0.11), and picture naming and figure copy (correlation coefficient = 0.12). After excluding picture naming and Color Trails Test (CTT) parts 1 and 2, a 3-factor structure was hypothesized for the remaining 13 tests. Confirmatory factor analysis demonstrated goodness of fit within acceptable limits (comparative fit index and Tucker-Lewis index = 0.98, standardized root-mean-square residual and root-mean-square error of approximation = 0.05-0.06). Mixed-model repeated-measures analysis of change from baseline to week 52 in RBANS and PSP cognitive composite score produced mean-to-standard-deviation ratios of 0.418 and 0.780, respectively. CONCLUSIONS: This novel composite endpoint, based on RBANS and designed to account for motor impairments in PSP, improves on current cognitive assessments PSP.

Research Involving Participants With Impaired Consent Capacity: An Examination of Methods to Determine Capacity to Consent.

OBJECTIVE: To examine methods of assessing consent capacity in research protocols involving participants with impaired consent capacity, and examine instruments used to evaluate research consent capacity. METHODS: A retrospective review of 330 active research protocols involving participants lacking capacity to consent over a 10-year period (January 1, 2009, through March 1, 2019) was conducted to collect protocol characteristics (medical specialty, level of risk and type of study, consent and assent procedures, and type of vulnerable or protected population). Methods to assess consent capacity are described, and instruments to assess consent capacity are summarized. RESULTS: The specialties most frequently involving participants with impaired consent capacity in research were Neurology (27.3%), Critical Care (16.7%), and Surgery (10%). Type of studies are observational (43.9%), clinical trials (33%), chart review (11.5%), biobank (6.1%), and biomarker (5.5%). Minimal risk (53.3%) outnumbered greater than minimal risk (46.7%) studies. Most obtained written informed consent (77%) and assent (40.9%). The most common method to assess consent capacity was direct assessment by investigators (32.7%). Only 86 (26%) studies used instruments to assess consent capacity. Of the 13 instruments used, the most common was the Evaluation of Decision-Making Capacity for Consent to Act as a Research Subject, and is the only instrument that assesses all four components of decisional capacity: understanding, appreciation, reasoning, and choice. CONCLUSION: Generally, there was lack of uniformity in determining capacity to consent to research participation. Very few studies used instruments to assess consent capacity. Institutional review boards can provide greater guidance for research consent capacity determination.

Improving Detection of Amnestic Mild Cognitive Impairment with Sex-Specific Cognitive Norms.

BackgroundDespite a female advantage in verbal memory, normative data for verbal memory tests used to diagnose Alzheimer's disease (AD) dementia and amnestic mild cognitive impairment (aMCI) often are not sex-adjusted.ObjectiveTo determine whether sex-adjusted norms improve aMCI diagnostic accuracy when accuracy was evaluated by progression to AD dementia over time.MethodsNon-sex-specific and sex-specific verbal memory test norms were incorporated into Jak/Bondi aMCI criteria and applied to older (age 65-90) non-demented women (N = 1,036) and men (N = 355) from the Rush Memory and Aging Project. Using sex-specific aMCI diagnosis as the "true" condition versus non-sex-specific aMCI diagnosis as the "predicted" condition, we identified True Positives, False Positives, True Negatives, and False Negatives and compared AD dementia risk over 10 years among groups.ResultsRates of aMCI were higher in men versus women (χ2 = 15.39, p < 0.001) when determined based on typical diagnostic criteria, but this difference reversed when using sex-specific diagnostic criteria (χ2 = 8.38, p = 0.004). We identified 8%of women as False Negatives and 12%of men as False Positives. Risk of incident AD dementia in False Positive men was significantly lower than in True Positive men (HR = 0.26, 95%CI = 0.12-0.58, p = 0.001). Risk of incident AD dementia in False Negative women was substantially higher than in True Negative women (HR = 3.11, 95%CI = 2.09-4.63, p < 0.001).ConclusionResults suggest that previous reports of higher aMCI rates in men versus women may be an artifact of non-sex-adjusted norms/cut-scores. Incorporation of sex-specific norms/cut-scores for verbal memory impairment into aMCI diagnostic criteria may improve diagnostic accuracy and avoid diagnostic errors in approximately 20%.

Screening and predicting progression from high-risk mild cognitive impairment to Alzheimer's disease.

Individuals with mild cognitive impairment (MCI) are clinically heterogeneous, with different risks of progression to Alzheimer's disease. Regular follow-up and examination may be time-consuming and costly, especially for MRI and PET. Therefore, it is necessary to identify a more precise MRI population. In this study, a two-stage screening frame was proposed for evaluating the predictive utility of additional MRI measurements among high-risk MCI subjects. In the first stage, the K-means cluster was performed for trajectory-template based on two clinical assessments. In the second stage, high-risk individuals were filtered out and imputed into prognosis models with varying strategies. As a result, the ADAS-13 was more sensitive for filtering out high-risk individuals among patients with MCI. The optimal model included a change rate of clinical assessments and three neuroimaging measurements and was significantly associated with a net reclassification improvement (NRI) of 0.246 (95% CI 0.021, 0.848) and integrated discrimination improvement (IDI) of 0.090 (95% CI - 0.062, 0.170). The ADAS-13 longitudinal models had the best discrimination performance (Optimism-corrected concordance index = 0.830), as validated by the bootstrap method. Considering the limited medical and financial resources, our findings recommend follow-up MRI examination 1 year after identification for high-risk individuals, while regular clinical assessments for low-risk individuals.

Enhancing the Sensitivity of Memory Tests: Reference Data for the Free and Cued Selective Reminding Test and the Logical Memory Task from Cognitively Healthy Subjects with Normal Alzheimer's Disease Cerebrospinal Fluid Biomarker Levels.

BACKGROUND: Cognitive performance of a given individual should be interpreted in the context of reference standards obtained in cognitively healthy populations. Recent evidence has shown that removing asymptomatic individuals with biomarker evidence of Alzheimer's disease pathology from normative samples increases the sensitivity of norms to detect memory impairments. These kind of norms may be useful for defining subtle cognitive decline, the transitional cognitive decline between normal cognition and mild cognitive impairment. OBJECTIVE: The present study aims to provide norms for the Free and Cued Selective Reminding Test (FCSRT) and the Logical Memory subtest of the Wechsler Memory Scale-IV in a sample of individuals aged 50-70 years with normal levels of amyloid-ß and tau cerebrospinal fluid (CSF) biomarkers. METHODS: The sample was composed of 248 individuals from the ALFA+ study with negative amyloid-ß and tau CSF biomarker levels. Regression-based norms were developed, including adjustments for age, education, and sex when applicable. RESULTS: We found that education was associated with the performance in all the variables of both tests while age had a marginal effect only in the delayed free recall of the FCSRT. Sex was also related to the performance in the FCSRT, with women outperforming men. Equations to calculate z-scores and normative percentile tables were created. As compared with previously published norms the reference data presented were more sensitive but less specific, as expected. CONCLUSION: The use of the norms provided in this work, in combination with the already published conventional norms, may contribute to detecting subtle memory impairment.

Demencia frontotemporal desde una mirada neuropsicológica / Frontotemporal dementia from a neuropsychological point of view

Introducción: La riqueza de las manifestaciones neuropsicológicas de la demencia frontotemporal, ha permitido la identificación de diferentes variantes de la enfermedad, sin embargo, existen pacientes en los que se entrelazan las características clínicas de más de una variante, lo que ha llevado a cuestionar lo relativo de las clasificaciones vigentes. Objetivo: Caracterizar el funcionamiento cognitivo de un paciente donde concomitan alteraciones conductuales y del lenguaje, típicas de la demencia frontotemporal. Caso clínico: Mujer diestra, de 50 años de edad, con cambios conductuales marcados, a los cuales, de forma progresiva, se sumaron alteraciones del lenguaje, en un periodo de evolución de aproximadamente un año y seis meses. Por imágenes de tomografía axial computarizada, se confirma atrofia cortical a predominio frontal. Se emplearon para la evaluación la batería neuropsicológica breve NEUROPSI, la escala Hasegawa y la batería de evaluación frontal de Litvan; se constata predominio de alteraciones en el lenguaje impresivo y expresivo, las funciones ejecutivas y en la memoria verbal. Conclusiones: Las alteraciones detectadas, confirman la coexistencia de manifestaciones de la variante conductual (con tendencia a la desinhibición) y la variante semántica de la demencia frontotemporal(AU)

Introduction: The richness of the neuropsychological manifestations of frontotemporal dementia has allowed the identification of different variants of the disease. However, there are patients in whom the clinical characteristics of more than one variant are intertwined, which has led to question the current classifications. Objective: To characterize the cognitive functioning of a patient with concomitant behavioral and language disorders, typical of frontotemporal dementia. Case presentation: Right-handed female, 50 years old, affected by marked behavioral changes, to which language alterations were progressively added in a period of evolution of approximately one year and six months. Images of Computerized Axial Tomography that confirm cortical atrophy mainly frontal. The Neuropsychological Battery abbreviated NEUROPSI, the Hasegawa Scale and the Litvan Frontal Evaluation Battery were used for the evaluation, with a predominance of alterations in printed and expressive language, executive functions and verbal memory. Conclusions: The alterations detected confirm the coexistence of manifestations of the behavioral variant (with a tendency to disinhibition) and the semantic variant of frontotemporal dementia(AU)