Memory impairment in Amyloidß-status Alzheimer's disease is associated with a reduction in CA1 and dentate gyrus volume: In vivo MRI at 7T.

INTRODUCTION: In Alzheimer's disease (AD), early diagnosis facilitates treatment options and leads to beneficial outcomes for patients, their carers and the healthcare system. The neuropsychological battery of the Uniform Data Set (UDSNB3.0) assesses cognition in ageing and dementia, by measuring scores across different cognitive domains such as attention, memory, processing speed, executive function and language. However, its neuroanatomical correlates have not been investigated using 7 Tesla MRI (7T MRI). METHODS: We used 7T MRI to investigate the correlations between hippocampal subfield volumes and the UDSNB3.0 in 24 individuals with Amyloidß-status AD and 18 age-matched controls, with respective age ranges of 60 (42-76) and 62 (52-79) years. AD participants with a Medial Temporal Atrophy scale of higher than 2 on 3T MRI were excluded from the study. RESULTS: A significant difference in the entire hippocampal volume was observed in the AD group compared to healthy controls (HC), primarily influenced by CA1, the largest hippocampal subfield. Notably, no significant difference in whole brain volume between the groups implied that hippocampal volume loss was not merely reflective of overall brain atrophy. UDSNB3.0 cognitive scores showed significant differences between AD and HC, particularly in Memory, Language, and Visuospatial domains. The volume of the Dentate Gyrus (DG) showed a significant association with the Memory and Executive domain scores in AD patients as assessed by the UDSNB3.0.. The data also suggested a non-significant trend for CA1 volume associated with UDSNB3.0 Memory, Executive, and Language domain scores in AD. In a reassessment focusing on hippocampal subfields and MoCA memory subdomains in AD, associations were observed between the DG and Cued, Uncued, and Recognition Memory subscores, whereas CA1 and Tail showed associations only with Cued memory. DISCUSSION: This study reveals differences in the hippocampal volumes measured using 7T MRI, between individuals with early symptomatic AD compared with healthy controls. This highlights the potential of 7T MRI as a valuable tool for early AD diagnosis and the real-time monitoring of AD progression and treatment efficacy. CLINICALTRIALS: GOV: ID NCT04992975 (Clinicaltrial.gov 2023).

Assessment of cognitive function in long-term Hodgkin lymphoma survivors, results based on data from a major treatment center in Hungary.

INTRODUCTION: Nowadays, more than 80% of newly diagnosed classical Hodgkin lymphoma (HL) patients can be cured and become long-term survivors due to risk and response-adapted treatment strategies. A well-known side effect is cognitive dysfunction that appears in HL patients after chemotherapy. In the present study, we aimed to measure cognitive dysfunction in our HL patients in this study and to find potential correlations between patient-related factors, the signs and symptoms of their diseases, or therapeutic factors. METHODS: We carried out a computer-assisted assessment (CANTAB) of cognitive dysfunction in 118 patients. We examined the domains of visual memory, attention, working memory, and planning. RESULTS: The median age of 64 females and 54 males at diagnosis was 29 (13-74) and 41 (21-81) years at the completion of CANTAB. Fifty-two percent of all patients showed cognitive impairment. Attention was impaired in 35% of patients, the working memory and planning were impaired in 25%, while visual memory was affected in 22%. All the three functions showed a significant association with inactive employments status. A close correlation was found between visual memory/working memory and planning, higher age at HL diagnosis or the completion of CANTAB test, and disability pensioner status. DISCUSSION: Our investigation suggests that patients with inactive employment status and older age require enhanced attention. Their cognitive function and quality of life can be improved if they return to work or, if it is not possible, they receive a cognitive training.

Screening for cognitive impairment in systemic lupus erythematosus: Application of the Montreal Cognitive Assessment (MoCA) in a Greek patient sample.

BACKGROUND: Cognitive impairment (CI) is one of the most frequent neuropsychiatric manifestations of systemic lupus erythematosus (SLE). Given that extensive neuropsychological testing is not always feasible in routine clinical practice, brief cognitive screening tools are desirable. The aim of this study was to evaluate the Montreal Cognitive Assessment (MoCA) as a screening tool for CI in SLE. METHODS: Consecutive SLE patients followed at a single centre were evaluated using MoCA and an extensive neuropsychological test battery (NPT), including the Digits Forward and Digits Backwards, Rey Auditory Verbal Learning Memory Test, Trail Making Test, Stroop Colour-Word Test, Semantic and Phonetic Verbal Fluency tests and a 25-problem version of the General Adult Mental Ability test. The criterion validity of MoCA was assessed through receiver operating characteristic (ROC) analyses using three different case definitions: i) against normative population data, ii) and iii) against average performance of a comparison group of rheumatoid arthritis (RA) patients, to adjust for possible confounding effects of chronic illness and inflammatory processes on cognitive performance. The effect of patient-related (age, years of education, anxiety, depression, fatigue and pain) and disease-related (activity, damage, age at diagnosis, disease duration, use of glucocorticoid, psychotropic and pain medication) parameters on the MoCA was examined. RESULTS: A total of 71 SLE patients were evaluated. MoCA significantly correlated with all NPT scores and was affected by education level (p < 0.001), but not by other demographic or clinical variables. The optimal cutoff for detecting CI, as defined on the basis of normative population data, was 23/30 points, demonstrating 73% sensitivity and 75% specificity. A cutoff of 22/30 points, using neuropsychological profiles of the RA group as inflammatory disease controls, exhibited higher sensitivity (100%, based on both definitions) and specificity (87% and 90%, depending on the definition). The standard cutoff of 26/30 points displayed excellent sensitivity (91-100%) with significant expenses in specificity (43-45%). CONCLUSION: The MoCA is an easily applied tool, which appears to be reliable for identifying CI in SLE patients. The standard cutoff score (26/30) ensures excellent sensitivity while lower cutoff scores (22-23/30) may, also, provide higher specificity.

Validation of Indian Council of Medical Research Neurocognitive Tool Box in Diagnosis of Mild Cognitive Impairment in India: Lessons from a Harmonization Process in a Linguistically Diverse Society.

BACKGROUND/AIMS: In a linguistically diverse country such as India, challenges remain with regard to diagnosis of early cognitive decline among the elderly, with no prior attempts made to simultaneously validate a comprehensive battery of tests across domains in multiple languages. This study aimed to determine the utility of the Indian Council of Medical Research-Neurocognitive Tool Box (ICMR-NCTB) in the diagnosis of mild cognitive impairment (MCI) and its vascular subtype (VaMCI) in 5 Indian languages. METHODS: Literate subjects from 5 centers across the country were recruited using a uniform process, and all subjects were classified based on clinical evaluations and a gold standard test protocol into normal cognition, MCI, and VaMCI. Following adaptation and harmonization of the ICMR-NCTB across 5 different Indian languages into a composite Z score, its test performance against standards, including sensitivity and specificity of the instrument as well as of its subcomponents in diagnosis of MCI, was evaluated in age and education unmatched and matched groups. RESULTS: Variability in sensitivity-specificity estimates was noted between languages when a total of 991 controls and 205 patients with MCI (157 MCI and 48 VaMCI) were compared due to a significant impact of age, education, and language. Data from a total of 506 controls, 144 patients with MCI, and 46 patients with VaMCI who were age- and education-matched were compared. Post hoc analysis after correction for multiple comparisons revealed better performance in controls relative to all-cause MCI. An optimum composite Z-score of -0.541 achieved a sensitivity of 81.1% and a specificity of 88.8% for diagnosis of all-cause MCI, with a high specificity for diagnosis of VaMCI. Using combinations of multiple-domain 2 test subcomponents retained a sensitivity and specificity of >80% for diagnosis of MCI. CONCLUSIONS: The ICMR-NCTB is a "first of its kind" approach at harmonizing neuropsychological tests across 5 Indian languages for the diagnosis of MCI due to vascular and other etiologies. Utilizing multiple-domain subcomponents also retains the validity of this instrument, making it a valuable tool in MCI research in multilingual settings.

Estimated GFR, Albuminuria, and Cognitive Performance: The Maastricht Study.

BACKGROUND: Reduced estimated glomerular filtration rate (eGFR) and albuminuria have been associated with worse cognitive performance. However, few studies have examined whether these associations are confined to older individuals or may be extended to the middle-aged population. STUDY DESIGN: Cross-sectional analyses of a prospective population-based cohort study. SETTING & PARTICIPANTS: 2,987 individuals aged 40 to 75 years from the general population (The Maastricht Study). PREDICTOR: eGFR and urinary albumin excretion (UAE). OUTCOMES: Memory function, information processing speed, and executive function. MEASUREMENTS: Analyses were adjusted for demographic variables (age, sex, and educational level), lifestyle factors (smoking behavior and alcohol consumption), depression, and cardiovascular disease risk factors (glucose metabolism status, waist circumference, total to high-density lipoprotein cholesterol ratio, triglyceride level, use of lipid-modifying medication, systolic blood pressure, use of antihypertensive medication, and prevalent cardiovascular disease). RESULTS: UAE was <15mg/24 h in 2,439 (81.7%) participants, 15 to <30 mg/24 h in 309 (10.3%), and ≥30mg/24 h in 239 (8.0%). In the entire study population, UAE≥30mg/24 h was associated with lower information processing speed as compared to UAE<15mg/24 h (ß [SD difference] = -0.148; 95% CI, -0.263 to -0.033) after full adjustment, whereas continuous albuminuria was not. However, significant interaction terms (P for interaction < 0.05) suggested that albuminuria was most strongly and extensively associated with cognitive performance in older individuals. Mean (±SD) eGFR, estimated by the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine-cystatin C equation (eGFRcr-cys), was 88.4±14.6 mL/min/1.73m2. eGFRcr-cys was not associated with any of the domains of cognitive performance after full adjustment. However, significant interaction terms (P for interaction < 0.05) suggested that eGFRcr-cys was associated with cognitive performance in older individuals. LIMITATIONS: Cross-sectional design, which limited causal inferences. CONCLUSIONS: In the entire study population, albuminuria was independently associated with lower information processing speed, whereas eGFRcr-cys was not associated with cognitive performance. However, both were more strongly and extensively associated with cognitive performance in older individuals.

Psychometric evaluation of ADAS-Cog and NTB for measuring drug response.

AIMS: To conduct a psychometric analysis to determine the adequacy of instruments that measure cognition in Alzheimer's disease trials. BACKGROUND: Both the Alzheimer's Disease Assessment Scale - Cognition (ADAS-Cog) and the Neuropsychological Test Battery (NTB) are validated outcome measures for clinical trials in Alzheimer's disease and are approved also for regulatory purposes. However, it is not clear how comparable they are in measuring cognitive function. In fact, many recent trials in Alzheimer's disease patients have failed and it has been questioned if ADAS-Cog still is a sensitive measure. MATERIALS AND METHODS: The present paper examines the psychometric properties of ADAS-Cog and NTB, based on a post hoc analysis of data from a clinical trial (NCT01024660), which was conducted by AstraZeneca, in mild-to-moderate Alzheimer's disease (AD) patients, with a Mini Mental State Examination (MMSE) Total score 16-24. Acceptability, reliability, different types of validity and ability to detect change were assessed using relevant statistical methods. Total scores of both tests, as well as separate domains of both tests, including the Wechsler Memory Scale (WMS), Rey Auditory Verbal Learning Test (RAVLT) and Delis-Kaplan Executive Function System (D-KEFS) Verbal Fluency Condition, were analyzed. RESULTS: Overall, NTB performed well, with acceptable reliability and ability to detect change, while ADAS-Cog had insufficient psychometric properties, including ceiling effects in 8 out of a total of 11 ADAS-Cog items in mild AD patients, as well as low test-retest reliability in some of the items. DISCUSSION: Based on a direct comparison on the same patient sample, we see advantages of the NTB compared with the ADAS-Cog for the evaluation of cognitive function in the population of mild-to-moderate AD patients. The results suggest that not all of ADAS-Cog items are relevant for both mild and moderate AD population. CONCLUSIONS: This validation study demonstrates satisfactory psychometric properties of the NTB, while ADAS-Cog was found to be psychometrically inadequate.

[An international neuropsychological assessment tool for children, adolescents, and adults with anorexia nervosa ­ the German adaptation of the Ravello Profile]. / Eine internationale neuropsychologische Testbatterie für Kinder, Jugendliche und Erwachsene mit Anorexia nervosa - die deutsche Adaptation des Ravello Profils

OBJECTIVE: Adults with anorexia nervosa (AN) show weaknesses in several cognitive functions before and after weight restoration. There is a great demand for standardized examinations of executive functioning in the field of child and adolescent AN. Previous studies exhibited methodological inconsistencies regarding test selection and operationalization of cognitive functions, making the interpretation of their findings difficult. In order to overcome these inconsistencies, a neuropsychological assessment tool, the "Ravello Profile," was developed, though previously not available in German. This paper presents a German adaptation of the Ravello Profile and illustrates its applicability in children and adolescents via three case descriptions. METHODS: The Ravello Profile was adapted for the German-speaking area. The applicability of the Ravello Profile was evaluated in three children and adolescents with AN. RESULTS AND CONCLUSIONS: The cases presented confirm the feasible implementation of this adaptation of the Ravello Profile, both in children and adolescents. Hence, it enables a methodologically consistent examination of executive functioning in German-speaking children, adolescents, and adults with AN. Using the Ravello Profile, the role of cognitive functions in the development of AN can be systematically examined over a broad age range.

Type 2 Diabetes Comorbidity and Cognitive Decline in Patients with Alzheimer's Disease.

BACKGROUND: Although insulin dysregulation and resistance likely participate in Alzheimer's disease (AD) etiologies, little is known about the correlation between type 2 diabetes mellitus (T2DM) and the progression of cognitive decline in patients with AD. OBJECTIVE: To determine whether AD patients with T2DM experience more rapid cognitive decline than those without T2DM. METHODS: All cognitive performance data and the presence or absence of T2DM comorbidity in patients with AD were derived from the US National Alzheimer's Coordinating Center's (NACC) Uniform Data Set (UDS). A search of the UDS identified 3,055 participants with AD who had more than one epoch completed. The data set culled clinically diagnosed AD dementia patients who were assessed for diabetes type identified during at least 1 visit. These patients were divided into 2 groups based on whether they had a diagnosis of T2DM. The data from these groups were then analyzed for differences in cognitive decline based on neuropsychological test battery scores and a Clinician Dementia Rating using a general linear model. RESULTS: Comparisons of the mean scores for 16 selected tests from the neuropsychological test battery showed no significant differences in baseline scores and scores at subsequent visits between the T2DM and nondiabetic groups. CONCLUSIONS: The results revealed no differences in cognitive decline metrics over the course of 5 visits in either study group. These data indicate that the presence of T2DM does not increase the rate of cognitive decline in AD. This finding contradicts expected disease burden and will need to be explored further.

Neuropsychological Assessment of Community-Dwelling Older Adults in Almaty, Kazakhstan.

Cognitive impairment in older adults is a major public concern for Kazakhstan's aging population. We aimed to (1) administer a neuropsychological test battery (NTB) in domains relevant to aging-associated cognitive impairment in a sample of adults aged 60+ without dementia in Almaty, Kazakhstan; (2) investigate the associations between demographic factors and test performance; and (3) provide information on the distribution of NTB scores as preliminary local normative data relevant for this population. A cross-sectional evaluation of 276 participants aged 60+ in Almaty, Kazakhstan, was conducted using cognitive instruments including tests of memory, attention, language, executive functions, visuospatial abilities, and processing speed. Multiple linear regression analyses were used to examine the association of demographic factors with neuropsychological test performance. The results from the regression analysis showed that those who are younger, have more years of education, are women, and are of Russian ethnicity had significantly better performance. The current study illustrated (1) the feasibility of administering the NTB to older adults in the general population in Kazakhstan; (2) the preliminary local normative neuropsychological measures; and (3) their independent associations with age, education, gender, and ethnicity. The findings are a platform for future research on dementia and cognitive impairment in older adults in Kazakhstan.

Item analysis of the Child Neuropsychological Assessment Test (TENI): Classical test theory and item response theory.

The aim of this study was to analyze the psychometric properties of the Brazilian version of the Test de Evaluación Neuropsicologica Infantil (TENI) using classical test theory (CTT), item response theory (IRT), and differential item functioning (DIF) models. The visuospatial working memory, focused attention, and matrix reasoning subtasks were analyzed. A total of 553 children, aged between 3 and 9 years of age, from eight public and private schools from the urban area of Belo Horizonte were assessed. In general, all subtasks can be treated essentially as unidimensional. Items' discrimination and difficulties increased in the order of presentation, as they were planned, using CTT and IRT. Items with DIF were found in all tasks, with higher probabilities of answering items correctly for boys and for private school children. Our results corroborated the partial use of some TENI subtasks as a promising digital instrument for non-verbal neuropsychological assessment for children.

A phase 1b/2a multicenter study of the safety and preliminary pharmacodynamic effects of selective muscarinic M1 receptor agonist HTL0018318 in patients with mild-to-moderate Alzheimer's disease.

INTRODUCTION: This study examined the safety and pharmacodynamic effects of selective muscarinic M1 receptor orthosteric agonist HTL0018318 in 60 patients with mild-to-moderate Alzheimer's disease (AD) on background donepezil 10 mg/day. METHODS: A randomized, double-blind, placebo-controlled 4-week safety study of HTL0018318 with up-titration and maintenance phases, observing exploratory effects on electrophysiological biomarkers and cognition. RESULTS: Treatment-emergent adverse events (TEAEs) were mild and less frequently reported during maintenance versus titration. Headache was most commonly reported (7-21%); 0 to 13% reported cholinergic TEAEs (abdominal pain, diarrhea, fatigue, nausea) and two patients discontinued due to TEAEs. At 1 to 2 hours post-dose, HTL0018318-related mean maximum elevations in systolic and diastolic blood pressure of 5 to 10 mmHg above placebo were observed during up-titration but not maintenance. Postive effects of HTL0018318 were found on specific attention and memory endpoints. DISCUSSION: HTL0018318 was well tolerated in mild-to-moderate AD patients and showed positive effects on attention and episodic memory on top of therapeutic doses of donepezil.

Validation Study of a German Cognitive Battery for Huntington's Disease: Relationship Between Cognitive Performance, Functional Decline, and Disease Burden.

OBJECTIVE: Cognitive decline is a key characteristic of Huntington's disease (HD). This study aimed to investigate the diagnostic accuracy of a cognitive battery with six tests used by most HD research centers to assess cognitive impairment in HD. METHOD: In total, 106 HD patients in different disease stages with more (HD-CD, N = 30) and less cognitive impairments (HD-NC, N = 70) and 100 healthy controls (NC) were matched by age, sex, and education and were examined using a standardized protocol including cognitive, motor, and functional assessments. RESULTS: One-way between-groups analysis of variance showed that controls performed significantly better than HD patients and that HD-NC significantly outperformed HD-CD patients in all cognitive tests (NC > HD-NC > HD-CD), with all Games-Howell post-hoc tests p < .001. Analyses using area under the receiver-operating characteristic curve (AUC) disclosed the diagnostic accuracy of all tests included in the battery to discriminate between NC and HD patients with AUC ranging from 0.809 to 0.862 (all p < .001) and between HD-CD and HD-NC patients with AUC ranging from 0.833 to 0.899 (all p < .001). In both analysis, Stroop Color Naming Test showed the highest discriminative potential. Additional analyses showed that cognitive deficits in all domains progressed with disease duration. Moreover, cognitive performance correlated with the severity of motor and functional impairment (all p < .001) and with the Disease Burden Score regardless of disease duration and age. CONCLUSION: Our results indicate that the cognitive battery is a suitable tool for assessing cognitive impairment in HD.

Home-Based, Adaptive Cognitive Training for Cognitively Normal Older adults: Initial Efficacy Trial.

OBJECTIVES: We examined whether a home-based, adaptive cognitive training (CT) program would lead to cognitive performance changes on a neuropsychological test battery in cognitively normal older adults. METHOD: Sixty-eight older adults (age = 70.0, SD = 3.74) were randomly assigned to either CT or an active control group (AC, casual computer games). Participants were instructed to train on their assigned programs for 42 min per day, 5 days per week, over 10 weeks (35 hr of total program usage). Participants completed tests of processing speed, working memory, and executive control before and after 10 weeks of training. RESULTS: Training groups did not differ in performance before training. After training, CT participants out-performed AC participants in the overall cognitive composite score, driven by processing speed and working memory domains. DISCUSSION: Our results show that a limited dose of home-based CT can drive cognitive improvements as measured with neuropsychological test battery, suggesting potential cognitive health maintenance implications for cognitively normal older adults.

Neuropsychological function in type 2 diabetes mellitus.

Type 2 diabetes mellitus (DM) is a major and growing health problem. Brain-related effects of type 2 DM have been studied in several ways over the past few decades. Results have shown effects on brain structure, incidence of dementia, and impairment of various cognitive functions. The present study examined a sample of clinically-referred patients with type 2 DM and compared them with a sample of control patients who were matched on a pairwise basis on age, education, and gender. Each patient was tested using a comprehensive, integrated neuropsychological test battery. Results showed a pattern of generalized and specific neuropsychological dysfunction affecting a broad range of neurocognitive and sensorimotor abilities. However, no differences were found on measures of attention/concentration, memory, or abstract reasoning. Nevertheless, the DM group consistently performed worse on all measures. The DM group's score on a summary measure of neuropsychological function (GNDS) reflected moderate brain-related impairment. A neurocognitive profile is identified that may help clinicians understand their DM patients.

Psychometric Properties and Validation of the EMOTICOM Test Battery in a Healthy Danish Population.

Disruptions in hot cognition, i.e., the processing of emotionally salient information, are prevalent in most neuropsychiatric disorders and constitute a potential treatment target. EMOTICOM is the first comprehensive neuropsychological test battery developed specifically to assess hot cognition. The aim of the study was to validate and establish a Danish language version and reference data for the EMOTICOM test battery. To evaluate the psychometric properties of 11 EMOTICOM tasks, we collected data from 100 healthy Danish participants (50 males, 50 females) including retest data from 49 participants. We assessed test-retest reliability, floor and ceiling effects, task-intercorrelations, and correlations between task performance and relevant demographic and descriptive factors. We found that test-retest reliability varied from poor to excellent while some tasks exhibited floor or ceiling effects. Intercorrelations among EMOTICOM task outcomes were low, indicating that the tasks capture different cognitive constructs. EMOTICOM task performance was largely independent of age, sex, education, and IQ as well as current mood, personality, and self-reported motivation and diligence during task completion. Overall, many of the EMOTICOM tasks were found to be useful and objective measures of hot cognition although select tasks may benefit from modifications to avoid floor and ceiling effects in healthy individuals.

Evaluation of the efficacy, safety and tolerability of orally administered BI 409306, a novel phosphodiesterase type 9 inhibitor, in two randomised controlled phase II studies in patients with prodromal and mild Alzheimer's disease.

BACKGROUND: There are currently no approved treatments for the prodromal stage of Alzheimer's disease (AD). Approved symptomatic treatments for mild-to-moderate AD include acetylcholinesterase inhibitors and memantine, but more efficacious treatments are needed. BI 409306 is a potent and selective phosphodiesterase 9 inhibitor assessed for the symptomatic treatment of AD. Efficacy and safety of BI 409306 was analysed in two phase II proof-of-concept clinical trials in cognitive impairment associated with prodromal AD (study 1) and mild AD (study 2). METHODS: Two multicentre, double-blind, parallel-group, randomised controlled phase II studies were conducted (North America/Europe). Following study run-in, eligible subjects were randomised to one of four oral doses of BI 409306 (10-50 mg daily) or placebo (1:1:1:1:2 ratio) for 12 weeks. The primary efficacy endpoint was the change from baseline in Neuropsychological Test Battery (NTB) total z-score after 12 weeks' treatment. Secondary efficacy assessments included change from baseline in Clinical Dementia Rating scale-Sum of Boxes (CDR-SB), Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-Cog11) and Alzheimer's Disease Cooperative Study-Activities of Daily Living scale (ADCS-ADL; mild cognitive impairment [MCI] version for prodromal patients) after 12 weeks' treatment. Safety and tolerability assessments included adverse event reporting and vital sign monitoring. Change from baseline in NTB total z-score (primary endpoint) and CDR-SB were analysed using the restricted maximum likelihood-based mixed-effects model with repeated measurement. An analysis of covariance model was used to assess other secondary endpoints. RESULTS: Four hundred fifty-seven patients were randomised (study 1 for prodromal AD, N = 128; study 2 for mild AD, N = 329); 427 (93.4%) completed. A prespecified pooled analysis of the primary endpoint revealed no significant changes in NTB total composite z-score at week 12 in the BI 409306 treatment groups compared with placebo, with similar findings observed in the individual studies. The analysis of all secondary endpoints, including pooled analysis of CDR-SB and ADAS-Cog11, ADCS-MCI-ADL (study 1), ADCS-ADL (study 2), also gave no indication of a treatment benefit for BI 409306, compared with placebo. BI 409306 was well tolerated. CONCLUSIONS: Overall, the data do not demonstrate efficacy of BI 409306 in improving cognition in patients with prodromal and mild AD. BI 409306 is well tolerated. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02240693 and NCT02337907 . Registered 15 September 2014 and 09 January 2015, respectively.

Psychometric Evaluation of the Neuropsychological Test Battery in Individuals with Normal Cognition, Mild Cognitive Impairment, or Mild to Moderate Alzheimer's Disease: Results from a Longitudinal Study.

BACKGROUND: The Neuropsychological Test Battery (NTB) is a combination of widely used clinical neuropsychological tests measuring memory and executive function and was designed to overcome some of the limitations of the traditionally used Alzheimer's disease Assessment Scale - Cognitive subscale (ADAS-Cog). A previously reported account indicated high levels of NTB reliability in patients with mild-to-moderate Alzheimer's disease (AD) and mild cognitive impairment (MCI). OBJECTIVES: We examined capacity of the Neuropsychological Test Battery (NTB) and its component subtests to measure cognitive change over time. Correlations with other cognitive and functional assessments were also determined. Design, Settings, Participants: This was a multicentre, prospective, non-interventional, longitudinal cohort study involving patients with mild-to-moderate AD (n=196), MCI (n=70), or cognitively normal control participants (NC, n=75). INTERVENTION: The NTB, as well as other Clinical Outcome Assessments including, ADAS-Cog, other cognitive measures, functional/behavioral questionnaires, health outcome questionnaires, and resource utilization tools were administered. RESULTS: Mean change from baseline for the NTB composite score and the six individual NTB subtests showed greater reductions in performance over time in the AD and MCI groups, compared with NC group. The ADAS-Cog was found to be more sensitive to change than the NTB in all three populations. CONCLUSIONS: The NTB showed high correlation with the ADAS-Cog and appears to be a sensitive and reliable assessment tool for measuring cognitive decline in patients with mild-to-moderate AD. However, the ADAS-Cog was found to be more sensitive to change over time in both the AD and MCI populations.

Sex Differences in Emotion Recognition and Working Memory Tasks.

It is proposed that emotional and cognitive functions may be differentiated based on sex. However, it is still unknown whether this assumption could be generalized for all emotional faces and working memory (WM) functions. To examine this, 50 females, and 60 males performed an emotion recognition task, consisting of a series of emotional faces as well as three working memory tasks from Cambridge Neuropsychological test battery (CANTAB); namely, spatial working memory (SWM), stocking of Cambridge (SOC), and intra/extradimensional shifts tasks (IED). The results found that females had faster response times in recognition of both positive and negative faces as compared to males. Furthermore, it was observed that while females were better on SWM task processing, males performed better on IED and four move SOC tasks, illustrating that processing of WM components may differentiate by sex. It has been concluded that emotional and cognitive functions are indeed sensitive to sex differences.

Reliability and validity of a self-administered tool for online neuropsychological testing: The Amsterdam Cognition Scan.

INTRODUCTION: To facilitate large-scale assessment of a variety of cognitive abilities in clinical studies, we developed a self-administered online neuropsychological test battery: the Amsterdam Cognition Scan (ACS). The current studies evaluate in a group of adult cancer patients: test-retest reliability of the ACS and the influence of test setting (home or hospital), and the relationship between our online and a traditional test battery (concurrent validity). METHOD: Test-retest reliability was studied in 96 cancer patients (57 female; Mage = 51.8 years) who completed the ACS twice. Intraclass correlation coefficients (ICCs) were used to assess consistency over time. The test setting was counterbalanced between home and hospital; influence on test performance was assessed by repeated measures analyses of variance. Concurrent validity was studied in 201 cancer patients (112 female; Mage = 53.5 years) who completed both the online and an equivalent traditional neuropsychological test battery. Spearman or Pearson correlations were used to assess consistency between online and traditional tests. RESULTS: ICCs of the online tests ranged from .29 to .76, with an ICC of .78 for the ACS total score. These correlations are generally comparable with the test-retest correlations of the traditional tests as reported in the literature. Correlating online and traditional test scores, we observed medium to large concurrent validity (r/ρ = .42 to .70; total score r = .78), except for a visuospatial memory test (ρ = .36). Correlations were affected-as expected-by design differences between online tests and their offline counterparts. CONCLUSIONS: Although development and optimization of the ACS is an ongoing process, and reliability can be optimized for several tests, our results indicate that it is a highly usable tool to obtain (online) measures of various cognitive abilities. The ACS is expected to facilitate efficient gathering of data on cognitive functioning in the near future.

Online cognition: factors facilitating reliable online neuropsychological test results.

OBJECTIVE: Online neuropsychological test batteries could allow for large-scale cognitive data collection in clinical studies. However, the few online neuropsychological test batteries that are currently available often still require supervision or lack proper psychometric evaluation. In this paper, we have outlined prerequisites for proper development and use of online neuropsychological tests, with the focus on reliable measurement of cognitive function in an unmonitored setting. METHOD: First, we identified several technical, contextual, and psychological factors that should be taken into account in order to facilitate reliable test results of online tests in the unmonitored setting. Second, we outlined a methodology of quality assurance needed in order to obtain reliable cognitive data in the long run. RESULTS: Based on factors that distinguish the online unmonitored test setting from the traditional face-to-face setting, we provide a set of basic requirements and suggestions for optimal development and use of unmonitored online neuropsychological tests, including suggestions on acquiring reliability, validity, and norm scores. CONCLUSIONS: When properly addressing factors that could hamper reliable test results during development and use, online neuropsychological tests could aid large-scale data collection for clinical studies in the future. Investment in both proper development of online neuropsychological test platforms and the performance of accompanying psychometric studies is currently required.