Unraveling brain fog in post-COVID syndrome: Relationship between subjective cognitive complaints and cognitive function, fatigue, and neuropsychiatric symptoms.

BACKGROUND AND PURPOSE: "Brain fog" is a frequent and disabling symptom that can occur after SARS-CoV-2 infection. However, its clinical characteristics and the relationships among brain fog and objective cognitive function, fatigue, and neuropsychiatric symptoms (depression, anxiety) are still unclear. In this study, we aimed to examine the characteristics of brain fog and to understand how fatigue, cognitive performance, and neuropsychiatric symptoms and the mutual relationships among these variables influence subjective cognitive complaints. METHODS: A total of 170 patients with cognitive complaints in the context of post-COVID syndrome were evaluated using a comprehensive neuropsychological protocol. The FLEI scale was used to characterize subjective cognitive complaints. Correlation analysis, regression machine-learning algorithms, and mediation analysis were calculated. RESULTS: Cognitive complaints were mainly attention and episodic memory symptoms, while executive functions (planning) issues were less often reported. The FLEI scale, a mental ability questionnaire, showed high correlations with a fatigue scale and moderate correlations with the Stroop test, and anxiety and depressive symptoms. Random forest algorithms showed an R2 value of 0.409 for the prediction of FLEI score, with several cognitive tests, fatigue and depression being the best variables used in the prediction. Mediation analysis showed that fatigue was the main mediator between objective and subjective cognition, while the effect of depression was indirect and mediated through fatigue. CONCLUSIONS: Brain fog associated with COVID-19 is mainly characterized by attention and episodic memory, and fatigue, which is the main mediator between objective and subjective cognition. Our findings contribute to understanding the pathophysiology of brain fog and emphasize the need to unravel the main mechanisms underlying brain fog, considering several aspects.

Diagnosis of Alzheimer's disease and behavioural variant frontotemporal dementia with machine learning-aided neuropsychological assessment using feature engineering and genetic algorithms.

BACKGROUND: Neuropsychological assessment is considered a valid tool in the diagnosis of neurodegenerative disorders. However, there is an important overlap in cognitive profiles between Alzheimer's disease (AD) and behavioural variant frontotemporal dementia (bvFTD), and the usefulness in diagnosis is uncertain. We aimed to develop machine learning-based models for the diagnosis using cognitive tests. METHODS: Three hundred and twenty-nine participants (170 AD, 72 bvFTD, 87 healthy control [HC]) were enrolled. Evolutionary algorithms, inspired by the process of natural selection, were applied for both mono-objective and multi-objective classification and feature selection. Classical algorithms (NativeBayes, Support Vector Machines, among others) were also used, and a meta-model strategy. RESULTS: Accuracies for the diagnosis of AD, bvFTD and the differential diagnosis between them were higher than 84%. Algorithms were able to significantly reduce the number of tests and scores needed. Free and Cued Selective Reminding Test, verbal fluency and Addenbrooke's Cognitive Examination were amongst the most meaningful tests. CONCLUSIONS: Our study found high levels of accuracy for diagnosis using exclusively neuropsychological tests, which supports the usefulness of cognitive assessment in diagnosis. Machine learning may have a role in improving the interpretation and test selection.

Different apathy clinical profile and neural correlates in behavioral variant frontotemporal dementia and Alzheimer's disease.

OBJECTIVES: Apathy is one of the most common and disabling syndromes of dementia. Clinical apathy expression and neuroanatomical basis of apathy seem to differ between behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD), although evidence is scarce and poorly understood. Our main purposes were to compare the clinical apathy profile from patients with bvFTD and AD and analyze the relationship between apathy and brain metabolism measured using positron emission tomography imaging with 18 F fluorodeoxyglucose (FDG-PET). METHODS: Forty-two bvFTD, 42 AD, and 30 healthy volunteers without cognitive or behavioral complaints were included. Apathy was defined using Robert's 2009 diagnostic criteria, and specific apathy characteristics were assessed with the Lille Apathy Rating Scale. All participants underwent FDG-PET brain scan to provide data for voxel-based morphometric analysis. RESULTS: Multivariate analysis showed that subjects affected by bvFTD displayed greater impairment of emotional apathy and self-awareness in comparison with AD sample. Additionally, FDG-PET imaging analyses revealed that apathy was associated with different neuroanatomical substrates in each dementia group: left lateral prefrontal, medial frontal/anterior cingulate, lateral orbitofrontal and anterior insular cortices in bvFTD, and right anterior cingulate in AD. CONCLUSIONS: These results support that apathy is a complex syndrome, with different clinical expressions across different pathological conditions. Those differences in qualitative aspects of apathy seem to be associated with differences in the damage sites, as shown by our FDG-PET imaging analysis. Our findings provide a better knowledge about pathophysiology of apathy in dementia, which could have practical implications for therapeutic management. Copyright © 2017 John Wiley & Sons, Ltd.

Conversion between Addenbrooke's Cognitive Examination III and Mini-Mental State Examination.

ABSTRACTBackground:We aim to provide a conversion between Addenbrooke's Cognitive Examination III (ACE-III) and Mini-Mental State Examination (MMSE) scores, to predict the MMSE result based on ACE-III, thus avoiding the need for both tests, and improving their comparability. METHODS: Equipercentile equating method was used to elaborate a conversion table using a group of 400 participants comprising healthy controls and Alzheimer's disease (AD) patients. Then, reliability was assessed in a group of 100 healthy controls and patients with AD, 52 with primary progressive aphasia and 22 with behavioral variant frontotemporal dementia. RESULTS: The conversion table between ACE-III and MMSE denoted a high reliability, with intra-class correlation coefficients of 0.940, 0.922, and 0.902 in the groups of healthy controls and AD, behavioral variant frontotemporal dementia, and primary progressive aphasia, respectively. CONCLUSION: Our conversion table between ACE-III and MMSE suggests that MMSE may be estimated based on the ACE-III score, which could be useful for clinical and research purposes.

Neural Basis of Cognitive Assessment in Alzheimer Disease, Amnestic Mild Cognitive Impairment, and Subjective Memory Complaints.

INTRODUCTION: Interpreting cognitive tests is often challenging. The same test frequently examines multiple cognitive functions, and the functional and anatomical basis underlying test performance is unknown in many cases. This study analyses the correlation of different neuropsychological test results with brain metabolism in a series of patients evaluated for suspected Alzheimer disease. METHODS: 20 healthy controls and 80 patients consulting for memory loss were included, in which cognitive study and 18F-fluorodeoxyglucose PET were performed. Patients were categorized according to Reisberg's Global Deterioration Scale. Voxel-based analysis was used to determine correlations between brain metabolism and performance on the following tests: Free and Cued Selective Reminding Test (FCSRT), Boston Naming Test (BNT), Trail Making Test, Rey-Osterrieth Complex Figure test, Visual Object and Space Perception Battery (VOSP), and Tower of London (ToL) test. RESULTS: Mean age in the patient group was 73.9 ± 10.6 years, and 47 patients were women (58.7%). FCSRT findings were positively correlated with metabolism in the medial and anterior temporal region bilaterally, the left precuneus, and posterior cingulate. BNT results were correlated with metabolism in the middle temporal, superior, fusiform, and frontal medial gyri bilaterally. VOSP results were related to the occipital and parietotemporal regions bilaterally. ToL scores were correlated to metabolism in the right temporoparietal and frontal regions. CONCLUSIONS: These results suggest that different areas of the brain are involved in the processes required to complete different cognitive tests. Ascertaining the functional basis underlying these tests may prove helpful for understanding and interpreting them.

Comparative Diagnostic Accuracy of the ACE-III, MIS, MMSE, MoCA, and RUDAS for Screening of Alzheimer Disease.

BACKGROUND: Our aim was to evaluate and compare the diagnostic properties of 5 screening tests for the diagnosis of mild Alzheimer disease (AD). METHODS: We conducted a prospective and cross-sectional study of 92 patients with mild AD and of 68 healthy controls from our Department of Neurology. The diagnostic properties of the following tests were compared: Mini-Mental State Examination (MMSE), Addenbrooke's Cognitive Examination III (ACE-III), Memory Impairment Screen (MIS), Montreal Cognitive Assessment (MoCA), and Rowland Universal Dementia Assessment Scale (RUDAS). RESULTS: All tests yielded high diagnostic accuracy, with the ACE-III achieving the best diagnostic properties. The area under the curve was 0.897 for the ACE-III, 0.889 for the RUDAS, 0.874 for the MMSE, 0.866 for the MIS, and 0.856 for the MoCA. The Mini-ACE score from the ACE-III showed the highest diagnostic capacity (area under the curve 0.939). Memory scores of the ACE-III and of the RUDAS showed a better diagnostic accuracy than those of the MMSE and of the MoCA. All tests, especially the ACE-III, conveyed a higher diagnostic accuracy in patients with full primary education than in the less educated group. Implementing normative data improved the diagnostic accuracy of the ACE-III but not that of the other tests. CONCLUSIONS: The ACE-III achieved the highest diagnostic accuracy. This better discrimination was more evident in the more educated group.

Addenbrooke's cognitive examination III: diagnostic utility for mild cognitive impairment and dementia and correlation with standardized neuropsychological tests.

BACKGROUND: Addenbrooke's Cognitive Examination III (ACE-III) is a screening test that was recently validated for diagnosing dementia. Since it assesses attention, language, memory, fluency, and visuospatial function separately, it may also be useful for general neuropsychological assessments. The aim of this study was to analyze the tool's ability to detect early stages of Alzheimer's disease and to examine the correlation between ACE-III scores and scores on standardized neuropsychological tests. METHODS: Our study included 200 participants categorized as follows: 25 healthy controls, 48 individuals with subjective memory complaints, 47 patients with amnestic mild cognitive impairment and 47 mild Alzheimer's disease, and 33 patients with other neurodegenerative diseases. RESULTS: The ACE-III memory and language domains were highly correlated with the neuropsychological tests specific to those domains (Pearson correlation coefficient of 0.806 for total delayed recall on the Free and Cued Selective Reminding Test vs. 0.744 on the Boston Naming Test). ACE-III scores discriminated between controls and patients with amnestic mild cognitive impairment (AUC: 0.906), and between controls and patients with mild Alzheimer's disease (AUC: 0.978). CONCLUSION: Our results suggest that ACE-III is a useful neuropsychological test for assessing the cognitive domains of attention, language, memory, and visuospatial function. It also enables detection of Alzheimer's disease in early stages.

Amyloid- and FDG-PET imaging in amyotrophic lateral sclerosis.

PURPOSE: We aimed to study brain metabolism and presence of beta-amyloid deposits using positron emission tomography (PET) in patients with amyotrophic lateral sclerosis (ALS). METHODS: This prospective cross-sectional study included 18 patients with definite or probable ALS according to the revised El Escorial diagnostic criteria, and 24 healthy controls. Patients underwent neurological and neuropsychological assessments, PET with (18)F-fluorodeoxyglucose (FDG), and amyloid-PET with (18)F-florbetaben. RESULTS: Patients with ALS showed hypometabolism in the frontal area and hypermetabolism in the cerebellum compared to healthy controls. Four patients (22 %) displayed cognitive impairment and decreased metabolism in the frontal area extending bilaterally to the parietal regions, and increased metabolism in the posterior area of the cerebellum. In patients with no cognitive impairment, metabolism was lower in the left superior frontal gyrus and higher in the anterior and posterior lobes of the cerebellum. In the individual analysis, six patients (35 %) displayed more anterior involvement with hypometabolism affecting the superior frontal, medial, and inferior gyri; six patients (35 %) exhibited a more posterior pattern with hypometabolism in the precentral and postcentral gyri and in the superior and inferior parietal lobules; two patients (11 %) showed a mixed pattern; and three patients (17 %) showed no alterations in brain metabolism. Three (16 %) showed increased (18)F-florbetaben uptake compared to controls. CONCLUSIONS: We have identified two main patterns of brain metabolism with an association to cognitive status. Only a subgroup of patients showed an increased uptake of the amyloid tracer. Our results suggest that ALS is heterogeneous from a clinical, metabolic, and molecular standpoint.

Validation of the Lille's Apathy Rating Scale in Very Mild to Moderate Dementia.

OBJECTIVE: Apathy is one of the most common and disabling syndromes of dementia and presents at all stages of the disease. Comprehensive and structured methods to assess apathy in dementia are still needed. Lille's Apathy Rating Scale (LARS) has shown good psychometric properties for apathy evaluation in Parkinson disease but has not been validated in dementia. The aim of this study was to validate the LARS in a cohort of patients with very mild to moderate dementia. METHODS: 101 patients with cognitive impairment (Clinical Dementia Rating ≤ 2) and 50 healthy subjects were recruited. Patient diagnoses included 43 individuals with Alzheimer disease, 41 frontotemporal dementia, and 17 primary progressive aphasia. In addition to LARS, the following assessments were administered: Clinical Dementia Rating, Interview for Deterioration in Daily Living Activities in Dementia, Functional Activities Questionnaire, Frontal Behavioral Inventory, Neuropsychiatric Inventory (NPI), and Hamilton Depression Rating Scale. RESULTS: Internal consistency for LARS (Cronbach's alpha) was 0.940. Test-retest intraclass correlation coefficient (ICC) was 0.940 and inter-rater ICC was 0.987. The correlation among LARS and NPI apathy scores (concurrent validity) was 0.834. Receiver operating characteristic analysis estimated an area under the curve of 0.987. The optimal cutoff point was -10. Although total LARS score was influenced by the presence of depression, this disorder was independent with respect to apathy. CONCLUSION: LARS is reliable and valid for detecting and quantifying apathy in patients with dementia, even in very early stages of the disease.

Normative Data for the Spanish Version of the Addenbrooke's Cognitive Examination III.

BACKGROUND: Addenbrooke's Cognitive Examination III (ACE-III) is a cognitive test that has been validated for the diagnosis of cognitive disorders. The aim of this study was to provide normative data for the ACE-III for age, education and gender. METHODS: The Spanish version of the ACE-III was administered to a group of 273 healthy subjects in a multicenter study in Spain. Correlation and determination coefficients for age, education and gender were estimated. The overlapping interval strategy and linear regression analyses were used to provide adjusted norms for demographic factors and to explore the potential influence of these factors in the performance of the test. RESULTS: Age and education correlated significantly with the total score and with all the domains. Gender correlated only with the domains of attention and visuospatial skills. Norms for the total score and for cognitive domains (attention, memory, fluency, language, and visuospatial skills) are provided. CONCLUSION: This study confirms the influence of demographic factors (especially age and education) on the performance in the ACE-III and provides normative data for the Spanish version of the ACE-III.

Evaluation of the new consensus criteria for the diagnosis of primary progressive aphasia using fluorodeoxyglucose positron emission tomography.

BACKGROUND: New consensus criteria have been proposed to classify primary progressive aphasia (PPA) into three variants: agrammatic, semantic, and logopenic. Some studies have subsequently addressed the usefulness of these criteria, with controversial results. We aimed to determine the correlation between the clinical diagnosis according to the new criteria and brain topography in (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET). METHODS: Patients meeting the PPA criteria were prospectively recruited in a single center during a period of 18 months. They were clinically classified according to the new criteria and underwent FDG-PET. The cerebral metabolism of each patient was compared to a healthy control group using statistical parametric mapping. The expected variant according to the analysis of PET imaging was compared with the clinical diagnosis using the consensus criteria. RESULTS: 32 patients were included. 90% of them fulfilled the consensus criteria and could be classified into one of the three clinical variants. The correlation with the cerebral metabolism was high: the kappa index was 0.91 in the agrammatic variant, 0.71 in the semantic variant, and 0.74 in the logopenic variant. CONCLUSIONS: A high correlation with the diagnosis obtained using FDG-PET was found. However, an overdiagnosis of the logopenic variant was observed. These results support the use of the new criteria, but some modifications or complementary studies may still be necessary.

Conversion between the Rowland Universal Dementia Assessment Scale and Mini-Mental State Examination test scores in majority and minority populations.

INTRODUCTION: Despite the Rowland Universal Dementia Assessment Scale (RUDAS) having significant advantages as a cognitive screening tool, particularly for minority populations, the Mini-Mental State Examination (MMSE) test is the most widely used test for cognitive screening in Alzheimer's disease (AD). This study aimed to develop a conversion table to predict MMSE scores from observed RUDAS scores, allowing an easy-to-use method to compare both screening tests. METHODS: The equipercentile equating method was used to develop the conversion table using a training sample consisting of cognitively intact participants and individuals with early-stage AD. The resulting conversion table was validated in two samples, comprising participants from majority and minority populations assessed in Spanish. RESULTS: The conversion table demonstrated excellent reliability with intraclass correlation coefficients of.92 in both validation samples. CONCLUSION: This study provides a conversion table between RUDAS and MMSE scores, improving the comparability of these cognitive screening tools for use in clinical and research purposes.

Cognitive dysfunction characteristics of multiple sclerosis with aging.

BACKGROUND: We aimed to investigate the characteristics of cognitive impairment in older people with multiple sclerosis (MS). METHODS: Cross-sectional study that included participants that were examined with a common and comprehensive neuropsychological protocol. The subjects were matched by sociodemographic variables and the following groups were generated for comparisons: young MS versus healthy controls (HC) (n = 246), old MS versus HC (n = 198), young MS vs old MS (n = 226), MS vs Alzheimer's disease (AD)(n = 70), and MS vs Parkinson's disease (PD) (n = 62). The ICCoDiMS criteria were used to define cognitive impairment in MS. RESULTS: Cognitive impairment was more frequent in young than old patients (70.8 % vs 52.2 %). Attention and speed processing is the most frequent cognitive domain impaired in MS (54.9 % of young MS vs 32.7 % of old MS). The frequency of impairment in attention/processing speed (54.9 % vs 32.7 %) and episodic memory (27.9 % vs 14.3) was higher in the young group than in the old group. There were no statistically significant differences in the distribution of impairment in executive function (46.0 % vs 35.3 %), visuospatial (17.9 % vs 9.5 %), and language (12.4 % vs 17.7 %). In those patients meeting the criteria for cognitive impairment, young MS patients showed lower performance in attention/processing speed tests. Conversely, old MS patients showed lower performance in episodic memory, verbal fluency, and planning. There were no differences in the correlations between SDMT and other neuropsychological tests in young and old patients, which suggests similar cognitive processes underlying SDMT performance in both groups. There were differences between old MS and prodromal AD, especially in episodic memory, while the cognitive profile of old MS was largely shared with PD. CONCLUSIONS: Our study found that the cognitive profile of MS is defined by a characteristic impairment in attention and processing speed, which is present during the lifespan. The impairment in processing speed is less prominent in old age, whereas the impairment of other cognitive functions becomes more relevant. These findings suggest potential differences in the pathophysiological processes associated with cognitive impairment between young and old ages that warrant further investigation.

Comparison of the Diagnostic Accuracy of Five Cognitive Screening Tests for Diagnosing Mild Cognitive Impairment in Patients Consulting for Memory Loss.

Objectives: We aimed to evaluate and compare the diagnostic capacity of five cognitive screening tests for the diagnosis of mild cognitive impairment (MCI) in patients consulting by memory loss. Methods: A cross-sectional study involving 140 participants with a mean age of 74.42 ± 7.60 years, 87 (62.14%) women. Patients were classified as MCI or cognitively unimpaired according to a comprehensive neuropsychological battery. The diagnostic properties of the following screening tests were compared: Mini-Mental State Examination (MMSE), Addenbrooke's Cognitive Examination III (ACE-III) and Mini-Addenbrooke (M-ACE), Memory Impairment Screen (MIS), Montreal Cognitive Assessment (MoCA), and Rowland Universal Dementia Assessment Scale (RUDAS). Results: The area under the curve (AUC) was 0.861 for the ACE-III, 0.867 for M-ACE, 0.791 for MoCA, 0.795 for MMSE, 0.731 for RUDAS, and 0.672 for MIS. For the memory components, the AUC was 0.869 for ACE-III, 0.717 for MMSE, 0.755 for MoCA, and 0.720 for RUDAS. Cronbach's alpha was 0.827 for ACE-III, 0.505 for MMSE, 0.896 for MoCA, and 0.721 for RUDAS. Correlations with Free and Cued Selective Reminding Test were moderate with M-ACE, ACE-III, and MoCA, and moderate for the other tests. The M-ACE showed the best balance between diagnostic capacity and time of administration. Conclusions: ACE-III and its brief version M-ACE showed better diagnostic properties for the diagnosis of MCI than the other screening tests. MoCA and MMSE showed adequate properties, while the diagnostic capacity of MIS and RUDAS was limited.

European cross-cultural neuropsychological test battery (CNTB) for the assessment of cognitive impairment in multiple sclerosis: Cognitive phenotyping and classification supported by machine learning techniques.

BACKGROUND: The European Cross-Cultural Neuropsychological Test Battery (CNTB) has been proposed as a comprehensive battery for cognitive assessment, reducing the potential impact of cultural variables. In this validation study, we aimed to evaluate the diagnostic capacity of CNTB for the assessment of participants with multiple sclerosis (pwMS) compared to the Neuronorma battery (NN) according to the International Classification of Cognitive Disorders in MS criteria, and to develop machine learning (ML) algorithms to improve the diagnostic capacity of CNTB and to select the most relevant tests. METHODS: Sixty pwMS and 60 healthy controls (HC) with no differences in sex, age, or years of education were enrolled. All participants completed the CNTB and pwMS were also examined with NN, depression, and fatigue scales. Impaired domains and cognitive phenotypes were defined following ICCoDiMS based on CNTB scores and compared to NN, according to -1SD and -1.5SD cutoff scores. To select the most relevant tests, random forest (RF) was performed for different binary classifications. RESULTS: PwMS showed a lower performance compared to HC with medium-large effect sizes, in episodic memory, executive function, attention, and processing speed, in accordance with their characteristic cognitive profile. There were no differences in impaired domains or cognitive phenotypes between CNTB and NN, highlighting the role of episodic memory, executive function, attention, and processing speed tests. The most relevant tests identified by RF were consistent with inter-group comparisons and allowed a better classification than SD cutoff scores. CONCLUSION: CNTB is a valid test for cognitive diagnosis in pwMS, including key tests for the most frequently impaired cognitive domains in MS. The use of ML techniques may also be useful to improve diagnosis, especially in some tests with lower sensitivity.

Detection of cerebrospinal fluid biomarkers changes of Alzheimer's disease using a cognitive stress test in persons with subjective cognitive decline and mild cognitive impairment.

Introduction: Timely and accurate diagnosis of the earliest manifestations of Alzheimer's disease (AD) is critically important. Cognitive challenge tests such as the Loewenstein Acevedo Scales for Semantic Interference and Learning (LASSI-L) have shown favorable diagnostic properties in a number of previous investigations using amyloid or FDG PET. However, no studies have examined LASSI-L performance against cerebrospinal fluid biomarkers of AD, which can be affected before the distribution of fibrillar amyloid and other changes that can be observed in brain neuroimaging. Therefore, we aimed to evaluate the relationship between LASSI-L scores and CSF biomarkers and the capacity of the cognitive challenge test to detect the presence of amyloid and tau deposition in patients with subjective cognitive decline and amnestic mild cognitive impairment (MCI). Methods: One hundred and seventy-nine patients consulting for memory loss without functional impairment were enrolled. Patients were examined using comprehensive neuropsychological assessment, the LASSI-L, and cerebrospinal fluid (CSF) biomarkers (Aß1-42/Aß1-40 and ptau181). Means comparisons, correlations, effect sizes, and ROC curves were calculated. Results: LASSI-L scores were significantly associated with CSF biomarkers Aß1-42/Aß1-40 in patients diagnosed with MCI and subjective cognitive decline, especially those scores evaluating the capacity to recover from proactive semantic interference effects and delayed recall. A logistic regression model for the entire sample including LASSI-L and age showed an accuracy of 0.749 and an area under the curve of 0.785 to detect abnormal amyloid deposition. Conclusion: Our study supports the biological validity of the LASSI-L and its semantic interference paradigm in the context of the early stages of AD. These findings emphasize the utility and the convenience of including sensitive cognitive challenge tests in the assessment of patients with suspicion of early stages of AD.

Normative Data in Cross-Cultural Neuropsychological Instruments in Spaniards and Colombians Living in Spain.

BACKGROUND: Cross-Cultural Dementia Screening (CCD), Rowland Universal Dementia Assessment Scale (RUDAS), and European Cross-cultural Neuropsychological Test Battery (CNTB) are three novel neuropsychological instruments developed from a cross-cultural perspective to reduce the impact of culture in cognitive assessment and improve the assessment in diverse populations. OBJECTIVE: We aimed to collect and present normative data on these tests in a majority population sample (Spaniards living in Spain) and in a minority population sample (Colombians living in Spain). METHODS: CCD, RUDAS, and CNTB were administered to a group of 300 cognitively healthy participants (150 Spaniards and 150 Colombians). Linear regression modeling strategy was used to provide adjusted norms for demographic factors and to explore the influence of these factors on test performance. RESULTS: Most of the CCD and CNTB scores were predicted by age and years of education, with some tests only predicted by age or showing a ceiling effect. The comparison of normative data between the two samples confirmed the favorable cross-cultural properties of these instruments, with only some differences in processing speed and executive functioning scores. CONCLUSIONS: Our study finds a comparable influence of demographic factors in both populations on the performance of CCD, RUDAS, and CNTB, confirming their adequate cross-cultural properties. We provide normative data for these tests in Spaniards and Colombians living in Spain.

Multi-Disease Validation of the RUDAS for Cognitive Screening in Alzheimer's Disease, Parkinson's Disease, and Multiple Sclerosis.

BACKGROUND: The Rowland Universal Dementia Assessment Scale (RUDAS) is a cognitive test with favorable diagnostic properties for detecting dementia and a low influence of education and cultural biases. OBJECTIVE: We aimed to validate the RUDAS in people with Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). METHODS: We enrolled one hundred and fifty participants (60 with AD, 30 with PD, 60 with MS, and 120 healthy controls (HC)). All clinical groups completed a comprehensive neuropsychological battery, RUDAS, and standard cognitive tests of each disorder: MMSE, SCOPA-COG, and Symbol Digit Modalities Test. Intergroup comparisons between clinical groups and HC and ROC curves were estimated. Random Forest algorithms were trained and validated to detect cognitive impairment using RUDAS and rank the most relevant scores. RESULTS: The RUDAS scores were lower in patients with AD, and patients with PD and MS showed cognitive impairment compared to healthy controls. Effect sizes were generally large. The total score was the most discriminative, followed by the memory score. Correlations with standardized neuropsychological tests were moderate to high. Random Forest algorithms obtained accuracies over 80-90% using the RUDAS for diagnosing AD and cognitive impairment associated with PD and MS. CONCLUSION: Our results suggest the RUDAS is a valid test candidate for multi-disease cognitive screening tool in AD, PD, and MS.

Validation of the European Cross-Cultural Neuropsychological Test Battery (CNTB) for the assessment of mild cognitive impairment due to Alzheimer's disease and Parkinson's disease.

Background: The Cross-Cultural Neuropsychological Test Battery (CNTB) is a novel test battery specifically designed to reduce the impact of multiculturality in cognitive assessment. Objective: We aimed to validate the CNTB in Spaniards in patients with Alzheimer's disease (AD), including patients at mild cognitive impairment (MCI) and mild dementia stages, and Parkinson's disease with MCI (PD-MCI). Methods: Thirty patients with AD-MCI, 30 with AD-dementia (AD-D), and 30 with PD-MCI were recruited. Each clinical group was compared against a healthy control group (HC) with no differences in sex, age, or years of education. Intergroup comparisons, ROC analysis, and cut-off scores were calculated. Results: AD-MCI scored lower than HC in those subtests associated with episodic memory and verbal fluency. AD-D also showed lower scores in executive functions and visuospatial tests. Effect sizes for all the subtests were large. PD-MCI showed lower performance than HC in memory and executive functions, particularly on error scores, with large effect sizes. Comparing AD-MCI and PD-MCI, AD-MCI had lower memory scores, while PD-MCI showed the worst performance in executive functions. CNTB showed appropriate convergent validity with standardized neuropsychological tests measuring the same cognitive domains. We obtained similar cut-off scores to previous studies performed in other populations. Conclusions: The CNTB showed appropriate diagnostic properties in AD and PD, including those stages with mild cognitive impairment. This supports the utility of the CNTB for the early detection of cognitive impairment in AD and PD.

FDG-PET-based neural correlates of Addenbrooke's cognitive examination III scores in Alzheimer's disease and frontotemporal degeneration.

Introduction: The Addenbrooke's Cognitive Examination III (ACE-III) is a brief test useful for neuropsychological assessment. Several studies have validated the test for the diagnosis of Alzheimer's disease (AD) and frontotemporal dementia (FTD). In this study, we aimed to examine the metabolic correlates associated with the performance of ACE-III in AD and behavioral variant FTD. Methods: We enrolled 300 participants in a cross-sectional study, including 180 patients with AD, 60 with behavioral FTD (bvFTD), and 60 controls. An 18F-Fluorodeoxyglucose positron emission tomography study was performed in all cases. Correlation between the ACE-III and its domains (attention, memory, fluency, language, and visuospatial) with the brain metabolism was estimated. Results: The ACE-III showed distinct neural correlates in bvFTD and AD, effectively capturing the most relevant regions involved in these disorders. Neural correlates differed for each domain, especially in the case of bvFTD. Lower ACE-III scores were associated with more advanced stages in both disorders. The ACE-III exhibited high discrimination between bvFTD vs. HC, and between AD vs. HC. Additionally, it was sensitive to detect hypometabolism in brain regions associated with bvFTD and AD. Conclusion: Our study contributes to the knowledge of the brain regions associated with ACE-III, thereby facilitating its interpretation, and highlighting its suitability for screening and monitoring. This study provides further validation of ACE-III in the context of AD and FTD.