Shared Proteins and Pathways of Cardiovascular and Cognitive Diseases: Relation to Vascular Cognitive Impairment.

One of the primary goals of systems medicine is the detection of putative proteins and pathways involved in disease progression and pathological phenotypes. Vascular cognitive impairment (VCI) is a heterogeneous condition manifesting as cognitive impairment resulting from vascular factors. The precise mechanisms underlying this relationship remain unclear, which poses challenges for experimental research. Here, we applied computational approaches like systems biology to unveil and select relevant proteins and pathways related to VCI by studying the crosstalk between cardiovascular and cognitive diseases. In addition, we specifically included signals related to oxidative stress, a common etiologic factor tightly linked to aging, a major determinant of VCI. Our results show that pathways associated with oxidative stress are quite relevant, as most of the prioritized vascular cognitive genes and proteins were enriched in these pathways. Our analysis provided a short list of proteins that could be contributing to VCI: DOLK, TSC1, ATP1A1, MAPK14, YWHAZ, CREB3, HSPB1, PRDX6, and LMNA. Moreover, our experimental results suggest a high implication of glycative stress, generating oxidative processes and post-translational protein modifications through advanced glycation end-products (AGEs). We propose that these products interact with their specific receptors (RAGE) and Notch signaling to contribute to the etiology of VCI.

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.

Cognitive outcomes in Susac syndrome: A 2-year neuropsychological follow-up study.

BACKGROUND AND PURPOSE: Susac syndrome (SuS) is a rare, autoimmune, neurological disease characterized by a clinical triad of branch retinal artery occlusion, sensorineural hearing loss and encephalopathy. Neuropsychological functioning in SuS is little researched and the prevalence, nature, and evolution over time of cognitive deficits in SuS remain unclear. This study aimed to better understand the long-term neuropsychological outcomes of patients with SuS. METHODS: Thirteen patients with SuS (mean [SD] age 39.5 [11.1] years) were enrolled at the Ghent University Hospital by their treating neurologist. The cognitive functioning and emotional well-being of each patient was evaluated by means of a thorough neuropsychological test battery at baseline and after 2 years. Follow-up testing after 2 years was performed in 11 patients (mean [SD] age 42.2 [11.5] years). RESULTS: Patients showed normal neuropsychological test results at a group level, both at baseline and follow-up testing. Significant improvements over time were found for information processing speed, verbal recognition, and semantic and phonological fluency. Individual test results showed interindividual variability at baseline, with most impairments being in attention, executive functioning and language, which improved after a 2-year period. In addition, patients reported significantly lower mental and physical well-being, both at baseline and follow-up testing. CONCLUSIONS: Our results suggest that neuropsychological dysfunction in SuS is limited at a group level and improves over time. Nonetheless, individual test results reveal interindividual variability, making cognitive screening essential. Furthermore, a high psycho-emotional burden of the disease was reported, for which screening and follow-up are necessary.

Cognitive Impairment and Depression in Mastocytosis: A Synthesis of the Literature.

PURPOSE OF REVIEW: Symptoms of depression and cognitive dysfunction are commonly reported in mastocytosis. The aims of this review paper are to summarize the current literature on cognitive dysfunction and depressive symptoms, elucidate some of the mechanistic pathways underlying depressive symptoms in mastocytosis, identify gaps in the literature, and offer guidance for future research in this area. RECENT FINDINGS: The study of cognition and depression in mastocytosis is in its infancy and the methodological flaws of the current literature limit interpretability. There is preliminary evidence that some individuals with mastocytosis might experience mild deficits in memory. On average, depression symptom scores fell within the mild to moderate or sub-syndromal range. Regrettably, only one study utilized a standardized diagnostic instrument to assess major depressive disorder. The authors' tendency to inaccurately equate depressive symptoms with a diagnosis of major depressive disorder presents a notable issue. The prevalence of cognitive deficits and depression appears to be similar to other chronic illnesses. Future work needs to better characterize cognition and characterize "depression" in this population.

Language Impairment in Vascular Dementia: A Clinical Review.

Vascular cognitive impairment (VCI) encompasses a wide range of conditions, including cognitive impairment associated with stroke or vascular brain injury, mild vascular cognitive impairment, and vascular dementia (VD). Knowledge of language impairment associated with VD is far less extensive than that of Alzheimer's disease. Although not prevalent in VD, impairment in language skills has been reported. A better understanding of the neurolinguistic features associated with the different presentations of VD could facilitate medical diagnosis. In this article, we report data on language impairment in VD, with particular attention to their primary or secondary functional origin. To better appreciate this functional origin, we also outline the main characteristics of impairment in other cognitive functions. Key elements that should be considered in the speech-language assessment of individuals with possible or proven VD are also highlighted.

The Telephone Language Screener (TLS): standardization of a novel telephone-based screening test for language impairment.

BACKGROUND: This study aimed at developing and standardizing the Telephone Language Screener (TLS), a novel, disease-nonspecific, telephone-based screening test for language disorders. METHODS: The TLS was developed in strict pursuance to the current psycholinguistic standards. It comprises nine tasks assessing phonological, lexical-semantic and morpho-syntactic components, as well as an extra Backward Digit Span task. The TLS was administered to 480 healthy participants (HPs), along with the Telephone-based Semantic Verbal Fluency (t-SVF) test and a Telephone-based Composite Language Index (TBCLI), as well as to 37 cerebrovascular/neurodegenerative patients-who also underwent the language subscale of the Telephone Interview for Cognitive Status (TICS-L). An HP subsample was also administered an in-person language battery. Construct validity, factorial structure, internal consistency, test-retest and inter-rater reliability were tested. Norms were derived via Equivalent Scores. The capability of the TLS to discriminate patients from HPs and to identify, among the patient cohort, those with a defective TICS-L, was also examined. RESULTS: The TLS was underpinned by a mono-component structure and converged with the t-SVF (p < .001), the TBCLI (p < .001) and the in-person language battery (p = .002). It was internally consistent (McDonald's ω = 0.67) and reliable between raters (ICC = 0.99) and at retest (ICC = 0.83). Age and education, but not sex, were predictors of TLS scores. The TLS optimally discriminated patients from HPs (AUC = 0.80) and successfully identified patients with an impaired TICS-L (AUC = 0.92). In patients, the TLS converged with TICS-L scores (p = 0.016). DISCUSSION: The TLS is a valid, reliable, normed and clinically feasible telephone-based screener for language impairment.

Association of 8-hydroxy-2'-deoxyguanosine with motoric cognitive risk in elderly Chinese people: RUGAO longevity and aging cross-sectional study.

BACKGROUND: Motor cognitive risk syndrome (MCR) represents a critical pre-dementia and disability state characterized by a combination of objectively measured slow walking speed and subjective memory complaints (SMCs). This study aims to identify risk factors for MCR and investigate the relationship between plasma levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and MCR among Chinese community-dwelling elderly populations. METHODS: A total of 1312 participants were involved in this study based on the data of the Rugao Longevity and Aging Study (RuLAS). The MCR was characterized by SMCs and slow walking speed. The SCCs were defined as a positive answer to the question 'Do you feel you have more problems with memory than most?' in a 15-item Geriatric Depression Scale. Slow walking speed was determined by one standard deviation or more below the mean value of the patient's age and gender group. The plasma of 8-OHdG were measured by a technician in the biochemistry laboratory of the Rugao People's Hospital during the morning of the survey. RESULTS: The prevalence of MCR was found to be 7.9%. After adjusting for covariates, significant associations with MCR were observed in older age (OR 1.057; p = 0.018), history of cerebrovascular disease (OR 2.155; p = 0.010), and elevated 8-OHdG levels (OR 1.007; p = 0.003). CONCLUSIONS: This study indicated the elevated plasma 8-OHdG is significantly associated with increased MCR risk in the elderly, suggesting its potential as a biomarker for early detection and intervention in MCR. This finding underscores the importance of monitoring oxidative DNA damage markers in predicting cognitive and motor function declines, offering new avenues for research and preventive strategies in aging populations.

Determining optimal cutoff scores of Cognitive Abilities Screening Instrument to identify dementia and mild cognitive impairment in Taiwan.

BACKGROUND: The early detection of dementia depends on efficient methods for the assessment of cognitive capacity. Existing cognitive screening tools are ill-suited to the differentiation of cognitive status, particularly when dealing with early-stage impairment. METHODS: The study included 8,979 individuals (> 50 years) with unimpaired cognitive functions, mild cognitive impairment (MCI), or dementia. This study sought to determine optimal cutoffs values for the Cognitive Abilities Screening Instrument (CASI) aimed at differentiating between individuals with or without dementia as well as between individuals with or without mild cognitive impairment. Cox proportional hazards models were used to evaluate the value of CASI tasks in predicting conversion from MCI to all-cause dementia, dementia of Alzheimer's type (DAT), or to vascular dementia (VaD). RESULTS: Our optimized cutoff scores achieved high accuracy in differentiating between individuals with or without dementia (AUC = 0.87-0.93) and moderate accuracy in differentiating between CU and MCI individuals (AUC = 0.67 - 0.74). Among individuals without cognitive impairment, scores that were at least 1.5 × the standard deviation below the mean scores on CASI memory tasks were predictive of conversion to dementia within roughly 2 years after the first assessment (all-cause dementia: hazard ratio [HR] = 2.81 - 3.53; DAT: 1.28 - 1.49; VaD: 1.58). Note that the cutoff scores derived in this study were lower than those reported in previous studies. CONCLUSION: Our results in this study underline the importance of establishing optimal cutoff scores for individuals with specific demographic characteristics and establishing profiles by which to guide CASI analysis.

An analysis of factors influencing cognitive dysfunction among older adults in Northwest China based on logistic regression and decision tree modelling.

BACKGROUND: Cognitive dysfunction is one of the leading causes of disability and dependence in older adults and is a major economic burden on the public health system. The aim of this study was to investigate the risk factors for cognitive dysfunction and their predictive value in older adults in Northwest China. METHODS: A cross-sectional study was conducted using a multistage sampling method. The questionnaires were distributed through the Elderly Disability Monitoring Platform to older adults aged 60 years and above in Northwest China, who were divided into cognitive dysfunction and normal cognitive function groups. In addition to univariate analyses, logistic regression and decision tree modelling were used to construct a model to identify factors that can predict the occurrence of cognitive dysfunction in older adults. RESULTS: A total of 12,494 valid questionnaires were collected, including 2617 from participants in the cognitive dysfunction group and 9877 from participants in the normal cognitive function group. Univariate analysis revealed that ethnicity, BMI, age, educational attainment, marital status, type of residence, residency status, current work status, main economic source, type of chronic disease, long-term use of medication, alcohol consumption, participation in social activities, exercise status, social support, total scores on the Balanced Test Assessment, total scores on the Gait Speed Assessment total score, and activities of daily living (ADL) were significantly different between the two groups (all P < 0.05). According to logistic regression analyses, ethnicity, BMI, educational attainment, marital status, residency, main source of income, chronic diseases, annual medical examination, alcohol consumption, exercise status, total scores on the Balanced Test Assessment, and activities of daily living (ADLs) were found to influence cognitive dysfunction in older adults (all P < 0.05). In the decision tree model, the ability to perform activities of daily living was the root node, followed by total scores on the Balanced Test Assessment, marital status, educational attainment, age, annual medical examination, and ethnicity. CONCLUSIONS: Traditional risk factors (including BMI, literacy, and alcohol consumption) and potentially modifiable risk factors (including balance function, ability to care for oneself in daily life, and widowhood) have a significant impact on the increased risk of cognitive dysfunction in older adults in Northwest China. The use of decision tree models can help health care workers better assess cognitive function in older adults and develop personalized interventions. Further research could help to gain insight into the mechanisms of cognitive dysfunction and provide new avenues for prevention and intervention.

Development and validation of prediction model for older adults with cognitive frailty.

OBJECTIVE: This study sought to develop and validate a 6-year risk prediction model in older adults with cognitive frailty (CF). METHODS: In the secondary analysis of Chinese Longitudinal Healthy Longevity Survey (CLHLS), participants from the 2011-2018 cohort were included to develop the prediction model. The CF was assessed by the Chinese version of Mini-Mental State Exam (CMMSE) and the modified Fried criteria. The stepwise regression was used to select predictors, and the logistic regression analysis was conducted to construct the model. The model was externally validated using the temporal validation method via the 2005-2011 cohort. The discrimination was measured by the area under the curve (AUC), and the calibration was measured by the calibration plot. A nomogram was conducted to vividly present the prediction model. RESULTS: The development dataset included 2420 participants aged 60 years or above, and 243 participants suffered from CF during a median follow-up period of 6.91 years (interquartile range 5.47-7.10 years). Six predictors, namely, age, sex, residence, body mass index (BMI), exercise, and physical disability, were finally used to develop the model. The model performed well with the AUC of 0.830 and 0.840 in the development and external validation datasets, respectively. CONCLUSION: The study could provide a practical tool to identify older adults with a high risk of CF early. Furthermore, targeting modifiable factors could prevent about half of the new-onset CF during a 6-year follow-up.

Toward digitally screening and profiling AD: A GAMLSS approach of MemTrax in China.

PURPOSES: To establish a normative range of MemTrax (MTx) metrics in the Chinese population. METHODS: The correct response percentage (MTx-%C) and mean response time (MTx-RT) were obtained and the composite scores (MTx-Cp) calculated. Generalized additive models for location, shape and scale (GAMLSS) were applied to create percentile curves and evaluate goodness of fit, and the speed-accuracy trade-off was investigated. RESULTS: 26,633 subjects, including 13,771 (51.71%) men participated in this study. Age- and education-specific percentiles of the metrics were generated. Q tests and worm plots indicated adequate fit for models of MTx-RT and MTx-Cp. Models of MTx-%C for the low and intermediate education fit acceptably, but not well enough for a high level of education. A significant speed-accuracy trade-off was observed for MTx-%C from 72 to 94. CONCLUSIONS: GAMLSS is a reliable method to generate smoothed age- and education-specific percentile curves of MTx metrics, which may be adopted for mass screening and follow-ups addressing Alzheimer's disease or other cognitive diseases. HIGHLIGHTS: GAMLSS was applied to establish nonlinear percentile curves of cognitive decline. Subjects with a high level of education demonstrate a later onset and slower decline of cognition. Speed-accuracy trade-off effects were observed in a subgroup with moderate accuracy. MemTrax can be used as a mass-screen instrument for active cognition health management advice.

Patterns of cognitive domain abnormalities enhance discrimination of dementia risk prediction: The ARIC study.

INTRODUCTION: The contribution of neuropsychological assessments to risk assessment for incident dementia is underappreciated. METHODS: We analyzed neuropsychological testing results in dementia-free participants in the Atherosclerosis Risk in Communities (ARIC) study. We examined associations of index domain-specific neuropsychological test performance with incident dementia using cumulative incidence curves and Cox proportional hazards models. RESULTS: Among 5296 initially dementia-free participants (mean [standard deviation] age of 75.8 [5.1] years; 60.1% women, 22.2% Black) over a median follow-up of 7.9 years, the covariate-adjusted hazard ratio varied substantially depending on the pattern of domain-specific performance and age, in an orderly manner from single domain language abnormalities (lowest risk) to single domain executive or memory abnormalities, to multidomain abnormalities including memory (highest risk). DISCUSSION: By identifying normatively defined cognitive abnormalities by domains based on neuropsychological test performance, there is a conceptually orderly and age-sensitive spectrum of risk for incident dementia that provides valuable information about the likelihood of progression. HIGHLIGHTS: Domain-specific cognitive profiles carry enhanced prognostic value compared to mild cognitive impairment. Single-domain non-amnestic cognitive abnormalities have the most favorable prognosis. Multidomain amnestic abnormalities have the greatest risk for incident dementia. Patterns of domain-specific risks are similar by sex and race.

[Application of the Trail Making Test in the schizophrenia research]. / A Trail Making Teszt alkalmazása a szkizofrénia-kutatásban.

Even the Kraepelinian concept of dementia praecox suggests a link between schizophrenia and various cognitive deficits. Although cognitive impairment is not a fundamental symptom of schizophrenia, it is considered to be one of the basic features of the disease. The deficit can affect a number of cognitive domains and is most often specific. One of the most pronounced cognitive symptoms of schizophrenia is impairment in attentional and executive functions. The Trail Making Test (TMT) is a screening test commonly used in the clinic that is very sensitive to impairments in attention and executive functions. The aim of the present study is to summarise the research conducted in the last five years in which the Trail Making Test has been used to screen schizophrenics. A search was conducted in the PubMed database using the keywords "schizophrenia" and "Trail Making Test". A total of 43 relevant studies have been published on this topic since 2018. A review of the research on this topic shows that the TMT can be used to identify cognitive deficits in schizophrenics, affecting executive functions and attention. It also shows that schizophrenic patients performed significantly worse on the test than healthy individuals.

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

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

[Better assessment, better care: Quetci, a questionnaire for assessing cognitive disorders in nursing practice]. / Mieux évaluer, mieux soigner : le Quetci, un questionnaire d'évaluation des troubles cognitifs IDE.

Cognitive disorders can have significant repercussions on the quality of care and daily life for patients. We have developed a new tool specifically designed for nursing practice to identify these problems in patients with brain tumors. The Cognitive Impairment Assessment Questionnaire for nursing practice is an objective, quick and easy-to-administer tool that is readily accepted by patients.

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

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

Predicting employment deterioration with the Processing Speed Test (PST) and SDMT in multiple sclerosis.

BACKGROUND: Employment deterioration is common in people with multiple sclerosis (PwMS). Clinicians often learn of job loss after its occurrence, leaving no opportunity for preventive measures. OBJECTIVES: Identify which neuropsychological measures discriminate between healthy volunteers (HVs) and employed/disabled PwMS at baseline and predict work deterioration over 2 years. METHODS: We examined 198 PwMS with computerized tests such as the Processing Speed Test (PST) and conventional tests such as the Symbol-Digit Modalities Test (SDMT), administered at baseline. Employment was assessed via Buffalo Vocational Monitoring Survey. Univariate and regression analyses identified significant predictors of PwMS categorized as work-stable versus work-deteriorated status. RESULTS: PwMS were impaired on all baseline assessments relative to HVs (p's < 0.001). Post hoc analyses showed that employed PwMS and HVs performed similarly and better than work-disabled PwMS. At the univariate level, both PST and SDMT discriminated between work-deteriorated and work-stable PwMS (p's < 0.01). The logistic regression model accounting for all measures retained PST and the computerized Walking Speed Test. PwMS with increased negative work events had lower PST (p < 0.001), SDMT (p < 0.001), and BVMT-R (p < 0.01) scores than stable PwMS. The related regression model retained PST and BVMT-R (p < 0.001). CONCLUSION: Cognition, as measured by the PST and BVMT-R, are predictive of job deterioration in PwMS and may be a useful screening tool to identify those at high risk of unemployment.

Neurophysiological MEG markers of cognitive impairment and performance validity in multiple sclerosis.

BACKGROUND: Suboptimal performance during neuropsychological testing frequently occurs in multiple sclerosis (MS), leading to unreliable cognitive outcomes. Neurophysiological alterations correlate with MS-related cognitive impairment, but studies have not yet considered performance validity. OBJECTIVES: To investigate neurophysiological markers of cognitive impairment in MS, while explicitly addressing performance validity. METHODS: Magnetoencephalography recordings, neuropsychological assessments, and performance validity testing were obtained from 90 MS outpatients with cognitive complaints. Spectral and resting-state functional connectivity (rsFC) properties were compared between cognitively impaired (CI), cognitively preserved (CP), and suboptimally performing (SUB) patients using regression models and permutation testing. RESULTS: CI had higher power in low-frequency bands and lower power in high bands compared to CP, indicating neuronal slowing. CI also showed lower beta power compared to SUB. Overall power spectra visually differed between CI and CP, and SUB showed overlap with both groups. CI had lower rsFC than CP and SUB patients. CP and SUB patients showed no differences. CONCLUSION: Neuronal slowing and altered rsFC can be considered cognitive markers in MS. Patients who performed suboptimally showed resemblance with patients with and without cognitive impairments, and although their overall neurophysiological profile was more similar to patients without impairments, it suggests heterogeneity regarding their pathophysiology.

Supervised, Self-Administered Tablet-Based Cognitive Assessment in Neurodegenerative Disorders and Stroke.

INTRODUCTION: As the population ages, the prevalence of cognitive impairment is expanding. Given the recent pandemic, there is a need for remote testing modalities to assess cognitive deficits in individuals with neurological disorders. Self-administered, remote, tablet-based cognitive assessments would be clinically valuable if they can detect and classify cognitive deficits as effectively as traditional in-person neuropsychological testing. METHODS: We tested whether the Miro application, a tablet-based neurocognitive platform, measured the same cognitive domains as traditional pencil-and-paper neuropsychological tests. Seventy-nine patients were recruited and then randomized to either undergo pencil-and-paper or tablet testing first. Twenty-nine age-matched healthy controls completed the tablet-based assessments. We identified Pearson correlations between Miro tablet-based modules and corresponding neuropsychological tests in patients and compared scores of patients with neurological disorders with those of healthy controls using t tests. RESULTS: Statistically significant Pearson correlations between the neuropsychological tests and their tablet equivalents were found for all domains with moderate (r > 0.3) or strong (r > 0.7) correlations in 16 of 17 tests (p < 0.05). All tablet-based subtests differentiated healthy controls from neurologically impaired patients by t tests except for the spatial span forward and finger tapping modules. Participants reported enjoyment of the tablet-based testing, denied that it provoked anxiety, and noted no preference between modalities. CONCLUSIONS: This tablet-based application was found to be widely acceptable to participants. This study supports the validity of these tablet-based assessments in the differentiation of healthy controls from patients with neurocognitive deficits in a variety of cognitive domains and across multiple neurological disease etiologies.

Slowing processing speed is associated with cognitive fatigue in newly diagnosed multiple sclerosis patients.

OBJECTIVE: To further investigate objective measures of cognitive fatigue (CF), defined as the inability to sustain performance over time, in newly diagnosed multiple sclerosis (MS) patients, by conducting a performance analysis on the Paced Auditory Serial Addition Test (PASAT) based on the type of errors (omissions vs. incorrect responses) committed. METHOD: Sixty-two newly diagnosed patients with MS (pwMS) and 41 healthy controls (HC) completed the PASAT. Analysis of the change in performance during the test was performed by comparing the number of correct responses, incorrect responses, and omissions in the 1st versus the 3rd tertile of the PASAT. RESULTS: A significant decline in accuracy over time was observed to be related to an increment in the number of omissions, significantly more pronounced in pwMS than in HC. No change in the number of incorrect responses throughout the PASAT was observed for either group. CONCLUSIONS: CF can be detected even in newly diagnosed pwMS and might objectively manifest as a progressive increase in omissions during a sustained highly demanding task (i.e., PASAT). This pattern may reflect slowed processing speed and increased fatigue in pwMS. Focusing on omissions on the PASAT instead of correct responses only may improve its specificity as an objective measure of CF.