Cognitive profile in multiple sclerosis and post-COVID condition: a comparative study using a unified taxonomy.

Post-COVID condition (PCC) and multiple sclerosis (MS) share some clinical and demographic features, including cognitive symptoms and fatigue. Some pathophysiological mechanisms well-known in MS, such as autoimmunity, neuroinflammation and myelin damage, have also been implicated in PCC. In this study, we aimed to compare the cognitive phenotypes of two large cohorts of patients with PCC and MS, and to evaluate the relationship between fatigue and cognitive performance. Cross-sectional study including 218 patients with PCC and 218 with MS matched by age, sex, and years of education. Patients were evaluated with a comprehensive neuropsychological protocol and were categorized according to the International Classification of Cognitive Disorders system. Fatigue and depression were also assessed. Cognitive profiles of PCC and MS largely overlapped, with a greater impairment in episodic memory in MS, but with small effect sizes. The most salient deficits in both disorders were in attention and processing speed. The severity of fatigue was greater in patients with PCC. Still, the correlations between fatigue severity and neuropsychological tests were more prominent in the case of MS. There were no differences in the severity of depression among groups. Our study found similar cognitive profiles in PCC and MS. Fatigue was more severe in PCC, but was more associated with cognitive performance in MS. Further comparative studies addressing the mechanisms related to cognitive dysfunction and fatigue may be of interest to advance the knowledge of these disorders and develop new therapies.

A multi-site study on sex differences in cortical thickness in non-demented Parkinson's disease.

Clinical, cognitive, and atrophy characteristics depending on sex have been previously reported in Parkinson's disease (PD). However, though sex differences in cortical gray matter measures in early drug naïve patients have been described, little is known about differences in cortical thickness (CTh) as the disease advances. Our multi-site sample comprised 211 non-demented PD patients (64.45% males; mean age 65.58 ± 8.44 years old; mean disease duration 6.42 ± 5.11 years) and 86 healthy controls (50% males; mean age 65.49 ± 9.33 years old) with available T1-weighted 3 T MRI data from four international research centers. Sex differences in regional mean CTh estimations were analyzed using generalized linear models. The relation of CTh in regions showing sex differences with age, disease duration, and age of onset was examined through multiple linear regression. PD males showed thinner cortex than PD females in six frontal (bilateral caudal middle frontal, bilateral superior frontal, left precentral and right pars orbitalis), three parietal (bilateral inferior parietal and left supramarginal), and one limbic region (right posterior cingulate). In PD males, lower CTh values in nine out of ten regions were associated with longer disease duration and older age, whereas in PD females, lower CTh was associated with older age but with longer disease duration only in one region. Overall, male patients show a more widespread pattern of reduced CTh compared with female patients. Disease duration seems more relevant to explain reduced CTh in male patients, suggesting worse prognostic over time. Further studies should explore sex-specific cortical atrophy trajectories using large longitudinal multi-site data.

A data-driven approach to complement the A/T/(N) classification system using CSF biomarkers.

AIMS: The AT(N) classification system not only improved the biological characterization of Alzheimer's disease (AD) but also raised challenges for its clinical application. Unbiased, data-driven techniques such as clustering may help optimize it, rendering informative categories on biomarkers' values. METHODS: We compared the diagnostic and prognostic abilities of CSF biomarkers clustering results against their AT(N) classification. We studied clinical (patients from our center) and research (Alzheimer's Disease Neuroimaging Initiative) cohorts. The studied CSF biomarkers included Aß(1-42), Aß(1-42)/Aß(1-40) ratio, tTau, and pTau. RESULTS: The optimal solution yielded three clusters in both cohorts, significantly different in diagnosis, AT(N) classification, values distribution, and survival. We defined these three CSF groups as (i) non-defined or unrelated to AD, (ii) early stages and/or more delayed risk of conversion to dementia, and (iii) more severe cognitive impairment subjects with faster progression to dementia. CONCLUSION: We propose this data-driven three-group classification as a meaningful and straightforward approach to evaluating the risk of conversion to dementia, complementary to the AT(N) system classification.

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.

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.

Hippocampal subfield abnormalities and biomarkers of pathologic brain changes: from SARS-CoV-2 acute infection to post-COVID syndrome.

BACKGROUND: Cognitive deficits are among the main disabling symptoms in COVID-19 patients and post-COVID syndrome (PCS). Within brain regions, the hippocampus, a key region for cognition, has shown vulnerability to SARS-CoV-2 infection. Therefore, in vivo detailed evaluation of hippocampal changes in PCS patients, validated on post-mortem samples of COVID-19 patients at the acute phase, would shed light into the relationship between COVID-19 and cognition. METHODS: Hippocampal subfields volume, microstructure, and perfusion were evaluated in 84 PCS patients and compared to 33 controls. Associations with blood biomarkers, including glial fibrillary acidic protein (GFAP), myelin oligodendrocyte glycoprotein (MOG), eotaxin-1 (CCL11) and neurofilament light chain (NfL) were evaluated. Besides, biomarker immunodetection in seven hippocampal necropsies of patients at the acute phase were contrasted against eight controls. FINDINGS: In vivo analyses revealed that hippocampal grey matter atrophy is accompanied by altered microstructural integrity, hypoperfusion, and functional connectivity changes in PCS patients. Hippocampal structural and functional alterations were related to cognitive dysfunction, particularly attention and memory. GFAP, MOG, CCL11 and NfL biomarkers revealed alterations in PCS, and showed associations with hippocampal volume changes, in selective hippocampal subfields. Moreover, post mortem histology showed the presence of increased GFAP and CCL11 and reduced MOG concentrations in the hippocampus in post-mortem samples at the acute phase. INTERPRETATION: The current results evidenced that PCS patients with cognitive sequalae present brain alterations related to cognitive dysfunction, accompanied by a cascade of pathological alterations in blood biomarkers, indicating axonal damage, astrocyte alterations, neuronal injury, and myelin changes that are already present from the acute phase. FUNDING: Nominative Grant FIBHCSC 2020 COVID-19. Department of Health, Community of Madrid. Instituto de Salud Carlos III through the project INT20/00079, co-funded by European Regional Development Fund "A way to make Europe" (JAMG). Instituto de Salud Carlos III (ISCIII) through Sara Borrell postdoctoral fellowship Grant No. CD22/00043) and co-funded by the European Union (MDC). Instituto de Salud Carlos III through a predoctoral contract (FI20/000145) (co-funded by European Regional Development Fund "A way to make Europe") (MVS). Fundación para el Conocimiento Madri+d through the project G63-HEALTHSTARPLUS-HSP4 (JAMG, SOM).

Are there cognitive and neuroimaging signatures in long COVID?

This scientific commentary refers to 'Markers of limbic system damage following SARS-CoV-2 infection', by Thomasson et al. (https://doi.org/10.1093/braincomms/fcad177).

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.

Transcranial direct current stimulation for post-COVID fatigue: a randomized, double-blind, controlled pilot study.

Fatigue is one of the most frequent and disabling symptoms of the post-COVID syndrome. In this study, we aimed to assess the effects of transcranial direct current stimulation on fatigue severity in a group of patients with post-COVID syndrome and chronic fatigue. We conducted a double-blind, parallel-group, sham-controlled study to evaluate the short-term effects of anodal transcranial direct current stimulation (2 mA, 20 min/day) on the left dorsolateral prefrontal cortex. The modified fatigue impact scale score was used as the primary endpoint. Secondary endpoints included cognition (Stroop test), depressive symptoms (Beck depression inventory) and quality of life (EuroQol-5D). Patients received eight sessions of transcranial direct current stimulation and were evaluated at baseline, immediately after the last session, and one month later. Forty-seven patients were enrolled (23 in the active treatment group and 24 in the sham treatment group); the mean age was 45.66 ± 9.49 years, and 37 (78.72%) were women. The mean progression time since the acute infection was 20.68 ± 6.34 months. Active transcranial direct current stimulation was associated with a statistically significant improvement in physical fatigue at the end of treatment and 1 month as compared with sham stimulation. No significant effect was detected for cognitive fatigue. In terms of secondary outcomes, active transcranial direct current stimulation was associated with an improvement in depressive symptoms at the end of treatment. The treatment had no effects on the quality of life. All the adverse events reported were mild and transient, with no differences between the active stimulation and sham stimulation groups. In conclusion, our results suggest that transcranial direct current stimulation on the dorsolateral prefrontal cortex may improve physical fatigue. Further studies are needed to confirm these findings and optimize stimulation protocols.

Development of criteria for cognitive dysfunction in post-COVID syndrome: the IC-CoDi-COVID approach.

BACKGROUND: We aimed to develop objective criteria for cognitive dysfunction associated with the post-COVID syndrome. METHODS: Four hundred and four patients with post-COVID syndrome from two centers were evaluated with comprehensive neuropsychological batteries. The International Classification for Cognitive Disorders in Epilepsy (IC-CoDE) framework was adapted and implemented. A healthy control group of 145 participants and a complementary data-driven approach based on unsupervised machine-learning clustering algorithms were also used to evaluate the optimal classification and cutoff points. RESULTS: According to the developed criteria, 41.2% and 17.3% of the sample were classified as having at least one cognitive domain impaired using -1 and -1.5 standard deviations as cutoff points. Attention/processing speed was the most frequently impaired domain. There were no differences in base rates of cognitive impairment between the two centers. Clustering analysis revealed two clusters, although with an important overlap (silhouette index 0.18-0.19). Cognitive impairment was associated with younger age and lower education levels, but not hospitalization. CONCLUSIONS: We propose a harmonization of the criteria to define and classify cognitive impairment in the post-COVID syndrome. These criteria may be extrapolated to other neuropsychological batteries and settings, contributing to the diagnosis of cognitive deficits after COVID-19 and facilitating multicenter studies to guide biomarker investigation and therapies.

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.

Multimodal neuroimaging in post-COVID syndrome and correlation with cognition.

Brain changes have been reported in the first weeks after SARS-CoV-2 infection. However, limited literature exists about brain alterations in post-COVID syndrome, a condition increasingly associated with cognitive impairment. The present study aimed to evaluate brain functional and structural alterations in patients with post-COVID syndrome, and assess whether these brain alterations were related to cognitive dysfunction. Eighty-six patients with post-COVID syndrome and 36 healthy controls were recruited and underwent neuroimaging acquisition and a comprehensive neuropsychological assessment. Cognitive and neuroimaging examinations were performed 11 months after the first symptoms of SARS-CoV-2. Whole-brain functional connectivity analysis was performed. Voxel-based morphometry was performed to evaluate grey matter volume, and diffusion tensor imaging was carried out to analyse white-matter alterations. Correlations between cognition and brain changes were conducted and Bonferroni corrected. Post-COVID syndrome patients presented with functional connectivity changes, characterized by hypoconnectivity between left and right parahippocampal areas, and between bilateral orbitofrontal and cerebellar areas compared to controls. These alterations were accompanied by reduced grey matter volume in cortical, limbic and cerebellar areas, and alterations in white matter axial and mean diffusivity. Grey matter volume loss showed significant associations with cognitive dysfunction. These cognitive and brain alterations were more pronounced in hospitalized patients compared to non-hospitalized patients. No associations with vaccination status were found. The present study shows persistent structural and functional brain abnormalities 11 months after the acute infection. These changes are associated with cognitive dysfunction and contribute to a better understanding of the pathophysiology of the post-COVID syndrome.

Multimodal visual system analysis as a biomarker of visual hallucinations in Parkinson's disease.

Visual hallucinations (VH) are present in up to 75% of Parkinson's disease (PD) patients. However, their neural bases and participation of the visual system in VH are not well-understood in PD. Seventy-four participants, 12 PD with VH (PDVH), 35 PD without VH (PDnoVH) and 27 controls underwent a battery of primary visual function and visual cognition tests, retinal optical coherence tomography and structural and resting-state functional brain MRI. We quantified cortical thickness with Freesurfer and functional connectivity (FC) of Visual (VIS), Fronto-Parietal (FP), Ventral Attention (VAN) and Dorsal Attention (DAN) networks with CONN toolbox. Group comparisons were performed with MANCOVA. Area Under the Curve (AUC) was computed to assess the ability of visual variables to differentiate PDVH and PDnoVH. There were no significant PDVH vs PDnoVH differences in disease duration, motor manifestations, general cognition or dopamine agonist therapy (DA) use. Compared to PDnoVH and HC, and regardless of DA use, PDVH showed significantly reduced contrast sensitivity, visuoperceptive and visuospatial abilities, increased retina photoreceptor layer thickness, reduced cortical thickness mostly in right visual associative areas, decreased between-network VIS-VAN and VAN-DAN connectivity and increased within-network DAN connectivity. The combination of clinical and imaging variables that best discriminated PDVH and PDnoVH (highest AUC), where within-network DAN FC, photoreceptor layer thickness and cube analysis test from Visual Object and Space Perception Battery (accuracy of 81.8%). Compared to PDnoVH, PDVH have specific functional and structural abnormalities within the visual system, which can be quantified non-invasively and could potentially constitute biomarkers for VH in PD.

Costs and effects of telerehabilitation in neurological and cardiological diseases: A systematic review.

Introduction: Telerehabilitation in neurological and cardiological diseases is an alternative rehabilitation that improves the quality of life and health conditions of patients and enhances the accessibility to health care. However, despite the reported benefits of telerehabilitation, it is necessary to study its impact on the healthcare system. Methods: The systematic review aims to investigate the costs and results of telerehabilitation in neurological and cardiological diseases. MEDLINE and EMBASE databases were searched from 2005 to 2021, for studies that assess the costs and results of telerehabilitation compared to traditional rehabilitation (center-based programs) in neurological and cardiological diseases. A narrative synthesis of results was carried out. Results: A total of 8 studies (865 participants) of 430 records were included. Three studies were related to the costs and results of telerehabilitation in neurological diseases (specifically in stroke). In total, five studies assessed telerehabilitation in cardiological diseases (chronic heart failure, coronary heart disease, acute coronary syndrome, and cardiovascular diseases). The duration of the telerehabilitation ranged from 6 to 48 weeks. The studies included cost-analysis, cost-benefit, cost-effectiveness, or cost-utility. In total, four studies found significant cost/savings per person between $565.66 and $2,352.00 (p < 0.05). In contrast, most studies found differences in costs and clinical effects between the telerehabilitation performed and the rehabilitation performed at the clinic. Just one study found quality-adjusted life years (QALY) significant differences between groups [Incremental cost-effectiveness ratio (ICER) per QALY ($-21,666.41/QALY). Discussion: Telerehabilitation is an excellent alternative to traditional center rehabilitation, which increases the accessibility to rehabilitation to more people, either due to the geographical situation of the patients or the limitations of the health systems. Telerehabilitation seems to be as clinical and cost-effective as traditional rehabilitation, even if, generally, telerehabilitation is less costly. More research is needed to evaluate health-related quality of life and cost-effectiveness in other neurological diseases. Systematic review registration: [https://figshare.com/articles/journal_ contribution/Review_Protocol_Costs_and_effects_of_Telerehabilitation_in_ Neurological_and_Cardiological_Diseases_A_Systematic_Review/19619838], identifier [19619838].

Fatigue and Cognitive Dysfunction Are Associated with Occupational Status in Post-COVID Syndrome.

Post-COVID syndrome (PCS) is a medical condition characterized by the persistence of a wide range of symptoms after acute infection by SARS-CoV-2. The work capacity consequences of this disorder have scarcely been studied. We aimed to analyze the factors associated with occupational status in patients with PCS. This cross-sectional study involved 77 patients with PCS on active work before SARS-CoV-2 infection. Patients were evaluated 20.71 ± 6.50 months after clinical onset. We conducted a survey on occupational activity and cognitive and clinical symptoms. The association between occupational activity and fatigue, depression, anxiety, sleep quality, and cognitive testing was analyzed. Thirty-eight (49.4%) patients were working, and thirty-nine (50.6%) patients were not. Of those not working at the moment of the assessment, 36 (92.3%) patients were on sick leave. In 63 patients (81.8% of the sample), sick leave was needed at some point due to PCS. The mean duration of sick leave was 12.07 ± 8.07 months. According to the patient's perspective, the most disabling symptoms were cognitive complaints (46.8%) and fatigue (31.2%). Not working at the moment of the assessment was associated with higher levels of fatigue and lower cognitive performance in the Stroop test. No association was found between occupational status with depression and anxiety questionnaires. Our study found an influence of PCS on work capacity. Fatigue and cognitive issues were the most frequent symptoms associated with loss of work capacity.

Beta amyloid deposition and cognitive decline in Parkinson's disease: a study of the PPMI cohort.

The accumulation of beta amyloid in the brain has a complex and poorly understood impact on the progression of Parkinson's disease pathology and much controversy remains regarding its role, specifically in cognitive decline symptoms. Some studies have found increased beta amyloid burden is associated with worsening cognitive impairment in Parkinson's disease, especially in cases where dementia occurs, while other studies failed to replicate this finding. To better understand this relationship, we examined a cohort of 25 idiopathic Parkinson's disease patients and 30 healthy controls from the Parkinson's Progression Marker Initiative database. These participants underwent [18F]Florbetaben positron emission tomography scans to quantify beta amyloid deposition in 20 cortical regions. We then analyzed this beta amyloid data alongside the longitudinal Montreal Cognitive Assessment scores across 3 years to see how participant's baseline beta amyloid levels affected their cognitive scores prospectively. The first analysis we performed with these data was a hierarchical cluster analysis to help identify brain regions that shared similarity. We found that beta amyloid clusters differently in Parkinson's disease patients compared to healthy controls. In the Parkinson's disease group, increased beta amyloid burden in cluster 2 was associated with worse cognitive ability, compared to deposition in clusters 1 or 3. We also performed a stepwise linear regression where we found an adjusted R2 of 0.495 (49.5%) in a model explaining the Parkinson's disease group's Montreal Cognitive Assessment score 1-year post-scan, encompassing the left gyrus rectus, the left anterior cingulate cortex, and the right parietal cortex. Taken together, these results suggest regional beta amyloid deposition alone has a moderate effect on predicting future cognitive decline in Parkinson's disease patients. The patchwork effect of beta amyloid deposition on cognitive ability may be part of what separates cognitive impairment from cognitive sparing in Parkinson's disease. Thus, we suggest it would be more useful to measure beta amyloid burden in specific brain regions rather than using a whole-brain global beta amyloid composite score and use this information as a tool for determining which Parkinson's disease patients are most at risk for future cognitive decline.

Neural basis of visuospatial tests in behavioral variant frontotemporal dementia.

Background: Recent models of visuospatial functioning suggest the existence of three main circuits emerging from the dorsal ("where") route: parieto-prefrontal pathway, parieto-premotor, and parieto-medial temporal. Neural underpinnings of visuospatial task performance and the sparing of visuospatial functioning in bvFTD are unclear. We hypothesized different neural and cognitive mechanisms in visuospatial tasks performance in bvFTD and AD. Methods: Two hundred and sixteen participants were enrolled for this study: 72 patients with bvFTD dementia and 144 patients with AD. Visual Object and Space Perception Battery Position Discrimination and Number Location (VOSP-PD and VOSP-NL) and Rey-Osterrieth Complex Figure (ROCF) were administered to examine visuospatial functioning, together with a comprehensive neuropsychological battery. FDG-PET was acquired to evaluate brain metabolism. Voxel-based brain mapping analyses were conducted to evaluate the brain regions associated with visuospatial function in bvFTD and AD. Results: Patients with AD performed worst in visuospatial tasks in mild dementia, but not at prodromal stage. Attention and executive functioning tests showed higher correlations in bvFTD than AD with ROCF, but not VOSP subtests. Visuospatial performance in patients with bvFTD was associated with bilateral frontal regions, including the superior and medial frontal gyri, supplementary motor area, insula and middle cingulate gyrus. Conclusion: These findings support the role of prefrontal and premotor regions in visuospatial processing through the connection with the posterior parietal cortex and other posterior cortical regions. Visuospatial deficits should be interpreted with caution in patients with bvFTD, and should not be regarded as hallmarks of posterior cortical dysfunction.

Validation of a brief cross-cultural cognitive screening test in Multiple Sclerosis.

BACKGROUND: Several batteries have been developed for the cognitive assessment of people with multiple sclerosis (MS). However, all these tests have some limitations in general clinical practice and from a cross-cultural perspective. In this study, we aimed to validate a novel cognitive screening test, the Cross-Cultural Dementia screening test (CCD), in pwMS. METHODS: Seventy-five participants with relapsing-remitting MS and 75 healthy controls were enrolled and completed a comprehensive neuropsychological battery and the CCD. Intergroup comparisons, effect sizes, and correlations with previously validated tests were calculated for a majority and a pilot study of a minority sample. ROC curves were estimated, and random forest classification models were developed. RESULTS: There were statistically significant differences between cognitively impaired MS (MS-CI) group and healthy controls, and between MS-CI and non-cognitively impaired MS group in all subtests of CCD with medium to large effect sizes. Correlations with standardized neuropsychological tests were moderate to high, supporting concurrent validity. These results were replicated in the minority sample. The random forest models showed a very accurate classification using the CCD. This test showed good psychometric properties compared with SDMT. CONCLUSIONS: Our study validates the CCD for cognitive impairment screening in MS, showing advantages over other routinely used cognitive tests.