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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. 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. 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, showing excellent reliability.

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.

Fatigue and cognitive deficits are common and disabling symptoms in patients experiencing post-COVID condition. This randomized parallel study aimed to evaluate the effects of transcranial direct current stimulation (tDCS) over the primary motor cortex combined with cognitive training (M1 + CT), compared to tDCS over the dorsolateral prefrontal cortex with cognitive training (DLPFC + CT), on fatigue, cognition, and other clinical symptoms in post-COVID. Sixty-three patients completed the treatment (n = 32 in the M1 + CT group and n = 31 in the DLPFC + CT group) with a mean age of 47 years and an average symptom duration of 32 months. Both groups underwent comprehensive neuropsychological and clinical evaluations, including ecological momentary assessments of fatigue, at baseline, post-treatment, and one-month follow-up. The Fatigue Severity Scale (FSS) was used as the primary endpoint. Patients were randomly assigned to the M1 + CT or DLPFC + CT groups and received 15 sessions of tDCS administered concurrently with adaptive CT. The M1 + CT group showed a slightly higher efficacy in reducing fatigue and improving sleep quality than the DLPFC + CT group. Both groups demonstrated significant improvements in cognition, anxiety, depression, pain, and sleep quality. These improvements were sustained over time. These findings indicate that tDCS combined with cognitive training is a feasible, safe, and effective approach for reducing fatigue and enhancing cognition in post-COVID patients. The results highlight the potential of brain stimulation and cognitive training to alleviate fatigue and cognitive impairment in post-COVID, warranting further confirmation through additional randomized controlled trials. Trial registration: ClinicalTrials.gov NCT05753202.

IntroductionPrimary progressive aphasia (PPA) is a neurodegenerative syndrome associated with Alzheimer’s disease and frontotemporal degeneration. Non-invasive brain stimulation (NIBS) is a promising treatment, especially associated with language therapy, but comparative efficacy and long-term effects between the different techniques (transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS)) remain unknown. The present study aims to investigate the effects of non-invasive brain stimulation, alone or associated (tDCS/TMS/tDCS plus TMS) combined with language therapy delivered during a period of 6 months, in the progression of language impairment in PPA, compared with sham stimulation combined with language therapy.Methods and analysisThe study is a randomised, double-blinded, parallel, sham-controlled clinical trial. Patients with PPA in early stages (global Clinical Dementia Rating equal to or less than 1) are eligible. They are to be randomised to one of the four treatment arms of the study (active tDCS-active TMS, active tDCS-sham TMS, sham tDCS-active TMS, sham tDCS-sham TMS). All patients will receive language therapy immediately after each session of NIBS, for 6 months. The primary outcome is the Mini-Linguistic State Examination. The secondary outcomes are naming of trained items, Addenbrooke’s Cognitive Examination, Interview for Deterioration in Daily Living Activities, Clinical Dementia Rating including behaviour and language domains, Neuropsychiatric Inventory and regional brain metabolism. Exploratory substudies will be conducted including blood biomarkers, quantitative electroencephalography and spontaneous speech assessment.Ethics and disseminationThe study is registered (ClinicalTrials.gov: NCT07158216) and approved by the Ethics Committee of the Hospital Clinico San Carlos (code 25/309-IC_P_CE). Patients will be enrolled after signing an informed consent form. Study outcomes will be disseminated through presentations at scientific conferences, publications in peer-reviewed journals and other academic forums.Trial registration numberNCT07158216.

The Cross-Cultural Neuropsychological Test Battery (CNTB) is a novel test battery specifically designed to reduce the impact of multiculturality in cognitive assessment. 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). 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. 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. 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.

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.

Background. Primary progressive aphasia (PPA) is a neurodegenerative syndrome in which diagnosis is usually challenging. Biomarkers are needed for diagnosis and monitoring. In this study, we aimed to evaluate Electroencephalography (EEG) as a biomarker for the diagnosis of PPA. Methods. We conducted a cross-sectional study with 40 PPA patients categorized as non-fluent, semantic, and logopenic variants, and 20 controls. Resting-state EEG with 32 channels was acquired and preprocessed using several procedures (quantitative EEG, wavelet transformation, autoencoders, and graph theory analysis). Seven machine learning algorithms were evaluated (Decision Tree, Elastic Net, Support Vector Machines, Random Forest, K-Nearest Neighbors, Gaussian Naive Bayes, and Multinomial Naive Bayes). Results. Diagnostic capacity to distinguish between PPA and controls was high (accuracy 75%, F1-score 83% for kNN algorithm). The most important features in the classification were derived from network analysis based on graph theory. Conversely, discrimination between PPA variants was lower (Accuracy 58% and F1-score 60% for kNN). Conclusions. The application of ML to resting-state EEG may have a role in the diagnosis of PPA, especially in the differentiation from controls. Future studies with high-density EEG should explore the capacity to distinguish between PPA variants.

Background: We aimed to evaluate personality traits in patients with post-COVID syndrome, as well as the association with neuropsychiatric symptoms present in this disorder. Methods: The Big Five Structure Inventory was administered to 93 consecutive patients with a diagnosis of post-COVID syndrome as defined by the WHO and to demographically matched controls. We also performed a comprehensive evaluation of depression, anxiety, fatigue, sleep quality, cognitive function, and olfactory function. Results: Patients with post-COVID syndrome scored lower for emotional stability, equanimity, positive mood, and self-control. Extraversion, emotional stability, and openness correlated negatively with anxiety and depression levels. Conscientiousness correlated negatively with anxiety. No statistically significant correlations were observed between personality traits and cognitive function, sleep quality, olfactory function, or fatigue. Personality scores explained 36.3% and 41% of the variance in scores on the anxiety and depression scales, respectively. Two personality profiles with lower levels of emotional stability were associated with depression and anxiety. Conclusions: Our study shows higher levels of neuroticism in patients with post-COVID syndrome. Personality traits were predictive of the presence of depression and anxiety, but not cognitive function, sleep quality, or fatigue, in the context of post-COVID syndrome. These findings may have implications for the detection of patients at risk of depression and anxiety in post-COVID syndrome, and for the development of preventive and therapeutic interventions.

Primary progressive aphasia (PPA) is a neurodegenerative syndrome characterized by language impairment there is currently no effective treatment. Non-invasive techniques like transcranial magnetic stimulation (TMS) have shown potential in improving symptoms, but their long-term effects in PPA are unknown. This study aimed to evaluate the efficacy of TMS combined with language therapy in PPA at 6 months. This double-blinded, prospective, randomized, parallel clinical trial enrolled 63 PPA patients (24 nonfluent PPA (nfvPPA), 12 semantic PPA (svPPA) and 27 logopenic (lvPPA)). Participants were randomized in a 2:1 ratio to either active TMS or sham TMS. The intervention involved a 6-month intermittent theta-burst stimulation protocol over the left dorsolateral prefrontal cortex (DLPFC) followed by language therapy based on Lexical Retrieval Cascade Treatment. The primary outcome was the standardized uptake value (SUV) in a brain region associated with PPA progression, measured at baseline and at 6 months using FDG-PET. Secondary outcomes included language performance (Mini-Linguistic State Examination, word naming, words per minute in spontaneous speech), functional independence, and neuropsychiatric symptoms, assessed at baseline, 3 months, and 6 months. The primary outcome showed a significant benefit in the active TMS group compared to the sham group at 6 months. Active TMS also improved secondary outcomes, including language abilities, functional independence, and neuropsychiatric symptoms, except in words per minute during spontaneous speech. Adherence was complete in 92% of participants. Intermittent theta-burst stimulation combined with language therapy for 6 months was associated with reduced decline in regional brain metabolism and improvements in language performance, functional independence, and neuropsychiatric symptoms in patients with PPA.

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.