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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.

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.

Patients with post-COVID condition (PCC) present with diverse symptoms which persist at long-term after SARS-CoV-2 infection. Among these symptoms, cognitive impairment is one of the most prevalent and has been related to brain structural and functional changes. The underlying mechanisms of these cognitive and brain alterations remain elusive but neuroinflammation and immune mechanisms have been majorly considered. In this sense, the choroid plexus (ChP) volume has been proposed as a marker of neuroinflammation in immune-mediated conditions and the ChP epithelium has been found particularly susceptible to the effects of SARS-CoV-2. The objective was to investigate the ChP in PCC and evaluate its relationships with cognition, brain, and immunological alterations. One-hundred and twenty-nine patients with PCC after a mean of 14.79 ± 7.17 months of evolution since the infection and 36 healthy controls were recruited. Participants underwent a neuropsychological, and neuroimaging assessment and immunological markers evaluation. Results revealed ChP volume enlargement in PCC compared to healthy controls. The ChP enlargement was associated with cognitive dysfunction, grey matter volume reduction in frontal and subcortical areas, white matter integrity and diffusivity changes and functional connectivity changes. These ChP changes were also related to intermediate monocytes levels. Findings suggest that the ChP integrity may play a relevant role in the pathophysiology of cognitive deficits and the observed brain changes in PCC. The previously documented function of the ChP in maintaining brain homeostasis and regulating the entry of immune cells into the brain supports the presence of neuroinflammatory mechanisms in this disorder.

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.

Background Primary progressive aphasia (PPA) is a neurodegenerative syndrome characterized by the progressive impairment of language abilities. However, recent findings suggest that other cognitive domains, beyond language, may also be affected in the early stages of the disease. Exploring cognitive domains could facilitate the diagnosis of PPA and its classification into the three main variants (non‐fluent (nfvPPA), semantic (svPPA) and logopenic (lvPPA)), which remains challenging. This study aimed to identify non‐linguistic cognitive alterations in PPA and its variants. Method A cross‐sectional study including 157 patients with PPA and 74 cognitively unimpaired controls. Patients were classified into nfvPPA (N = 58), svPPA (N = 19), and lvPPA (N = 80) using a language battery, FDG‐PET, and CSF biomarkers. The mean age was 69,97 ± 8.12 years, and the 61.04% were females. Four cognitive domains (attention and working memory, executive functions, episodic memory and visuospatial abilities) were assessed using the ACE‐III and the following cognitive tests: Digit Span, TMT‐A and B, Rey‐Osterrieth Complex Figure (copy and 3‐minute recall), VOSP and Tower of London. Result All PPA variants scored significantly worse than the control group across most explored domains. The lvPPA and svPPA groups scored lower on episodic memory compared to the nfvPPA group. The lvPPA group performed worse on visuospatial abilities and executive function than the svPPA group. The nfvPPA group scored lower on attention and working memory tasks compared to the svPPA group. Conclusion This study highlights the impairment of non‐linguistic cognitive domains in PPA and its variants, identifying distinct cognitive profiles across variants that may aid in the patient diagnosis, classification, and monitoring of disease progression.

Primary progressive aphasia (PPA) is a neurodegenerative syndrome characterized by the progressive impairment of language abilities. However, recent findings suggest that other cognitive domains, beyond language, may also be affected in the early stages of the disease. Exploring cognitive domains could facilitate the diagnosis of PPA and its classification into the three main variants (non-fluent (nfvPPA), semantic (svPPA) and logopenic (lvPPA)), which remains challenging. This study aimed to identify non-linguistic cognitive alterations in PPA and its variants. A cross-sectional study including 157 patients with PPA and 74 cognitively unimpaired controls. Patients were classified into nfvPPA (N = 58), svPPA (N = 19), and lvPPA (N = 80) using a language battery, FDG-PET, and CSF biomarkers. The mean age was 69,97 ± 8.12 years, and the 61.04% were females. Four cognitive domains (attention and working memory, executive functions, episodic memory and visuospatial abilities) were assessed using the ACE-III and the following cognitive tests: Digit Span, TMT-A and B, Rey-Osterrieth Complex Figure (copy and 3-minute recall), VOSP and Tower of London. All PPA variants scored significantly worse than the control group across most explored domains. The lvPPA and svPPA groups scored lower on episodic memory compared to the nfvPPA group. The lvPPA group performed worse on visuospatial abilities and executive function than the svPPA group. The nfvPPA group scored lower on attention and working memory tasks compared to the svPPA group. This study highlights the impairment of non-linguistic cognitive domains in PPA and its variants, identifying distinct cognitive profiles across variants that may aid in the patient diagnosis, classification, and monitoring of disease progression.

Background 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. Method 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. Result 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. Conclusion 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.

Attention/ processing speed deficits with or without executive function and episodic memory deficits have been suggested as a relatively characteristic cognitive profile of people with post-COVID condition (PCC). Most studies have been performed using standardized paper and pencil neuropsychological assessment. Sensitive and applicable tests are needed to improve the diagnostic capacity of patients with PCC. In this study, we aimed to investigate the dimensions of a comprehensive computerized neuropsychological battery and to characterize the cognitive characteristics of patients with PCC. Five hundred and eight participants were enrolled in the study (PCC = 227, Healthy Controls, HC = 281) and underwent cognitive assessment focused on attention, concentration, executive functions, and episodic memory. We conducted a multi-group confirmatory factor analysis. Factor scores were obtained to compare the PCC and HC groups and partial invariance analysis was performed to identify relevant cognitive processes that differentiate the two groups. The proposed four-factor model showed adequate fit indices. There were differences in attention, concentration, and executive functions factor scores with small to moderate effect sizes and with a particular implication of attention processes based on measurement invariance analysis. Impairments in reaction times and divided attention were especially relevant in patients with PCC. The battery revealed four factors representing attention, concentration, executive functions, and episodic memory. The PCC group performed worse than the HC group in attention, concentration, and executive functions. These findings suggest the validity of computerized neuropsychological assessment, which could be particularly useful in PCC.

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.