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One of the most prevalent symptoms of post-COVID condition is cognitive impairment, which results in a significant degree of disability and low quality of life. In studies with large sample sizes, attention, memory, and executive function were reported as long-term cognitive symptoms. This study aims to describe cognitive dysfunction in large post-COVID condition individuals, compare objective neuropsychological performance in those post-COVID condition individuals with and without cognitive complaints, and identify short cognitive exams that can differentiate individuals with post-COVID symptoms from controls. To address these aims, the Nautilus project was started in June 2021. During the first year, we collected 428 participants' data, including 319 post-COVID and 109 healthy controls (18-65 years old) from those who underwent a comprehensive neuropsychological battery for cognitive assessment. Scores on tests assessing global cognition, learning and long-term memory, processing speed, language and executive functions were significantly worse in the post-COVID condition group than in healthy controls. Montreal Cognitive Assessment, digit symbol test, and phonetic verbal fluency were significant in the binomial logistic regression model and could effectively distinguish patients from controls with good overall sensitivity and accuracy. Neuropsychological test results did not differ between those with and without cognitive complaints. Our research suggests that patients with post-COVID conditions experience significant cognitive impairment and that routine tests like the Montreal Cognitive Assessment, digit symbol, and phonetic verbal fluency test might identify cognitive impairment. Thus, the administration of these tests would be helpful for all patients with post-COVID-19 symptoms, regardless of whether cognitive complaints are present or absent., Study Registration: www.ClinicalTrials.gov, identifiers NCT05307549 and NCT05307575., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ariza, Cano, Segura, Adan, Bargalló, Caldú, Campabadal, Jurado, Mataró, Pueyo, Sala-Llonch, Barrué, Bejar, Cortés, NAUTILUS-Project Collaborative Group, Junqué and Garolera.)

Previous evidence suggests that transcranial direct current stimulation (tDCS) to the left dorsolateral prefrontal cortex (l-DLPFC) can enhance episodic memory in subjects with subjective cognitive decline (SCD), known to be at risk of dementia. Our main goal was to replicate such findings in an independent sample and elucidate if baseline magnetic resonance imaging (MRI) characteristics predicted putative memory improvement. Thirty-eight participants with SCD (aged: 60-65 years) were randomly assigned to receive active ( N = 19) or sham ( N = 19) tDCS in a double-blind design. They underwent a verbal learning task with 15 words (DAY-1), and 24 h later (DAY-2) stimulation was applied for 15 min at 1.5 mA targeting the l-DLPFC after offering a contextual reminder. Delayed recall and recognition were measured 1 day after the stimulation session (DAY-3), and at 1-month follow-up (DAY-30). Before the experimental session, structural and functional MRI were acquired. We identified a group ∗ time interaction in recognition memory, being the active tDCS group able to maintain stable memory performance between DAY-3 and DAY-30. MRI results revealed that individuals with superior tDCS-induced effects on memory reconsolidation exhibited higher left temporal lobe thickness and greater intrinsic FC within the default-mode network. Present findings confirm that tDCS, through the modulation of memory reconsolidation, is capable of enhancing performance in people with self-perceived cognitive complaints. Results suggest that SCD subjects with more preserved structural and functional integrity might benefit from these interventions, promoting maintenance of cognitive function in a population at risk to develop dementia., Competing Interests: AP-L was listed as an inventor on several issued and pending patents on the real-time integration of non-invasive brain stimulation with electroencephalography and magnetic resonance imaging. He was co-founder of Linus Health and TI Solutions AG; serves on the scientific advisory boards for Starlab Neuroscience, Magstim Inc., Nexstim, and MedRhythms, and is an Associate Editor for Annals of Neurology. AP-L serves on the scientific advisory boards for Starlab Neuroscience, Neuroelectrics, Axilum Robotics, Constant Therapy, NovaVision, Cognito, Magstim, Nexstim, and Neosync, and is listed as an inventor on several issued and pending patents on the real-time integration of transcranial magnetic stimulation with electroencephalography and magnetic resonance imaging. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Vaqué-Alcázar, Mulet-Pons, Abellaneda-Pérez, Solé-Padullés, Cabello-Toscano, Macià, Sala-Llonch, Bargalló, Solana, Cattaneo, Tormos, Pascual-Leone and Bartrés-Faz.)

A better and non-invasive characterization of the preclinical phases of Alzheimer's disease (AD) is important to advance its diagnosis and obtain more effective benefits from potential treatments. The TgF344-AD rat model has been well characterized and shows molecular, behavioral and brain connectivity alterations that resemble the silent period of the pathology. Our aim was to longitudinally investigate functional brain connectivity in established resting-state networks (RSNs) obtained by independent component analysis (ICA) in a cohort of TgF344-AD and control rats every 3 months, from 5 to 18 months of age, to cover different stages of the disease. Before each acquisition, working memory performance was evaluated by the delayed non match-to-sample (DNMS) task. Differences in the temporal evolution were observed between groups in the amplitude and shape of the somatosensorial and sensorimotor networks but not in the whole default mode network (DMN). Subsequent high dimensional ICA analysis showed early alterations in the anterior DMN subnetwork activity of TgF344-AD rats compared to controls. Performance of DNMS task was positively correlated with somatosensorial network at 5 months of age in the wild-type (WT) animals but not in the Tg-F344 rats. At different time points, DMN showed negative correlation with cognitive performance in the control group while in the transgenic group the correlation was positive. In addition, behavioral differences observed at 5 months of age correlated with alterations in the posterior DMN subnetwork. We have demonstrated that functional connectivity using ICA represents a useful biomarker also in animal models of AD such as the TgF344AD rats, as it allows the identification of alterations associated with the progression of the disease, detecting differences in specific networks even at very early stages.

Ageing entails cognitive and motor decline as well as brain changes such as loss of gray (GM) and white matter (WM) integrity, neurovascular and functional connectivity alterations. Regarding connectivity, reduced resting-state fMRI connectivity between anterior and posterior nodes of the Default Mode Network (DMN) relates to cognitive function and has been postulated to be a hallmark of ageing. However, the relationship between age-related connectivity changes and other neuroimaging-based measures in ageing is fragmentarily investigated. In a sample of 116 healthy elders we aimed to study the relationship between antero-posterior DMN connectivity and measures of WM integrity, GM integrity and cerebral blood flow (CBF), assessed with an arterial spin labeling sequence. First, we replicated previous findings demonstrating DMN connectivity decreases in ageing and an association between antero-posterior DMN connectivity and memory scores. The results showed that the functional connectivity between posterior midline structures and the medial prefrontal cortex was related to measures of WM and GM integrity but not to CBF. Gray and WM correlates of anterio-posterior DMN connectivity included, but were not limited to, DMN areas and cingulum bundle. These results resembled patterns of age-related vulnerability which was studied by comparing the correlates of antero-posterior DMN with age-effect maps. These age-effect maps were obtained after performing an independent analysis with a second sample including both young and old subjects. We argue that antero-posterior connectivity might be a sensitive measure of brain ageing over the brain. By using a comprehensive approach, the results provide valuable knowledge that may shed further light on DMN connectivity dysfunctions in ageing.