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Introduction: Sepsis is defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. Mounting evidence suggests that many cognitively impaired sepsis survivors show long-term neurocognitive deficits in neuropsychological tasks. To date, the underlying mechanisms of these deficits are insufficiently understood. Based on previous evaluations we hypothesized that visual attention and working memory may be affected in a sample of cognitively impaired sepsis survivors. Methods: We utilized psychophysical whole-and partial-report paradigms based on the computational theory of visual attention (TVA) to determine (i) whether sepsis survivors show changes in basic parameters of visual attention and working memory, (ii) whether the affected parameters are related to neuropsychological test results in a standard battery in sepsis survivors and matched healthy control participants, (iii) whether between-group differences in these basic parameters of visual attention could account for underperformance of sepsis survivors in neuropsychological tests when adjusting for potentially relevant clinical variables. Results: We showed that, in sepsis survivors, the maximum number of elements consciously maintained in an instant, i.e. the working memory storage capacity K, is reduced (sepsis survivors: M = 3.0; healthy controls: M = 3.4). Moreover, K explained variance in neurocognitive outcomes -17% in attentional and 16 % in executive functions - in a standard neuropsychological battery. The association remained stable when adjusting for clinical variables. Discussion: Thus, in our sample of cognitively impaired sepsis survivors, a reduction in working memory capacity seems to be a critical determinant of the neurocognitive sequelae. It should be the subject of future work on mechanisms but may also serve as surrogate outcome measure in interventional studies.
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In this chapter, we describe the use of quantitative metrics of white matter obtained from the diffusion tensor model based on diffusion-weighted imaging in Alzheimer's disease (AD). Our description synthesizes insights not only from patient populations with AD dementia but also from participants at risk for AD dementia (e.g., amnestic mild cognitive impairment, subjective cognitive decline, or familial AD mutation carriers). A reference to studies examining correlations with behavioral variables is also included. Our main message is to caution against the overinterpretation of diffusion metrics and to favor analyses that focus on regions of interest or major white matter tracts for biomarker studies in AD.
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Doença de Alzheimer , Substância Branca , Humanos , Imagem de Tensor de Difusão/métodos , Doença de Alzheimer/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Imagem de Difusão por Ressonância Magnética , Encéfalo/diagnóstico por imagemRESUMO
BACKGROUND: Mild cognitive impairment (MCI) involves cognitive decline beyond typical age-related changes, but without significant daily activity disruption. It can encompass various cognitive domains as the causes of MCI are diverse. MCI as well as frequent comorbid neuropsychiatric conditions like depression and anxiety affect individuals' quality of life. Early interventions are essential, and computerized cognitive training (cCT) is an established treatment method. This paper presents the protocol for the NeuroNation MED Effectiveness Study, evaluating the self-administered mobile cCT intervention ("NeuroNation MED") in individuals with MCI to assess training effects on cognitive domains, health competence, neuropsychiatric symptoms, psychological well-being, and the general application usability. METHODS: This study protocol presents a single-blinded multicenter randomized controlled trial that will be carried out in six study centers in Germany and Luxembourg. We included adults with MCI (existing F06.7 ICD-10-GM diagnosis and TICS ≥ 21 and ≤ 32). The intervention group will use a mobile, multi-domain cCT ("NeuroNation MED") for 12 weeks. Meanwhile, the wait list control group will receive standard medical care or no care. The eligibility of volunteers will be determined through a telephone screening. After completion of the baseline examination, patients will be randomly assigned to one of the experimental conditions in a 2:1 ratio. In total, 286 participants will be included in this study. The primary outcome is the change of cognitive performance measured by the index score of the screening module of the Neuropsychological Assessment Battery. Secondary outcomes are changes in the Cognitive Failures Questionnaire, Hospital Anxiety and Depression Scale, Health-49, Health Literacy Questionnaire, among others. All of the primary and secondary outcomes will be assessed at baseline and after the 12-week post-allocation period. Furthermore, the intervention group will undergo an assessment of the System Usability Scale, and the training data of the NeuroNation MED application will be analyzed. DISCUSSION: This study aims to assess the effectiveness of a mobile self-administered cCT in enhancing cognitive abilities among individuals diagnosed with MCI. Should the findings confirm the effectiveness of the NeuroNation MED app, it may confer possible benefits for the care management of patients with MCI, owing to the accessibility, cost-effectiveness, and home-based setting it provides. Specifically, the cCT program could provide patients with personalized cognitive training, educational resources, and relaxation techniques, enabling participants to independently engage in cognitive training sessions at home without further supervision. TRIAL REGISTRATION: German Clinical Trials Register DRKS00025133. Registered on November 5, 2021.
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Cognição , Disfunção Cognitiva , Aplicativos Móveis , Estudos Multicêntricos como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Disfunção Cognitiva/terapia , Disfunção Cognitiva/psicologia , Disfunção Cognitiva/diagnóstico , Método Simples-Cego , Resultado do Tratamento , Terapia Assistida por Computador/métodos , Fatores de Tempo , Qualidade de Vida , Alemanha , Idoso , Masculino , Feminino , Terapia Cognitivo-Comportamental/métodos , Treino CognitivoRESUMO
Background: COVID-19 survivors may experience a wide range of chronic cognitive symptoms for months or years as part of post-COVID-19 conditions (PCC). To date, there is no definitive objective cognitive marker for PCC. We hypothesised that a key common deficit in people with PCC might be generalised cognitive slowing. Methods: To examine cognitive slowing, patients with PCC completed two short web-based cognitive tasks, Simple Reaction Time (SRT) and Number Vigilance Test (NVT). 270 patients diagnosed with PCC at two different clinics in UK and Germany were compared to two control groups: individuals who contracted COVID-19 before but did not experience PCC after recovery (No-PCC group) and uninfected individuals (No-COVID group). All patients with PCC completed the study between May 18, 2021 and July 4, 2023 in Jena University Hospital, Jena, Germany and Long COVID clinic, Oxford, UK. Findings: We identified pronounced cognitive slowing in patients with PCC, which distinguished them from age-matched healthy individuals who previously had symptomatic COVID-19 but did not manifest PCC. Cognitive slowing was evident even on a 30-s task measuring simple reaction time (SRT), with patients with PCC responding to stimuli â¼3 standard deviations slower than healthy controls. 53.5% of patients with PCC's response speed was slower than 2 standard deviations from the control mean, indicating a high prevalence of cognitive slowing in PCC. This finding was replicated across two clinic samples in Germany and the UK. Comorbidities such as fatigue, depression, anxiety, sleep disturbance, and post-traumatic stress disorder did not account for the extent of cognitive slowing in patients with PCC. Furthermore, cognitive slowing on the SRT was highly correlated with the poor performance of patients with PCC on the NVT measure of sustained attention. Interpretation: Together, these results robustly demonstrate pronounced cognitive slowing in people with PCC, which distinguishes them from age-matched healthy individuals who previously had symptomatic COVID-19 but did not manifest PCC. This might be an important factor contributing to some of the cognitive impairments reported in patients with PCC. Funding: Wellcome Trust (206330/Z/17/Z), NIHR Oxford Health Biomedical Research Centre, the Thüringer Aufbaubank (2021 FGI 0060), German Forschungsgemeinschaft (DFG, FI 1424/2-1) and the Horizon 2020 Framework Programme of the European Union (ITN SmartAge, H2020-MSCA-ITN-2019-859890).
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Here, we investigated whether fractional anisotropy (FA) of hippocampus-relevant white-matter tracts mediates the association between baseline Mediterranean diet adherence (MeDiAd) and verbal episodic memory over four years. Participants were healthy older adults with and without subjective cognitive decline and patients with amnestic mild cognitive impairment from the DELCODE cohort study (n = 376; age: 71.47 ± 6.09 years; 48.7 % female). MeDiAd and diffusion data were obtained at baseline. Verbal episodic memory was assessed at baseline and four yearly follow-ups. The associations between baseline MeDiAd and white matter, and verbal episodic memory's mean and rate of change over four years were tested with latent growth curve modeling. Baseline MeDiAd was associated with verbal episodic memory four years later (95 % confidence interval, CI [0.01, 0.32]) but not with its rate of change over this period. Baseline Fornix FA mediated - and, thus, explained - that association (95 % CI [0.002, 0.09]). Fornix FA may be an appropriate response biomarker of Mediterranean diet interventions on verbal memory in older adults.