Effects of diagnosis threat on cognitive complaints after COVID-19.

OBJECTIVE: The term "long-COVID" refers to the persistence of neurological symptoms after being ill with COVID-19 (e.g., headaches, fatigue, and attentional impairment). Providing information about long-COVID (i.e., "diagnosis threat") increased subjective cognitive complaints among recovered COVID-19 patients compared with those exposed to neutral information (Winter & Braw, 2022). Notably, this effect was particularly prominent among more suggestible participants. Our aim in the current study was to validate these initial findings and to explore the impact of additional variables (e.g., suggestibility). METHOD: Recovered patients (n = 270) and controls (n = 290) reported daily cognitive failures after being randomly assigned to either a diagnosis threat (exposure to an article providing information regarding long-COVID) or a control condition. RESULTS: Recovered patients, but not controls, reported more cognitive failures in the diagnosis threat condition compared with the control condition. Diagnosis threat added significantly to the prediction of cognitive complaints based on relevant demographic variables and suggestibility. Diagnosis threat and suggestibility interacted (i.e., suggestible individuals were particularly vulnerable to the impact of a diagnosis threat). CONCLUSIONS: Diagnosis threat may contribute to the persistence of complaints regarding cognitive impairment among recovered COVID-19 patients. Suggestibility may be an underlying mechanism that increases the impact of diagnosis threat. Other factors, such as vaccination status, may be at play though we are only at the initial stages of research concerning their impact. These may be the focus of future research, aiding in identifying risk factors for experiencing COVID-19 symptoms past the resolution of its acute phase. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Acute TNFα levels predict cognitive impairment 6-9 months after COVID-19 infection.

BACKGROUND: A neurocognitive phenotype of post-COVID-19 infection has recently been described that is characterized by a lack of awareness of memory impairment (i.e., anosognosia), altered functional connectivity in the brain's default mode and limbic networks, and an elevated monocyte count. However, the relationship between these cognitive and brain functional connectivity alterations in the chronic phase with the level of cytokines during the acute phase has yet to be identified. AIM: Determine whether acute cytokine type and levels is associated with anosognosia and functional patterns of brain connectivity 6-9 months after infection. METHODS: We analyzed the predictive value of the concentration of acute cytokines (IL-1RA, IL-1ß, IL-6, IL-8, IFNγ, G-CSF, GM-CSF) (cytokine panel by multiplex immunoassay) in the plasma of 39 patients (mean age 59 yrs, 38-78) in relation to their anosognosia scores for memory deficits via stepwise linear regression. Then, associations between the different cytokines and brain functional connectivity patterns were analyzed by MRI and multivariate partial least squares correlations for the whole group. RESULTS: Stepwise regression modeling allowed us to show that acute TNFα levels predicted (R2 = 0.145; ß = -0.38; p = .017) and were associated (r = -0.587; p < .001) with scores of anosognosia for memory deficits observed 6-9 months post-infection. Finally, high TNFα levels were associated with hippocampal, temporal pole, accumbens nucleus, amygdala, and cerebellum connectivity. CONCLUSION: Increased plasma TNFα levels in the acute phase of COVID-19 predict the presence of long-term anosognosia scores and changes in limbic system functional connectivity.

Cognitive impairment in young adults with post COVID-19 syndrome.

In this study, we aimed to examine different cognitive domains in a large sample of patients with post COVID-19 syndrome. Two hundred and fourteen patients, 85.04% women, ranged 26 to 64 years (mean = 47.48 years) took part in this investigation. Patients' processing speed, attention, executive functions and various language modalities were examined online using a comprehensive task protocol designed for this research. Alteration in some of the tasks was observed in 85% of the participants, being the attention and executive functions tests the ones that show the highest percentage of patients with severe impairment. Positive correlations were observed between the age of the participants in almost all the tasks assessed, implying better performance and milder impairment with increasing age. In the comparisons of patients according to age, the oldest patients were found to maintain their cognitive functions relatively preserved, with only a mild impairment in attention and speed processing, while the youngest showed the most marked and heterogeneous cognitive impairment. These results confirm the subjective complaints in patients with post COVID-19 syndrome and, thanks to the large sample size, allow us to observe the effect of patient age on performance, an effect never reported before in patients with these characteristics.

Multifactorial White Matter Damage in the Acute Phase and Pre-Existing Conditions May Drive Cognitive Dysfunction after SARS-CoV-2 Infection: Neuropathology-Based Evidence.

BACKGROUND: There is an urgent need to better understand the mechanisms underlying acute and long-term neurological symptoms after COVID-19. Neuropathological studies can contribute to a better understanding of some of these mechanisms. METHODS: We conducted a detailed postmortem neuropathological analysis of 32 patients who died due to COVID-19 during 2020 and 2021 in Austria. RESULTS: All cases showed diffuse white matter damage with a diffuse microglial activation of a variable severity, including one case of hemorrhagic leukoencephalopathy. Some cases revealed mild inflammatory changes, including olfactory neuritis (25%), nodular brainstem encephalitis (31%), and cranial nerve neuritis (6%), which were similar to those observed in non-COVID-19 severely ill patients. One previously immunosuppressed patient developed acute herpes simplex encephalitis. Acute vascular pathologies (acute infarcts 22%, vascular thrombosis 12%, diffuse hypoxic-ischemic brain damage 40%) and pre-existing small vessel diseases (34%) were frequent findings. Moreover, silent neurodegenerative pathologies in elderly persons were common (AD neuropathologic changes 32%, age-related neuronal and glial tau pathologies 22%, Lewy bodies 9%, argyrophilic grain disease 12.5%, TDP43 pathology 6%). CONCLUSIONS: Our results support some previous neuropathological findings of apparently multifactorial and most likely indirect brain damage in the context of SARS-CoV-2 infection rather than virus-specific damage, and they are in line with the recent experimental data on SARS-CoV-2-related diffuse white matter damage, microglial activation, and cytokine release.

Cognitive consequences of COVID-19: results of a cohort study from South America.

BACKGROUND: Neurological and psychiatric manifestations associated with SARS-CoV-2 infection have been reported throughout the scientific literature. However, studies on post-COVID cognitive impairment in people with no previous cognitive complaint are scarce. OBJECTIVE: We aim to investigate the impact of COVID-19 on cognitive functions in adults without cognitive complaints before infection and to study cognitive dysfunction according to disease severity and cognitive risk factors. METHODS: Forty-five post-COVID-19 patients and forty-five controls underwent extensive neuropsychological evaluation, which assessed cognitive domains such as memory, language, attention, executive functions, and visuospatial skills, including psychiatric symptomatology scales. Data were collected on the severity of infection, premorbid medical conditions, and functionality for activities of daily living before and after COVID-19. RESULTS: Significant differences between groups were found in cognitive composites of memory (p=0.016, Cohen's d= 0.73), attention (p<0.001, Cohen's d=1.2), executive functions (p<0.001, Cohen's d=1.4), and language (p=0.002, Cohen's d=0.87). The change from premorbid to post-infection functioning was significantly different between severity groups (WHODAS, p=0.037). Self-reported anxiety was associated with the presence of cognitive dysfunction in COVID-19 subjects (p=0.043). CONCLUSION: Our results suggest that the presence of cognitive symptoms in post-COVID-19 patients may persist for months after disease remission and argue for the inclusion of cognitive assessment as a protocolized stage of the post-COVID examination. Screening measures may not be sufficient to detect cognitive dysfunction in post-COVID-19 patients.

A 30-Year-Old Woman with an 8-Week History of Anxiety, Depression, Insomnia, and Mild Cognitive Impairment Following COVID-19 Who Responded to Accelerated Bilateral Theta-Burst Transcranial Magnetic Stimulation Over the Prefrontal Cortex.

BACKGROUND This report is of a 30-year-old woman with an 8-week history of anxiety, depression, insomnia, and mild cognitive impairment following COVID-19 infection, who responded to accelerated bilateral theta-burst transcranial magnetic stimulation (TBS) over the prefrontal cortex. CASE REPORT A previously healthy 30-year-old woman visited our psychiatric clinic for symptoms including anxiety, depression, insomnia, and brain fog (mild cognitive impairment) for more than 8 weeks after being diagnosed with COVID-19 on May 9, 2022. Continuous TBS of the right dorsolateral prefrontal cortex (DLPFC), followed by intermittent TBS of the left DLPFC, was performed twice daily over 5 days for a total of 10 sessions. The Beck Depression Inventory (BDI), Hamilton Depression Rating Scale (HAMD), Beck Anxiety Inventory (BAI), Pittsburgh Sleep Quality Index (PSQI), and subsets of the Wechsler Memory Scale (WMS)-Third Edition were administered at baseline and at the end of treatment. After 10 sessions of treatment, her BAI, BDI, HAMD, PSQI, WMS-Logical Memory, WMS-Faces, WMS-Verbal Paired Associates, and WMS-Family Pictures scores had improved from 4, 18, 10, 14, 8, 10, 12, and 8, respectively, to 0, 7, 1, 10, 15, 15, 15, and 10, respectively. CONCLUSIONS Accelerated TBS over the bilateral DLPFC may ameliorate long-COVID-associated neuropsychiatric symptoms. Additional trials are warranted to evaluate the effect of neuropsychiatric symptoms following COVID-19.

Cognitive dysfunction, diabetes mellitus 2 and arterial hypertension: Sequelae up to one year of COVID-19.

BACKGROUND: Covid symptoms reflect its multisystem nature, in addition to its positive relationship between the severity of the condition and the severity of the long COVID. OBJECTIVE: To identify the factors associated with the prevalence of SEQUELAE DUE TO COVID-19 one year after their hospital discharge due to severe pneumonia. METHOD: Longitudinal, analytical, prospective and comparative study. 71 covid-19 pneumonia survivors were followed. Two telephone interviews were conducted to each patient; the first at 5 months of discharge and the second at 12 months from the mentioned date. We included questions of 40 symptoms, in addition to the questioning of diabetes mellitus and/or systemic hypertension with a mentioned onset during the hospitalization or after hospital discharge due to COVID-19. RESULTS: Of the 37 patients without complications and without comorbidities prior to hospitalization, 11 (29.7%) developed arterial hypertension during or after discharge and 17 (45.9%) developed diabetes mellitus before five months. Short-term memory loss was an upward sequel in the two measurements, 24.3% and 41.9% respectively. CONCLUSIONS: Type 2 diabetes mellitus and high blood pressure detected at five months was temporary and reversed in many cases at twelve months. It will be important to deepen the study of brain damage and cognitive dysfunction, characterized by memory loss.

Brain correlates of subjective cognitive complaints in COVID-19 survivors: A multimodal magnetic resonance imaging study.

Cognitive impairment represents a leading residual symptom of COVID-19 infection, which lasts for months after the virus clearance. Up-to-date scientific reports documented a wide spectrum of brain changes in COVID-19 survivors following the illness's resolution, mainly related to neurological and neuropsychiatric consequences. Preliminary insights suggest abnormal brain metabolism, microstructure, and functionality as neural under-layer of post-acute cognitive dysfunction. While previous works focused on brain correlates of impaired cognition as objectively assessed, herein we investigated long-term neural correlates of subjective cognitive decline in a sample of 58 COVID-19 survivors with a multimodal imaging approach. Diffusion Tensor Imaging (DTI) analyses revealed widespread white matter disruption in the sub-group of cognitive complainers compared to the non-complainer one, as indexed by increased axial, radial, and mean diffusivity in several commissural, projection and associative fibres. Likewise, the Multivoxel Pattern Connectivity analysis (MVPA) revealed highly discriminant patterns of functional connectivity in resting-state among the two groups in the right frontal pole and in the middle temporal gyrus, suggestive of inefficient dynamic modulation of frontal brain activity and possible metacognitive dysfunction at rest. Beyond COVID-19 actual pathophysiological brain processes, our findings point toward brain connectome disruption conceivably translating into clinical post-COVID cognitive symptomatology. Our results could pave the way for a potential brain signature of cognitive complaints experienced by COVID-19 survivors, possibly leading to identify early therapeutic targets and thus mitigating its detrimental long-term impact on quality of life in the post-COVID-19 stages.

Evaluation of cognitive functions in adult individuals with COVID-19.

BACKGROUND AND PURPOSE: Cognitive deficits that are associated with coronavirus disease 2019 (COVID-19) and occur in the acute period are gaining importance. While most studies have focused on the elderly severely affected during acute infection, it remains unclear whether mild to moderate COVID-19 results in cognitive deficits in young patients. This study aims to evaluate the post-infection cognitive functions of young adults with mild to moderate symptoms of COVID-19. METHODS: A total of 100 adults with similar age and educational background were included in the study. Half of those had been infected with COVID-19 in the last 60 days (N = 50), and the other half had not (N = 50). Global cognitive skills of the participants were evaluated through Montreal Cognitive Assessment Scale (MoCA) and Clock-Drawing Test; memory functions with Öktem Verbal Memory Processes Test (Ö-VMPT); attention span with Digit Span Test; executive functions with Fluency Tests, Stroop Test, and Trail Making Test; visual perceptual skills with Rey Osterrieth Complex Figure Test (ROCF); and neuropsychiatric status with Neuropsychiatric Inventory (NPI). Evaluations were performed in the experimental group for 21 to 60 days from the onset of the disease, and throughout the study, in the control group. RESULTS: It was found that global cognitive skills, verbal memory, visual memory, executive function, and neuropsychiatric status were affected during COVID-19 (p < 0.05). CONCLUSION: When the cases were analyzed according to disease severity, no relationship was found between cognitive deficits and disease severity.

Cognition Before and After COVID-19 Disease in Older Adults: An Exploratory Study.

BACKGROUND: Older age is a major risk factor for severe COVID-19 disease which has been associated with a variety of neurologic complications, both acutely and chronically. OBJECTIVE: We sought to determine whether milder COVID-19 disease in older vulnerable individuals is also associated with cognitive and behavioral sequelae. METHODS: Neuropsychological, behavioral, and clinical outcomes before and after contracting COVID-19 disease, were compared in members of two ongoing longitudinal studies, the Arizona APOE Cohort and the national Alzheimer's Disease Research Center (ADRC). RESULTS: 152 APOE and 852 ADRC cohort members, mean age overall roughly 70 years, responded to a survey that indicated 21 APOE and 57 ADRC members had contracted COVID-19 before their ensuing (post-COVID) study visit. The mean interval between test sessions that preceded and followed COVID was 2.2 years and 1.2 years respectively for the APOE and ADRC cohorts. The magnitude of change between the pre and post COVID test sessions did not differ on any neuropsychological measure in either cohort. There was, however, a greater increase in informant (but not self) reported cognitive change in the APOE cohort (p = 0.018), but this became nonsignificant after correcting for multiple comparisons. CONCLUSION: Overall members of both cohorts recovered well despite their greater age-related vulnerability to more severe disease.

Brain positron emission tomography (PET) and cognitive abnormalities one year after COVID-19.

Emerging evidence indicates that the etiologic agent responsible for coronavirus disease 2019 (COVID-19), can cause neurological complications. COVID-19 may induce cognitive impairment through multiple mechanisms. The aim of the present study was to describe the possible neuropsychological and metabolic neuroimaging consequences of COVID-19 12 months after patients' hospital discharge. We retrospectively recruited 7 patients (age [mean ± SD] = 56 years ± 12.39, 4 men) who had been hospitalized for COVID-19 with persistent neuropsychological deficits 12 months after hospital discharge. All patients underwent cognitive assessment and brain (18F-FDG) PET/CT, and one also underwent 18F-amyloid PET/CT. Of the seven patients studied, four had normal glucose metabolism in the brain. Three patients showed various brain hypometabolism patterns: (1) unilateral left temporal mesial area hypometabolism; (2) pontine involvement; and (3) bilateral prefrontal area abnormalities with asymmetric parietal impairment. The patient who showed the most widespread glucose hypometabolism in the brain underwent an 18F-amyloid PET/CT to assess the presence of Aß plaques. This examination showed significant Aß deposition in the superior and middle frontal cortex, and in the posterior cingulate cortex extending mildly in the rostral and caudal anterior cingulate areas. Although some other reports have already suggested that brain hypometabolism may be associated with cognitive impairment at shorter intervals from SarsCov-2 infection, our study is the first to assess cognitive functions, brain metabolic activity and in a patient also amyloid PET one year after COVID-19, demonstrating that cerebral effects of COVID-19 can largely outlast the acute phase of the disease and even be followed by amyloid deposition.

Predictors of cognitive dysfunction one-year post COVID-19.

OBJECTIVES: (a) To characterize the frequency of objective cognitive deficits and self-perceived cognitive difficulties and (b) to explore demographic and clinical predictors of cognitive dysfunction and cognitive complaints. METHOD: One hundred and ten adults diagnosed with COVID-19 between March and November 2020, aged ≤ 74 years underwent a brief neuropsychological evaluation 12 months after infection, which included: Brief Visuospatial Memory Test-Revised, California Verbal Learning Test, and Symbol Digit Modalities Test. T scores < 38 were considered abnormal performance; cognitive dysfunction was defined as ≥ 2 abnormal tests. Participants also completed Broadbent's Cognitive Failure Questionnaires (CFQ), Hospital Anxiety and Depression Scale, Modified Fatigue Impact Scale, and Short-Form Health Survey. CFQ ≥ 43 was considered indicative of cognitive complaints. RESULTS: Twenty participants (18.2%) had cognitive dysfunction and 36 (33.3%) had cognitive complaints. Cognitive dysfunction was related to lower education, preinfection history of headache/migraine, and acute COVID-19 symptoms of headache and sleep disturbance. Cognitive complaints were more likely to occur in women, those with fewer years of education, and acute COVID-19 symptoms of headache and sleep disturbance. Cognitive complaints were also significantly related to symptoms of anxiety, depression, and fatigue. Sex and psychopathology were not significant predictors of cognitive dysfunction. Modest associations were found between CFQ total score and cognitive test performance. DISCUSSION: A subset of individuals develops cognitive difficulties in the context of post-COVID syndrome. Results may support the protective effect of education, a known proxy of cognitive reserve. COVID-19 infection symptoms of headache and sleep disturbance appear to be risk factors for long-term cognitive difficulties. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Cognitive impairment, anxiety and depression: a map of Cochrane evidence relevant to rehabilitation for people with post COVID-19 condition.

INTRODUCTION: Currently, no evidence exists on specific treatments for post COVID-19 condition (PCC). However, rehabilitation interventions that are effective for similar symptoms in other health conditions could be applied to people with PCC. With this overview of systematic reviews with mapping, we aimed to describe the Cochrane evidence on rehabilitation interventions proposed for cognitive impairment, anxiety and depression in different health conditions that can be relevant for PCC. EVIDENCE ACQUISITION: We searched the last five years' Cochrane Systematic Review (CSRs) using the terms "cognitive impairment," "depressive disorder," "anxiety disorder," their synonyms and variants, and "rehabilitation" in the Cochrane Library. We extracted and summarized the available evidence using a map. We grouped the included CSRs for health conditions and interventions, indicating the effect and the quality of evidence. EVIDENCE SYNTHESIS: We found 3596 CSRs published between 2016 and 2021, and we included 17 on cognitive impairment and 37 on anxiety and depression. For cognitive impairment, we found 7 CSRs on participants with stroke, 3 with cancer, 2 with Parkinson's disease, and one each for five other health conditions. Each intervention improved a different domain, and included exercises, cognitive and attention-specific training, and computerized cognition-based training (from very low to high-quality evidence). For anxiety and depression, we found 10 CSRs including participants with cancer, 8 with stroke, 3 with chronic obstructive pulmonary disease, and 2 or 1 each in 11 other health conditions. Exercise training, physical activity and yoga resulted effective in several pathologies (very low- to moderate-quality evidence). In specific diseases, we found effective acupuncture, animal-assisted therapy, aromatherapy, educational programs, home-based multidimensional survivorship programs, manual acupressure massage, memory rehabilitation, non-invasive brain stimulation, pulmonary rehabilitation, and telerehabilitation (very low- to moderate-quality evidence). CONCLUSIONS: These results are the first step of indirect evidence able to generate helpful hypotheses for clinical practice and future research. They served as the basis for the three recommendations on treatments for these PCC symptoms published in the current WHO Guidelines for clinical practice.

[The state of cognitive functions in patients with coronavirus infection in the acute period of the disease (outbreaks in 2020-2022)]. / Sostoyanie kognitivnykh funktsii u patsientov v ostrom periode novoi koronavirusnoi infektsii (epidemiologicheskie volny 2020­2022 gg.).

OBJECTIVE: To assess the state of cognitive functions in patients in the acute period of coronavirus infection with pneumonia during periods of hospitalization in 2020-2022. MATERIAL AND METHODS: The study included 3 groups of people of different ages. The first and second groups are inpatients in the acute period of coronavirus infection with viral pneumonia during treatment in a hospital in Krasnoyarsk. Group 1 was hospitalized in the period December 2020 - March 2021. The second group was hospitalized in the period November 2021 - January 2022. The control group consisted of clinically healthy individuals. MMSE, MoCA, FAB, CDT were used to assess the neuropsychological status. Anxiety and depression were assessed using HADS. Patients in the groups were tested on the first day after stabilization of the condition, then again for discharge or transfer to another hospital. The control group was tested once. RESULTS: Statically significant cognitive impairments were detected in patients with coronavirus infection with viral pneumonia in the acute period of the disease, both at admission and at discharge, compared with the control group. Patients admitted for the period December 2020 - March 2021 had more pronounced cognitive impairment than patients admitted for the period November 2021 - January 2022. Anxiety and depression were not detected on HADS. CONCLUSION: Coronavirus infection with viral pneumonia causes cognitive impairment in patients in the acute period of the disease. The severity of changes of cognitive functions was different depending on outbreaks of infection, which may probably be due to a mutation of the virus for the period 2020-2022.

Cognitive impairments among patients in a long-COVID clinic: Prevalence, pattern and relation to illness severity, work function and quality of life.

BACKGROUND: A considerable proportion of people experience lingering symptoms after Coronavirus Disease 2019 (COVID-19). The aim of this study was to investigate the frequency, pattern and functional implications of cognitive impairments in patients at a long-COVID clinic who were referred after hospitalisation with COVID-19 or by their general practitioner. METHODS: Patients underwent cognitive screening and completed questionnaires regarding subjective cognition, work function and quality of life. Patients' cognitive performance was compared with that of 150 age-, sex-, and education-matched healthy controls (HC) and with their individually expected performance calculated based on their age, sex and education. RESULTS: In total, 194 patients were assessed, on average 7 months (standard deviation: 4) after acute COVID-19.44-53 % of the patients displayed clinically relevant cognitive impairments compared to HC and to their expected performance, respectively. Moderate to large impairments were seen in global cognition and in working memory and executive function, while mild to moderate impairments occurred in verbal fluency, verbal learning and memory. Hospitalised (n = 91) and non-hospitalised (n = 103) patients showed similar degree of cognitive impairments in analyses adjusted for age and time since illness. Patients in the cognitively impaired group were older, more often hospitalised, had a higher BMI and more frequent asthma, and were more often female. More objective cognitive impairment was associated with more subjective cognitive difficulties, poorer work function and lower quality of life. LIMITATIONS: The study was cross-sectional, which precludes causality inferences. CONCLUSIONS: These findings underscore the need to assess and treat cognitive impairments in patients at long-COVID clinics.