COVID-19 and cognitive function: Evidence for increased processing speed variability in COVID-19 survivors and multifaceted impairment with long-COVID symptoms.

BACKGROUND: There is increasing evidence for cognitive function to be negatively impacted by COVID-19. There is, however, limited research evaluating cognitive function pre- and post-COVID-19 using objective measures. METHODS: We examined processing speed, attention, working memory, executive function and memory in adults (≤69 years) with a history of COVID-19 (n = 129, none acutely unwell), compared to those with no known history of COVID-19 (n = 93). We also examined cognitive changes in a sub-group of COVID (n = 30) and non-COVID (n = 33) participants, compared to their pre-COVID-19 pandemic level. RESULTS: Cross-sectionally, the COVID group showed significantly larger intra-individual variability in processing speed, compared to the non-COVID group. The COVID sub-group also showed significantly larger intra-individual variability in processing speed, compared to their pre-COVID level; no significant change occurred in non-COVID participants over the same time scale. Other cognitive indices were not significantly impacted in the cross-sectional or within-subjects investigations, but participants (n = 20) who had needed hospitalisation due to COVID-19 showed poor attention and executive function relative to those who had not required hospitalisation (n = 109). Poor health and long-COVID symptoms correlated with poor cognitive function across domains in the COVID group. CONCLUSIONS: The findings indicate a limited cognitive impact of COVID-19 with only intra-individual variability in processing speed being significantly impacted in an adult UK sample. However, those who required hospitalisation due to COVID-19 severity and/or experience long-COVID symptoms display multifaceted cognitive impairment and may benefit from repeated cognitive assessments and remediation efforts.

Systematic Review and Meta-Analysis of Clinically Relevant Executive Functions Tests Performance after COVID-19.

It is widely known that COVID-19 has a number of prolonged effects on general health, wellbeing, and cognitive functioning. However, studies using differentiated performance measures of cognitive functions are still not widely spread making it hard to assess the exact functions that get impaired. Taking into account the similarities between post-COVID 'brain fog' and chemofog, we hypothesized that executive functions (EF) would be impaired. Literature search yielded six studies with 14 effect sizes of interest; pooled effect size was small to medium (d = -0.35). Combined with a narrative synthesis of six studies without a comparison group, these results show that EF get impaired after COVID-19; although, in most cases the impairment is transient and does not seem to be severe. These results specify the picture of 'brain fog' and may help to discover its mechanisms and ways of helping people with long COVID.

Cognitive deficit in post-acute COVID-19: an opportunity for EEG evaluation?

BACKGROUND AND PURPOSE: Among the most common post-COVID symptoms, many patients experienced subjective cognitive deficit, commonly named "brain fog," that might be present also in those individuals without severe acute COVID-19 respiratory involvement. Some studies have investigated some of the mechanisms that might be associated with the brain fog with objective techniques including transcranial magnetic stimulation and neuroimaging. METHODS: The aim of this study was to investigate the presence of electroencephalographic (EEG) alterations in people with post-COVID self-reported cognitive deficit. RESULTS: Out of the 90 patients attending the post-COVID neurology ambulatory service, twenty patients presenting brain fog at least 4 weeks after acute non-severe COVID-19 infection, and without previous history of epilepsy, were investigated with 19-channel EEG, Montreal Cognitive Assessment (MoCA), and magnetic resonance imaging (MRI). EEG was found altered in 65% of the sample, among which 69% presented a slowing activity and 31% were characterized by epileptic discharges principally in the frontal areas. None of the patients showed DWI MRI lesions. CONCLUSIONS: These findings highlight the usefulness of EEG analysis to objectively describe possible neurophysiological abnormalities in post-COVID patients presenting subjective cognitive deficit.

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 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.

The negative impact of COVID-19 on working memory revealed using a rapid online quiz.

Although coronavirus disease 2019 (COVID-19) affects the respiratory system, it can also have neurological consequences leading to cognitive deficits such as memory problems. The aim of our study was to assess the impact of COVID-19 on working memory function. We developed and implemented an online anonymous survey with a working memory quiz incorporating aspects of gamification to engage participants. 5428 participants successfully completed the survey and memory quiz between 8th December 2020 and 5th July 2021 (68.6% non-COVID-19 and 31.4% COVID-19). Most participants (93.3%) completed the survey and memory quiz relatively rapidly (mean time of 8.84 minutes). Categorical regression was used to assess the contribution of COVID status, age, time post-COVID (number of months elapsed since having had COVID), symptoms, ongoing symptoms and gender, followed by non-parametric statistics. A principal component analysis explored the relationship between subjective ratings and objective memory scores. The objective memory scores were significantly correlated with participants' own assessment of their cognitive function. The factors significantly affecting memory scores were COVID status, age, time post-COVID and ongoing symptoms. Our main finding was a significant reduction in memory scores in all COVID groups (self-reported, positive-tested and hospitalized) compared to the non-COVID group. Memory scores for all COVID groups combined were significantly reduced compared to the non-COVID group in every age category 25 years and over, but not for the youngest age category (18-24 years old). We found that memory scores gradually increased over a period of 17 months post-COVID-19. However, those with ongoing COVID-19 symptoms continued to show a reduction in memory scores. Our findings demonstrate that COVID-19 negatively impacts working memory function, but only in adults aged 25 years and over. Moreover, our results suggest that working memory deficits with COVID-19 can recover over time, although impairments may persist in those with ongoing symptoms.

Neuropsychological manifestations of long COVID in hospitalized and non-hospitalized Brazilian Patients.

BACKGROUND: There has been a significant increase in number of patients seeking neuropsychological rehabilitation months after the acute phase of COVID-19 infection. OBJECTIVE: Identify the cognitive and psychiatric disorders in patients with long COVID or Post-Acute Sequelae of COVID (PASC) and explore the association between disease severity during the acute phase and persistent neuropsychological manifestations. METHODS: 614 adults were assessed an average of eight months post-infection. Participants were, on average, 47.6 y.o., who sought rehabilitation for neuropsychological problems. Patients were evaluated using the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS), Phonemic Verbal Fluency and Clock Drawing tests (NEUPSILIN) for executive functions, and the Hospital Anxiety and Depression Scale (HADS). RESULTS: The BNIS score was significantly below reference values in all subscales, especially affect and memory. Verbal Fluency and Clock Drawing subtest results were also lower. Patients with PASC tested high for anxiety/depression, but there was no statistically significant relationship between HADS and BNIS scores. Neuropsychological evaluations showed no differences in cognitive or psychiatric profiles between hospitalized and non-hospitalized patients. CONCLUSIONS: Neuropsychological results suggest executive function problems and high incidence of anxiety/depression, irrespective of acute-phase severity, underscoring a need for neurorehabilitation programs while providing data for public policy initiatives.

Implementation of a Hybrid Teleneuropsychology Method to Assess Middle Aged and Older Adults During the COVID-19 Pandemic.

OBJECTIVE: Hybrid teleneuropsychology has emerged as a useful assessment method to manage physical distancing requirements during the COVID-19 pandemic. We describe the development of a hybrid teleneuropsychology clinic and compare results of six neuropsychological tasks across testing modalities, as well as a participant experience survey. METHOD: Healthy middle-aged and older adults completed a face-to-face assessment two years previously. Participants either completed reassessment face-to-face or via the hybrid setup. Results were compared across time points and delivery modality. RESULTS: There were no significant differences in scores at reassessment between face-to-face and a hybrid setup on nonverbal fluid intelligence, verbal memory, visual memory, language, working memory or verbal initiation. Retest reliability was moderate to excellent for verbal and visual memory, attention and naming. Results of an anonymous survey indicated that participants felt comfortable and established good rapport with the examiner. CONCLUSIONS: This hybrid method of teleneuropsychology can be used to obtain high quality and reliable results including on tasks yet to be evaluated for teleneuropsychology, including the Graded Naming Test and the Topographical Recognition Memory Test.

Cognitive phenotyping of post-infectious SARS-CoV-2 patients.

BACKGROUND: SARS-CoV-2 infection entails neuroinvasive, neuroinflammatory, and treatment-related features accounting for cognitive deficits in COVID-19-recovered patients. Although screening for such dysfunctions in this population is considered clinically relevant, contributions to cognitive phenotyping including premorbid and disease-related confounders are scarcely represented. This study thus aimed at describing the cognitive outcome at the function-/domain-level of post-infectious SARS-CoV-2 patients being already at risk (RCD +) or not (RCD -) for cognitive decline. METHODS: Fifty-four COVID-19-recovered individuals were classified as either RCD + or RCD - according to medical records. The Mini-Mental State Examination (MMSE), Addebrooke Cognitive Examination-Revised (ACE-R), Frontal Assessment Battery (FAB), and Attentive Matrices (AM) were administered (N = 54, 34, 28, and 28 patients, respectively). RESULTS: Prevalence of defective (cutoff = 24.89) MMSE scores was 24.3% in RCD + patients and 5.9% in the RCD - group. ACE-R-total below cutoff scores were less frequent (RCD + : 5.4%; RCD - : 5.9%). Abnormal performances at the FAB an AM were respectively detected in 18.9% and 8.1% of RCD + patients and 0% and 11.8% of the RCD - group. Within the ACE-R subtests, those assessing orientation, attention, and fluency were the most frequently impaired in both groups. Disease-related variables were mostly unassociated with cognitive measures. DISCUSSION: Both RCD + and RCD - COVID-19-recovered individuals might show cognitive deficits within the dysexecutive-inattentive and amnesic spectrum. Non-instrumental, executive/attentive dysfunctions are predominant in this population and can be detected by both screening and domain-specific psychometric tests-although the latter might be more sensitive in RCD - patients.

One-year cognitive follow-up of COVID-19 hospitalized patients.

BACKGROUND AND PURPOSE: Cognitive dysfunction has been observed following recovery from COVID-19. To the best of our knowledge, however, no study has assessed the progression of cognitive impairment after 1 year. The aim was to assess cognitive functioning at 1 year from hospital discharge, and eventual associations with specific clinical variables. METHODS: Seventy-six patients (aged 22-74 years) who had been hospitalized for COVID-19 were recruited. Patients received neuropsychological assessments at 5 (n = 76) and 12 months (n = 53) from hospital discharge. RESULTS: Over half (63.2%) of the patients had deficits in at least one test at 5 months. Compared to the assessment at 5 months, verbal memory, attention and processing speed improved significantly after 1 year (all p < 0.05), whereas visuospatial memory did not (all p > 0.500). The most affected domains after 1 year were processing speed (28.3%) and long-term visuospatial (18.1%) and verbal (15.1%) memory. Lower PaO2 /FiO2 ratios in the acute phase were associated with worse verbal long-term memory (p = 0.029) and visuospatial learning (p = 0.041) at 5 months. Worse visuospatial long-term memory at 5 months was associated with hyposmia (p = 0.020) and dysgeusia (p = 0.037). CONCLUSION: Our study expands the results from previous studies showing that cognitive impairment can still be observed after 1 year. Patients with severe COVID-19 should receive periodic cognitive follow-up evaluations, as cognitive deficits in recovered patients could have social and occupational implications.

The cognitive and psychiatric subacute impairment in severe Covid-19.

Neurologic impairment persisting months after acute severe SARS-CoV-2 infection has been described because of several pathogenic mechanisms, including persistent systemic inflammation. The objective of this study is to analyze the selective involvement of the different cognitive domains and the existence of related biomarkers. Cross-sectional multicentric study of patients who survived severe infection with SARS-CoV-2 consecutively recruited between 90 and 120 days after hospital discharge. All patients underwent an exhaustive study of cognitive functions as well as plasma determination of pro-inflammatory, neurotrophic factors and light-chain neurofilaments. A principal component analysis extracted the main independent characteristics of the syndrome. 152 patients were recruited. The results of our study preferential involvement of episodic and working memory, executive functions, and attention and relatively less affectation of other cortical functions. In addition, anxiety and depression pictures are constant in our cohort. Several plasma chemokines concentrations were elevated compared with both, a non-SARS-Cov2 infected cohort of neurological outpatients or a control healthy general population. Severe Covid-19 patients can develop an amnesic and dysexecutive syndrome with neuropsychiatric manifestations. We do not know if the deficits detected can persist in the long term and if this can trigger or accelerate the onset of neurodegenerative diseases.

[Steinert's disease and refusal to treatment]. / Enfermedad de Steinert y rechazo de la actuación médica.

TITLE: Enfermedad de Steinert y rechazo de la actuación médica.

A behavioral protocol to assess the relationship between three cognitive biases and future depression severity.

According to the cognitive model of depression, memory bias, interpretation bias, and attention bias are associated with the development and maintenance of depression. Here, we present a protocol for investigating whether and how the novel coronavirus disease 2019 (COVID-19) pandemic may affect the relationship between current cognitive biases and future depression severity in a population with non-clinical depression. This protocol can also be used in other contexts, including cognitive bias-related studies and depression-related functional magnetic resonance imaging (fMRI) studies. For complete details on the use and execution of this protocol, please refer to Zhang et al. (2021).

Neuropsychology of COVID-19: Anticipated cognitive and mental health outcomes.

OBJECTIVE: Discuss anticipated patterns of cognitive and emotional dysfunction, prognostic indicators, and treatment considerations based on review of (a) neuroinvasive properties of prior human coronaviruses and (b) extensively researched disorders which share similar neurological mechanisms. METHOD: A web-based comprehensive search of peer-reviewed journals was conducted based on a variety of key terms (and variants of) including coronavirus, neuroinvasion, cognitive dysfunction, viral pandemics, respiratory illness, critical illness, and metabolic disease. Articles were chosen based on relevance to the current topic and ability to provide unique thematic information. Historical articles were included if these added scientific merit to recent literature. Review of information in widely disseminated news articles was followed-up with direct review of cited scientific literature. Databases searched included Google Scholar, PubMed, and Ovid Medline. RESULTS: Based on neuroinvasive properties of prior coronaviruses and existing research on similar neurophysiological conditions with detrimental cognitive effects, COVID-19-especially those with severe symptoms-are at risk for cognitive decline and significant psychiatric/behavioral sequela. CONCLUSIONS: There are few studies examining cognitive outcomes in COVID-19. This review argues that neuropsychological sequelae are to be expected in patients with COVID-19. Considerations for clinicians working with this unique population are discussed. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Low molecular weight heparin in COVID-19 patients prevents delirium and shortens hospitalization.

BACKGROUND: COVID-19 patients present with delirium during their hospitalization. AIMS: To assess the incidence of delirium in hospitalized COVID-19 patients and analyze the possible association with demographic, clinical, laboratory, and pharmacological factors. METHODS: COVID-19 patients were assessed for clinical signs of delirium and administered the assessment test for delirium and cognitive impairment (4AT) and the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) scales. RESULTS: Out of the 56 patients of our cohort, 14 (25.0%) experienced delirium. The use of low molecular weight heparin (LMWH) (enoxaparin 1 mg/kg/daily) was less frequent in patients with delirium (p = 0.004) and was accompanied by lower C reactive protein (CRP) levels (p = 0.006). DISCUSSION: The use of LMWH was associated with absence of delirium, independently of comorbidities and age. CONCLUSIONS: The use of LMWH may help preventing the occurrence of delirium in COVID-19 patients, with possible reduction of length of stay in the hospital and sequelae.

COVID-19 cognitive deficits after respiratory assistance in the subacute phase: A COVID-rehabilitation unit experience.

INTRODUCTION: COVID-19 complications can include neurological, psychiatric, psychological, and psychosocial impairments. Little is known on the consequences of SARS-COV-2 on cognitive functions of patients in the sub-acute phase of the disease. We aimed to investigate the impact of COVID-19 on cognitive functions of patients admitted to the COVID-19 Rehabilitation Unit of the San Raffaele Hospital (Milan, Italy). MATERIAL AND METHODS: 87 patients admitted to the COVID-19 Rehabilitation Unit from March 27th to June 20th 2020 were included. Patients underwent Mini Mental State Evaluation (MMSE), Montreal Cognitive Assessment (MoCA), Hamilton Rating Scale for Depression, and Functional Independence Measure (FIM). Data were divided in 4 groups according to the respiratory assistance in the acute phase: Group1 (orotracheal intubation), Group2 (non-invasive ventilation using Biphasic Positive Airway Pressure), Group3 (Venturi Masks), Group4 (no oxygen therapy). Follow-ups were performed at one month after home-discharge. RESULTS: Out of the 87 patients (62 Male, mean age 67.23 ± 12.89 years), 80% had neuropsychological deficits (MoCA and MMSE) and 40% showed mild-to-moderate depression. Group1 had higher scores than Group3 for visuospatial/executive functions (p = 0.016), naming (p = 0.024), short- and long-term memory (p = 0.010, p = 0.005), abstraction (p = 0.024), and orientation (p = 0.034). Group1 was younger than Groups2 and 3. Cognitive impairments correlated with patients' age. Only 18 patients presented with anosmia. Their data did not differ from the other patients. FIM (<100) did not differ between groups. Patients partly recovered at one-month follow-up and 43% showed signs of post-traumatic stress disorder. CONCLUSION: Patients with severe functional impairments had important cognitive and emotional deficits which might have been influenced by the choice of ventilatory therapy, but mostly appeared to be related to aging, independently of FIM scores. These findings should be integrated for correct neuropsychiatric assistance of COVID-19 patients in the subacute phase of the disease, and show the need for long-term psychological support and treatment of post-COVID-19 patients.

Effects of COVID-19 Home Confinement on Mental Health in Individuals with Increased Risk of Alzheimer's Disease.

We explored the impact of the Spanish COVID-19 strict home confinement on mental health and cognition in non-infected subjects (N = 16, 60-80 years) diagnosed with subjective cognitive decline and APOEɛ3/ɛ4 carriers. Mental health was monitored for 2 months on a daily, weekly, or monthly basis, and compared to pre-confinement values. Emotional distress, anxiety, and depression scores increased to pathological threshold values during and after confinement. Those with lower mood during confinement experienced a decline in their mood after confinement. Cognition did not change. These preliminary results suggest that mental health consequences of corona measures in preclinical stages of Alzheimer's disease should be further evaluated.

COVID-19-related encephalopathy: a case series with brain FDG-positron-emission tomography/computed tomography findings.

AIM: The aim of this paper is to describe the clinical features of COVID-19-related encephalopathy and their metabolic correlates using brain 2-desoxy-2-fluoro-D-glucose (FDG)-positron-emission tomography (PET)/computed tomography (CT) imaging. BACKGROUND AND PURPOSE: A variety of neurological manifestations have been reported in association with COVID-19. COVID-19-related encephalopathy has seldom been reported and studied. METHODS: We report four cases of COVID-19-related encephalopathy. The diagnosis was made in patients with confirmed COVID-19 who presented with new-onset cognitive disturbances, central focal neurological signs, or seizures. All patients underwent cognitive screening, brain magnetic resonance imaging (MRI), lumbar puncture, and brain 2-desoxy-2-fluoro-D-glucose (FDG)-positron-emission tomography (PET)/computed tomography (CT) (FDG-PET/CT). RESULTS: The four patients were aged 60 years or older, and presented with various degrees of cognitive impairment, with predominant frontal lobe impairment. Two patients presented with cerebellar syndrome, one patient had myoclonus, one had psychiatric manifestations, and one had status epilepticus. The delay between first COVID-19 symptoms and onset of neurological symptoms was between 0 and 12 days. None of the patients had MRI features of encephalitis nor significant cerebrospinal fluid (CSF) abnormalities. SARS-CoV-2 RT-PCR in the CSF was negative for all patients. All patients presented with a consistent brain FDG-PET/CT pattern of abnormalities, namely frontal hypometabolism and cerebellar hypermetabolism. All patients improved after immunotherapy. CONCLUSIONS: Despite varied clinical presentations, all patients presented with a consistent FDG-PET pattern, which may reflect an immune mechanism.

[Ethics, care and ageing during the Covid-19 pandemic]. / Éthique, soin et grand âge pendant l'épidémie de Covid-19.

At the beginning of the Covid-19 epidemic, National forum for ethical reflection on Alzheimer's disease and neurodegenerative diseases conducted a national survey to identify the difficulties encountered by professionals working in the field of old age and autonomy, families and volunteers, and the initiatives they have implemented. Seven major difficulties were identified: the isolation induced by the prohibition of visits, the lack of protective equipment and tests, the difficulties of people with cognitive difficulties in understanding measures to avoid the spread of the epidemic, the sustainability of overwork for professionals, the concern of the families of residents, complex situations at home and difficulties in accessing care. Four initiatives are being implemented: information and training for teams, compensation for interrupted visits, consultations and exchanges between professionals, actions to benefit people living at home. The Covid-19 epidemic hit the elderly sector at a very special moment in its history, several years of effort by the sector to reinvent itself around strong values. They have been a resource during this period of crisis. An ambitious law on old age and autonomy therefore appears to be a necessity.