Assessment of Neurocognitive Functions, Olfaction, Taste, Mental, and Psychosocial Health in COVID-19 in Adults: Recommendations for Harmonization of Research and Implications for Clinical Practice.

OBJECTIVE: To propose a set of internationally harmonized procedures and methods for assessing neurocognitive functions, smell, taste, mental, and psychosocial health, and other factors in adults formally diagnosed with COVID-19 (confirmed as SARS-CoV-2 + WHO definition). METHODS: We formed an international and cross-disciplinary NeuroCOVID Neuropsychology Taskforce in April 2020. Seven criteria were used to guide the selection of the recommendations' methods and procedures: (i) Relevance to all COVID-19 illness stages and longitudinal study design; (ii) Standard, cross-culturally valid or widely available instruments; (iii) Coverage of both direct and indirect causes of COVID-19-associated neurological and psychiatric symptoms; (iv) Control of factors specifically pertinent to COVID-19 that may affect neuropsychological performance; (v) Flexibility of administration (telehealth, computerized, remote/online, face to face); (vi) Harmonization for facilitating international research; (vii) Ease of translation to clinical practice. RESULTS: The three proposed levels of harmonization include a screening strategy with telehealth option, a medium-size computerized assessment with an online/remote option, and a comprehensive evaluation with flexible administration. The context in which each harmonization level might be used is described. Issues of assessment timelines, guidance for home/remote assessment to support data fidelity and telehealth considerations, cross-cultural adequacy, norms, and impairment definitions are also described. CONCLUSIONS: The proposed recommendations provide rationale and methodological guidance for neuropsychological research studies and clinical assessment in adults with COVID-19. We expect that the use of the recommendations will facilitate data harmonization and global research. Research implementing the recommendations will be crucial to determine their acceptability, usability, and validity.

Criterion validity of the brief test of adult cognition by telephone (BTACT) for mild traumatic brain injury.

OBJECTIVES: There is a growing demand for remote assessment options for measuring cognition after mild traumatic brain injury (mTBI). The current study evaluated the criterion validity of the Brief Test of Adult Cognition by Telephone (BTACT) in distinguishing between adults with mTBI and trauma controls (TC) who sustained injuries not involving the head or neck. METHODS: The BTACT was administered to the mTBI (n = 46) and TC (n = 35) groups at 1-2 weeks post-injury. Participants also completed the Rivermead Post Concussion Symptoms Questionnaire. RESULTS: The BTACT global composite score did not significantly differ between the groups (t(79) = -1.04, p = 0.30); the effect size was small (d = 0.23). In receiver operating characteristic curve analyses, the BTACT demonstrated poor accuracy in differentiating between the groups (AUC = 0.567, SE = 0.065, 95% CI [0.44, 0.69]). The BTACT's ability to discriminate between mTBI and TCs did not improve after excluding mTBI participants (n = 15) who denied ongoing cognitive symptoms (AUC = 0.567, SE = 0.072, 95% CI [0.43, 0.71]). CONCLUSIONS: The BTACT may lack sensitivity to subacute cognitive impairment attributable to mTBI (i.e., not explained by bodily pain, post-traumatic stress, and other nonspecific effects of injury).

Brain abnormalities in COVID-19 acute/subacute phase: A rapid systematic review.

OBJECTIVE: This systematic review aimed to synthesize early data on typology and topography of brain abnormalities in adults with COVID-19 in acute/subacute phase. METHODS: We performed systematic literature search via PubMed, Google Scholar and ScienceDirect on articles published between January 1 and July 05, 2020, using the following strategy and key words: ((covid[Title/Abstract]) OR (sars-cov-2[Title/Abstract]) OR (coronavirus[Title/Abstract])) AND (brain[Title/Abstract]). A total of 286 non-duplicate matches were screened for original contributions reporting brain imaging data related to SARS-Cov-2 presentation in adults. RESULTS: The selection criteria were met by 26 articles (including 21 case reports, and 5 cohort studies). The data analysis in a total of 361 patients revealed that brain abnormalities were noted in 124/361 (34%) reviewed cases. Neurologic symptoms were the primary reason for referral for neuroimaging across the studies. Modalities included CT (-angiogram, -perfusion, -venogram), EEG, MRI (-angiogram, functional), and PET. The most frequently reported brain abnormalities were brain white matter (WM) hyperintensities on MRI 66/124 (53% affected cases) and hypodensities on CT (additional 23% affected cases), followed by microhemorrhages, hemorrhages and infarcts, while other types were found in <5% affected cases. WM abnormalities were most frequently noted in bilateral anterior and posterior cerebral WM (50% affected cases). CONCLUSION: About a third of acute/subacute COVID-19 patients referred for neuroimaging show brain abnormalities suggestive of COVID-19-related etiology. The predominant neuroimaging features were diffuse cerebral WM hypodensities / hyperintensities attributable to leukoencephalopathy, leukoaraiosis or rarefield WM.

A Framework for Ethical Decision Making in the Rehabilitation of Patients with Anosognosia.

Currently, the number of patients diagnosed with impaired self-awareness of their own deficits after brain injury-anosognosia-is increasing. One reason is a growing understanding of this multifaceted phenomenon. Another is the development and accessibility of alternative measurements that allow more detailed diagnoses. Anosognosia can adversely affect successful rehabilitation, as often patients lack confidence in the need for treatment. Planning such treatment can become a complex process full of ethical dilemmas. To date, there is no systematic way to deal with different aspects of anosognosia rehabilitation planning. This is the first article to present a framework for ethical decision making in establishing rehabilitation plans that are focused on increasing patients' self-awareness of their own deficits after brain injury. It concentrates especially on addressing the ethical dilemmas that may arise, and describes stepwise procedures that can be applied to distinct theoretical approaches, as well as diagnostic and rehabilitation methods. To show the flexibility of the use of this framework, alternative approaches are discussed.

Factors associated with prolonged COVID-related PTSD-like symptoms among adults diagnosed with mild COVID-19 in Poland.

COVID-19 has been considered a possible cause of post-traumatic stress disorder (PTSD) or similar conditions. However, what specific disease symptoms may contribute most to prolonged PTSD-like symptoms in COVID-19 survivors is unclear. The study aimed to present the factor structure of COVID-19 symptoms and identify which symptoms of COVID-19 best explain the subsequent presence of PTSD-like symptoms in mild COVID-19 survivors. COVID-positive adults (n = 341) completed online self-report scales at the baseline assessment (T1) and after approximately 4 months (T2), including The Patient Health Questionnaire Anxiety-Depression Scale; The Scale of Psychosocial Experience Related to COVID-19, The Primary Care PTSD Screen for DSM-5; and self-designed questionnaires evaluating the severity of COVID-related medical and neurocognitive symptoms and pre-pandemic variables. Exploratory factor analysis revealed five factors of COVID-19 symptoms: flu-like, respiratory, cold, neurological, and neurocognitive. Hierarchical logistic regression showed that besides selected control variables (anxiety and depression, presence of PTSD-like symptoms, COVID-related stigma in T1), neurocognitive symptoms of COVID-19 in T1 but not other symptoms of the disease were a significant predictor of the presence of PTSD-like symptom in T2. Findings suggest a need for a comprehensive neurocognitive assessment of people diagnosed with COVID-19 and prompt interventions targeting the prevention of potential risks for long-term PTSD-like states at the community level.

Global occurrence of depressive symptoms during the COVID-19 pandemic.

OBJECTIVE: This study aimed to estimate the occurrence of depressive symptoms in a global population of young, middle-aged and older adults amid the COVID-19 pandemic. Study data also assessed the impact of the social restrictions caused by the pandemic on depressive symptomatology. METHODS: A self-administered internet-based survey was completed by 111,225 individuals residing in 176 countries (March-April 2020). We retained: demographic data, depressive symptoms (PHQ8), anxieties specific to the COVID-19, personality traits (Big-Five Personality Questionnaire), comorbidity frequency, health quality, behavioral variables (i,e., staying at home, avoiding social gatherings, social distancing in the past week). Occurrence of depressive symptoms was estimated using standard cut-offs (total PHQ8 score ≥ 10). Hierarchical regression modeling examined correlates of depressive symptoms (PHQ8 score) in three groups stratified by age, i.e., 18-34, 35-54 and 55+ years. RESULTS: Moderate to severe depressive symptoms were present in 27% of young, 15% middle-aged and 9% older adults. Younger age, female gender, not partnered, higher anxiety, and poorer health were associated with elevated depressive symptoms. Staying at home/not attending social gatherings were minor contributors to depressive symptoms in young and middle-aged adults. These were not significant in older adults. Social distancing was a marginal contributor in middle-aged and near significant in older adults, but not significant in young adults. CONCLUSIONS: The occurrence of depressive symptoms is decreasing with advancing age. Increased risk of depressive symptoms was associated with being a younger adult, females, single/divorced, poorer health and higher anxiety. In all age groups, the presence of depressive symptoms was greater than global estimates preceding the COVID-19 pandemic. Social restrictions amid the COVID-19 pandemic were marginal risks for depressive symptoms.

The laminar pattern of resting state in human cerebral cortex.

Resting state functional Magnetic Resonance Imaging (RS-fMRI) provides the means to measure neuronal activity. One of the most commonly used methods to explore the RS-fMRI signal is the Probabilistic Independent Component Analysis (PICA). PICA allows to depict brain functional connectivity (FC) networks. Yet most of the IC maps obtained with this method do not represent any particular FC network. Consequently, those IC maps are classified as artifacts or noise of an unknown source. We hypothesized that the unexplained RS-fMRI signal patterns that are picked up by the PICA can be related to the differences in oxygen metabolism and blood flow in cortical layers. This study aimed at (1) providing preliminary evidence to the effects of laminar organization of neocortex on the RS-fMRI signal, and (2) evaluating the application of laminar maps to aid the classification of IC maps. We created laminar maps 1-4 that depict relative cortical thickness of layers IV and VI. Our data show that the RS-fMRI signal is significantly related to the relative thickness of the cortical layer VI but not layer IV. Importantly, the laminar maps 1-4 overlap with four separate IC maps. Thus, the laminar maps 1-4 improve classification and interpretation of the IC maps. Moreover, the laminar maps 1-4 may be considered as FC networks that are the bridging piece between particular cognitive functions. Together, these data provide preliminary evidence to the fundamental questions about the role of cortical layering in the RS-fMRI signal and brain FC networks.

Neuropsychological disorders after COVID-19. Urgent need for research and clinical practice.

Purpose: Numerous studies suggest that infection with coronavirus SARS-CoV-2, which causes acute respiratory distress syndrome and COVID-19 illness, can lead to changes in the central nervous system (CNS). Consequently, some individuals with SARS-CoV-2 infection may also present the symptoms of neuropsychological disorders. The goals of this literature review is the synthesis of various perspectives and up-to-date scientific knowledge as well as the formulation of initial recommendations for clinical practice. Views: According to current state of knowledge, numerous SARS-CoV-2 infection-specific and nonspecific risk factors exist for brain damage, which might lead to neuropsychological impairments in individuals who have recovered from COVID-19. The emerging evidence suggests significant behavioral and cognitive deficits in COVID-19 survivors, which are present in the early phase after recovery and persist for several months. Neuropsychological disturbances can potentially include a wide spectrum of disorders, yet deficits of attention, memory, executive functions, language and visuospatial orientation are among most commonly identified. The relationship between cognitive impairment, emotional disturbances and severity of COVID-19 symptoms needs to be submitted to further research. Conclusions: The scientific knowledge resulting from neuropsychological empirical studies during the COVID-19 pandemic allows for a postulate of an urgent evidence-based systematic neuropsychological research to be conducted among COVID-19 survivors. More than anything, the recovered individuals must be provided with adequate neuropsychological help in the form of neuropsychological diagnosis, monitoring and rehabilitation.

In Search for the Meaning of Illness: Content of Narrative Discourse Is Related to Cognitive Deficits in Stroke Patients.

Stroke survivors undergo a thorough cognitive diagnosis that often involves administration of multiple standardized tests. However, patient's narrative discourse can provide clinicians with additional knowledge on patient's subjective experience of illness, attitude toward current situation, and motivation for treatment. We evaluated the methods of analyzing thematic content and story types in relationship to cognitive impairment in stroke survivors with no aphasia (including 9 left hemisphere damage - LHD patients, and 16 right hemisphere damage - RHD patients). Cognitive impairment was evaluated in comparison to a group of 25 patients with orthopaedic injury not involving the brain. Our findings primarily show that higher elaboration on own cognitive problems, physical ailments or coping strategies in LHD patients and cognitive problems, emotional issues and circumstances of illness onset in RHD patients is related to deficits in executive functions and retrieval of information from memory. Furthermore, RHD patients who use more chaos story type show lower executive functioning. However, these results did not survive the significance threshold of p < 0.05 after Bonferroni adjustment for multiple comparisons. In conclusion, this study provides preliminary evidence that stroke survivor's narrative can constitute an additional source of clinically-relevant information regarding patient's experience of illness and attitude toward recovery. This knowledge can aid clinicians and nurses in everyday interactions with the patients and support individualized strategy to treatment. Still, the current results need be confirmed with future studies in a larger cohort of stroke patients.

Not Just for Joints: The Associations of Moderate-to-Vigorous Physical Activity and Sedentary Behavior with Brain Cortical Thickness.

INTRODUCTION: Cortical thinning is associated with aging; however, lifestyle factors can moderate this relationship. Two distinct lifestyle behaviors associated with brain health are regular moderate-to-vigorous physical activity (MVPA) and limited sedentary behavior (SB). However, it is unclear whether MVPA and SB levels contribute to cortical thickness independent of each other. We therefore investigated the independent relationships of MVPA and SB with cortical thickness using baseline data from a randomized controlled trial. METHODS: At baseline, we measured MVPA and SB for 7 d using the SenseWear Mini. A subset of the randomized controlled trial participants (n = 30) underwent a 3T magnetic resonance imaging scan, wherein region-specific cortical surface morphometric analyses were performed using T1-weighted structural magnetic resonance imaging. We conducted regression analyses using a surface-based cluster size exclusion method for multiple comparisons within FreeSurfer neuroimaging software to determine if MVPA and SB are independently correlated with region-specific cortical thickness. RESULTS: This subset of participants had a mean age of 61 yr (SD = 9 yr), and 80% were female. Higher MVPA was associated with greater cortical thickness in the temporal pole (cluster size, 855 mm; cortical thickness range, 2.59-3.72 mm; P < 0.05) and superior frontal gyrus (cluster size, 1204 mm; cortical thickness range, 2.41-3.15 mm; P < 0.05) of the left hemisphere, independent of SB. Sedentary behavior was not associated with greater cortical thickness in any region, independent of MVPA. CONCLUSIONS: Our results indicate that adults with greater MVPA-independent of SB-are associated with greater cortical thickness in regions, which are susceptible to age-associated atrophy.

HIV and age underlie specific patterns of brain abnormalities and cognitive changes in high functioning patients.

OBJECTIVE: Findings on the influence of age and HIV on brain and cognition remain equivocal, particularly in aviremic subjects without other age or HIV-related comorbidities. We aimed to (a) examine the effect of HIV status and age on structural brain measurements and cognition, and (b) apply the machine learning technique to identify brain morphometric and cognitive features that are most discriminative between aviremic subjects with HIV on stable combination antiretroviral therapy (cART) and healthy controls. METHOD: Fifty-three HIV-seropositive patients and 62 healthy controls underwent neuropsychological testing (executive functions, attention, memory, learning, psychomotor speed, fluency) and volumetric MRI scans. Voxel-based morphometry, ANCOVAs, machine learning, and multivariate regression were conducted to determine the between group differences in terms of relationship of HIV status, age, and their interaction on neurocognitive and structural brain measures. RESULTS: Volume and gray matter (GM) thickness of the caudate, parahippocampus, insula, and inferior frontal gyrus were smaller in seropositive subjects in comparison with healthy controls (HC). They also performed worse in complex attention and cognitive fluency tasks. Support vector machine (SVM) analysis revealed that the best between-groups classification accuracy was obtained based on cognitive scores encompassing complex attention and psychomotor speed, as well as volumetric measures of white matter and total gray matter; third, fourth, and lateral ventricles; amygdala; caudate; and putamen. Both voxel-based morphometry (VBM) and regression analysis yielded that HIV and aging independently increase brain vulnerability and cognitive worsening. CONCLUSION: Patients with HIV on effective cART demonstrate smaller volumetric measures and worse cognitive functioning relative to seronegative individuals. There is no interaction between HIV infection and aging. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

HIV infection across aging: Synergistic effects on intrinsic functional connectivity of the brain.

The objective of the study was to examine additive and synergistic effects of age and HIV infection on resting state (RS) intra- and inter-network functional connectivity (FC) of the brain. We also aimed to assess relationships with neurocognition and determine clinical-, treatment-, and health-related factors moderating intrinsic brain activity in aging HIV-positive (HIV+) individuals. The current report presents data on 54 HIV+ individuals (age M = 41, SD = 12 years) stabilized on cART and 54 socio-demographically matched healthy (HIV-) comparators (age M = 43, SD = 12 years), with cohort education mean of 16 years (SD = 12). Age at seroconversion ranged 20-55 years old. ANOVA assessed additive and synergistic effects of age and HIV in 133 ROIs. Bivariate statistics examined relationships of FC indices vulnerable to age-HIV interactions and neurocognitive domains T-scores (attention, executive, memory, psychomotor, semantic skills). Multivariate logistic models determined covariates of FC. This study found no statistically significant age-HIV effects on RS-FC after correcting for multiple comparisons except for synergistic effects on connectivity within cingulo-opercular network (CON) at the trending level. However, for uncorrected RS connectivity analyses, we observed HIV-related strengthening between regions of fronto-parietal network (FPN) and default mode network (DMN), and particular DMN regions and sensorimotor network (SMN). Simultaneously, FC weakening was observed within FPN and between other regions of DMN-SMN, in HIV+ vs. HIV- individuals. Ten ROI pairs revealed age-HIV interactions, with FC decreasing with age in HIV+, while increasing in controls. FC correlated with particular cognitive domains positively in HIV+ vs. negatively in HIV- group. Proportion of life prior-to-after HIV-seroconversion, post-infection years, and treatment determined within-FPN and SMN-DMN FC. In sum, highly functioning HIV+/cART+ patients do not reveal significantly altered RS-FC from healthy comparators. Nonetheless, the current findings uncorrected for multiple comparisons suggest that HIV infection may lead to simultaneous increases and decreases in FC in distinct brain regions even in patients successfully stabilized on cART. Moreover, RS-fMRI ROI-based analysis can be sensitive to age-HIV interactions, which are especially pronounced for inter-network FC in relation to neurocognition. Aging and treatment-related factors partially explain RS-FC in aging HIV+ patients.

Age and HIV effects on resting state of the brain in relationship to neurocognitive functioning.

This study examined the effects of age and HIV infection on the resting state (RS) functional connectivity (FC) of the brain and cognitive functioning. The objective was to evaluate the moderating role of age and HIV on the relationship between RS-FC and cognition. To examine RS-FC we implemented the Independent Component Analysis (ICA) and Regional Homogeneity (ReHo). Neurocognition was evaluated with comprehensive battery of standardized neuropsychological tests. Age and HIV were entered as the independent variables. The independent effects of age, HIV, and interaction effects of age-HIV on RS-fMRI measures (ICA, ReHo) were tested in 108 participants (age M = 42). RS-FC indices that exhibited age-HIV interactions were entered into further analysis. Bivariate correlation analysis was performed between the retained RS-FC indices and T-scores of neurocognitive domains (Attention, Executive, Memory, Psychomotor, Semantic Skills). Multivariate regression modeling determined the impact of age and HIV on these relationships. We found that in the ICA measures, HIV-seropositivity was decreasing RS-FC in the left middle occipital gyrus (p < .001). Age-HIV interaction was observed in the left superior frontal gyrus (LSupFrontG), where FC was decreasing with age in HIV+ (p < .001) and increasing in HIV- (p = .031). ReHo indices did not reveal significant effects. HIV strengthened the relationship between RS-FC in LSupFrontG, Memory and Psychomotor Factor scores. Aging weakened those relationships only in control group. In sum, age-HIV interaction effects are prominent rather in remote than local RS-FC. Seroconversion strengthens relationships between intrinsic brain activity and neurocognition, but no acceleration with years of age was noted in HIV+ individuals.