Central Nervous System Manifestations of COVID-19: A Critical Review and Proposed Research Agenda.

OBJECTIVE: On March 11, 2020, the World Health Organization declared an outbreak of a new viral entity, coronavirus 2019 (COVID-19), to be a worldwide pandemic. The characteristics of this virus, as well as its short- and long-term implications, are not yet well understood. The objective of the current paper was to provide a critical review of the emerging literature on COVID-19 and its implications for neurological, neuropsychiatric, and cognitive functioning. METHOD: A critical review of recently published empirical research, case studies, and reviews pertaining to central nervous system (CNS) complications of COVID-19 was conducted by searching PubMed, PubMed Central, Google Scholar, and bioRxiv. RESULTS: After considering the available literature, areas thought to be most pertinent to clinical and research neuropsychologists, including CNS manifestations, neurologic symptoms/syndromes, neuroimaging, and potential long-term implications of COVID-19 infection, were reviewed. CONCLUSION: Once thought to be merely a respiratory virus, the scientific and medical communities have realized COVID-19 to have broader effects on renal, vascular, and neurological body systems. The question of cognitive deficits is not yet well studied, but neuropsychologists will undoubtedly play an important role in the years to come.

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.

Generalized anxiety and depressive symptoms in various age groups during the COVID-19 lockdown in Poland. Specific predictors and differences in symptoms severity.

BACKGROUND: Previous studies carried out in different countries have indicated that young adults experienced higher levels of emotional distress, in the form of depressive and anxiety symptoms, than older age groups during the COVID-19 pandemic. However, little is known about which pandemic-related difficulties and factors may contribute to these forms of emotional distress in various age groups. PURPOSE: The aim of the current study was to investigate: (i) differences in levels of depressive and generalized anxiety symptoms in four age groups in the Polish population during the COVID-19 lockdown; (ii) differences in perceived difficulties related to the pandemic in these groups; and (iii) which factors and difficulties related to the pandemic are the best predictors of generalized anxiety and depressive symptoms in various age groups during the COVID-19 lockdown. METHOD: A total of 1115 participants (aged 18-85) took part in the study. The sample was representative of the Polish population in terms of sex, age, and place of residence. Participants completed the following online: the Patient Health Questionnaire-9, the Generalized Anxiety Disorder-7, a Scale of Perceived Health and Life Risk of COVID-19, a Social Support Scale, and a Scale of Pandemic-Related Difficulties. RESULTS: Younger age groups (18-29 and 30-44) experienced higher levels of depressive and generalized anxiety symptoms than older adults (45-59 and 60-85 years). Household relationship difficulties were among the most significant predictors of depressive and generalized anxiety symptoms in all age groups. Fear and uncertainty related to the spread of the virus was one of the most important predictors of emotional distress in all the groups apart from the adults between 18 and 29 years, whereas difficulties related to external restrictions were one of the most significant predictors of depressive and anxiety symptoms exclusively in the youngest group. CONCLUSIONS: The youngest adults and those experiencing difficulties in relationships among household members are the most vulnerable to depressive and generalized anxiety symptoms during the COVID-19 lockdown. It is important to plan preventive and therapeutic interventions to support these at-risk individuals in dealing with the various challenges related to the COVID-19 pandemic.

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.

The Characteristics of the Reduction of Interference Effect during Dual-Task Cognitive-Motor Training Compared to a Single Task Cognitive and Motor Training in Elderly: A Randomized Controlled Trial.

Many studies have indicated a weakening in several areas of cognitive functioning associated with the normal ageing process. One of the methods supporting cognitive functions in older adults is dual-task training which is based on performing cognitive and motor exercises at the same time. The study aimed at examining the characteristics of dual-task training compared to single-task training in participants over 65 years of age. Sixty-five subjects took part in the study. They were randomly assigned to three groups: dual-task cognitive-motor training (CM), single-task cognitive training (CT), and single-task motor training (MT). The training program in all groups encompassed 4 weeks and consisted of three, 30-min meetings a week. Specialized software was designed for the study. The main indicators, such as orientation and planning time and the number of errors, were monitored during the whole training in all groups. The obtained results have shown that the dual-task training was associated with a significantly greater number of movement errors, but not with a longer task planning time compared to the single-task condition training. There was a decrease in the time needed to plan a path in the mazes by subjects training in the CM, CT, and MT groups. The results indicate that after each type of training, the number of errors and the time needed to plan the path decrease, despite the increasing difficulty of the tasks. The length of planning time was strongly correlated with the number of errors made by individuals in the CM group (r = 0.74, p = 0.04), compared to the ST group-for which the said correlation was not significant (r = 0.7, p = 0.06). The dual-task cognitive-motor training is more cognitively demanding compared to the single-task cognitive and motor training. It manifests in a greater number of errors, but it does not extend the orientation and planning time.

Ethical issues in clinical neuropsychology: International diversity perspectives.

OBJECTIVE: Much of the information about the ethical practice of clinical neuropsychology has focused on North America. Additionally, of the scholarly publications on the intersection of ethical issues and cultural diversity practices in neuropsychology, most have focused on North America. The extent to which practitioners in other parts of the world are aware of, and find useful, such information is largely unknown. Similarly, the extent to which North American neuropsychologists are familiar with ethical issues and challenges encountered around the world is unknown. The purpose of this article is to advance the discussion of ethical issues in clinical neuropsychology from an international diversity perspective. METHOD: The article presents, via a panel interview format, the thoughts and experiences of a small sample of neuropsychologists who represent all continents except North America (and Antarctica). RESULTS: Neuropsychologists across continents share an ethical commitment to providing services that are beneficial, and not harmful, to the recipients of the services. Professional competence is at the heart of such services. CONCLUSIONS: Through continued and expanded dialogue about ethical issues with neuropsychology colleagues around the world, the potential exists for improvement in the provision of effective and compassionate care in our own towns.

[Depression or apathy? A diagnostic trap: a huge right frontal lobe meningioma diagnosed and treated as mild atypical depression episode--a case study]. / Depresja czy apatia? Pulapki diagnostyczne: olbrzymi oponiak prawego plata czolowego rozpoznany i leczony jako epizod depresji umiarkowanej atypowej--opis przypadku.

Neurobehavioral changes observed in patients with brain tumours may appear as cognitive deficits, mood disturbances, changes in behaviour or decreased adaptability (e.g., drowsiness, apathy, loss of spontaneity, fatigue). They are initially subtle, develop insidiously, and their severity often changes. Serious diagnostic problems can be caused by mood disorders, psychotic symptoms, personality changes, from disinhibition to apathy, observed in such patients. The problem in distinguishing them from organic psychiatric disorders, often poses a challenge for psychiatrists, neurologists and general practitioners. We describe a case difficult to diagnose because of apathy, due to a brain tumour in the right frontal lobe, diagnosed as depression. Another difficulty, rather suggesting mood disorder, was rheumatoid arthritis. Thorough and meticulous analysis of clinical data, neuropsychological assessment and neuroimaging diagnosis may help to assess aetiology of the observed disorders which can have similar clinical pictures but various causes.

The cognitive and cognitive-motor training contribution to the improvement of different aspects of executive functions in healthy adults aged 65 years and above-A randomized controlled trial.

AIMS: The study aimed at examining the effectiveness of cognitive-motor dual-task and single-task cognitive training on executive and attention functions in participants over 65 years of age. METHODS: The study comprised 68 participants. They were randomly assigned to dual-task cognitive-motor training (DTT), single-task cognitive training (STT) or a control group (C). The training program in all groups encompassed 4 weeks and consisted of three, 30-min meetings a week. Specialized software was designed for the purposes of the study. Both before and after the training, the cognitive functioning was assessed using: Color Trials Test, Ruff Figural Fluency Test, Wisconsin Sorting Card Test, Digit Span, Verbal Fluency Test, Stroop Color-Word Test. RESULTS: After the cognitive-motor training, improvement was achieved in the control and inhibition of reactions. Moreover, after the cognitive training, improvements in abstract thinking and categorization were reported. CONCLUSION: Despite the small sample limitation, the preliminary result shows each form of the training supports a different aspect of executive functions but does not contribute to the improvement in attention.

Factors associated with burnout in Polish healthcare workers during the COVID-19 pandemic.

Introduction: The COVID-19 pandemic has placed the healthcare system under substantial strain that has caused elevated psychological distress among healthcare workers (HCWs). Previous studies have found a high prevalence of burnout among HCWs exacerbated by the COVID-19 pandemic and have delineated some associated factors, but further research is needed. Little is known, for example, whether the economic status of HCWs or experiencing negative and positive emotions contribute to burnout. The present study was meant to fill this gap. Methods: A total of 412 HCWs (i.e.: nurses - 47%, physicians-28%, psychologists-14%, and other healthcare professionals-11%), aged 21-69 years (M = 36.63; SD = 11.76) participated in a web-based cross-sectional study. Data was collected from June to November 2020. The participants filled out measures assessing two dimensions of burnout (Exhaustion and Disengagement), depression, generalized anxiety, positive and negative emotions, along with the survey evaluating organizational aspects of their work during the pandemic. Results: Burnout thresholds were met by 54 and 66% of respondents for Disengagement and Exhaustion, respectively, which is high but comparable to levels found in other countries during the pandemic. Similarly to previous work, depression and anxiety were high in HCWs, with 24 % of them being in the risk group for clinical severity of depression and 34% in the risk group for a clinical generalized anxiety disorder (GAD). Regression analysis showed that the intensity of negative emotions was the strongest predictor of Exhaustion, whereas the intensity of positive emotions was the strongest predictor of Disengagement. Depression and GAD symptoms were positively related to Exhaustion, and economic status was inversely related to Disengagement. Discussion: These results suggest that distress in HCWs during the pandemic was related to symptoms of burnout, whereas higher income and experiencing positive emotions were associated with reduced burnout levels. Our findings call for the development of burnout intervention programs that could build capacities for dealing with depression and other negative emotions and at the same time teach skills on how to increase positive emotions in HCWs.

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.

Higher order language impairments can predict the transition of ultrahigh risk state to psychosis-An empirical study.

AIM: Higher order language skills, for example, non-literal language, humour, prosody deal with 'what is meant' and they are necessary for communicative exchange and relationships; No study has investigated their link with conversion to psychosis. The purpose of this study was to determine whether such skills could act as predictors of the onset of psychosis, and compare those of individuals converting and non-converting to psychosis with control of cognitive functions. METHODS: Seventy-three patients, aged 15 to 32 years, fulfilling ultrahigh risk criteria took part: 14% of whom were receiving antipsychotic drugs. The study was observational, prospective and longitudinal in nature, and scheduled for 60 months. Pragmatic language skills were evaluated using the Polish version of the right hemisphere language battery. The ultrahigh risk (UHR) criteria were evaluated with Comprehensive Assessment of At-Risk Mental States; attention, intelligence and verbal fluency were controlled. RESULTS: The conversion rate was 25%; converters demonstrated impaired humour comprehension and metaphor explanation abilities; composite score of pragmatic language was associated with a hazard ratio of 6.0 (95% CI 1.8-20.5) and AUC of .73. Verbal fluency was an independent predictor of conversion, but attention and intelligence were not; pragmatic language skills were associated with social function but not with prodromal symptoms. CONCLUSIONS: The results suggest that deficits in humour comprehension and metaphor explanation could predict conversion to psychosis. These findings could improve diagnosis and create implications for speech and language therapy in UHR groups. Further studies on the mechanisms of pragmatic skills should analyze their relationship with abstract measures and semantic coherence.

Risk of Developing Post-traumatic Stress Disorder in Severe COVID-19 Survivors, Their Families and Frontline Healthcare Workers: What Should Mental Health Specialists Prepare For?

Given the high mortality of the coronavirus disease 2019 (COVID-19), having severe COVID-19 may be a life-threatening event, especially for individuals at high risk of complications. Therefore, in the article we try to answer two questions that are relevant to public mental health: Can we define groups who are at higher risk of developing pandemic-related PTSD? How can health specialists prepare for it? Given the results of previous research on PTSD in epidemic (e.g., SARS) survivors, we suggest that mental health professionals in countries touched by the pandemic should prepare for an increase in the PTSD prevalence, specifically in: individuals who have had severe COVID-19; family members of these patients and of patients who have died; and frontline healthcare workers witnessing COVID-19 patients' sudden deaths, or numerous life-threatening situations. We postulate that these groups at risk should be routinely screened for PTSD in primary medical and pediatric care. Mental health services should prepare for providing therapeutic interventions for individuals with PTSD in the vulnerable groups, and support to their families, especially children.

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.

Introduction to the special issue: Are modern neuropsychological assessment methods really "modern"? Reflections on the current neuropsychological test armamentarium.

OBJECTIVE: We introduce this special issue which focuses on how advances in neuroscience and technology can modernize and transform clinical neuropsychological assessment. METHOD: We included both invited and solicited papers to reflect on the strengths and weaknesses of currently used, standardized neuropsychological tests and to explore how we might incorporate new technologies and neuroscientific advances to modernize neuropsychological assessment methods. RESULTS: The papers are organized along the following themes: (1) A critique of the current clinical neuropsychological test armamentarium; (2) A description of new opportunities for collecting neurobehavioral data with technology; (3) Digital science, biomedical big data and the internet; (4) Integrating neuropsychological, neuroimaging, and neurophysiological assessments; (5) Modernization, globalization and culture. CONCLUSION: The process of modernizing methods of assessment in clinical neuropsychology is laborious and requires a coordinated, sustained effort among clinicians, researchers, and the test industry. While embracing technology is necessary, we must also be aware of unintended consequences as we navigate this exciting new territory.

Many ways to forget - Neurophysiology of directed forgetting mechanisms in schizophrenia.

Numerous studies have shown dysfunctional mechanism of interaction between bottom-up emotional and top-down cognitive processes in persons with schizophrenia (SCZ). During the emotional directed forgetting (DF) paradigm participants have to apply volitional mechanisms to resist automatic emotional enhancement of the memory. Here we sought to compare mechanisms underlying emotional DF in SCZ and in healthy persons (HC). Eighteen SCZ and eighteen HC completed a DF paradigm with neutral and negative pictures. EEG was recorded during study and test phase of the task. We analyzed both the behavioral outcomes and event-related potential components, indicating emotional enhancement of memory (Late Positive Potential elicited by pictures) and DF strategies (N2/P3 elicited by forget/remember cues during study-phase; "old/new" and "reversed old/new" effects during test-phase of the task). Directed forgetting effects and emotional enhancement of memory were observed in both groups, even despite overall lower recognition rates in SCZ. Furthermore, cue presentation elicited similar pattern of N2/P3s in SCZ and in HC. However, "reversed old/new" effect was observed only in HC for negative stimuli. Patients may show similar reaction to affective stimuli as healthy controls during the emotional DF task. However, further investigation is needed to elicit the specific mechanisms underlying the DF strategies in SCZ.

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.

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).

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.