Sex-Specific Neurocognitive Impairment.

This article explores sex-specific neurocognitive impairment. It first defines relevant terms such as gender and sex. Next, it describes the nature of the problem including under-representation of women and other gender and sexual minorities in neuroscience research, including cognitive studies. A biopsychosocial framework is employed to account for structural and social determinants of health in sex/gender-specific neurocognitive impairment. Issues in assessment including the use of gender/sex-specific normative data are also discussed. Lastly, the article covers the current state of research as it relates to sex/gender-specific neurocognitive impairment across a range of medical conditions including neurodegenerative diseases and coronavirus disease-2019.

Neurocognitive disorders

There are many reasons why patients are admitted to, and treated in, the intensive care unit (ICU), including individuals who require close monitoring and support for critical organ systems such as the cardiovascular, respiratory, neurologic, and renal system. The increasing prevalence of critical illness, coupled with improvements in its treatment, has resulted in a substantial increase in the number of ICU survivors. Some survivors will recover and return to their pre-illness baseline level of function;however, one third to one half of all survivors are not so fortunate and will develop postintensive care syndrome. This chapter focuses on cognitive outcomes of critical illness survivors treated in the ICU for acute respiratory failure, sepsis, and other medical or surgical conditions. It discusses the prevalence, characteristics, risk factors, assessment, management, and the short- and long-term neurologic outcomes for survivors of critical illness and critically ill survivors of COVID-19 including neurocognitive disorders. The chapter explores the psychologist's role in caring for survivors of critical illness and covers integrative concepts that require collaboration among members of the interdisciplinary team. The chapter also discusses Interventions to improve outcomes, including environmental management, tracking mental status, pharmacologic interventions, family intervention and support, and rehabilitation interventions. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

HIV-Associated Conditions in Older Adults.

Geriatric practices will see more people living with human immunodeficiency virus (HIV), as their life expectancy is close to the general population due to effective antiretroviral therapy (ART). Geriatricians focus more on HIV-associated, non-acquired immunodeficiency syndrome (AIDS) disorders than HIV alone. We will review the most common chronic illnesses and conditions associated with aging and HIV. Even though fall frequency in older adults living with HIV is similar to or lower than in people without HIV, fall assessment is appropriate, especially in the high-risk elderly living with HIV. HIV also impacts motor function and memory loss, especially in advanced cases. ART doesn't cross the blood-brain barrier, leading to major neurocognitive disorders with age. The etiology of HIV and cardiovascular disease (CVD) is multifactorial, including the effect of ART. Pitavastatin and pravastatin cause fewer interactions with ART. While the treatment for HIV decreases the risk of opportunistic infections, it may cause several bone-related abnormalities, including low bone mineral density (BMD), osteoporosis, and fractures. Polypharmacy is associated with disability and mortality and may increase the risk of ART drug-drug interaction. The oral health status of HIV-infected patients is commonly inadequate, and the presence of dental care managers may improve clinical outcomes and increase medication adherence. Furthermore, people aging with HIV (PAWH) have an increased mortality risk when co-infected with coronavirus disease 2019 (COVID-19). In summary, older adults living with HIV may face unique challenges. Therefore, providing comprehensive medical care and psychosocial support through an interdisciplinary team can significantly impact their lives.

Pre-existing mental health disorders and fear of COVID-19 pandemic: Data from a phone survey in community-dwelling older adults recruited in the NutBrain study.

Background: COVID-19 has caused a parallel epidemic of fear, anxiety, depression, stress, and frustration, particularly among the most fragile and vulnerable individuals, such as older people and those with previous mental health disorders. The present study aims to investigate the association between pre-existing mental health disorders, particularly depressive symptoms and Mild Cognitive Impairment (MCI), and the fear of COVID-19 and to explore which cognitive domains were involved in coping with fear in older people. Materials and methods: In April 2020, we conducted a phone-interview questionnaire on community-dwelling older adults living in Lombardy Region (Italy) who participated in the NutBrain study. At baseline, socio-demographic characteristics along with lifestyles, and medical history were recorded. Participants underwent a neuropsychological battery exploring the global cognitive function and specific cognitive domains, to detect cases of MCI. The Center for Epidemiologic Studies Depression scale (CES-D) was used for screening depressive symptoms. During the phone survey, respondents were assessed using a structured questionnaire querying about fear of the COVID-19 pandemic. We performed multivariate logistic regression models to study the association between MCI and depressive symptomatology and fear. We also explored which cognitive domains were associated with fear. Odds Ratios (OR) with Confidence Intervals (95%CI) were estimated adjusting for potential confounders. Results: Out of the 351 respondents (mean age 73.5 ± 6.1 years, 59.8% women, 49.1% high education), at baseline, 22.9% had MCI and 18.8% had depressive symptoms. In the multivariate analyses gender, age, and body mass index were significantly associated with the fear score. Considering different domains of fear, MCI was associated with fear of being infected themselves (OR 2.55, 95%CI 1.39-4.70) while depressive symptoms were associated with fear of contagion for family members (OR 2.38, 95%CI 1.25-4.52). Impaired executive cognitive function was positively associated with the highest tertile of the fear score (OR 3.28, 95%CI 1.37-7.74) and with fear of contagion for themselves (OR 3.39, 95%CI 1.61-7.17). Conclusion: Older adults experienced different fear reactions, particularly when suffering from neurocognitive disorders and depressive symptoms; executive dysfunction was associated with increased fear. These results highlighted the need to pay attention to the psychological effects of the outbreak of COVID-19 to target intervention, especially among vulnerable subgroups of individuals. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT04461951].

Social, Academic, and Health Status Impact of Long COVID on Children and Young People: An Observational, Descriptive, and Longitudinal Cohort Study.

There is a lack of evidence of the health impacts due to long COVID among children and young people (CYP). The objective of this study is to determine the main clinical characteristics of long COVID in CYP and to investigate the academic, social, and health status impacts of long COVID in this population. An observational, descriptive, and longitudinal study on CYP who presented COVID-19 symptoms for more than twelve weeks after SARS-CoV-2 infection was performed between December 2020 and May 2021. Fifty CYP were included, with a median age of 14.1 years, 33 (66%) were female, and 17 (34%) had a relative diagnosed with long COVID. Since the initial infection and up to the first visit, CYP had persisting symptoms for a median of 4.1 months, and for 18 (36%) CYP these symptoms persisted for more than 6 months. Fatigue (100%), neurocognitive disorders (74%), muscular weakness (74%), and headache (72%) were the most reported symptoms. A total of 9 (18%) CYP could not attend school, 17 (34%) had a reduced schedule, 33 (66%) showed a decreased school performance, and 68% had stopped extracurricular activities. This preliminary study shows the impact that long COVID has on the health, academic, and social life of CYP.

Neurocognitive Disorders

This chapter discusses the prevalence, characteristics, risk factors, assessment, management, and short- and long-term neurologic outcomes for survivors of critical illness and critically ill survivors of COVID-19 including neurocognitive disorders with an emphasis on the role of delirium. The psychologist’s role in caring for survivors of critical illness is discussed along with coverage of integrative concepts that require collaboration between members of the interdisciplinary team. Interventions to improve outcomes are reviewed, including environmental management, tracking mental status, pharmacologic intervention, family intervention, and support and rehabilitation interventions are also reviewed. The chapter also discusses future goals and research to improve outcomes following critical illness. © Oxford University Press 2022. All rights reserved.

HIV-associated dementia presenting predominantly with clinical motor deficits: A case report.

HIV-associated dementia is commonly seen in older individuals and presents as a subcortical dementia associated with concentration, attention, and memory impairments. Motor signs, such as difficulty with gait, and mood changes are less prominent findings but are considered during diagnosis. We present a case of HIV-associated dementia in a young 29-year-old man who presented with progressive lower extremity weakness and difficulty ambulating.

Clinical and Imaging Determinants of Neurocognitive Disorders in Post-Acute COVID-19 Patients with Cognitive Complaints.

BACKGROUND: Neurocognitive disorders (NCDs) are a part of the post-acute coronavirus disease (COVID-19) syndrome. No study has specifically evaluated NCDs in post-acute COVID-19 patients with cognitive complaints or their MRI determinants. OBJECTIVE: To characterize NCDs in post-acute COVID-19 patients with cognitive complaints. The secondary objectives were to assess their clinical and MRI determinants. METHODS: We included 46 patients with a post-acute COVID-19 cognitive complaint referred to the Amiens University Hospital Memory Center. They underwent a neuropsychological assessment and 36 had cerebral MRI. The G3 overall summary score was the sum of the mean z scores for the executive function, language, and action speed domains. Neuropsychological profiles were compared in a general linear model. Clinical determinants were analyzed by stepwise linear regression. White matter hyperintensities (WMH) masks were analyzed using parcel-based WMH symptom mapping to identify the locations of WMHs associated with cognitive performance. RESULTS: Repeated ANOVA showed a group effect (p = 0.0001) due to overall lower performance for patients and a domain effect (p = 0.0001) due to a lower (p = 0.007) action speed score. The G3 overall summary score was significantly associated with solely the requirement for oxygen (R2 = 0.319, p = 0.031). WHMs were associated with the G3 overall summary score in the following structures, all right-sided (p < 0.01): superior frontal region, postcentral region, cingulum, cortico-spinal tract, inferior longitudinal fasciculus, internal capsule, and posterior segment of the arcuate fasciculus. CONCLUSION: Post-acute COVID-19 patients with cognitive complaints had NCD, with prominent action slowing, significantly associated with the acute phase oxygen requirement and a right-sided WMH structure pattern.

Cognitive, Functional, and Emotional Changes During the COVID-19 Pandemic in Greek Patients with Neurocognitive Disorders.

BACKGROUND: Prolonged periods of social deprivation, such as COVID-19-related lockdowns, are associated with deleterious effects on cognitive functions. OBJECTIVE: The aim of this study was to gauge the effect of prolonged social isolation on the cognitive function of older adults with neurocognitive disorders. METHODS: We recruited 125 older adults with minor or major neurocognitive disorders divided into two groups. The control group was tested at the first period of the study (October 2018-May 2019), whereas the experimental group was evaluated at the second chronological period of the study (October 2020-May 2021) during the second wave of COVID-19. Neuropsychological tests were performed at baseline and six months after baseline. RESULTS: In the control group, significant changes in the scores from the Montreal Cognitive Assessment (MoCA; p = 0.049) and the Functional Rating Scale for Symptoms of Dementia (FRSSD; p = 0.005) were found between baseline and follow-up assessments, whereas no changes were identified in Mini-Mental State Examination (MMSE; p = 0.229) and Geriatric Depression Scale (GDS; p = 0.619) scores. In the experimental group, the scores from all neuropsychological tests (MoCA, MMSE, GDS, and FRSSD; p < 0.001 for all) were significantly different at follow-up when compared with those at baseline measurements. Moreover, significant deterioration of specific functions assessed in MMSE and FRSSD was detected, especially in the experimental group. CONCLUSION: This study highlights cognitive functions directly affected by social deprivation of individuals with neurocognitive disorders. The findings can be used in the rehabilitation from confinement and its negative consequences.

The Karolinska NeuroCOVID study protocol: Neurocognitive impairment, biomarkers and advanced imaging in critical care survivors.

BACKGROUND: This is the study plan of the Karolinska NeuroCOVID study, a study of neurocognitive impairment after severe COVID-19, relating post-intensive care unit (ICU) cognitive and neurological deficits to biofluid markers and MRI. The COVID-19 pandemic has posed enormous health challenges to individuals and health-care systems worldwide. An emerging feature of severe COVID-19 is that of temporary and extended neurocognitive impairment, exhibiting a myriad of symptoms and signs. The causes of this symptomatology have not yet been fully elucidated. METHODS: In this study, we aim to investigate patients treated for severe COVID-19 in the ICU, as to describe and relate serum-, plasma- and cerebrospinal fluid-borne molecular and cellular biomarkers of immune activity, coagulopathy, cerebral damage, neuronal inflammation, and degeneration, to the temporal development of structural and functional changes within the brain as evident by serial MRI and extensive cognitive assessments at 3-12 months after ICU discharge. RESULTS: To date, we have performed 51 3-month follow-up MRIs in the ICU survivors. Of these, two patients (~4%) have had incidental findings on brain MRI findings requiring activation of the Incidental Findings Management Plan. Furthermore, the neuropsychological and neurological examinations have so far revealed varying and mixed patterns. Several patients expressed cognitive and/or mental concerns and fatigue, complaints closely related to brain fog. CONCLUSION: The study goal is to gain a better understanding of the pathological mechanisms and neurological consequences of this new disease, with a special emphasis on neurodegenerative and neuroinflammatory processes, in order to identify targets of intervention and rehabilitation.

Androgen-deprivation therapy and cognitive decline in the NEON-PC prospective study during the COVID-19 pandemic.

BACKGROUND: Androgen-deprivation therapy (ADT) has been associated with cognitive decline, but results are conflicting. This study describes changes in cognitive performance in patients with prostate cancer, according to ADT, during the first year after prostate cancer diagnosis. PATIENTS AND METHODS: Patients with prostate cancer treated at the Portuguese Institute of Oncology of Porto (n = 366) were evaluated with the Montreal Cognitive Assessment (MoCA), before treatment and after 1 year. All baseline evaluations were performed before the coronavirus disease 2019 (COVID-19) pandemic and 69.7% of the 1-year assessments were completed after the first lockdown. Cognitive decline was defined as the decrease in MoCA from baseline to the 1-year evaluation below 1.5 standard deviations of the distribution of changes in the whole cohort. Participants scoring below age- and education-specific normative reference values in the MoCA were considered to have cognitive impairment. Age- and education-adjusted odds ratios (aORs) were computed for the association between ADT and cognitive outcomes. RESULTS: Mean MoCA scores increased from baseline to the 1-year evaluation (22.3 versus 22.8, P < 0.001). Cognitive decline was more frequent in the ADT group, and even more after the onset of the COVID-19 pandemic (aOR 6.81 versus 1.93, P for interaction = 0.233). The 1-year cumulative incidence of cognitive impairment was 6.9% (9.1% before and 3.7% after the pandemic onset), which was higher among patients receiving ADT, but only after the pandemic (aOR 5.53 versus 0.49, P for interaction = 0.044). CONCLUSIONS: ADT was associated with worse cognitive performance of patients with prostate cancer, mostly among those evaluated after the first COVID-19 lockdown.

Binge Drinking Relates to Worse Neurocognitive Functioning Among Adults Aging with HIV.

OBJECTIVE: Given the aging population of people with HIV (PWH), along with increasing rates of binge drinking among both PWH and the general older adult population, this study examined the independent and interactive effects of HIV, binge drinking, and age on neurocognition. METHOD: Participants were 146 drinkers stratified by HIV and binge drinking status (i.e., ≥4 drinks for women and ≥5 drinks for men within approximately 2 h): HIV+/Binge+ (n = 30), HIV-/Binge+ (n = 23), HIV+/Binge- (n = 55), HIV-/Binge- (n = 38). All participants completed a comprehensive neuropsychological battery measuring demographically-corrected global and domain-specific neurocognitive T scores. ANCOVA models examined independent and interactive effects of HIV and binge drinking on neurocognitive outcomes, adjusting for overall alcohol consumption, lifetime substance use, sex, and age. Subsequent multiple linear regressions examined whether HIV/Binge group moderated the relationship between age and neurocognition. RESULTS: HIV+/Binge+ participants had worse global neurocognition, processing speed, delayed recall, and working memory than HIV-/Binge- participants (p's < .05). While there were significant main effects of HIV and binge drinking, their interaction did not predict any of those neurocognitive outcomes (p's > .05). Significant interactions between age and HIV/Binge group showed that HIV+/Binge+ participants demonstrated steeper negative relationships between age and neurocognitive outcomes of learning, delayed recall, and motor skills compared to HIV-/Binge- participants (p's < .05). CONCLUSIONS: Results showed adverse additive effects of HIV and binge drinking on neurocognitive functioning, with older adults demonstrating the most vulnerability to these effects. Findings support the need for interventions to reduce binge drinking, especially among older PWH.

Prodrug Therapies for Infectious and Neurodegenerative Diseases.

Prodrugs are bioreversible drug derivatives which are metabolized into a pharmacologically active drug following chemical or enzymatic modification. This approach is designed to overcome several obstacles that are faced by the parent drug in physiological conditions that include rapid drug metabolism, poor solubility, permeability, and suboptimal pharmacokinetic and pharmacodynamic profiles. These suboptimal physicochemical features can lead to rapid drug elimination, systemic toxicities, and limited drug-targeting to disease-affected tissue. Improving upon these properties can be accomplished by a prodrug design that includes the careful choosing of the promoiety, the linker, the prodrug synthesis, and targeting decorations. We now provide an overview of recent developments and applications of prodrugs for treating neurodegenerative, inflammatory, and infectious diseases. Disease interplay reflects that microbial infections and consequent inflammation affects neurodegenerative diseases and vice versa, independent of aging. Given the high prevalence, personal, social, and economic burden of both infectious and neurodegenerative disorders, therapeutic improvements are immediately needed. Prodrugs are an important, and might be said a critical tool, in providing an avenue for effective drug therapy.

Strategies to evaluate outcomes in long-COVID-19 and post-COVID survivors.

SARS-CoV-2 infection can impact the physical, cognitive, mental health of patients, especially in those recovered in intensive care units. Moreover, it was proved that the effects of the virus may persist for weeks or months. The term long-COVID or post-COVID syndrome is commonly used for indicating a variety of physical and psychological symptoms that continue after the resolution of the acute phase. This narrative review is aimed at providing an updated overview of the impact of physical, cognitive, and psychological health disorders in COVID-19 survivors, by summarizing the data already published in literature in the last year. Studies cited were found through PubMed searches. We also presented an overview of the post-COVID-19 health consequences on three important aspects: nutritional status, neurological disorders, and physical health. Moreover, to activate a correct health planning policy, a multidisciplinary approach for addressing the post- COVID-19 issue, has been proposed. Finally, the involvement of health professionals is necessary even after the pandemic, to reduce expected post-pandemic psychosocial responses and mental health disorders.

Effectiveness of a Randomized Controlled Trial of Individual Reminiscence Therapy on Cognition, Mood and Quality of Life in Azorean Older Adults with Neurocognitive Disorders.

Reminiscence therapy (RT) is a form of cognitive stimulation therapy that incorporates discussion of past activities, events, and experiences to stimulate individual memories; it has had some success in treating persons with neurocognitive disorders. This research aims to evaluate the ability of individual RT, using a simple reminiscence format, to improve the overall cognitive function, memory, executive functions, emotional status, and quality of life in older adults with neurocognitive disorders who received social care and support services. A multicenter randomized controlled trial was completed in the Azores archipelago (an independent region of Portugal) using repeated measures (pre-intervention, post-intervention, and follow-up). The intervention group underwent individual RT sessions, twice weekly for 13 weeks, while the control group completed regular activities administered as part of their program. Results did not reveal any significant differences between the intervention and control groups. While results did not reveal significant effects, a number of historical and contextual factors are considered as possible explanations for the lack of effects-namely, data collection occurring during the COVID-19 global pandemic, participant cohort effects, and therapist heterogeneity.

Depressive and Neurocognitive Disorders in the Context of the Inflammatory Background of COVID-19.

The dysfunctional effects of the coronavirus disease 2019 (COVID-19) infection on the nervous system are established. The manifestation of neuropsychiatric symptoms during and after infection is influenced by the neuroinvasive and neurotrophic properties of SARS-CoV-2 as well as strong inflammation characterised by a specific "cytokine storm". Research suggests that a strong immune response to a SARS-CoV-2 infection and psychological stressors related to the pandemic may cause chronic inflammatory processes in the body with elevated levels of inflammatory markers contributing to the intensification of neurodegenerative processes. It is suggested that neuroinflammation and associated central nervous system changes may significantly contribute to the etiopathogenesis of depressive disorders. In addition, symptoms after a COVID-19 infection may persist for up to several weeks after an acute infection as a post-COVID-19 syndrome. Moreover, previous knowledge indicates that among SSRI (selective serotonin reuptake inhibitor) group antidepressants, fluoxetine is a promising drug against COVID-19. In conclusion, further research, observation and broadening of the knowledge of the pathomechanism of a SARS-CoV-2 infection and the impact on potential complications are necessary. It is essential to continue research in order to assess the long-term neuropsychiatric effects in COVID-19 patients and to find new therapeutic strategies.

Opioid and neuroHIV Comorbidity - Current and Future Perspectives.

With the current national opioid crisis, it is critical to examine the mechanisms underlying pathophysiologic interactions between human immunodeficiency virus (HIV) and opioids in the central nervous system (CNS). Recent advances in experimental models, methodology, and our understanding of disease processes at the molecular and cellular levels reveal opioid-HIV interactions with increasing clarity. However, despite the substantial new insight, the unique impact of opioids on the severity, progression, and prognosis of neuroHIV and HIV-associated neurocognitive disorders (HAND) are not fully understood. In this review, we explore, in detail, what is currently known about mechanisms underlying opioid interactions with HIV, with emphasis on individual HIV-1-expressed gene products at the molecular, cellular and systems levels. Furthermore, we review preclinical and clinical studies with a focus on key considerations when addressing questions of whether opioid-HIV interactive pathogenesis results in unique structural or functional deficits not seen with either disease alone. These considerations include, understanding the combined consequences of HIV-1 genetic variants, host variants, and µ-opioid receptor (MOR) and HIV chemokine co-receptor interactions on the comorbidity. Lastly, we present topics that need to be considered in the future to better understand the unique contributions of opioids to the pathophysiology of neuroHIV. Graphical Abstract Blood-brain barrier and the neurovascular unit. With HIV and opiate co-exposure (represented below the dotted line), there is breakdown of tight junction proteins and increased leakage of paracellular compounds into the brain. Despite this, opiate exposure selectively increases the expression of some efflux transporters, thereby restricting brain penetration of specific drugs.

Systematic Review on the Mental Health and Treatment Impacts of COVID-19 on Neurocognitive Disorders.

Objectives. The COVID-19 pandemic has had many public health impacts, especially on vulnerable individuals including adults with neurocognitive disorders (NCD). With increasing literature, this systematic literature review aimed to address the mental health effects of COVID-19 on people with NCD in addition to examine the impact of the pandemic on treatments/resources for NCD. Methods. A literature search was conducted in the electronic databases of PubMed, PsycINFO, Web of Science and Google Scholar. Studies were included so long as they assessed the mental health or therapeutic effects of COVID-19 on NCD. Results. Among the retrieved articles, 59 met eligibility criteria. First, the pandemic and resulting self-isolation led to many detrimental effects on psychological well-being. Exacerbation and relapses of neurocognitive and behavioral symptoms were observed, as well as emergences of new psychological symptoms (i.e., depression, anxiety). Second, therapeutic and community services for individuals suffering from NCD, such as social support services and outpatient clinics, were disrupted or reduced leading to postponed appointments and evaluations, as well as reduced access to medications. These issues were somewhat palliated with the growth of telemedicine. Conclusions. This systematic review highlights the extent of the effects of the pandemic, and the topics addressed should be taken into consideration by healthcare practitioners, institutions, and policymakers to ensure that proper measures are employed to protect this population from additional harm.