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1.
J Acad Consult Liaison Psychiatry ; 63(2): 133-143, 2022.
Article in English | MEDLINE | ID: covidwho-1804387

ABSTRACT

BACKGROUND: There is a limited understanding of the cognitive and psychiatric sequelae of COVID-19 during the post-acute phase, particularly among racially and ethnically diverse patients. OBJECTIVE: We sought to prospectively characterize cognition, mental health symptoms, and functioning approximately four months after an initial diagnosis of COVID-19 in a racially and ethnically diverse group of patients. METHODS: Approximately four months after COVID-19 diagnosis, patients in the Johns Hopkins Post-Acute COVID-19 Team Pulmonary Clinic underwent a clinical telephone-based assessment of cognition, depression, anxiety, trauma, and function. RESULTS: Most Johns Hopkins Post-Acute COVID-19 Team patients assessed were women (59%) and members of racial/ethnic minority groups (65%). Of 82 patients, 67% demonstrated ≥1 abnormally low cognitive score. Patients requiring intensive care unit (ICU) stays displayed greater breadth and severity of impairment than those requiring less intensive treatment. Processing speed (35%), verbal fluency (26%-32%), learning (27%), and memory (27%) were most commonly impaired. Among all patients, 35% had moderate symptoms of depression (23%), anxiety (15%), or functional decline (15%); 25% of ICU patients reported trauma-related distress. Neuropsychiatric symptoms and functional decline did not differ by post-ICU versus non-ICU status and were unrelated to global cognitive composite scores. CONCLUSIONS: At approximately 4 months after acute illness, cognitive dysfunction, emotional distress, and functional decline were common among a diverse clinical sample of COVID-19 survivors varying in acute illness severity. Patients requiring ICU stays demonstrated greater breadth and severity of cognitive impairment than those requiring less intensive treatment. Findings help extend our understanding of the nature, severity, and potential duration of neuropsychiatric morbidity after COVID-19 and point to the need for longitudinal assessment of cognitive and mental health outcomes among COVID-19 survivors of different demographic backgrounds and illness characteristics.


Subject(s)
COVID-19 , Cognitive Dysfunction , COVID-19 Testing , Cognitive Dysfunction/epidemiology , Female , Humans , Intensive Care Units , Minority Groups , SARS-CoV-2
2.
Int J Environ Res Public Health ; 19(7)2022 Mar 28.
Article in English | MEDLINE | ID: covidwho-1785634

ABSTRACT

Older adults are vulnerable towards cognitive frailty that can lead to adverse health outcomes and telerehabilitation appears to be a potential platform to reverse cognitive frailty among older adults. The aim of this coping review is to identify the usage of telerehabilitation and its common platform of delivery among older adults with mild cognitive impairment (MCI) or cognitive frailty (CF). Articles published from January 2015 until October 2020 were selected. Out of the 1738 articles retrieved, six studies were identified. Two articles were randomized controlled trials, one was a pilot study and three were qualitative studies. The outcome suggests that telerehabilitation may improve the quality of life among participants as well as it can be a useful and supportive digital platform for health care. Some types of technologies commonly used were smartphones or telephones with internet, television-based assistive integrated technology, mobile application and videoconference. Telerehabilitation utilization in managing cognitive frailty among older adults is still limited and more research is required to evaluate its feasibility and acceptability. Although telerehabilitation appears to be implemented among older adults with MCI and CF, some social support is still required to improve the adherence and effectiveness of telerehabilitation. Future research should focus on the evaluation of acceptance and participants' existing knowledge towards telerehabilitation to achieve its target.


Subject(s)
Cognitive Dysfunction , Frailty , Telerehabilitation , Aged , Cognition , Cognitive Dysfunction/psychology , Humans , Pilot Projects , Quality of Life , Randomized Controlled Trials as Topic
3.
BMJ Open ; 12(4): e055038, 2022 Apr 11.
Article in English | MEDLINE | ID: covidwho-1784816

ABSTRACT

INTRODUCTION: A substantial number of patients diagnosed with COVID-19 experience long-term persistent symptoms. First evidence suggests that long-term symptoms develop largely independently of disease severity and include, among others, cognitive impairment. For these symptoms, there are currently no validated therapeutic approaches available. Cognitive training interventions are a promising approach to counteract cognitive impairment. Combining training with concurrent transcranial direct current stimulation (tDCS) may further increase and sustain behavioural training effects. Here, we aim to examine the effects of cognitive training alone or in combination with tDCS on cognitive performance, quality of life and mental health in patients with post-COVID-19 subjective or objective cognitive impairments. METHODS AND ANALYSIS: This study protocol describes a prospective randomised open endpoint-blinded trial. Patients with post-COVID-19 cognitive impairment will either participate in a 3-week cognitive training or in a defined muscle relaxation training (open-label interventions). Irrespective of their primary intervention, half of the cognitive training group will additionally receive anodal tDCS, all other patients will receive sham tDCS (double-blinded, secondary intervention). The primary outcome will be improvement of working memory performance, operationalised by an n-back task, at the postintervention assessment. Secondary outcomes will include performance on trained and untrained tasks and measures of health-related quality of life at postassessment and follow-up assessments (1 month after the end of the trainings). ETHICS AND DISSEMINATION: Ethical approval was granted by the Ethics Committee of the University Medicine Greifswald (number: BB 066/21). Results will be available through publications in peer-reviewed journals and presentations at national and international conferences. TRIAL REGISTRATION NUMBER: NCT04944147.


Subject(s)
COVID-19 , Cognitive Dysfunction , Transcranial Direct Current Stimulation , Brain , COVID-19/therapy , Cognition , Cognitive Dysfunction/therapy , Double-Blind Method , Humans , Prospective Studies , Quality of Life , Randomized Controlled Trials as Topic
4.
Front Public Health ; 9: 706322, 2021.
Article in English | MEDLINE | ID: covidwho-1775821

ABSTRACT

Objective: Social support plays a critical role in the detection and management of mild cognitive impairment (MCI). However, socioeconomic inequalities exist in both social support and health care services. Our study aimed to compare the level of social support received by MCI patients in comparison with those without MCI and to determine its link with income. Methods: Secondary data analyses were performed. Social support was measured using the Duke Social Support Index (DSSI) and satisfaction ratings. Multivariate logistic regression models were constructed to determine the associations of personal income and MCI with social support after adjustment for variations in the sociodemographic and health characteristics of the respondents. The multiplicative and additive interaction effects of income and MCI were further examined through introducing the MCI*Income variable to the regression models and using the relative excess risk due to interaction (RERI) analysis, respectively. Results: The logistic regression models showed that the respondents with MCI had significantly lower social support as measured by the DSSI scores (AOR = 33.03, p < 0.001) and satisfaction ratings (AOR = 7.48, p < 0.001) compared with those without MCI. Similarly, social support decreased with lower personal income (p < 0.001). There existed a significant multiplicative interaction effect between personal income and MCI on social support (AOR = 0.30-0.32, p < 0.01). The gap in social support between those with and without MCI was higher in the higher income group compared with the lower income group (p < 0.001). No significant additive interaction effects on social support were found between MCI and income. Conclusions: There are significant disparities in social support between people living with and without MCI. Such a gap is more profound in people with higher income. The inequality in social support associated with MCI may present a significant challenge to the successful implementation of community MCI detection and management.


Subject(s)
Cognitive Dysfunction , Social Support , Aged , China/epidemiology , Cognitive Dysfunction/epidemiology , Cross-Sectional Studies , Humans , Middle Aged , Social Support/statistics & numerical data
5.
Front Public Health ; 9: 750340, 2021.
Article in English | MEDLINE | ID: covidwho-1775932

ABSTRACT

Social isolation and loneliness in older adults are associated with poor health outcomes and have been linked to an increased risk of cognitive impairment and incident dementia. Social engagement has been identified as a key factor in promoting positive health behaviors and quality of life and preventing social isolation and loneliness. Studies involving cognitively healthy older adults have shown the protective effects of both in-person and technology-based social engagement. However, the benefits of social engagement for people who are already at-risk of developing dementia, namely those with mild cognitive impairment (MCI), have yet to be elucidated. We present a narrative review of the literature, summarizing the research on social engagement in MCI. First, we identified social networks (quality, size, frequency, and closeness) and social activities (frequency, format, purpose, type, and content) as two overarching dimensions of an integrative framework for social engagement derived from literature examining typical cognitive aging. We then used this framework as a lens to examine studies of social engagement in MCI to explore (i) the relationship between in-person and technology-based social engagement and cognitive, emotional, and physical health, and (ii) interventions that target social engagement including technology-based approaches. Overall, we found that persons with MCI (PwMCI) may have different levels of social engagement than those experiencing typical cognitive aging. Moreover, in-person social engagement can have a positive impact on cognitive, emotional, and physical health for PwMCI. With respect to activity and network dimensions in our framework, we found that cognitive health has been more widely examined in PwMCI relative to physical and emotional health. Very few intervention studies have targeted social engagement, but both in-person and technology-based interventions appear to have promising health and well-being outcomes. Our multidimensional framework of social engagement provides guidance for research on characterizing the protective benefits of social engagement for PwMCI and informs the development of novel interventions including technology-based approaches.


Subject(s)
Cognitive Dysfunction , Aged , Cognitive Dysfunction/psychology , Humans , Quality of Life , Social Participation , Technology
6.
Cardiovasc Toxicol ; 22(4): 311-325, 2022 04.
Article in English | MEDLINE | ID: covidwho-1773006

ABSTRACT

Hypertension is one of the most prevalent cardiovascular disorders worldwide, affecting 1.13 billion people, or 14% of the global population. Hypertension is the single biggest risk factor for cerebrovascular dysfunction. According to the American Heart Association, high blood pressure (BP), especially in middle-aged individuals (~ 40 to 60 years old), is associated with an increased risk of dementia, later in life. Alzheimer's disease and cerebrovascular disease are the two leading causes of dementia, accounting for around 80% of the total cases and usually combining mixed pathologies from both. Little is known regarding how hypertension affects cognitive function, so the impact of its treatment on cognitive impairment has been difficult to assess. The brain renin-angiotensin system (RAS) is essential for BP regulation and overactivity of this system has been established to precede the development and maintenance of hypertension. Angiotensin II (Ang-II), the main peptide within this system, induces vasoconstriction and impairs neuro-vascular coupling by acting on brain Ang-II type 1 receptors (AT1R). In this review, we systemically analyzed the association between RAS and biological mechanisms of cognitive impairment, from the perspective of AT1R located in the central nervous system. Additionally, the possible contribution of brain AT1R to global cognition decline in COVID-19 cases will be discussed as well.


Subject(s)
COVID-19 , Cognitive Dysfunction , Hypertension , Adult , Angiotensin II/metabolism , Blood Pressure/physiology , COVID-19/complications , Cognitive Dysfunction/diagnosis , Humans , Hypertension/diagnosis , Middle Aged , Receptor, Angiotensin, Type 1/metabolism , Renin-Angiotensin System
7.
J Alzheimers Dis ; 84(4): 1539-1550, 2021.
Article in English | MEDLINE | ID: covidwho-1771006

ABSTRACT

BACKGROUND: Approximately 50% of older adults with cognitive impairment suffer from insomnia. When untreated, pre-existing cognitive problems may be exacerbated and potentially contribute to further cognitive decline. One promising approach to maintain cognitive health is to improve sleep quantity and quality. OBJECTIVE: To determine feasibility, acceptability, and preliminary efficacy of Sleep Health Using the Internet for Older Adult Sufferers of Insomnia and Sleeplessness (SHUTi OASIS), an Internet-delivered cognitive behavioral therapy for insomnia (CBT-I) program in older adults with mild cognitive impairment (MCI). METHODS: Older adults with MCI and insomnia were recruited from hospital-based memory and sleep disorders clinics and enrolled in a single-arm pilot study. Participants completed the six cores of SHUTi OASIS, over nine weeks with two-week baseline and post-assessments using self-reported sleep diaries. Feasibility and acceptability were informed by usage statistics and qualitative interviews; preliminary efficacy was informed by patient-generated sleep data. RESULTS: Twelve participants enrolled and, on average, were 75.8 years of age. Ten participants completed the study and logged in most days. Most participants reported a positive overall experience, and interviews revealed successful and independent program management and completion. There were significant changes on all baseline to post-assessment sleep measures, including clinically meaningful improvements on the Insomnia Severity Index (13.5 to 8.3, p < 0.01), sleep efficiency, wake after sleep onset, and sleep onset latency (ps < 0.02). There was no statistically significant change in cognitive measures (p > 0.05). CONCLUSION: This study supports that older adults with cognitive impairment can independently complete CBT-I via the Internet and achieve clinical sleep improvements.


Subject(s)
Cognitive Behavioral Therapy , Cognitive Dysfunction/complications , Internet-Based Intervention , Sleep Initiation and Maintenance Disorders/therapy , Aged , Feasibility Studies , Female , Humans , Male , Pilot Projects , Self Report , Treatment Outcome
8.
BMJ Open ; 12(3): e055990, 2022 03 28.
Article in English | MEDLINE | ID: covidwho-1769916

ABSTRACT

INTRODUCTION: More than 50 million people worldwide are living with dementia in 2020, and this number is expected to double every 20 years. Physical exercise is a growing field in non-pharmacological interventions for dementia care. Due to public health measures during the COVID-19 pandemic, more people have considered adapting to technology-based exercise via digital devices. This scoping review will explore evidence relating to the use of technology-based group exercise by people with dementia or mild cognitive impairment. METHODS AND ANALYSIS: This review will follow the Joanna Briggs Institute scoping review methodology to review literature published between June and December 2021. This review is designed to identify existing types of technology-based group exercise interventions for people with dementia. The review will provide a synthesis of current evidence on the outcome and impacts of technology-based group exercise. The context of this review will include homes, assisted living facilities and memory care services but exclude hospitals. The review will include a three-step search strategy: (a) identify keywords from MEDLINE and Embase, (b) search using the identified keywords in databases (MEDLINE/PubMed, CINAHL, Web of Science, Embase, Cochrane Library, PsychInfo and Google) and (c) review references from included studies to identify additional studies. Only studies in English will be included. Four researchers will independently assess titles and abstracts and then review the full text of the selected articles, applying the inclusion criteria. The extracted data will be presented in tables and summarised narratively. ETHICS AND DISSEMINATION: Scoping review data will be collected from publicly available articles; research ethics approval is not required. The findings will be disseminated to healthcare practitioners and the public through a peer-reviewed publication and conference presentations.


Subject(s)
COVID-19 , Cognitive Dysfunction , Dementia , Cognitive Dysfunction/therapy , Dementia/therapy , Exercise Therapy , Humans , Pandemics , Research Design , Review Literature as Topic , Technology
9.
Sci Rep ; 12(1): 5496, 2022 Mar 31.
Article in English | MEDLINE | ID: covidwho-1768853

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is accompanied by chronic neurological sequelae such as cognitive decline and mood disorder, but the underlying mechanisms have not yet been elucidated. We explored the possibility that the brain-infiltrating SARS-CoV-2 spike protein contributes to the development of neurological symptoms observed in COVID-19 patients in this study. Our behavioral study showed that administration of SARS-CoV-2 spike protein S1 subunit (S1 protein) to mouse hippocampus induced cognitive deficit and anxiety-like behavior in vivo. These neurological symptoms were accompanied by neuronal cell death in the dorsal and ventral hippocampus as well as glial cell activation. Interestingly, the S1 protein did not directly induce hippocampal cell death in vitro. Rather, it exerted neurotoxicity via glial cell activation, partially through interleukin-1ß induction. In conclusion, our data suggest a novel pathogenic mechanism for the COVID-19-associated neurological symptoms that involves glia activation and non-cell autonomous hippocampal neuronal death by the brain-infiltrating S1 protein.


Subject(s)
COVID-19 , Cognitive Dysfunction , Animals , Antibodies, Viral/metabolism , Anxiety , Cell Death , Cognition , Cognitive Dysfunction/etiology , Hippocampus/metabolism , Humans , Membrane Glycoproteins/metabolism , Mice , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/metabolism , Viral Envelope Proteins/metabolism
11.
CNS Neurosci Ther ; 28(4): 470-483, 2022 04.
Article in English | MEDLINE | ID: covidwho-1745958

ABSTRACT

Postoperative neurological disorders, including postoperative delirium (POD), postoperative cognitive dysfunction (POCD), postoperative covert ischemic stroke, and hemorrhagic stroke, are challenging clinical problems in the emerging aged surgical population. These disorders can deteriorate functional outcomes and long-term quality of life after surgery, resulting in a substantial social and financial burden to the family and society. Understanding predisposing and precipitating factors may promote individualized preventive treatment for each disorder, as several risk factors are modifiable. Besides prevention, timely identification and treatment of etiologies and symptoms can contribute to better recovery from postoperative neurological disorders and lower risk of long-term cognitive impairment, disability, and even death. Herein, we summarize the diagnosis, risk factors, prevention, and treatment of these postoperative complications, with emphasis on recent advances and perspectives.


Subject(s)
Cognitive Dysfunction , Delirium , Postoperative Cognitive Complications , Aged , Cognitive Dysfunction/etiology , Humans , Postoperative Complications , Quality of Life , Risk Factors
12.
J Alzheimers Dis ; 85(4): 1573-1582, 2022.
Article in English | MEDLINE | ID: covidwho-1745159

ABSTRACT

BACKGROUND: Subjective cognitive decline (SCD), an at-risk condition of Alzheimer's disease (AD), can involve various cognitive domains, such as memory, language, planning, and attention. OBJECTIVE: We aim to explore the difference in amyloid load between the single memory domain SCD (sd-SCD) and the multidomain SCD (md-SCD) and assess the relationship of amyloid pathology with quantitative SCD scores and objective cognition. METHODS: A total of 63 SCD participants from the SILCODE study underwent the clinical evaluation, neuropsychological assessment, and 18F-florbetapir PET scan. Global amyloid standard uptake value ratio (SUVr) was calculated. Additionally, regional amyloid SUVr was quantified in 12 brain regions of interests. A nonparametric rank ANCOVA was used to compare the global and regional amyloid SUVr between the md-SCD (n = 34) and sd-SCD (n = 29) groups. A multiple linear regression analysis was conducted to test the relationship of amyloid SUVr with quantitative SCD scores and objective cognition. RESULTS: Compared with individuals with sd-SCD, individuals with md-SCD had increased global amyloid SUVr (F = 5.033, p = 0.029) and regional amyloid SUVr in the left middle temporal gyrus (F = 12.309, p = 0.001; Bonferroni corrected), after controlling for the effects of age, sex, and education. When pooling all SCD participants together, the increased global amyloid SUVr was related with higher SCD-plus sum scores and lower Auditory Verbal Learning Test-delayed recall scores. CONCLUSION: According to our findings, individuals with md-SCD showed higher amyloid accumulation than individuals with sd-SCD, suggesting that md-SCD may experience a more advanced stage of SCD. Additionally, increased global amyloid load was predictive of a poorer episodic memory function in SCD individuals.


Subject(s)
Amyloid/metabolism , Cognitive Dysfunction/pathology , Aged , Brain/pathology , Female , Humans , Male , Neuropsychological Tests/statistics & numerical data , Positron-Emission Tomography
13.
Rehabil Nurs ; 47(2): 72-81, 2022.
Article in English | MEDLINE | ID: covidwho-1741065

ABSTRACT

PURPOSE: The primary objective of this scoping review was to identify prominent cognitive impairment sequelae in adult survivors of an intensive care unit admission for acute respiratory distress syndrome (ARDS). DESIGN: A scoping review was performed. METHODS: Search terms were entered into multiple EBSCOhost databases. Articles pertaining to pediatric survivors, not in English, lacking cognitive impairment sequelae, or focused on a single sequela were excluded; 12 articles remained. RESULTS: Cognitive impairment developed in 83.5% of patients with ARDS prior to discharge and persisted in 51.3% (n = 300/585) of survivors at the 1 year mark after discharge (range: 16.7%-100% across studies). Prominent sequelae included impairments in executive function, mental processing speed, immediate memory, and attention/concentration. CONCLUSIONS: Survivors of an intensive care unit stay for ARDS often develop cognitive impairment persisting long after their admission. Clinicians in rehabilitation facilities should screen for these sequelae and connect survivors with treatment to improve cognitive outcomes. CLINICAL RELEVANCE: Early recognition of prominent cognitive impairment sequelae by rehabilitation clinicians and referrals to neuropsychologists by providers are critical to limiting the severity of impairment.


Subject(s)
Cognitive Dysfunction , Respiratory Distress Syndrome , Adult , Child , Cognitive Dysfunction/etiology , Humans , Intensive Care Units , Patient Discharge , Respiratory Distress Syndrome/complications , Respiratory Distress Syndrome/therapy , Survivors/psychology
14.
Alzheimers Dement ; 18(4): 700-789, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1739115

ABSTRACT

This article describes the public health impact of Alzheimer's disease (AD), including incidence and prevalence, mortality and morbidity, use and costs of care, and the overall impact on family caregivers, the dementia workforce and society. The Special Report discusses consumers' and primary care physicians' perspectives on awareness, diagnosis and treatment of mild cognitive impairment (MCI), including MCI due to Alzheimer's disease. An estimated 6.5 million Americans age 65 and older are living with Alzheimer's dementia today. This number could grow to 13.8 million by 2060 barring the development of medical breakthroughs to prevent, slow or cure AD. Official death certificates recorded 121,499 deaths from AD in 2019, the latest year for which data are available. Alzheimer's disease was officially listed as the sixth-leading cause of death in the United States in 2019 and the seventh-leading cause of death in 2020 and 2021, when COVID-19 entered the ranks of the top ten causes of death. Alzheimer's remains the fifth-leading cause of death among Americans age 65 and older. Between 2000 and 2019, deaths from stroke, heart disease and HIV decreased, whereas reported deaths from AD increased more than 145%. More than 11 million family members and other unpaid caregivers provided an estimated 16 billion hours of care to people with Alzheimer's or other dementias in 2021. These figures reflect a decline in the number of caregivers compared with a decade earlier, as well as an increase in the amount of care provided by each remaining caregiver. Unpaid dementia caregiving was valued at $271.6 billion in 2021. Its costs, however, extend to family caregivers' increased risk for emotional distress and negative mental and physical health outcomes - costs that have been aggravated by COVID-19. Members of the dementia care workforce have also been affected by COVID-19. As essential care workers, some have opted to change jobs to protect their own health and the health of their families. However, this occurs at a time when more members of the dementia care workforce are needed. Average per-person Medicare payments for services to beneficiaries age 65 and older with AD or other dementias are almost three times as great as payments for beneficiaries without these conditions, and Medicaid payments are more than 22 times as great. Total payments in 2022 for health care, long-term care and hospice services for people age 65 and older with dementia are estimated to be $321 billion. A recent survey commissioned by the Alzheimer's Association revealed several barriers to consumers' understanding of MCI. The survey showed low awareness of MCI among Americans, a reluctance among Americans to see their doctor after noticing MCI symptoms, and persistent challenges for primary care physicians in diagnosing MCI. Survey results indicate the need to improve MCI awareness and diagnosis, especially in underserved communities, and to encourage greater participation in MCI-related clinical trials.


Subject(s)
Alzheimer Disease , COVID-19 , Cognitive Dysfunction , Aged , Alzheimer Disease/diagnosis , Caregivers/psychology , Cognitive Dysfunction/epidemiology , Health Care Costs , Humans , Medicare , United States/epidemiology
15.
PLoS One ; 17(3): e0264331, 2022.
Article in English | MEDLINE | ID: covidwho-1731597

ABSTRACT

BACKGROUND: Long Covid is a public health concern that needs defining, quantifying, and describing. We aimed to explore the initial and ongoing symptoms of Long Covid following SARS-CoV-2 infection and describe its impact on daily life. METHODS: We collected self-reported data through an online survey using convenience non-probability sampling. The survey enrolled adults who reported lab-confirmed (PCR or antibody) or suspected COVID-19 who were not hospitalised in the first two weeks of illness. This analysis was restricted to those with self-reported Long Covid. Univariate comparisons between those with and without confirmed COVID-19 infection were carried out and agglomerative hierarchical clustering was used to identify specific symptom clusters, and their demographic and functional correlates. RESULTS: We analysed data from 2550 participants with a median duration of illness of 7.6 months (interquartile range (IQR) 7.1-7.9). 26.5% reported lab-confirmation of infection. The mean age was 46.5 years (standard deviation 11 years) with 82.8% females and 79.9% of participants based in the UK. 89.5% described their health as good, very good or excellent before COVID-19. The most common initial symptoms that persisted were exhaustion, chest pressure/tightness, shortness of breath and headache. Cognitive dysfunction and palpitations became more prevalent later in the illness. Most participants described fluctuating (57.7%) or relapsing symptoms (17.6%). Physical activity, stress, and sleep disturbance commonly triggered symptoms. A third (32%) reported they were unable to live alone without any assistance at six weeks from start of illness. 16.9% reported being unable to work solely due to COVID-19 illness. 37.0% reported loss of income due to illness, and 64.4% said they were unable to perform usual activities/duties. Acute systems clustered broadly into two groups: a majority cluster (n = 2235, 88%) with cardiopulmonary predominant symptoms, and a minority cluster (n = 305, 12%) with multisystem symptoms. Similarly, ongoing symptoms broadly clustered in two groups; a majority cluster (n = 2243, 88.8%) exhibiting mainly cardiopulmonary, cognitive symptoms and exhaustion, and a minority cluster (n = 283, 11.2%) exhibiting more multisystem symptoms. Belonging to the more severe multisystem cluster was associated with more severe functional impact, lower income, younger age, being female, worse baseline health, and inadequate rest in the first two weeks of the illness, with no major differences in the cluster patterns when restricting analysis to the lab-confirmed subgroup. CONCLUSION: This is an exploratory survey of Long Covid characteristics. Whilst this is a non-representative population sample, it highlights the heterogeneity of persistent symptoms, and the significant functional impact of prolonged illness following confirmed or suspected SARS-CoV-2 infection. To study prevalence, predictors and prognosis, research is needed in a representative population sample using standardised case definitions.


Subject(s)
COVID-19/psychology , Cognitive Dysfunction/etiology , Dyspnea/etiology , Sleep Wake Disorders/etiology , Adolescent , Adult , COVID-19/complications , COVID-19/pathology , COVID-19/virology , Cluster Analysis , Cross-Sectional Studies , Delivery of Health Care , Female , Humans , Male , Middle Aged , SARS-CoV-2/isolation & purification , Self Report , Stress, Physiological , Surveys and Questionnaires , Young Adult
16.
Neurol Neuroimmunol Neuroinflamm ; 9(3)2022 05.
Article in English | MEDLINE | ID: covidwho-1731569

ABSTRACT

BACKGROUND AND OBJECTIVES: Although patients hospitalized with COVID-19 frequently present with encephalopathy, those with mild initial COVID-19 disease who never required hospitalization also often develop neurologic symptoms as part of postacute sequelae of severe acute respiratory coronavirus type 2 (SARS-CoV-2) infection (neuro-PASC). The pathogenic mechanisms of COVID-19 encephalopathy and neuro-PASC are unknown. We sought to establish biochemical evidence of CNS injury in those patients and their association with neuropsychiatric manifestations and SARS-CoV-2 antigenemia. METHODS: We recruited hospitalized, posthospitalized, and nonhospitalized patients with confirmed diagnosis of COVID-19 with neurologic symptoms in addition to healthy control (HC) subjects. Plasma neurofilament light chain (pNfL), plasma glial fibrillary acidic protein (pGFAP), and plasma SARS-CoV-2 Nucleocapsid antigen (pN Ag) were measured by HD-X Simoa analyzer (Quanterix) and compared with neuropsychiatric symptoms, patient-reported quality-of-life measures, and standardized cognitive assessments. Neuroglial scores (pGFAP/pNfL) were calculated to estimate the relative contribution of astroglial and neuronal involvement. RESULTS: We enrolled a total of 64 study participants, including 9 hospitalized patients with COVID-19 encephalopathy (CE), 9 posthospitalization neuro-PASC (PNP) patients, 38 nonhospitalized neuro-PASC (NNP) patients, and 8 HC subjects. Patients with CE were older, had higher pNfL and pGFAP concentrations, and more frequent pN Ag detection than all neuro-PASC groups. PNP and NNP patients exhibited similar PASC symptoms, decreased quality-of-life measures, and cognitive dysfunction, and 1 of the 38 (2.6%) NNP patients had pN Ag detectable 3 weeks postsymptoms onset. Patients with neuro-PASC presenting with anxiety/depression had higher neuroglial scores, which were correlated with increased anxiety on quality-of-life measures. DISCUSSION: pNfL, pGFAP, and pN Ag measurements indicate neuronal dysfunction and systemic involvement in hospitalized COVID-19 patients with encephalopathy. Detection of SARS-CoV-2 N Ag in blood 3 weeks after symptoms onset in a nonhospitalized patient suggests that prolonged antigenic stimulation, or possibly latent infection, may occur. Anxiety was associated with evidence of astroglial activation in patients with neuro-PASC. These data shed new light on SARS-Cov-2 neuropathogenesis and demonstrate the value of plasma biomarkers across the COVID-19 disease spectrum.


Subject(s)
COVID-19 , Cognitive Dysfunction , Biomarkers , COVID-19/complications , Disease Progression , Humans , SARS-CoV-2
17.
Alzheimers Res Ther ; 14(1): 36, 2022 02 22.
Article in English | MEDLINE | ID: covidwho-1724541

ABSTRACT

BACKGROUND: An aging society has increased rates of late onset Alzheimer disease dementia (ADD), the most common form of age-related dementia. This neurodegenerative disease disproportionately affects women. METHODS: We use data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to examine sex differences in cortical thickness (CT) and memory performance. Analyses of covariance (ANCOVA) models were used to examine effects of sex and diagnosis (DX) on CT and verbal memory. For regions demonstrating significant interaction effects of sex and DX, we tested whether sex moderated cognition-thickness relationships. We used machine learning as a complementary method to explore multivariate CT differences between women and men. RESULTS: Women demonstrated greater CT in many brain regions. More specifically, men showed relatively consistent CT declines in all stages, from normal control (NC) to ADD in the bilateral cingulate cortex, bilateral temporal regions, and left precuneus; women had more stable CT in these regions between NC and mild cognitive impairment (MCI) stages, but sharper declines from MCI to ADD. Similarly, for the Rey Auditory Verbal Learning Test (RAVLT), ANCOVA analyses showed that women had significantly better immediate and delayed recall scores than men, at NC and MCI stages, but greater differences, cross-sectionally, from MCI to ADD than men. We found significant sex moderation effects between RAVLT-immediate scores and CT of right isthmus-cingulate for all subjects across DX. Partial correlation analyses revealed that increased CT of right isthmus-cingulate was associated with better verbal learning in women, driven by positron emission tomography defined amyloid positive (Aß+) subjects. Significant sex-moderation effects in cognition-thickness relationships were further found in the right middle-temporal, left precuneus, and left superior temporal regions in Aß+ subjects. Using a machine learning approach, we investigated multivariate CT differences between women and men, showing an accuracy in classification of 75% for Aß+ cognitively NC participants. CONCLUSIONS: Sex differences in memory and CT can play a key role in the different vulnerability and progression of ADD in women compared to men. Machine learning indicates sex differences in CT are most relevant early in the ADD neurodegeneration.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Neurodegenerative Diseases , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/psychology , Cognitive Dysfunction/diagnostic imaging , Female , Healthy Volunteers , Humans , Male , Positron-Emission Tomography , Sex Characteristics
19.
Neuropharmacology ; 209: 109023, 2022 05 15.
Article in English | MEDLINE | ID: covidwho-1720668

ABSTRACT

Acute neurological alterations have been associated with SARS-CoV-2 infection. Additionally, it is becoming clear that coronavirus disease 2019 (COVID-19) survivors may experience long-term neurological abnormalities, including cognitive deficits and mood alterations. The mechanisms underlying acute and long-term impacts of COVID-19 in the brain are being actively investigated. Due to the heterogeneous manifestations of neurological outcomes, it is possible that different mechanisms operate following SARS-CoV-2 infection, which may include direct brain infection by SARS-CoV-2, mechanisms resulting from hyperinflammatory systemic disease, or a combination of both. Inflammation is a core feature of COVID-19, and both central and systemic inflammation are known to lead to acute and persistent neurological alterations in other diseases. Here, we review evidence indicating that COVID-19 is associated with neuroinflammation, along with blood-brain barrier dysfunction. Similar neuroinflammatory signatures have been associated with Alzheimer's disease and major depressive disorder. Current evidence demonstrates that patients with pre-existing cognitive and neuropsychiatric deficits show worse outcomes upon infection by SARS-CoV-2 and, conversely, COVID-19 survivors may be at increased risk of developing dementia and mood disorders. Considering the high prevalence of COVID-19 patients that recovered from infection in the world and the alarming projections for the prevalence of dementia and depression, investigation of possible molecular similarities between those diseases may shed light on mechanisms leading to long-term neurological abnormalities in COVID-19 survivors.


Subject(s)
COVID-19/complications , Cognitive Dysfunction/etiology , Depression/etiology , /physiopathology , Affect/physiology , Blood-Brain Barrier/metabolism , COVID-19/physiopathology , Cognitive Dysfunction/physiopathology , Depression/physiopathology , Humans , Inflammation/physiopathology , SARS-CoV-2 , Virus Diseases/complications
20.
Sensors (Basel) ; 22(4)2022 Feb 14.
Article in English | MEDLINE | ID: covidwho-1715640

ABSTRACT

The early prediction of Alzheimer's disease (AD) can be vital for the endurance of patients and establishes as an accommodating and facilitative factor for specialists. The proposed work presents a robotized predictive structure, dependent on machine learning (ML) methods for the forecast of AD. Neuropsychological measures (NM) and magnetic resonance imaging (MRI) biomarkers are deduced and passed on to a recurrent neural network (RNN). In the RNN, we have used long short-term memory (LSTM), and the proposed model will predict the biomarkers (feature vectors) of patients after 6, 12, 21 18, 24, and 36 months. These predicted biomarkers will go through fully connected neural network layers. The NN layers will then predict whether these RNN-predicted biomarkers belong to an AD patient or a patient with a mild cognitive impairment (MCI). The developed methodology has been tried on an openly available informational dataset (ADNI) and accomplished an accuracy of 88.24%, which is superior to the next-best available algorithms.


Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Alzheimer Disease/diagnosis , Alzheimer Disease/pathology , Biomarkers , Cognitive Dysfunction/diagnostic imaging , Humans , Magnetic Resonance Imaging/methods , Memory, Short-Term
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