Leveraging molecular targeted drugs and immune checkpoint inhibitors treat advanced thyroid carcinoma to achieve thyroid carcinoma redifferentiation.

Thyroid cancer can be classified into three different types based on the degree of differentiation: well-differentiated, poorly differentiated, and anaplastic thyroid carcinoma. Well-differentiated thyroid cancer refers to cancer cells that closely resemble normal thyroid cells, while poorly differentiated and anaplastic thyroid carcinoma are characterized by cells that have lost their resemblance to normal thyroid cells. Advanced thyroid carcinoma, regardless of its degree of differentiation, is known to have a higher likelihood of disease progression and is generally associated with a poor prognosis. However, the process through which well-differentiated thyroid carcinoma transforms into anaplastic thyroid carcinoma, also known as "dedifferentiation", has been a subject of intensive research. In recent years, there have been significant breakthroughs in the treatment of refractory advanced thyroid cancer. Clinical studies have been conducted to evaluate the efficacy and safety of molecular targeted drugs and immune checkpoint inhibitors in the treatment of dedifferentiated thyroid cancer. These drugs work by targeting specific molecules or proteins in cancer cells to inhibit their growth or by enhancing the body's immune response against the cancer cells. This article aims to explore some of the possible mechanisms behind the dedifferentiation process in well-differentiated thyroid carcinoma. It also discusses the clinical effects of molecular targeted drugs and immune checkpoint inhibitors in thyroid cancer patients with different degrees of differentiation. Furthermore, it offers insights into the future trends in the treatment of advanced thyroid cancer, highlighting the potential for improved outcomes and better patient care.

G-quadruplexes on chromosomal DNA negatively regulates topoisomerase 1 activity.

Human DNA topoisomerase 1 (Top1) is a crucial enzyme responsible for alleviating torsional stress on DNA during transcription and replication, thereby maintaining genome stability. Previous researches had found that non-working Top1 interacted extensively with chromosomal DNA in human cells. However, the reason for its retention on chromosomal DNA remained unclear. In this study, we discovered a close association between Top1 and chromosomal DNA, specifically linked to the presence of G-quadruplex (G4) structures. G4 structures, formed during transcription, trap Top1 and hinder its ability to relax neighboring DNAs. Disruption of the Top1-G4 interaction using G4 ligand relieved the inhibitory effect of G4 on Top1 activity, resulting in a further reduction of R-loop levels in cells. Additionally, the activation of Top1 through the use of a G4 ligand enhanced the toxicity of Top1 inhibitors towards cancer cells. Our study uncovers a negative regulation mechanism of human Top1 and highlights a novel pathway for activating Top1.

Nickel Nanoparticles Protruding from Molybdenum Carbide Micropillars with Carbon Layer-Protected Biphasic 0D/1D Heterostructures for Efficient Water Splitting.

It remains a tremendous challenge to achieve high-efficiency bifunctional electrocatalysts for both the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) for hydrogen production by water splitting. Herein, a novel hybrid of 0D nickel nanoparticles dispersed on the one-dimensional (1D) molybdenum carbide micropillars embedded in the carbon layers (Ni/Mo2C@C) was successfully prepared on nickel foam by a facile pyrolysis strategy. During the synthesis process, the nickel nanoparticles and molybdenum carbide were simultaneously generated under H2 and C2H2 mixed atmospheres and conformally encapsulated in the carbon layers. Benefiting from the distinctive 0D/1D heterostructure and the synergistic effect of the biphasic Mo2C and Ni together with the protective effect of the carbon layer, the reduced activation energy barriers and fast catalytic reaction kinetics can be achieved, resulting in a small overpotential of 96 mV for the HER and 266 mV for the OER at the current density of 10 mA cm-2 together with excellent durability in 1.0 M KOH electrolyte. In addition, using the developed Ni/Mo2C@C as both the cathode and anode, the constructed electrolyzer exhibits a small voltage of 1.55 V for the overall water splitting. The novel designed Ni/Mo2C@C may give inspiration for the development of efficient bifunctional catalysts with low-cost transition metal elements for water splitting.

Discovery of distinct cancer cachexia phenotypes using an unsupervised machine-learning algorithm.

OBJECTIVES: Cancer cachexia is a debilitating condition with widespread negative effects. The heterogeneity of clinical features within patients with cancer cachexia is unclear. The identification and prognostic analysis of diverse phenotypes of cancer cachexia may help develop individualized interventions to improve outcomes for vulnerable populations. The aim of this study was to show that the machine learning-based cancer cachexia classification model generalized well on the external validation cohort. METHODS: This was a nationwide multicenter observational study conducted from October 2012 to April 2021 in China. Unsupervised consensus clustering analysis was applied based on demographic, anthropometric, nutritional, oncological, and quality-of-life data. Key characteristics of each cluster were identified using the standardized mean difference. We used logistic and Cox regression analysis to evaluate 1-, 3-, 5-y, and overall mortality. RESULTS: A consensus clustering algorithm was performed for 4329 patients with cancer cachexia in the discovery cohort, and four clusters with distinct phenotypes were uncovered. From clusters 1 to 4, the clinical characteristics of patients showed a transition from almost unimpaired to mildly, moderately, and severely impaired. Consistently, an increase in mortality from clusters 1 to 4 was observed. The overall mortality rate was 32%, 40%, 54%, and 68%, and the median overall survival time was 21.9, 18, 16.7, and 13.6 mo for patients in clusters 1 to 4, respectively. Our machine learning-based model performed better in predicting mortality than the traditional model. External validation confirmed the above results. CONCLUSIONS: Machine learning is valuable for phenotype classifications of patients with cancer cachexia. Detection of clinically distinct clusters among cachexic patients assists in scheduling personalized treatment strategies and in patient selection for clinical trials.

Association of Adipokines with Alzheimer's Disease in a Chinese Cohort.

BACKGROUND: The correlation between plasma adipose factor levels and Alzheimer's patients is not entirely clear. OBJECTIVE: We aimed to investigate associations between AD and plasma levels of three adipokines including plasma adiponectin, leptin, and resistin. METHODS: A single-center, cross-sectional study recruited AD patients (n = 148) and cognitively normal (CN) controls (n = 110). The multivariate logistic regression analysis was applied to determine associations of adiponectin, leptin, and resistin with the presence of AD. The receiver operating characteristic (ROC) analysis was employed to determine the diagnostic power of adiponectin, leptin and resistin for AD. RESULTS: After adjusted for the conventional risk factors, plasma levels of leptin (OR = 0.417, 95% CI: 0.272-0.638, p < 0.0001) and adiponectin (OR = 1.249, 95% CI: 1.151-1.354, p < 0.0001) were associated with the presence of AD. In total participants, the plasma adiponectin level was negatively correlated with MMSE scores (p < 0.0001) and was positively with CDR scores (p < 0.0001) and age (p < 0.0001). The plasma level of leptin was negatively correlated with CDR scores (p < 0.0001) and positively correlated with MMSE scores (p < 0.0001). Both adiponectin (p < 0. 0001) and leptin (p < 0. 0001) featured higher AUC than the random chance. CONCLUSIONS: Plasma adiponectin and leptin were associated with the presence, symptomatic severity, and diagnostic power of AD, suggesting a potential role of adipokines in the pathogenesis of AD.

Effects of maize straw and its biochar application on soil organic carbon chemical composition and carbon degradation genes in a Moso bamboo forest.

We investigated the effects of maize straw and its biochar application on soil organic carbon chemical composition, the abundance of carbon degradation genes (cbhI) and the composition of cbhI gene community in a Moso bamboo forest, to provide the theoretical and scientific basis for enhancing carbon sequestration. We conducted a one-year field experiment in a subtropical Moso bamboo forest with three treatments: control (0 t C·hm-2), maize straw (5 t C·hm-2), and maize straw biochar (5 t C·hm-2). Soil samples were collected at the 3rd and 12th months after the treatment. Soil organic carbon chemical composition, the abundance and community composition of cbhI gene were determined by solid-state 13C NMR, real-time fluorescence quantitative PCR, and high-throughput sequencing, respectively. The results showed that compared with the control, maize straw treatment significantly increased the content of O-alkyl C and decreased aromatic C content, while maize straw biochar treatment showed an opposite effect. Maize straw treatment significantly increased the abundance of cbhI gene and the relative abundance of Penicillium, Gaeumannomyces and Marasmius. However, maize straw biochar treatment reduced the abundance of this gene. The relative abundance of dominant cbhI in soils was positively correlated with the content of O-alkyl C and negatively correlated with the content of aromatic C. Results of redundancy analysis showed that maize straw treatment had a significant effect on the microbial community composition of cbhI gene by changing soil O-alkyl C content, while maize straw biochar affected the microbial community composition of cbhI gene by changing soil pH, organic carbon, and aromatic C content. Maize straw biochar treatment was more effective in increasing soil organic carbon stability and reducing microbial activity associated with carbon degradation in the subtropical Moso bamboo forest ecosystem compared with maize straw treatment. Therefore, the application of biochar has positive significance for maintaining soil carbon storage in subtropical forest ecosystems.

Ultrasensitive Silicon Nanowire Biosensor with Modulated Threshold Voltages and Ultra-Small Diameter for Early Kidney Failure Biomarker Cystatin C.

Acute kidney injury (AKI) is a frequently occurring severe disease with high mortality. Cystatin C (Cys-C), as a biomarker of early kidney failure, can be used to detect and prevent acute renal injury. In this paper, a biosensor based on a silicon nanowire field-effect transistor (SiNW FET) was studied for the quantitative detection of Cys-C. Based on the spacer image transfer (SIT) processes and channel doping optimization for higher sensitivity, a wafer-scale, highly controllable SiNW FET was designed and fabricated with a 13.5 nm SiNW. In order to improve the specificity, Cys-C antibodies were modified on the oxide layer of the SiNW surface by oxygen plasma treatment and silanization. Furthermore, a polydimethylsiloxane (PDMS) microchannel was involved in improving the effectiveness and stability of detection. The experimental results show that the SiNW FET sensors realize the lower limit of detection (LOD) of 0.25 ag/mL and have a good linear correlation in the range of Cys-C concentration from 1 ag/mL to 10 pg/mL, exhibiting its great potential in the future real-time application.

Ultracompact single-nanowire-morphed grippers driven by vectorial Lorentz forces for dexterous robotic manipulations.

Ultracompact and soft pairwise grippers, capable of swift large-amplitude multi-dimensional maneuvering, are widely needed for high-precision manipulation, assembly and treatment of microscale objects. In this work, we demonstrate the simplest construction of such robotic structures, shaped via a single-nanowire-morphing and powered by geometry-tailored Lorentz vectorial forces. This has been accomplished via a designable folding growth of ultralong and ultrathin silicon NWs into single and nested omega-ring structures, which can then be suspended upon electrode frames and coated with silver metal layer to carry a passing current along geometry-tailored pathway. Within a magnetic field, the grippers can be driven by the Lorentz forces to demonstrate swift large-amplitude maneuvers of grasping, flapping and twisting of microscale objects, as well as high-frequency or even resonant vibrations to overcome sticky van de Waals forces in microscale for a reliable releasing of carried payloads. More sophisticated and functional teamwork of mutual alignment, precise passing and selective light-emitting-diode unit testing and installation were also successfully accomplished via pairwise gripper collaborations. This single-nanowire-morphing strategy provides an ideal platform to rapidly design, construct and prototype a wide range of advanced ultracompact nanorobotic, mechanical sensing and biological manipulation functionalities.

Lin28a maintains a subset of adult muscle stem cells in an embryonic-like state.

During homeostasis and after injury, adult muscle stem cells (MuSCs) activate to mediate muscle regeneration. However, much remains unclear regarding the heterogeneous capacity of MuSCs for self-renewal and regeneration. Here, we show that Lin28a is expressed in embryonic limb bud muscle progenitors, and that a rare reserve subset of Lin28a+Pax7- skeletal MuSCs can respond to injury at adult stage by replenishing the Pax7+ MuSC pool to drive muscle regeneration. Compared with adult Pax7+ MuSCs, Lin28a+ MuSCs displayed enhanced myogenic potency in vitro and in vivo upon transplantation. The epigenome of adult Lin28a+ MuSCs showed resemblance to embryonic muscle progenitors. In addition, RNA-sequencing revealed that Lin28a+ MuSCs co-expressed higher levels of certain embryonic limb bud transcription factors, telomerase components and the p53 inhibitor Mdm4, and lower levels of myogenic differentiation markers compared to adult Pax7+ MuSCs, resulting in enhanced self-renewal and stress-response signatures. Functionally, conditional ablation and induction of Lin28a+ MuSCs in adult mice revealed that these cells are necessary and sufficient for efficient muscle regeneration. Together, our findings connect the embryonic factor Lin28a to adult stem cell self-renewal and juvenile regeneration.

Adult progenitor rejuvenation with embryonic factors.

During ageing, adult stem cells' regenerative properties decline, as they undergo replicative senescence and lose both their proliferative and differentiation capacities. In contrast, embryonic and foetal progenitors typically possess heightened proliferative capacities and manifest a more robust regenerative response upon injury and transplantation, despite undergoing many rounds of mitosis. How embryonic and foetal progenitors delay senescence and maintain their proliferative and differentiation capacities after numerous rounds of mitosis, remains unknown. It is also unclear if defined embryonic factors can rejuvenate adult progenitors to confer extended proliferative and differentiation capacities, without reprogramming their lineage-specific fates or inducing oncogenic transformation. Here, we report that a minimal combination of LIN28A, TERT, and sh-p53 (LTS), all of which are tightly regulated and play important roles during embryonic development, can delay senescence in adult muscle progenitors. LTS muscle progenitors showed an extended proliferative capacity, maintained a normal karyotype, underwent myogenesis normally, and did not manifest tumorigenesis nor aberrations in lineage differentiation, even in late passages. LTS treatment promoted self-renewal and rescued the pro-senescence phenotype of aged cachexia patients' muscle progenitors, and promoted their engraftment for skeletal muscle regeneration in vivo. When we examined the mechanistic basis for LIN28A's role in the LTS minimum combo, let-7 microRNA suppression could not fully explain how LIN28A promoted muscle progenitor self-renewal. Instead, LIN28A was promoting the translation of oxidative phosphorylation mRNAs in adult muscle progenitors to optimize mitochondrial reactive oxygen species (mtROS) and mitohormetic signalling. Optimized mtROS induced a variety of mitohormetic stress responses, including the hypoxic response for metabolic damage, the unfolded protein response for protein damage, and the p53 response for DNA damage. Perturbation of mtROS levels specifically abrogated the LIN28A-driven hypoxic response in Hypoxia Inducible Factor-1α (HIF1α) and glycolysis, and thus LTS progenitor self-renewal, without affecting normal or TS progenitors. Our findings connect embryonically regulated factors to mitohormesis and progenitor rejuvenation, with implications for ageing-related muscle degeneration.

Lycium barbarum glycopeptide targets PER2 to inhibit lipogenesis in glioblastoma by downregulating SREBP1c.

Lycium barbarum polysaccharide (LBP) is a substance with various biological activities extracted from Lycium barbarum. LbGPs are peptidoglycans with a short peptide backbone and a complex, branched glycan moiety, which is further extracted and isolated from LBPs. Previous studies have shown that LbGP can inhibit cancer cell growth, but its specific mechanism is not completely clear. In this study, we found that LbGP could inhibit the proliferation of glioma cells and promote the expression of period 2 (PER2) through the PKA-CREB pathway. In addition, LbGP could inhibit the de novo synthesis of lipids by downregulating SREBP1c and its target genes, which depended on the expression of PER2. Moreover, PER2 negatively regulated the expression of SREBP1c via suppressing PI3K/AKT/mTOR pathway. In summary, LbGP may upregulate the expression of PER2 to reduce the expression of SREBP1c, inhibit lipid synthesis in glioblastoma, and inhibit glioblastoma cell proliferation. This study provides an alternative drug for the treatment of glioma and elucidates its potential mechanism.

A meta-analysis of the efficacy and toxicity of tyrosine kinase inhibitors in treating patients with different types of thyroid cancer: how to choose drugs appropriately?

PURPOSE OF REVIEW: Because the high risk of death and poor prognosis of patients with refractory thyroid cancer (TC), studies related to tyrosine kinase inhibitors (TKIs) in treating different types of refractory TC have gradually attracted attention. Thus, we conducted a meta-analysis of published randomized controlled trials and single-arm trials to evaluate tyrosine kinase inhibitors' efficacy and safety profile treatment in TC patients. RECENT FINDINGS: The studies of 29 in 287 met the criteria, 9 were randomized controlled trials and 20 were single-arm trials, involving 11 TKIs (Apatinib, Anlotinib, Cabozantinib, Imatinib, Lenvatinib, Motesanib, Pazopanib, Sorafenib, Sunitinib, Vandetanib, Vemurafenib). Treatment with TKIs significantly improved progression-free survival [hazard ratio [HR] 0.34 (95% confidence interval [CI]: 0.24, 0.48), P < 0.00001] and overall survival [OS] [HR 0.76, (95% CI: 0.64, 0.91), P = 0.003] in randomized controlled trials, but adverse events (AEs) were higher than those in the control group (P < 0.00001). The result of the objective response rate (ORR) in single-arm trials was statistically significant [odds ratio [OR] 0.49 (95% CI: 0.32, 0.75), P = 0.001]. SUMMARY: TKIs significantly prolonged progression-free survival and OS or improved ORR in patients with different types of TC (P < 0.01). Our recommendation is to select appropriate TKIs to treat different types of TC patients, and to prevent and manage drug-related AEs after using TKIs.

Expression and clinical significance of VISTA, B7-H3, and PD-L1 in glioma.

Immune checkpoint (IC) therapy has led to a breakthrough in cancer treatment. However, the interaction of ICs is controversial in glioma. We detected features of ICs using transcriptome data and a multicolor immunofluorescence assay. We discovered that B7-H3 increased with grade and age and predicted worse overall survival (OS) at the transcriptional and proteomic levels. VISTA and PD-L1 were associated with OS and grade at the RNA level. At the protein level, VISTA was primarily expressed in tumor cells and TAMs. B7-H3 and VISTA were positively correlated with PD-L1. There was a strong correlation between PD-L1 and CD3 and between VISTA and IBA-1. PD-L1 was coexpressed with T cells. VISTA was coexpressed with TAMs. In T cells, we found a strong correlation in ICs, which worsened in TAMs and tumor cells. In conclusion, B7-H3 is a vital prognostic target for immunotherapy. We provided a potential mechanism for the immunosuppressive microenvironment in glioma.

Acinar ATP8b1/LPC pathway promotes macrophage efferocytosis and clearance of inflammation during chronic pancreatitis development.

Noninflammatory clearance of dying cells by professional phagocytes, termed efferocytosis, is fundamental in both homeostasis and inflammatory fibrosis disease but has not been confirmed to occur in chronic pancreatitis (CP). Here, we investigated whether efferocytosis constitutes a novel regulatory target in CP and its mechanisms. PRSS1 transgenic (PRSS1Tg) mice were treated with caerulein to mimic CP development. Phospholipid metabolite profiling and epigenetic assays were performed with PRSS1Tg CP models. The potential functions of Atp8b1 in CP model were clarified using Atp8b1-overexpressing adeno-associated virus, immunofluorescence, enzyme-linked immunosorbent assay(ELISA), and lipid metabolomic approaches. ATAC-seq combined with RNA-seq was then used to identify transcription factors binding to the Atp8b1 promoter, and ChIP-qPCR and luciferase assays were used to confirm that the identified transcription factor bound to the Atp8b1 promoter, and to identify the specific binding site. Flow cytometry was performed to analyze the proportion of pancreatic macrophages. Decreased efferocytosis with aggravated inflammation was identified in CP. The lysophosphatidylcholine (LPC) pathway was the most obviously dysregulated phospholipid pathway, and LPC and Atp8b1 expression gradually decreased during CP development. H3K27me3 ChIP-seq showed that increased Atp8b1 promoter methylation led to transcriptional inhibition. Atp8b1 complementation substantially increased the LPC concentration and improved CP outcomes. Bhlha15 was identified as a transcription factor that binds to the Atp8b1 promoter and regulates phospholipid metabolism. Our study indicates that the acinar Atp8b1/LPC pathway acts as an important "find-me" signal for macrophages and plays a protective role in CP, with Atp8b1 transcription promoted by the acinar cell-specific transcription factor Bhlha15. Bhlha15, Atp8b1, and LPC could be clinically translated into valuable therapeutic targets to overcome the limitations of current CP therapies.

Efficacy and safety of multi-kinase inhibitors in patients with radioiodine-refractory differentiated thyroid cancer: a systematic review and meta-analysis of clinical trials.

OBJECTIVES: Radioiodine-refractory differentiated thyroid cancer (RAI-rDTC) has frequently been associated with poor prognosis. We conducted a meta-analysis of published randomized controlled trials to evaluate multi-kinase inhibitors' efficacy and safety profile treatment. METHODS: A comprehensive search was conducted using PubMed, Embase, Cochrane, and Medline databases. The quality of literature and trial risk of bias was assessed using the Cochrane risk of bias tool, while the results of progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated using RevMan5.3 software. RESULTS: Treatment with MKIs significantly improved PFS and OS, but AEs were significantly higher than those in the control group (P < 0.01). The studies demonstrated the median PFS (HR 0.30, 95% CI: 0.18-0.50, P < 0.00001) and OS (HR 0.70, 95% CI: 0.57-0.88, P = 0.002) in RAI-rDTC patients treated with MKIs, and the median PFS of papillary thyroid carcinoma (HR0.28, 95% CI: 0.22-0.37, P < 0.00001) along with follicular thyroid carcinoma (HR0.14, 95%CI 0.09-0.24, P < 0.00001) were extended. CONCLUSION: MKIs significantly prolonged PFS and OS in patients with RAI-rDTC (P < 0.01). Our recommendation is to use MKIs carefully in patients after evaluating their health status to maximize treatment benefits and minimize adverse effects.

Effects of Chemotherapy on Neuroinflammation, Neuronal Damage, Neurogenesis, and Behavioral Performance in Bone Marrow Transplantation Recipient Mice.

As bone marrow transplant (BMT) is gradually applied to the study of central nervous system (CNS) disease, it is needed to investigate the proper dose of chemotherapy to eradicate bone marrow cells while bringing little damage to brain. In the present study, we established a BMT model with varied busulfan and cyclophosphamide (Bu-Cy) dosages. The recipient mice's chimera rate, neuronal death, neuroinflammation, and behavioral functions were all investigated. Chimerism of peripheral blood cells was shown to rise with Bu-Cy treatment doses, with 60.7% in the Bu(20 mg/kg)/Cy(100 mg/kg) group and 93.0% in the Bu(35 mg/kg)/Cy(100 mg/kg) group. Recipients with Bu(35 mg/kg)/Cy(100 mg/kg) therapy had brain injury, increased neuroinflammation, diminished neurogenesis and cognitive abnormalities, whereas animals given a lesser dosage had no such brain damages. Conclusively, considering the chimerism and the possibility to damage brain, we recommend Bu(20 mg/kg)/Cy(100 mg/kg) is the ideal dose in BMT for studying CNS diseases in the C57/BL6 mouse strain.

Circulating Naturally Occurring Antibodies to P2RY2 Are Decreased in Alzheimer's Disease.

BACKGROUND: The G protein-coupled receptor P2RY2 protein of the purinergic receptor family is involved in the pathogenesis of Alzheimer's disease (AD). Naturally occurring antibodies against P2RY2 (NAbs-P2RY2) are present in human plasma, with their clinical relevance in AD unknown. OBJECTIVE: To explore the alteration of NAbs-P2RY2 in AD patients and its associations with biomarkers and cognition of AD patients. METHODS: The levels of naturally occurring antibodies against the four extracellular domains of P2RY2 (NAbs-P2RY2-1, NAbs-P2RY2-2, NAbs-P2RY2-3, and NAbs-P2RY2-4) were measured in the plasma of 55 AD patients, 28 non-AD dementia patients, and 70 cognitively normal participants. The correlations of autoantibody levels with cognitive scale scores, AD plasma biomarkers, and brain amyloid burden were examined. RESULTS: NAbs-P2RY2-1, NAbs-P2RY2-3, and NAbs-P2RY2-4 were reduced in AD patients. Plasma levels of NAbs-P2RY2-2 and NAbs-P2RY2-3 levels were positively associated with cognitive and functional performances. Among these antibodies, plasma NAbs-P2RY2-2 levels were positively associated with plasma amyloid-ß 42 levels. While plasma NAbs-P2RY2-3 levels were negatively associated with brain amyloid burden in AD patients. CONCLUSION: These findings indicate an alteration of humoral immunity against P2RY2 in AD patients. Further mechanistical investigations are needed to reveal the role of NAbs-P2RY2 in the pathogenesis of AD.

One-Year Trajectory of Cognitive Changes in Older Survivors of COVID-19 in Wuhan, China: A Longitudinal Cohort Study.

Importance: Determining the long-term impact of COVID-19 on cognition is important to inform immediate steps in COVID-19 research and health policy. Objective: To investigate the 1-year trajectory of cognitive changes in older COVID-19 survivors. Design, Setting, and Participants: This cohort study recruited 3233 COVID-19 survivors 60 years and older who were discharged from 3 COVID-19-designated hospitals in Wuhan, China, from February 10 to April 10, 2020. Their uninfected spouses (N = 466) were recruited as a control population. Participants with preinfection cognitive impairment, a concomitant neurological disorder, or a family history of dementia were excluded, as well as those with severe cardiac, hepatic, or kidney disease or any kind of tumor. Follow-up monitoring cognitive functioning and decline took place at 6 and 12 months. A total of 1438 COVID-19 survivors and 438 control individuals were included in the final follow-up. COVID-19 was categorized as severe or nonsevere following the American Thoracic Society guidelines. Main Outcomes and Measures: The main outcome was change in cognition 1 year after patient discharge. Cognitive changes during the first and second 6-month follow-up periods were assessed using the Informant Questionnaire on Cognitive Decline in the Elderly and the Telephone Interview of Cognitive Status-40, respectively. Based on the cognitive changes observed during the 2 periods, cognitive trajectories were classified into 4 categories: stable cognition, early-onset cognitive decline, late-onset cognitive decline, and progressive cognitive decline. Multinomial and conditional logistical regression models were used to identify factors associated with risk of cognitive decline. Results: Among the 3233 COVID-19 survivors and 1317 uninfected spouses screened, 1438 participants who were treated for COVID-19 (691 male [48.05%] and 747 female [51.95%]; median [IQR] age, 69 [66-74] years) and 438 uninfected control individuals (222 male [50.68%] and 216 female [49.32%]; median [IQR] age, 67 [66-74] years) completed the 12-month follow-up. The incidence of cognitive impairment in survivors 12 months after discharge was 12.45%. Individuals with severe cases had lower Telephone Interview of Cognitive Status-40 scores than those with nonsevere cases and control individuals at 12 months (median [IQR]: severe, 22.50 [16.00-28.00]; nonsevere, 30.00 [26.00-33.00]; control, 31.00 [26.00-33.00]). Severe COVID-19 was associated with a higher risk of early-onset cognitive decline (odds ratio [OR], 4.87; 95% CI, 3.30-7.20), late-onset cognitive decline (OR, 7.58; 95% CI, 3.58-16.03), and progressive cognitive decline (OR, 19.00; 95% CI, 9.14-39.51), while nonsevere COVID-19 was associated with a higher risk of early-onset cognitive decline (OR, 1.71; 95% CI, 1.30-2.27) when adjusting for age, sex, education level, body mass index, and comorbidities. Conclusions and Relevance: In this cohort study, COVID-19 survival was associated with an increase in risk of longitudinal cognitive decline, highlighting the importance of immediate measures to deal with this challenge.