Long-term follow-up of brain regional changes and the association with cognitive impairment in quarantined COVID-19 survivors.

OBJECTIVE: This study aimed to evaluate the neuropsychiatric symptoms of quarantined COVID-19 survivors 15 months after discharge and explore its potential association with structural and functional brain changes and inflammation. METHODS: A total of 51 quarantined COVID-19 survivors and 74 healthy controls were included in this study. Cognitive function was assessed using the THINC-integrated tool. Structural brain changes were examined through both surface- and volume-based analyses, and functional changes were assessed using resting-state amplitude low-frequency fluctuation (ALFF). Serum inflammatory markers were measured by a multiplexed flow cytometric assay. RESULTS: COVID-19 survivors exhibited subjective cognitive decline compared to healthy controls, despite no significant differences in objective cognitive tasks. Structural analysis revealed significantly increased gray matter volume and cortical surface area in the left transverse temporal gyrus (Heschl's gyrus) in quarantined COVID-19 survivors. This enlargement was negatively correlated with cognitive impairment. The ALFF analysis showed decreased neural activity in multiple brain regions. Elevated levels of serum inflammatory markers were also found in COVID-19 survivors, including MIP-1a, MIP-1b, TNF-a, and IL-8, which correlated with functional abnormalities. CONCLUSIONS: Our findings indicate a subjective cognitive decline in quarantined COVID-19 survivors 15 months after discharge, which is associated with brain structural alterations in the left Heschl's gyrus. The observed elevation of inflammatory markers suggests a potential mechanism involving inflammation-induced neurogenesis. These results contribute to our understanding of the possible mechanisms underlying long-term neuropsychiatric consequences of COVID-19 and highlight the need for further research to develop targeted interventions.

Common and distinct patterns of task-related neural activation abnormalities in patients with remitted and current major depressive disorder: A systematic review and coordinate-based meta-analysis.

Whether remitted major depressive disorder (rMDD) and MDD present common or distinct neuropathological mechanisms remains unclear. We performed a meta-analysis of task-related whole-brain functional magnetic resonance imaging (fMRI) using anisotropic effect-size signed differential mapping software to compare brain activation between rMDD/MDD patients and healthy controls (HCs). We included 18 rMDD studies (458 patients and 476 HCs) and 120 MDD studies (3746 patients and 3863 HCs). The results showed that MDD and rMDD patients shared increased neural activation in the right temporal pole and right superior temporal gyrus. Several brain regions, including the right middle temporal gyrus, left inferior parietal, prefrontal cortex, left superior frontal gyrus and striatum, differed significantly between MDD and rMDD. Meta-regression analyses revealed that the percentage of females with MDD was positively associated with brain activity in the right lenticular nucleus/putamen. Our results provide valuable insights into the underlying neuropathology of brain dysfunction in MDD, developing more targeted and efficacious treatment and intervention strategies, and more importantly, providing potential neuroimaging targets for the early screening of MDD.

Long term neuropsychiatric consequences in COVID-19 survivors: Cognitive impairment and inflammatory underpinnings fifteen months after discharge.

BACKGROUND: Emerging evidence shows that cognitive dysfunction may occur following coronavirus disease 19 (COVID-19) infection which is one of the most common symptoms reported in researches of "Long COVID". Several inflammatory markers are known to be elevated in COVID-19 survivors and the relationship between long-term inflammation changes and cognitive function remains unknown. METHODS: We assessed cognitive function and neuropsychiatric symptoms of 66 COVID-19 survivors and 79 healthy controls (HCs) matched with sex, age, and education level using a digital, gamified cognitive function evaluation tool and questionnaires at 15 months after discharge. Venous blood samples were collected to measure cytokine levels. We performed correlation analyses and multiple linear regression analysis to identify the factors potentially related to cognitive function. RESULTS: The COVID-19 survivors performed less well on the Trails (p = 0.047) than the HCs, but most of them did not report subjective neuropsychiatric symptoms. Intensive care unit experience (ß = -2.247, p < 0.0001) and self-perceived disease severity (ß = -1.522, p = 0.007) were positively correlated, whereas years of education (ß = 0.098, p = 0.013) was negatively associated with the performance on the Trails. Moreover, the abnormally elevated TNF-α levels (r = -0.19, p = 0.040) were negatively correlated with performance on the Trails in COVID-19 group. CONCLUSION: Our findings suggest that COVID-19 survivors show long-term cognitive impairment in executive function, even at 15 months after discharge. Serum TNF-α levels may be an underlying mechanism of long-term cognitive impairment in patients recovering from COVID-19.

Social anxiety disorder in an adolescent with agenesis of the corpus callosum: a case report.

BACKGROUND: The agenesis of corpus callosum (ACC) could impair the connectivity of the hemispheres of the cerebral cortex and cause cognitive impairments, social and behavioral issues, and even psychiatric disorders. Although social deficits are common in ACC patients, it is rare for a social anxiety disorder to occur. CASE PRESENTATION: To report a 17-year-old adolescent with complete ACC associated with social anxiety disorder, depression, impulsive behavior, and other neurodevelopmental defects such as intellectual disabilities. His avoidance and fear were improved after treatment with sertraline. CONCLUSIONS: This is the first report of social anxiety disorder in ACC patients. The possible relationship between brain structural abnormities and anxiety syndrome should be investigated in more studies.

Brachial-ankle pulse wave velocity as a measurement for increased carotid intima-media thickness: A comparison with carotid-femoral pulse wave velocity in a Chinese community-based cohort.

Carotid-femoral pulse wave velocity (cfPWV) and brachial-ankle pulse wave velocity (baPWV) act as two most frequently applied indicators to evaluate arterial stiffness. Limited studies have systematically compared the relationships between cfPWV/baPWV and increased carotid intima-media thickness (cIMT). This study aimed to investigate the associations of the two PWV indices with cIMT in a Chinese community-based population. A total of 6026 Chinese participants from an atherosclerosis cohort were included in our analysis. Increased cIMT was defined as the maximum of cIMT > 0.9 mm in end-systolic period of carotid artery. Mean (SD) cfPWV and baPWV were 8.55±1.83  and 16.79±3.35 m/s, respectively. The prevalence of increased cIMT was 59.58%. In multivariable logistic regression, both PWVs were independently associated with increased cIMT after adjustment for various confounders (for 1 m/s increase of cfPWV: OR = 1.07, 95% CI: 1.02-1.11; for 1 m/s increase of baPWV: OR = 1.03, 95% CI: 1.00-1.05). The highest cfPWV and baPWV quartile groups had higher prevalence of increased cIMT when compared with the lowest quartile groups (for cfPWV: OR = 1.28, 95% CI: 1.06-1.55; for baPWV: OR = 1.23, 95% CI: 1.00-1.50). However, when both PWVs were added into multivariable model simultaneously, only cfPWV was associated with odds of increased cIMT. Subgroup analyses further showed cfPWV was more strongly associated with increased cIMT than baPWV in males, participants aged ≥65 years, and those with other cardiovascular risk factors. In conclusion, both cfPWV and baPWV are associated with increased cIMT in a Chinese community-based population. Furthermore, cfPWV is more strongly correlated with increased cIMT compared to baPWV.

Association of depressive symptoms with the progression of carotid intima-media thickness in a community-based cohort in Beijing, China.

OBJECTIVES: To determine the relationship between depressive symptoms and progression of carotid intima-media thickness (cIMT) in a Beijing community-based population. DESIGN: Prospective cohort study between 2014 and 2018. SETTING: Dwellers without cardiovascular disease, hypertension or diabetes from a Beijing community. PARTICIPANTS: 3849 Chinese community-dwelling individuals who underwent baseline screening for depressive symptoms were invited to participate in the study in 2014 and follow-up visit in 2018. Among them, 2124 participants completed carotid ultrasound examination both at baseline and a follow-up visit. After further excluding patients with a history of stroke, myocardial infarction or lower extremity arterial stenosis and those with a diagnosis of hypertension or diabetes and ankle-brachial index ≤0.9 at baseline, 1011 eligible participants were finally included. PRIMARY OUTCOME MEASURE: The rate of mean cIMT change. RESULTS: Over a median follow-up period of 4.40 years, the overall rate of mean cIMT change was 2.23% (-5.64% to 9.51%). After adjustment for 13 covariates, there was an increase of 2.36% (ß=2.36, 95% CI: 0.37 to 4.36, p=0.020) for the rates of mean cIMT change in the depressive group compared with the control group. Furthermore, this association was modified by drinking status (ß=3.22, 95% CI: 1.25 to 5.19, P-interaction=0.006). CONCLUSION: Depressive symptoms were independently associated with progression of mean cIMT in a community-based cohort in Beijing, China. Furthermore, this relationship was modified by drinking status.

Heart Rate Predicts the Risk of New-Onset Peripheral Arterial Disease in a Community-Based Population in China.

INTRODUCTION: Elevated heart rate is linked with poor prognosis and has been shown to accelerate the progress of atherosclerosis. However, the association between heart rate and new-onset PAD is unknown. METHODS: A total of 3463 participants without PAD at baseline from a community-based cohort in Beijing were included and followed up for 2.3 years. PAD was defined as ankle-brachial index (ABI) ≤0.9. We used multivariate logistic regression models to investigate the association of heart rate and the risk of new-onset PAD. RESULTS: Participants were 56.67 ± 8.54 years old, and 36.12% were men. The baseline ABI was 1.11 ± 0.08, and the incidence of new-onset PAD was 2.97%. Multivariate regression models, adjusted for sex, age, risk factor of atherosclerosis, medications, and baseline ABI, showed that heart rate was significantly associated with incidence of PAD (odds ratio [OR] = 1.22, 95% confidence interval [CI]: 1.03-1.43, P = 0.020); every increase of 10 heart beats per minute (bpm) was associated with a 22% increase in the odds of developing new-onset PAD. Respondents in the higher-heart rate group (≥80 bpm) had an increased risk of new-onset PAD, compared with those in the lower-heart rate group (<80 bpm) (OR = 1.73, 95% CI: 1.14-2.63, P = 0.010). Subgroup analyses revealed no significant heterogeneity among the analyzed subgroups. CONCLUSION: Elevated heart rate was independently associated with the risk of new-onset PAD in a community-based population in Beijing. Heart rate management should be considered for the purpose of PAD prevention.

Sex modification of the association of the radial augmentation index and incident hypertension in a Chinese community-based population.

BACKGROUND: Arterial stiffness, as assessed by aortic ultrasound and pulse wave velocity, is associated with incident hypertension. However, there is still no consensus on whether the augmentation index (AI) affects new onset of hypertension. This study investigated the relationship of radial AI (rAI) and incident hypertension in a Chinese community-based population without hypertension at baseline. METHOD: A total of 1,615 Chinese non-hypertensive participants from an atherosclerosis cohort in Beijing, China were included in our analysis. Baseline rAI normalized to heart rate of 75 beats/min (rAIp75) was obtained using HEM-9000AI. New-onset hypertension was defined as blood pressure ≥ 140/90 mmHg or self-reported hypertension or taking anti-hypertensive medications at the follow up survey. Multivariate regression models were used to evaluate the impact of rAIp75 on the risk of new-onset hypertension. RESULTS: After a mean 2.35-year follow-up, 213 (13.19%) participants developed incident hypertension. No significant relation between rAIp75 and incident hypertension was observed in the whole population after adjustment for possible confounders (adjusted odds ratio (OR) and 95% confidence interval (CI): 1.09 [0.95-1.27];P = 0.2260). However, rAIp75 was significantly associated with incident hypertension in women, but not in men (adjusted OR and 95% CI: 1.29 [1.06-1.56],P = 0.0113 for women; 0.91 [0.72-1.15],P = 0.4244 for men; P for interaction = 0.0133). CONCLUSIONS: Sex modified the effect of the rAI on incident hypertension in a Chinese, community-based, non-hypertensive population. Screening of the rAI could be considered in women with a high risk of hypertension for the purpose of primary intervention.

Lipid profiles and the risk of new-onset hypertension in a Chinese community-based cohort.

BACKGROUND AND AIMS: Dyslipidemia and hypertension, key risk factors for cardiovascular disease, may share similar pathophysiological processes. A longitudinal association was reported between dyslipidemia and new-onset hypertension, but few data were published in Asian. We aimed to investigate the association of lipid profiles with new-onset hypertension in a Chinese community-based non-hypertensive cohort without lipid-lowering treatment (n = 1802). METHODS AND RESULTS: New-onset hypertension was defined as any self-reported history of hypertension, systolic blood pressure ≥140 mmHg, or diastolic blood pressure ≥90 mmHg, or receiving antihypertensive medications at follow-up. Logistic regression models were used to evaluate the associations. Participants were aged 53.97 ± 7.49 years, 31.19% were men, and 64.54% with dyslipidemia. During a median of 2.30 years follow-up, the incidence of new-onset hypertension was 12.99%. Multivariate adjusted risks of new-onset hypertension increased with triglyceride increases (odds ratio [OR] = 1.14, 95% confidence interval [CI]: 1.03-1.27) and high-density lipoprotein cholesterol (HDL-C) decreases (OR = 0.47, 95% CI: 0.29-0.76) for one unit. However, threshold effects were observed for total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and non-HDL-C. Compared with subjects with hyperlipidemia, in those with normal concentrations of TC, LDL-C, and non-HDL-C increased risks of new-onset hypertension were observed with OR (95% CI) of 1.65 (1.10-2.46), 1.58 (1.07-2.33), and 1.57 (1.15-2.15) for one unit increasement, respectively, after adjusting for all covariates. CONCLUSION: Higher TG and lower HDL-C increased the risk of new-onset hypertension, but for TC, LDL-C and non-HDLC, the risk of new-onset hypertension was increased only at normal concentrations in a Chinese community-based cohort.

Joint Effects of Plasma Homocysteine Concentration and Traditional Cardiovascular Risk Factors on the Risk of New-Onset Peripheral Arterial Disease.

PURPOSE: Hyperhomocysteinemia is an independent risk factor for cardio- and cerebrovascular diseases. However, the relationship between plasma homocysteine (Hcy) concentration and peripheral arterial disease (PAD) has not been completely characterized. The aim of the present study was to determine the relationship between plasma Hcy concentration and new-onset PAD and to assess the effects of combinations of Hcy and traditional cardiovascular risk factors. PATIENTS AND METHODS: We conducted a prospective community-based cohort study of 3119 Chinese participants who did not have PAD at baseline, with a median follow-up period of 2.30 years. We used multivariate logistic regression models to evaluate the relationship between high Hcy (≥10µmol/L) and new-onset PAD. The effects of combinations of high Hcy and traditional cardiovascular risk factors were assessed using logistic regression analysis. RESULTS: After adjustment for 14 covariates, high Hcy concentration was significantly associated with new-onset PAD (odds ratio [OR]=2.08, 95% confidence interval [CI]: 1.08-4.03, P=0.030). Smokers with high Hcy concentration were substantially more likely to have new-onset PAD than non-smokers with normal Hcy concentration (OR=4.44, 95% CI: 1.77-11.12, P=0.001). The effect of diabetes on PAD became significant when present in combination with high Hcy concentration (OR=3.67, 95% CI: 1.25-10.80, P=0.018). Participants with both elevated Hcy levels and older age had the highest risk of new-onset PAD (OR=4.28, 95% CI: 1.83-10.01, P<0.001). With regard to the joint effect of Hcy and hypertension, dyslipidemia or sex, there was also a trend towards increased risk across four different groups (P for trend=0.026, 0.035, 0.016, respectively). CONCLUSION: High plasma Hcy concentration independently predicts the incidence of PAD. Furthermore, there is a joint effect of high Hcy concentration and traditional cardiovascular risk factors such as smoking, diabetes and aging on the incidence of PAD.

Brachial-ankle pulse wave velocity is independently associated with urine albumin-to-creatinine ratio in a Chinese community-based cohort.

PURPOSE: Arterial stiffness is important in the development of albuminuria. The brachial-ankle pulse wave velocity (baPWV) acts as an indicator of arterial stiffness and may be associated with cardiovascular disease morbidity and mortality. The urine albumin-to-creatinine ratio (UACR) is a metric used to diagnose albuminuria and has also been shown to be associated with cardiovascular disease. Here, we aim to elucidate the relationship between the baPWV and UACR in the Chinese community. METHODS: A community-based cohort of 3669 subjects was selected for the analysis. The BaPWV and UACR were measured from each subject. UACR ≥ 30 mg/g was defined as pathological albuminuria. RESULTS: The mean baPWV was 1536.59 ± 305.89 cm/s, and the median UACR value was 6.11 mg/g (interquartile range 4.17, 10.68). A threshold-effect analysis was conducted, and the results showed that the cut-off value for the baPWV was 1269 cm/s. In subjects with baPWV values lower than 1269 cm/s, the prevalence of microalbuminuria and macroalbuminuria was not significantly associated with the baPWV (odds ratio 0.77, 95% confidence interval 0.57-1.03, P = 0.08). However, in participants with baPWV ≥ 1269 cm/s, the prevalence of microalbuminuria and macroalbuminuria increased with increasing baPWV 100 cm/s (odds ratio 1.16, 95% confidence interval 1.11-1.22, P < 0.001). CONCLUSIONS: These findings suggest that, in this Chinese community-based cohort, elevated baPWV is independently associated with pathological albuminuria with a cut-off value of 1269 cm/s as determined by threshold-effect analysis.

Metabolic Syndrome Is Associated With Rapid Estimated Glomerular Filtration Rate Decline In A Chinese Community-Based Population.

PURPOSE: This study aimed to determine the relationship between the metabolic syndrome (MetS) and rapid estimated glomerular filtration rate (eGFR) decline in a Chinese community-based population. PATIENTS AND METHODS: A total of 3108 participants were recruited between December 2011 and July 2014 from an observational study cohort designed for the study of atherosclerotic diseases in Beijing, China. The outcome was a rapid eGFR decline. Subgroup and interaction analyses were performed with respect to a number of covariates. RESULTS: Over a median follow-up period of 2.34 (IQR: 2.29-2.41) years, the overall incidence of rapid eGFR decline was 7.24%. We found that the MetS was significantly associated with the risk of rapid eGFR decline (odds ratio [OR]=1.69, 95% confidence interval [CI]: 1.28-2.23, p<0.001) in a model adjusted for age, sex, and eGFR, and this relationship remained significant after adjustment for smoking, drinking, and low-density lipoprotein-cholesterol (OR=1.78, 95% CI: 1.34-2.35, p<0.001). Waist circumference (OR=1.38, 95% CI: 1.04-1.83, p=0.027), triglycerides (OR=1.40, 95% CI: 1.05-1.86, p=0.022), blood pressure (OR=2.05, 95% CI: 1.49-2.82, p<0.001), and fasting plasma glucose (OR=2.12, 95% CI: 1.57-2.85, p<0.001), but not high-density lipoprotein-cholesterol (OR=1.26, 95% CI: 0.94-1.69, p=0.117), were positively associated with the risk of rapid eGFR decline. Similarly, an increase in the number of MetS components present was associated with an increase in the risk of rapid eGFR decline. Furthermore, this association was modified by smoking status (OR=3.78, 95% CI: 1.68-8.49, p-interaction=0.030). CONCLUSION: The MetS independently predicted rapid eGFR decline in a Chinese community-based cohort recruited for the study of atherosclerosis. The relationship between the MetS and the risk of rapid eGFR decline was modified by smoking status.