The effect of childhood trauma, ApoE genotype and HIV-1 viral protein R variants on change in cognitive performance

Abstract Objective Gene–environment interactions contribute to the development of HIV-associated neurocognitive disorders. We examined whether childhood trauma, apolipoprotein E isoforms and viral protein R (Vpr) variants were associated with change in cognitive performance. Seventy-three seropositive women completed neuropsychological assessments at baseline and 1-year follow-up. We conducted genetic analyses using DNA obtained from blood and calculated risk scores based on Vpr amino acid 37, 41 and 55 variants that were previously associated with cognitive performance. Results Global cognitive scores declined significantly over the 1-year study period (p = 0.029). A reduction in global cognitive scores was associated with childhood trauma experience (p = 0.039).

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Effect of polygenic risk scores on depression in childhood trauma

The British Journal of Psychiatry ◽

10.1192/bjp.bp.113.143081 ◽

2014 ◽

Vol 205 (2) ◽

pp. 113-119 ◽

Cited By ~ 105

Author(s):

Wouter J. Peyrot ◽

Yuri Milaneschi ◽

Abdel Abdellaoui ◽

Patrick F. Sullivan ◽

Jouke J. Hottenga ◽

...

Keyword(s):

Childhood Trauma ◽

Meta Analysis ◽

Genetic Effect ◽

Risk Scores ◽

Environment Interaction ◽

Polygenic Risk ◽

Gene Environment Interaction ◽

Gene Environment ◽

Genome Wide ◽

Direct Genetic Effect

BackgroundResearch on gene×environment interaction in major depressive disorder (MDD) has thus far primarily focused on candidate genes, although genetic effects are known to be polygenic.AimsTo test whether the effect of polygenic risk scores on MDD is moderated by childhood trauma.MethodThe study sample consisted of 1645 participants with a DSM-IV diagnosis of MDD and 340 screened controls from The Netherlands. Chronic or remitted episodes (severe MDD) were present in 956 participants. The occurrence of childhood trauma was assessed with the Childhood Trauma Interview and the polygenic risk scores were based on genome-wide meta-analysis results from the Psychiatric Genomics Consortium.ResultsThe polygenic risk scores and childhood trauma independently affected MDD risk, and evidence was found for interaction as departure from both multiplicativity and additivity, indicating that the effect of polygenic risk scores on depression is increased in the presence of childhood trauma. The interaction effects were similar in predicting all MDD risk and severe MDD risk, and explained a proportion of variation in MDD risk comparable to the polygenic risk scores themselves.ConclusionsThe interaction effect found between polygenic risk scores and childhood trauma implies that (1) studies on direct genetic effect on MDD gain power by focusing on individuals exposed to childhood trauma, and that (2) individuals with both high polygenic risk scores and exposure to childhood trauma are particularly at risk for developing MDD.

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Linking Neuroinflammation and Extracellular Free Water in HIV Infection: A Longitudinal Study

10.21203/rs.3.rs-121836/v1 ◽

2020 ◽

Author(s):

Md Nasir Uddin ◽

Abrar Faiyaz ◽

Lu Wang ◽

Yuchuan Zhuang ◽

Kyle D Murray ◽

...

Keyword(s):

White Matter ◽

Hiv Infection ◽

Cognitive Performance ◽

Brain Mri ◽

Free Water ◽

Neurofilament Light Chain ◽

Neurofilament Light ◽

Linear Mixed Effects ◽

Neuropsychological Assessments

Abstract Background Initiation of combination antiretroviral therapy (cART) reduces inflammation in HIV-infected (HIV+) individuals. Recent studies demonstrated that diffusion MRI based extracellular free water (FW) modeling can be sensitive to neuroinflammation. However, no studies to date have investigated the FW in HIV infection, its temporal evolution, nor its association with brain-derived blood markers. Methods Ninety-six age-matched participants underwent brain MRI and clinical and neuropsychological assessments at baseline. HIV- participants underwent follow-up evaluation annually for two years while HIV + participants were seen 12 weeks after initiating cART and annually thereafter. Whole brain grey and white matter FW measures were compared between groups and correlated with clinical characteristics and cognitive scores. In addition, several pre-specified subcortical grey and white matter regions-of-interest (ROIs) were explored. Results At baseline, FW was significantly elevated in grey and white matter in cART-naïve HIV + participants compared to HIV- participants. Similarly, at baseline, HIV + participants had increased neurofilament light chain (NfL) values that correlated with FW and CD4 count, and decreased cognitive performance compared to HIV- participants. FW decreased in grey and white matter in HIV + participants after 12 weeks of cART treatment. 12-week cART treatment was also associated with a decrease in NfL and improvement in cognitive performance. Linear mixed effects regression models also revealed that FW was significantly reduced in most ROIs after 12 weeks of cART treatment. No significant FW differences were noted between the HIV + and HIV- participants at 1 and 2-year follow-up. Conclusions FW elevation in cART-naïve HIV + participants is likely due to neuroinflammation. The correlation between FW and NfL and the improvement in both FW and NfL after 12 weeks of cART treatment further reinforces this conclusion. The longer follow-up at 1 and 2 years suggests that cART helped control neuroinflammation as inferred by FW. Therefore, FW could be used as a biomarker to monitor HIV-associated neuroinflammation.

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Delirium in older patients undergoing aortic valve replacement Incidence, predictors, and cognitive prognosis

10.21203/rs.3.rs-48406/v1 ◽

2020 ◽

Author(s):

Marc Humbert ◽

Christophe J Büla ◽

Olivier Müller ◽

Hélène Krief ◽

Pierre Monney

Keyword(s):

Aortic Valve ◽

Aortic Valve Replacement ◽

Cognitive Performance ◽

Valve Replacement ◽

Older Patients ◽

Mmse Score ◽

Academic Medical Center ◽

Cognitive Status ◽

Risk Scores

Abstract Background: To determine delirium incidence, predictors, and relationship with cognitive performance at 3-month follow-up in older patients undergoing aortic valve replacement (AVR).Methods: Patients (N=93) aged 70 years and older, undergoing transcatheter (TAVR, N=66) or surgical (SAVR, N=27) aortic valve replacement in an academic medical center were enrolled in this prospective cohort study. Delirium was assessed using the Confusion Assessment Method (CAM) on postoperative days 1, 2, 3, and 7. Data on patients’ socio-demographics, functional status (including instrumental activities of daily living (IADL), and surgical risk scores (including Society of Thoracic Surgeons (STS) risk score), were collected at baseline. Cognitive status was assessed with the Mini-Mental Status Exam (MMSE) and the Clock Drawing Test (CDT) at baseline and 3 months after AVR.Results: Delirium occurred in 21 (22.6%) patients, within the first three postoperative days in 95% (20/21) of the cases. Delirium incidence was lower in TAVR (13/66=20%) than SAVR (8/27=30%) patients, but this difference was not statistically significant (p=.298). Patients with delirium had lower baseline cognitive performance (median MMSE score 27.0±3.0 vs 28.0±3.0, p=.029), lower performance in IADL (7.0 vs 8.0, p=.038), and higher STS risk scores (4.7±2.7 vs 2.9±2.3, p=.020). In multivariate analyses, patients with intermediate (score>3 to ≤8) and high (score>8) STS scores had 4.3 (95%CI 1.2-15.1, p=.025) and 16.5 (95%CI 2.0-138.2, p=.010), respectively, higher odds of incident delirium compared to patients with low (score≤3) STS scores. At 3-month follow-up (N=77), patients with delirium still had lower MMSE score (27.0±8.0 vs 28.0±2.0, p=.007) but this difference did not remain significant once adjusting for baseline MMSE (β-coefficient 1.11, 95%CI [-3.03-0.80], p=.248).Conclusions: Delirium occurred in about one in five older patients undergoing AVR, almost essentially within the first three postoperative days. Beside cognitive performance, STS score could enhance the identification of high-risk older patients to better target preventative interventions.

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Delirium in older patients undergoing aortic valve replacement: Incidence, predictors, and cognitive prognosis.

10.21203/rs.3.rs-48406/v2 ◽

2020 ◽

Author(s):

Marc Humbert ◽

Christophe J Büla ◽

Olivier Müller ◽

Hélène Krief ◽

Pierre Monney

Keyword(s):

Aortic Valve ◽

Aortic Valve Replacement ◽

Cognitive Performance ◽

Valve Replacement ◽

Risk Score ◽

Older Patients ◽

Mmse Score ◽

Cognitive Status ◽

Risk Scores

Abstract Objectives: To determine delirium incidence, predictors, and relationship with cognitive performance at 3-month follow-up in older patients undergoing aortic valve replacement (AVR).Methods: Patients (N=93) aged 70 years and older, undergoing transcatheter (TAVR, N=66) or surgical (SAVR, N=27) aortic valve replacement in an academic medical center were enrolled in this prospective cohort study. Delirium was assessed using the Confusion Assessment Method (CAM) on postoperative days 1, 2, 3, and 7. Data on patients’ socio-demographics, functional status (including instrumental activities of daily living (IADL), and surgical risk scores (including Society of Thoracic Surgeons (STS) risk score), were collected at baseline. Cognitive status was assessed with the Mini-Mental Status Exam (MMSE) and the Clock Drawing Test (CDT) at baseline and 3 months after AVR.Results: Delirium occurred in 21 (22.6%) patients, within the first three postoperative days in 95% (20/21) of the cases. Delirium incidence was lower in TAVR (13/66=20%) than SAVR (8/27=30%) patients, but this difference was not statistically significant (p=.298). Patients with delirium had lower baseline cognitive performance (median MMSE score 27.0±3.0 vs 28.0±3.0, p=.029), lower performance in IADL (7.0 vs 8.0, p=.038), and higher STS risk scores (4.7±2.7 vs 2.9±2.3, p=.020). In multivariate analyses, patients with intermediate (score>3 to ≤8) and high (score>8) STS risk scores had 4.3 (95%CI 1.2-15.1, p=.025) and 16.5 (95%CI 2.0-138.2, p=.010), respectively, higher odds of incident delirium compared to patients with low (score≤3) STS risk scores. At 3-month follow-up (N=77), patients with delirium still had lower MMSE score (27.0±8.0 vs 28.0±2.0, p=.007) but this difference did not remain significant once adjusting for baseline MMSE (β-coefficient 1.11, 95%CI [-3.03-0.80], p=.248).Conclusions: Delirium occurred in about one in five older patients undergoing AVR, almost essentially within the first three postoperative days. Beside cognitive performance, STS risk score could enhance the identification of high-risk older patients to better target preventative interventions.

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Delirium in older patients undergoing aortic valve replacement: incidence, predictors, and cognitive prognosis

BMC Geriatrics ◽

10.1186/s12877-021-02100-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Marc Humbert ◽

Christophe J. Büla ◽

Olivier Muller ◽

Hélène Krief ◽

Pierre Monney

Keyword(s):

Aortic Valve ◽

Aortic Valve Replacement ◽

Cognitive Performance ◽

Valve Replacement ◽

Risk Score ◽

Older Patients ◽

Mmse Score ◽

Cognitive Status ◽

Risk Scores

Abstract Background Transcatheter aortic valve replacement is increasingly performed in frail older patients who were previously ineligible for a standard surgical procedure. The objectives of this study are to determine delirium incidence, predictors, and relationship with cognitive performance at 3-month follow-up in older patients undergoing aortic valve replacement (AVR). Methods Patients (N = 93) aged 70 years and older, undergoing transcatheter (TAVR, N = 66) or surgical (SAVR, N = 27) aortic valve replacement in an academic medical center were enrolled in this prospective cohort study. Delirium was assessed using the Confusion Assessment Method (CAM) on postoperative days 1, 2, 3, and 7. Data on patients’ socio-demographics, functional status (including instrumental activities of daily living (IADL), and surgical risk scores (including Society of Thoracic Surgeons (STS) risk score), were collected at baseline. Cognitive status was assessed with the Mini-Mental Status Exam (MMSE) and the Clock Drawing Test (CDT) at baseline and 3 months after AVR. Results Delirium occurred in 21 (23%) patients, within the first three postoperative days in 95% (20/21) of the cases. Delirium incidence was lower in TAVR (13/66 = 20%) than SAVR (8/27 = 30%) patients, but this difference was not statistically significant (p = .298). Patients with delirium had lower baseline cognitive performance (median MMSE score 27.0 ± 3.0 vs 28.0 ± 3.0, p = .029), lower performance in IADL (7.0 vs 8.0, p = .038), and higher STS risk scores (4.7 ± 2.7 vs 2.9 ± 2.3, p = .020). In multivariate analyses, patients with intermediate (score > 3 to ≤8) and high (score > 8) STS risk scores had 4.3 (95%CI 1.2–15.1, p = .025) and 16.5 (95%CI 2.0–138.2, p = .010), respectively, higher odds of incident delirium compared to patients with low (score ≤ 3) STS risk scores. At 3-month follow-up (N = 77), patients with delirium still had lower MMSE score (27.0 ± 8.0 vs 28.0 ± 2.0, p = .007) but this difference did not remain significant once adjusting for baseline MMSE (β-coefficient 1.11, 95%CI [− 3.03–0.80], p = .248). Conclusions Delirium occurred in about one in five older patients undergoing AVR, almost essentially within the first three postoperative days. Beside cognitive performance, STS risk score could enhance the identification of high-risk older patients to better target preventative interventions.

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Delirium in older patients undergoing aortic valve replacement Incidence, predictors, and cognitive prognosis.

10.21203/rs.3.rs-48406/v3 ◽

2020 ◽

Author(s):

Marc Humbert ◽

Christophe J Büla ◽

Olivier Müller ◽

Hélène Krief ◽

Pierre Monney

Keyword(s):

Aortic Valve ◽

Aortic Valve Replacement ◽

Cognitive Performance ◽

Valve Replacement ◽

Risk Score ◽

Older Patients ◽

Mmse Score ◽

Cognitive Status ◽

Risk Scores

Abstract Background: Transcatheter aortic valve replacement is increasingly performed in frail older patients who were previously ineligible for a standard surgical procedure. The objectives of this study are to determine delirium incidence, predictors, and relationship with cognitive performance at 3-month follow-up in older patients undergoing aortic valve replacement (AVR).Methods: Patients (N=93) aged 70 years and older, undergoing transcatheter (TAVR, N=66) or surgical (SAVR, N=27) aortic valve replacement in an academic medical center were enrolled in this prospective cohort study. Delirium was assessed using the Confusion Assessment Method (CAM) on postoperative days 1, 2, 3, and 7. Data on patients’ socio-demographics, functional status (including instrumental activities of daily living (IADL), and surgical risk scores (including Society of Thoracic Surgeons (STS) risk score), were collected at baseline. Cognitive status was assessed with the Mini-Mental Status Exam (MMSE) and the Clock Drawing Test (CDT) at baseline and 3 months after AVR.Results: Delirium occurred in 21 (22.6%) patients, within the first three postoperative days in 95% (20/21) of the cases. Delirium incidence was lower in TAVR (13/66=20%) than SAVR (8/27=30%) patients, but this difference was not statistically significant (p=.298). Patients with delirium had lower baseline cognitive performance (median MMSE score 27.0±3.0 vs 28.0±3.0, p=.029), lower performance in IADL (7.0 vs 8.0, p=.038), and higher STS risk scores (4.7±2.7 vs 2.9±2.3, p=.020). In multivariate analyses, patients with intermediate (score>3 to ≤8) and high (score>8) STS risk scores had 4.3 (95%CI 1.2-15.1, p=.025) and 16.5 (95%CI 2.0-138.2, p=.010), respectively, higher odds of incident delirium compared to patients with low (score≤3) STS risk scores. At 3-month follow-up (N=77), patients with delirium still had lower MMSE score (27.0±8.0 vs 28.0±2.0, p=.007) but this difference did not remain significant once adjusting for baseline MMSE (β-coefficient 1.11, 95%CI [-3.03-0.80], p=.248). Conclusions: Delirium occurred in about one in five older patients undergoing AVR, almost essentially within the first three postoperative days. Beside cognitive performance, STS risk score could enhance the identification of high-risk older patients to better target preventative interventions.

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Catatonia is associated with worse cognitive performance in patients with first-episode psychosis antipsychotic-naive: a 3-month follow-up study

10.26226/morressier.5971be84d462b80290b5267b ◽

2017 ◽

Author(s):

Jorge Cuevas Esteban

Keyword(s):

Cognitive Performance ◽

First Episode Psychosis ◽

First Episode ◽

Follow Up Study ◽

Episode Psychosis

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Analysis of risk scores and duration of hospital stay in prognosis of STEMI patients after pPCI

European Heart Journal Acute Cardiovascular Care ◽

10.1093/ehjacc/zuab020.128 ◽

2021 ◽

Vol 10 (Supplement_1) ◽

Author(s):

SR Thangasami ◽

JS Prajapati ◽

GL Dubey ◽

VR Pandey ◽

PM Shaniswara ◽

...

Keyword(s):

Length Of Stay ◽

Hospital Stay ◽

Early Discharge ◽

Risk Scores ◽

Timi Score ◽

Study Population ◽

Event Rates ◽

Grace Score

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Advances in the immediate management of ST elevation myocardial infarction (STEMI) have led to a dramatic decline in mortality and reduction in hospital length of stay (LOS). We analysed the prognostic value of selected risk models in STEMI treated with primary percutaneous coronary intervention (PPCI) and to identify additional parameters to strengthen risk scores in categorizing patients for safe early discharge and to identify parameters prolonging hospital stay. Purpose To assess parameters and risk scores to categorize patients for safe early discharge following STEMI and to assess the composite of death, MI, unstable angina (UA), stroke, unplanned hospitalization at the end of 30 days, 6 months and at 1year follow up. Methods The study included 222 patients, who were diagnosed as STEMI, treated with successful pPCI. The risk scores like TIMI score, GRACE score, ZWOLLE score, CADILLAC score were calculated for all patients from the baseline clinical data collected on admission. Routine blood investigations along with Brain natri-uretic peptide (BNP) were done for all patients. The entire cohort was divided into three groups on the basis of length of stay: ≤3 days (n = 150), 4–5 days (n = 47), and >5 days (n = 25). All-cause mortality and major cardiovascular events (MACEs) were assessed up to 1 year. Results The mean age group (yrs) of the study population was 53.92 ± 12.9. Patients in LOS <3 days had a mean age (yrs) of 52.41 ± 11.74, patients in LOS 4-5 days group had 54.19 ±13.59 and patient with LOS >5 days had 62.52 ± 15.32. The most important parameters that predicted hospital stay in our study are BNP levels OR: 1.003, 95% CI: 1.002-1.004, P < 0.001, GRACE score OR: 1.02 ,95% CI: 1.01-1.03, P < 0.001, TIMI score OR: 1.35, 95% CI: 1.18-1.55, P = 0.007, ZWOLLE score OR: 1.26, 95% CI: 1.16-1.37, P < 0.001, CADILLAC score OR: 1.24, 95% CI; 1.15-1.3: P < 0.001. 32 (14.4%) patients expired in the study population. 36% patients of LOS >5 days expired in 1year follow up with maximum mortality in the first 6 months. 56% of the patients in LOS > 5 days had an adverse cardiac event in 1 year follow up. Patients in LOS >5 days had increased event rates in 30 days,6 months and in 1 year follow up. Patients with LOS 4-5 days (30%) had increased event rates than patients in LOS < 3 days (19%).Unadjusted Kaplan Meir survival curves for 1 year mortality among hospital survivors showed a significant increase in mortality at 6 months in length of stay> 5 days group. (P value < 0.001). CONCLUSION Long hospital stay after PCI among patients with STEMI was associated with increased long-term all-cause mortality. Addition of BNP to this risk scores can better predict the course of hospital stay and adverse clinical outcomes in follow up. Long hospital stay may be used as a marker to identify patients at higher risk for long-term mortality. Abstract Figure. Kaplan meir survival curve

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Cognitive decline in patients with prostate cancer: study protocol of a prospective cohort, NEON-PC

BMJ Open ◽

10.1136/bmjopen-2020-043844 ◽

2021 ◽

Vol 11 (2) ◽

pp. e043844

Author(s):

Natalia Araujo ◽

Samantha Morais ◽

Ana Rute Costa ◽

Raquel Braga ◽

Ana Filipa Carneiro ◽

...

Keyword(s):

Prostate Cancer ◽

Cognitive Decline ◽

Cognitive Performance ◽

Androgen Deprivation Therapy ◽

Survival Rates ◽

Cardiovascular Complications ◽

Androgen Deprivation ◽

High Survival ◽

The Impact

IntroductionProstate cancer is the most prevalent oncological disease among men in industrialised countries. Despite the high survival rates, treatments are often associated with adverse effects, including metabolic and cardiovascular complications, sexual dysfunction and, to a lesser extent, cognitive decline. This study was primarily designed to evaluate the trajectories of cognitive performance in patients with prostate cancer, and to quantify the impact of the disease and its treatments on the occurrence of cognitive decline.MethodsParticipants will be recruited from two main hospitals providing care to approximately half of the patients with prostate cancer in Northern Portugal (Portuguese Institute of Oncology of Porto and São João Hospital Centre), and will comprise a cohort of recently diagnosed patients with prostate cancer proposed for different treatment plans, including: (1) radical prostatectomy; (2) brachytherapy and/or radiotherapy; (3) radiotherapy in combination with androgen deprivation therapy and (4) androgen deprivation therapy (with or without chemotherapy). Recruitment began in February 2018 and is expected to continue until the first semester of 2021. Follow-up evaluations will be conducted at 1, 3, 5, 7 and 10 years. Sociodemographic, behavioural and clinical characteristics, anxiety and depression, health literacy, health status, quality of life, and sleep quality will be assessed. Blood pressure and anthropometrics will be measured, and a fasting blood sample will be collected. Participants’ cognitive performance will be evaluated before treatments and throughout follow-up (Montreal Cognitive Assessment and Cube Test as well as Brain on Track for remote monitoring). All participants suspected of cognitive impairment will undergo neuropsychological tests and clinical observation by a neurologist.Ethics and disseminationThe study was approved by the Ethics Committee of the hospitals involved. All participants will provide written informed consent, and study procedures will be developed to ensure data protection and confidentiality. Results will be disseminated through publication in peer-reviewed journals and presentation in scientific meetings.

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