Association between late-life hypercholesterolemia and progression of dementia severity among older adults

Abstract Progression of dementia severity varies widely by individuals and multiple factors might influence the progression. The aim of this study was to examine the relationship between late-life hypercholesterolemia and progression of dementia severity in older adults. We used prospectively collected longitudinal data from 2,686 adults aged ≥65 years in the National Alzheimer’s Coordinating Center. Progression of dementia severity was measured using both Clinical Dementia Rating (CDR) - Sum of Boxes (SOB) and Global scores. Kaplan Meier curves were plotted to estimate the association between hypercholesterolemia and progression of dementia severity. We also conducted multivariate Cox regression models to estimate the association of hypercholesterolemia with the outcomes adjusting for age, gender, race, ethnicity, marital status, living status, education, smoking, heart failure, atrial fibrillation, blood pressure, and diabetes. Hypercholesterolemia had significant association with CDR-SOB ≥ 1 point increase (unadjusted HR, 1.23; 95% CI, 1.13-1.35; p<0.001; adjusted HR, 1.17; 95% CI, 1.07-1.28; p<0.001). In addition, hypercholesterolemia had significant association with CDR-Global ≥ 0.5 point increase (unadjusted HR, 1.14; 95% CI, 1.04-1.25; p<0.001; adjusted HR, 1.11; 95% CI, 1.01-1.22 p=0.036). If these findings can be replicated in future studies, future studies need to examine if proper management of cholesterol may reduce the risk of Alzheimer’s dementia in late-life older adults.

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Association Between Late-Life Hypertension and Resilience to Alzheimer Dementia Among Older Adults

Innovation in Aging ◽

10.1093/geroni/igab046.1180 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 304-305

Author(s):

Mo-kyung Sin ◽

Yan Cheng

Keyword(s):

Older Adults ◽

Late Life ◽

Braak Stage ◽

Clinical Dementia Rating ◽

Chi Square ◽

Alzheimer Dementia ◽

Student’S T ◽

The Relationship ◽

Untreated Hypertension

Abstract While midlife hypertension is known as one contributing factor for cognitive impairment and Alzheimer dementia in late-life older adults, less is known about the role of late-life hypertension in resilience to Alzheimer dementia. We examined the relationship between late-life hypertension and Alzheimer dementia resilience among older adults using the National Alzheimer’s Coordinating Center data from 2005-2020 (n=3,170). Hypertension, captured within 5 years prior to death, was defined as blood pressure (BP) ≥ 140/90 mmHg in at least two visits and/or ever treated with anti-hypertensive agents. Resilience was defined as positive Alzheimer disease (AD) pathology (CERAD score moderate or severe and BRAAK stage V or VI) from autopsy and Clinical Dementia Rating (CDR) - Sum of Boxes (SOB): 0.5-2.5 or CDR global (0-0.5) from last data point before autopsy. Student’s t-tests and Chi-square tests were conducted to compare patients with and without resilience. A multivariate logistic regression was conducted to estimate the association between late-life hypertension and resilience, adjusting for covariates of demographics and neuropathological characteristics. We had 55 resilient cases among 1,195 positive AD pathology cases. Those resilient were older (88±6.7) and had higher systolic BP (136 ± 18.2 mmHg) than non-resilient (82±7.9 years old, 130±20 mmHg. Untreated hypertension had a protective effect on resilience (adjusted OR: 3.69 (1.10-13.5, p=0.05). Patients with a systolic BP in the range of 135-145 mmHg and a diastolic BP in the range of 65-75 mmHg had the highest resilience possibility. Unlike midlife hypertension, late-life hypertension may have different effect on dementia, prompting further studies.

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Predictors of Mortality in Older Adults With Epilepsy

Neurology ◽

10.1212/wnl.0000000000011079 ◽

2020 ◽

Vol 96 (1) ◽

pp. e93-e101

Author(s):

Leah J. Blank ◽

Emily K. Acton ◽

Allison W. Willis

Keyword(s):

Older Adults ◽

Disease Burden ◽

Cox Regression ◽

Health Care Systems ◽

Underlying Disease ◽

Medicare Beneficiaries ◽

Future Studies ◽

Premature Deaths ◽

Point Increase ◽

Care Systems

ObjectiveTo determine the incidence of epilepsy and subsequent 5-year mortality among older adults, as well as characteristics associated with mortality.MethodsThis was a retrospective cohort study of Medicare beneficiaries age 65 or above with at least 2 years enrollment before January 2009. Incident epilepsy cases were identified in 2009 using ICD-9-CM code-based algorithms; death was assessed through 2014. Cox regression models examined the association between 5-year mortality and incident epilepsy, and whether mortality differed by sociodemographic characteristics or comorbid disorders.ResultsAmong the 99,990 of 33,615,037 beneficiaries who developed epilepsy, most were White (79.7%), female (57.3%), urban (80.5%), and without Medicaid (71.3%). The 5-year mortality rate for incident epilepsy was 62.8% (62,838 deaths). In multivariable models, lower mortality was associated with female sex (adjusted hazards ratio [AHR] 0.85, 95% confidence interval [CI] 0.84–0.87), Asian race (AHR 0.82, 95% CI 0.76–0.88), and Hispanic ethnicity (AHR 0.81, 95% CI 0.76–0.84). Hazard of death increased with comorbid disease burden (per 1-point increase: AHR 1.27, 95% CI 1.26–1.27) and Medicaid coinsurance (AHR 1.17, 95% CI 1.14–1.19). Incident epilepsy was particularly associated with higher mortality when diagnosed after another neurologic condition: Parkinson disease (AHR 1.29, 95% CI 1.21–1.38), multiple sclerosis (AHR 2.13, 95% CI 1.79–2.59), dementia (AHR 1.33, 95% CI 1.31–1.36), traumatic brain injury (AHR 1.55, 95% CI 1.45–1.66), and stroke/TIA (AHR 1.20, 95% CI 1.18–1.21).ConclusionsNewly diagnosed epilepsy is associated with high 5-year mortality among Medicare beneficiaries. Future studies that parse the interplay of effects from underlying disease, race, sex, and poverty on mortality will be critical in the design of learning health care systems to reduce premature deaths.

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Cognitive Functioning and Late-Life Depression

Journal of the International Neuropsychological Society ◽

10.1017/s1355617714000198 ◽

2014 ◽

Vol 20 (5) ◽

pp. 461-467 ◽

Cited By ~ 47

Author(s):

Aaron M. Koenig ◽

Rishi K. Bhalla ◽

Meryl A. Butters

Keyword(s):

Older Adults ◽

Depressive Symptoms ◽

Cognitive Functioning ◽

Neuropsychological Assessment ◽

Cognitive Deficits ◽

Late Life ◽

Cognitive Outcomes ◽

Review Of The Literature ◽

Late Life Depression ◽

The Relationship

AbstractThis brief report provides an introduction to the topic of cognitive functioning in late-life depression (LLD). In addition to providing a review of the literature, we present a framework for understanding the heterogeneity of cognitive outcomes in this highly prevalent disorder. In addition, we discuss the relationship between LLD and dementia, and highlight the importance of regularly assessing cognitive functioning in older adults who present with depressive symptoms. If cognitive deficits are discovered during a neuropsychological assessment, we recommend referral to a geriatric psychiatrist or cognitive neurologist, for evaluation and treatment of the patient’s symptoms. (JINS, 2014, 20, 1–7)

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NDRG3 overexpression is associated with a poor prognosis in patients with hepatocellular carcinoma

Bioscience Reports ◽

10.1042/bsr20180907 ◽

2018 ◽

Vol 38 (6) ◽

Cited By ~ 1

Author(s):

Ji-sheng Jing ◽

Hongbo Li ◽

Shun-cai Wang ◽

Jiu-ming Ma ◽

La-qing Yu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Cox Regression ◽

Survival Curve ◽

Disease Free Survival ◽

Prognostic Indicator ◽

Clinicopathological Characteristics ◽

Pcr Analysis ◽

Kaplan Meier ◽

Tumor Tissues ◽

The Relationship

N-myc downstream-regulated gene 3 (NDRG3), an important member of the NDRG family, is involved in cell proliferation, differentiation, and other biological processes. The present study analyzed NDRG3 expression in hepatocellular carcinoma (HCC) and explored the relationship between expression of NDRG3 in HCC patients and their clinicopathological characteristics. We performed quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) analysis and immunohistochemistry (IHC) analyses on HCC tissues to elucidate NDRG3 expression characteristics in HCC patients. Kaplan–Meier survival curve and Cox regression analyses were used to evaluate the prognoses of 102 patients with HCC. The results revealed that compared with non-tumor tissues, HCC tissues showed significantly higher NDRG3 expression. In addition, our analyses showed that NDRG3 expression was statistically associated with tumor size (P=0.048) and pathological grade (P=0.001). Survival analysis and Kaplan–Meier curves revealed that NDRG3 expression is an independent prognostic indicator for disease-free survival (P=0.002) and overall survival (P=0.005) in HCC patients. The data indicate that NDRG3 expression may be considered as a oncogenic biomarker and a novel predictor for HCC prognosis.

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Predictors of three-month mortality among hospitalized older adults in Togo

10.21203/rs.3.rs-38973/v2 ◽

2020 ◽

Author(s):

Fifonsi Adjidossi GBEASOR-KOMLANVI ◽

Martin Kouame TCHANKONI ◽

Akila Wimima BAKOUBAYI ◽

Matthieu Yaovi LOKOSSOU ◽

Arnold SADIO ◽

...

Keyword(s):

Older Adults ◽

Hospital Mortality ◽

Cox Regression ◽

Sub Saharan Africa ◽

Mortality Data ◽

Kaplan Meier ◽

All Cause Mortality ◽

Hospitalized Older Adults ◽

Sub Saharan

Abstract Background: Assessing hospital mortality and its predictors is important as some of these can be prevented through appropriate interventions. Few studies have reported hospital mortality data among older adults in sub-Saharan Africa. The objective of this study was to assess the mortality and associated factors among hospitalized older adults in Togo.Methods: We conducted a prospective cohort study from February 2018 to September 2019 among patients ≥50 years admitted in medical and surgical services of six hospitals in Togo. Data were recorded during hospitalization and through telephone follow-up survey within 90 days after admission. The main outcome was all-cause mortality at 3 months. Survival curves were estimated using the Kaplan-Meier method and Cox regression analyses were performed to assess predictors of mortality.Results: The median age of the 650 older adults included in the study period was 61 years, IQR: [55-70] and at least one comorbidity was identified in 59.7% of them. The all-cause mortality rate of 17.2% (95%CI: 14.4-20.4) and the majority of death (93.7%) occurred in hospital. Overall survival rate was 85.5% and 82.8% after 30 and 90 days of follow-up, respectively. Factors associated with 3-month mortality were the hospital level in the health pyramid, hospitalization service, length of stay, functional impairment, depression and malignant diseases.Conclusion: Togolese health system needs to adjust its response to an aging population in order to provide the most effective care.

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Abstract P441: Dental Caries a Risk Factor for Intracerebral Hemorrhage

Stroke ◽

10.1161/str.52.suppl_1.p441 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

Elizabeth A La Valley ◽

Souvik Sen ◽

James Curtis ◽

Rebecca F Gottesman ◽

Wayne D Rosamond ◽

...

Keyword(s):

Risk Factor ◽

Dental Caries ◽

Intracerebral Hemorrhage ◽

Cox Regression ◽

Collagen Binding ◽

Future Studies ◽

Kaplan Meier ◽

Chart Abstraction ◽

Metalloproteinase 9 ◽

Prior Stroke

Introduction: Streptococcus mutans is a known cause of dental caries that contains a collagen-binding protein, Cnm, and shows inhibition of platelet aggregation and matrix metalloproteinase-9 activation. This strain has been linked to aggravation of experimental intracerebral hemorrhage (ICH) and may be a risk factor for intracerebral hemorrhage. Methods: Presence of dental caries was assessed in subjects from the Dental Atherosclerosis in Communities Study (DARIC) without prior stroke or intracerebral hemorrhage. This cohort was followed for a period of incident intracerebral hemorrhage, subsequently verified by chart abstraction. Cox regression with time-dependent covariate was used to compute crude and adjusted hazards ratio stratified as <15 years and ≥15 years from the initial dental assessment. Results: Among 6506 subjects, dental caries were recorded in 1227 (19%) subjects. 47 (1%) had ICH over a period of 30 years. Those with dental caries versus those without dental caries had a greater proportion of younger (mean age 61.8±5.6 vs. 62.5±5.6, p<0.001), male (24% vs. 16%, p<0.001), African-American (53% vs 12%, p<0.001) and hypertensive (24% vs. 16%, p<0.001) patients. The association between dental caries and ICH in the first 15 years was not higher (crude HR 1.0, 95% CI 0.4-2.3) and remained so after adjusting for age, gender, race, and hypertension (adj. HR 1.1, 95% CI 0.5-2.9). The association between caries and ICH in the second 15 years was higher (crude HR 3.7, 95% CI 1.1-12.0) and strengthened after adjustment (adjusted OR 4.5, 95% CI 1.3-15.5). This is depicted in the Kaplan-Meier curve below. Conclusion: We report a significant association between dental caries and ICH. Future studies are needed to determine if early treatment of dental caries can reduce the risk of ICH.

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Abstract W P225: The Relationship between Leukocytosis and Time to Neurodeterioration

Stroke ◽

10.1161/str.45.suppl_1.wp225 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Amelia K Boehme ◽

James E Siegler ◽

Karen C Albright ◽

Alexander J George ◽

Dominique Monlezun ◽

...

Keyword(s):

Functional Outcome ◽

Functional Outcomes ◽

Stroke Severity ◽

Modified Rankin Scale ◽

Poor Functional Outcome ◽

Improve Outcome ◽

Future Studies ◽

Point Increase ◽

Stroke Center ◽

The Relationship

Background: Previous research has illustrated how leukocytosis after acute ischemic stoke (AIS) is related to poor functional outcome. A main predictor of poor functional outcome is neurodeterioration (ND). We sought to explore the relationship between leukocytosis and time to ND to identify a risk factor for a process that predicts poor functional outcome. Methods: Patients admitted to our stroke center (07/08-06/12) were retrospectively assessed. Leukocytosis was defined as WBC >11,000, ND was characterized as ≥ 2 point increase in NIHSS scale and poor functional outcome was classified as modified Rankin Scale (mRS) of 3-6. Patients were grouped into 2 categories: (1) the leukocytosis group- those who developed leukocytosis ≥24 hours after admission and those who presented with leukocytosis and remained at 24 hours and, (2) the non-leukocytosis group- those that did not have leukocytosis and those where the leukocytosis resolved within 24 hours of admission. Results: A cohort of AIS patients (N=476) with median age 64 years, 43% female and 69% Black were assessed. Of the patients with ND (27%), median time to ND was 43 hours. In the leukocytosis group (N=84), 42 (50.6%) of them developed ND. In the non-leukocytosis group (N=312), 75 (24.5%) developed ND. Leukocytosis within 24 hours of admission is predictive of earlier time to ND (p<0.0001; Figure 1). Adjusting for age, stroke severity, glucose, tPA and infection, the leukocytosis group had a 2 times greater risk for developing ND (HR 2.49, 95%CI 1.61-3.84, p<0.0001). Conclusion: Having leukocytosis persist from admission to 24 hours or developing leukocytosis within 24 hours of admission is a significant predictor of early ND, which often results in poor functional outcome. Identifying such a predictor can enable physicians to identify those at risk for ND and subsequent poor functional outcomes. Future studies are needed to identify if interventions targeting leukocytosis may improve outcome after stroke.

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High TRAF3IP3 Level Predicts Poor Prognosis of Patients with Gliomas

10.21203/rs.3.rs-96115/v1 ◽

2020 ◽

Author(s):

Guorong Yang ◽

Shu Tang ◽

Jie Zhang ◽

Ling Qin

Keyword(s):

Signaling Pathway ◽

Cox Regression ◽

The Body ◽

High Expression ◽

Clinicopathological Parameters ◽

Signal Pathways ◽

Primary Therapy ◽

Kaplan Meier ◽

Wilcoxon Rank Sum Test ◽

The Relationship

Abstract Purpose: TRAF3IP3 is involved in the maturation of immune cells, the development of immune tissues and the immune response of the body. TRAF3IP3 is shown to expressed in a variety of malignant tumor cell lines. Down-regulated expression of TRAF3IP3 in malignant melanoma can inhibit tumor growth. However, the role of TRAF3IP3 in glioma is still unknown. In this study, we aimed to study the relationship between TRAF3IP3 and glioma based on TCGA data.Method: We used the Wilcoxon rank sum test to compare the expression of TRAF3IP3 in glioma and normal tissues. Subsequently, Kruskal-Wallis test, Wilcoxon rank sum test, and logistics regression were used to evaluate the relationship between TRAF3IP3 and clinicopathological parameters of glioma patients. GSEA was used to verify the key signal pathways involved in TRAF3IP3. We used the ssGSEA method to analyze the relationship between the expression level of TRAF3IP3 and the immune infiltration in the glioma tumor microenvironment. Finally, we used Kaplan-Meier and COX regression to evaluate the prognostic value of TRAF3IP3.Results: TRAF3IP3 transcription level was highly expressed in gliomas(P<0.001). And the high expression of TRAF3IP3 and WHO grade(OR=3.57(2.42-5.34), P<0.001), IDH status (OR=4.79(3.40-6.83), P<0.001), 1P /19q codeletion (OR=0.07(0.04-0.11), P<0.001), EGFR status (OR=2.77(1.65-4.81), P<0.001), histological type (OR=3.64(2.48-5.43), P<0.001), age (OR=1.64(1.13-2.41), P=0.01), and primary therapy outcome (OR=2.29(1.47-3.61), P<0.001) were significantly correlated. GSEA showed that six signaling pathways were significantly enriched in the TRAF3IP3 high expression phenotype group, including JAK STAT signaling pathway, interferon-γ signaling pathway, apoptosis, P53 signaling pathway, PD-1 signaling pathway, and CTLA4 signaling pathway. ssGSEA showed that the expression of TRAF3IP3 was significantly positively correlated with the infiltration of Macrophages, Th17 cells, etc. Multivariate COX regression showed that TRAF3IP3 was an independent prognostic factor for glioma OS (HR=2.169(1.301-3.615), P=0.003). Kaplan-Meier analysis showed that high expression of TRAF3IP3 was associated with worse PFS(HR=2.39(1.39-3.01), P<0.001), DFS(HR=3.02(2.27-4.01), P<0.001) and OS(HR=2.87(2.20-3.75), P<0.001).Conclusion: TRAF3IP3 may play an important role in the occurrence and development of glioma, and may be a potential biomarker for the diagnosis and prognosis of glioma.

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PROTECTIVE EFFECT OF LIFETIME EXPERIENCES ON FUNCTIONAL STATUS IN YOUNG-ONSET DEMENTIA

Innovation in Aging ◽

10.1093/geroni/igz038.436 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S118-S119 ◽

Cited By ~ 1

Author(s):

Tram N Pham ◽

Lauren Massimo ◽

Katheryn A Cousins

Keyword(s):

Functional Status ◽

Disease Duration ◽

Rating Scale ◽

Leisure Activities ◽

Late Life ◽

Clinical Dementia Rating ◽

Young Onset ◽

Young Onset Dementia ◽

The Relationship ◽

Cognitive Lifestyle

Abstract Patients with Frontotemporal degeneration (FTD), a common form of young-onset dementia, experience decline in cognitive, social and daily functioning as the disease progresses. Research shows that lifestyle factors may be an important modifiable risk factor for dementia, but this has not been well studied in FTD. In this study, we test the hypothesis that lifetime experiences, including education, occupation, and leisure activities, are associated with better functional status in individuals with FTD. We also evaluated the relationship between timing of experiences (early, mid-life, and late-life) and functional status. Thirty-five patients (mean age 61.6±8.7; 74% male; mean disease duration 3.4 ± 2.6; mean MMSE 24.0 ± 5.5) completed the Lifetime of Experiences Questionnaire (LEQ), a comprehensive assessment of lifelong cognitive lifestyle, and the Clinical Dementia Rating Scale (CDR), which was used to assess functional status. Linear regression tested the relationship between cognitive lifestyle and functional status, with age and disease duration included as covariates. Higher total LEQ score was associated with better functional status (lower score on CDR) (β = -0.047, p = 0.009). While Young Adulthood LEQ score was not significantly associated with total CDR (β = -0.047, p = 0.176), both Mid-life (β = -0.117, p = 0.011) and Late-life (β = -0.133, p = 0.013) LEQ score significantly contributed to functional status. Our results indicate that functional status is mediated in part by cognitive lifestyle and that experiences accumulated in mid-life and late-life have a greater effect on functional status at time of diagnosis.

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Lymphopenia Is Associated with Gross Target Volumes and Fractions in Hepatocellular Carcinoma Patients Treated with External Beam Radiation Therapy and Also Indicates Worse Overall Survival

Canadian Journal of Gastroenterology and Hepatology ◽

10.1155/2019/9691067 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Hai-Ge Zhang ◽

Ping Yang ◽

Tao Jiang ◽

Jian-Ying Zhang ◽

Xue-Juan Jin ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Cox Regression ◽

External Beam Radiation ◽

Rank Test ◽

Beam Radiation ◽

Kaplan Meier ◽

Target Volumes ◽

The Relationship

Purpose. To investigate whether lymphocyte nadir induced by radiation is associated with survival and explore its underlying risk factors in patients with hepatocellular carcinoma (HCC). Methods. Total lymphocyte counts were collected from 184 HCC patients treated by radiotherapy (RT) with complete follow-up. Associations between gross tumor volumes (GTVs) and radiation-associated parameters with lymphocyte nadir were evaluated by Pearson/Spearman correlation analysis and multiple linear regression. Kaplan–Meier analysis, log-rank test, as well as univariate and multivariate Cox regression were performed to assess the relationship between lymphocyte nadir and overall survival (OS). Results. GTVs and fractions were negatively related with lymphocyte nadir (p<0.001 and p=0.001, respectively). Lymphocyte nadir and Barcelona Clinic Liver Cancer (BCLC) stage were independent prognostic factors predicting OS of HCC patients (all p<0.001). Patients in the GTV ≤55.0 cc and fractions ≤16 groups were stratified by lymphocyte nadir, and the group with the higher lymphocyte counts (LCs) showed longer survival than the group with lower LCs (p<0.001 and p=0.006, respectively). Patient distribution significantly differed among the RT fraction groups according to BCLC stage (p<0.001). However, stratification of patients in the same BCLC stage by RT fractionation showed that the stereotactic body RT (SBRT) group achieved the best survival. Furthermore, there were significant differences in lymphocyte nadir among patients in the SBRT group. Conclusions. A lower lymphocyte nadir during RT was associated with worse survival among HCC patients. Smaller GTVs and fractions reduced the risk of lymphopenia.

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