Chemotherapy and Anesthesia in Colorectal Cancer Survivors and the Risk of Alzheimer’s Disease

Abstract Exposures common in cancer patients––chemotherapy, surgical injury and/or anesthesia, alone or in combination with predisposing factors––have been suggested as potential risk factors for Alzheimer’s disease (AD). We explored the relationship between chemotherapy and cumulative anesthesia exposure, and development of AD in colorectal cancer survivors. We conducted a retrospective cohort study of individuals age 65 and older diagnosed with colorectal cancer between 1998 and 2013, drawing on SEER-Medicare data and employing a proportional hazards model. We found that exposure to chemotherapy in colorectal cancer survivors demonstrated a protective effect for AD HR=0.821 (0.784-0.860). The beneficial effect held in race-, sex-, cancer-stage-specific subgroups, across chemotherapy agents (e.g., Fluorouracil, Oxaliplatin, or Fluorouracil+Leucovorin), in multivariable analyses, and in propensity score-based pseudorandomization based on 70 demographic, socioeconomic, cancer-diagnosis-related, and comorbidity variables. The effect was diminished or absent when non-AD dementias were analyzed. Findings further demonstrated that the association between chemotherapy exposure and AD was not affected by competing risk of long-term mortality or possible correlation between choosing chemotherapy and higher cognitive score or use of alternative health insurance. The effect of anesthesia on AD was not significant (0.998 per hour, 0.992-1.005) and this effect held in all subgroups, multivariable analyses, and for pseudorandomized subpopulations. Harmful effect was detected for cerebral degeneration, excluding AD, cognitive deficits following cerebral hemorrhage, cognitive disorder due to injury, hepatic encephalopathy, and hepatolenticular degeneration. Sensitivity analyses focused on SEER-Registry-specific effects and possible misspecifications in anesthesia records with alternative models demonstrated stability of estimates.

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Chemotherapy and the Risk of Alzheimer's Disease in Colorectal Cancer Survivors: Evidence From the Medicare System

JCO Oncology Practice ◽

10.1200/op.20.00729 ◽

2021 ◽

pp. OP.20.00729

Author(s):

Igor Akushevich ◽

Arseniy P. Yashkin ◽

Julia Kravchenko ◽

Miklos D. Kertai

Keyword(s):

Colorectal Cancer ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cancer Survivors ◽

Proportional Hazards Model ◽

Inverse Probability Weighting ◽

Probability Weighting ◽

Inverse Probability ◽

Colorectal Cancer Survivors ◽

The Relationship

PURPOSE: Evidence on the nature of the relationship between patients receiving chemotherapy as an essential part of guideline-concordant cancer care and the onset of Alzheimer's Disease (AD) and other adverse cognitive outcomes has been mixed. Biological mechanisms were proposed to support both a potentially beneficial and an adverse role. To explore the relationship between chemotherapy and onset of AD and other neurocognitive disorders (ND) in colorectal cancer survivors. METHODS: We conducted a retrospective cohort study of 135,834 individuals older than 65 years diagnosed with colorectal cancer between 1998 and 2007, using SEER-Medicare data. A proportional hazards model was used before and after the use of inverse probability weighting to account for populational differences between the chemotherapy and nonchemotherapy groups. Weights were normalized to the total sample size. RESULTS: After inverse probability weighting, chemotherapy was associated with decreased AD risk (hazard ratio [HR]: 0.791; 95% CI: 0.758 to 0.824) and lower risk for the majority of other ND including AD-related diseases (HR: 0.823; CI: 0.802 to 0.844), dementia (permanent mental disorder) (HR: 0.807; CI: 0.782 to 0.832), and dementia (senile) (HR: 0.772; CI: 0.745 to 0.801). The only adverse effect to remain significant was cerebral degeneration (excluding AD) (HR: 1.067; CI: 1.033 to 1.102). The effects for AD remained after treatment was stratified by chemotherapy agent type and remained significant for up to 6 years past diagnosis. CONCLUSION: Chemotherapy use in colorectal cancer survivors demonstrated an association with reduced risk for AD and other ND.

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Changes in Metabolic Syndrome Status and Risk of Dementia

Journal of Clinical Medicine ◽

10.3390/jcm9010122 ◽

2020 ◽

Vol 9 (1) ◽

pp. 122 ◽

Cited By ~ 2

Author(s):

Ji Eun Lee ◽

Dong Wook Shin ◽

Kyungdo Han ◽

Dahye Kim ◽

Jung Eun Yoo ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Blood Pressure ◽

Alzheimer's Disease ◽

Metabolic Syndrome ◽

Vascular Dementia ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Screening Program ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model

This study investigated the effects of changes in metabolic syndrome (MS) status and each component on subsequent dementia occurrence. The study population was participants of a biennial National Health Screening Program in 2009–2010 and 2011–2012 in Korea. Participants were divided into four groups according to change in MS status during the two-year interval screening: sustained normal, worsened (normal to MS), improved (MS to normal), and sustained MS group. Risk of dementia among the groups was estimated from the second screening date to 31 December 2016 using a Cox proportional hazards model. A total of 4,106,590 participants were included. The mean follow-up was 4.9 years. Compared to the sustained normal group, adjusted hazard ratios (aHR) (95% confidence interval) were 1.11 (1.08–1.13) for total dementia, 1.08 (1.05–1.11) for Alzheimer’s disease, and 1.20 (1.13–1.28) for vascular dementia in the worsened group; 1.12 (1.10–1.15), 1.10 (1.07–1.13), and 1.19 (1.12–1.27) for the improved group; and 1.18 (1.16–1.20), 1.13 (1.11–1.15), and 1.38 (1.32–1.44) for the sustained MS group. Normalization of MS lowered the risk of all dementia types; total dementia (aHR 1.18 versus 1.12), Alzheimer’s disease (1.13 versus 1.10), and vascular dementia (1.38 versus 1.19). Among MS components, fasting glucose and blood pressure showed more impact. In conclusion, changes in MS status were associated with the risk of dementia. Strategies to improve MS, especially hyperglycemia and blood pressure, may help to prevent dementia.

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Bayesian Cox Proportional Hazards Model in Survival Analysis of HACE1 Gene with Age at Onset of Alzheimer's Disease

International Journal of Clinical Biostatistics and Biometrics ◽

10.23937/2469-5831/1510014 ◽

2017 ◽

Vol 3 (1) ◽

Author(s):

Wang Ke-Sheng ◽

Liu Ying ◽

Gong Shaoqing ◽

Xu Chun ◽

Xie Xin ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Survival Analysis ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Age At Onset ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Hazards Model

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Active Smoking and Mortality Among Colorectal Cancer Survivors: The Cancer Prevention Study II Nutrition Cohort

Journal of Clinical Oncology ◽

10.1200/jco.2014.58.3831 ◽

2015 ◽

Vol 33 (8) ◽

pp. 885-893 ◽

Cited By ~ 35

Author(s):

Baiyu Yang ◽

Eric J. Jacobs ◽

Susan M. Gapstur ◽

Victoria Stevens ◽

Peter T. Campbell

Keyword(s):

Colorectal Cancer ◽

Cancer Survivors ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Active Smoking ◽

Current Smoking ◽

Colorectal Cancer Survivors ◽

All Cause Mortality ◽

Specific Mortality ◽

Cancer Specific Mortality

Purpose Active smoking is associated with higher colorectal cancer risk, but its association with survival after colorectal cancer diagnosis is unclear. We investigated associations of smoking, before and after diagnosis, with all-cause and colorectal cancer–specific mortality among colorectal cancer survivors. Patients and Methods From a cohort of adults who were initially free of colorectal cancer, we identified 2,548 persons diagnosed with invasive, nonmetastatic colorectal cancer between baseline (1992 or 1993) and 2009. Vital status and cause of death were determined through 2010. Smoking was self-reported on the baseline questionnaire and updated in 1997 and every 2 years thereafter. Postdiagnosis smoking information was available for 2,256 persons (88.5%). Results Among the 2,548 colorectal cancer survivors, 1,074 died during follow-up, including 453 as a result of colorectal cancer. In multivariable-adjusted Cox proportional hazards regression models, prediagnosis current smoking was associated with higher all-cause mortality (relative risk [RR], 2.12; 95% CI, 1.65 to 2.74) and colorectal cancer–specific mortality (RR, 2.14; 95% CI, 1.50 to 3.07), whereas former smoking was associated with higher all-cause mortality (RR, 1.18; 95% CI, 1.02 to 1.36) but not with colorectal cancer–specific mortality (RR, 0.89; 95% CI, 0.72 to 1.10). Postdiagnosis current smoking was associated with higher all-cause (RR, 2.22; 95% CI, 1.58 to 3.13) and colorectal cancer–specific mortality (RR, 1.92; 95% CI, 1.15 to 3.21), whereas former smoking was associated with all-cause mortality (RR, 1.21; 95% CI, 1.03 to 1.42). Conclusion This study adds to the existing evidence that cigarette smoking is associated with higher all-cause and colorectal cancer–specific mortality among persons with nonmetastatic colorectal cancer.

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Association of Dietary Prebiotic Consumption with Reduced Risk of Alzheimer’s Disease in a Multiethnic Population

Current Alzheimer Research ◽

10.2174/1567205019666211222115142 ◽

2021 ◽

Vol 19 ◽

Author(s):

Mia Nishikawa ◽

Adam M. Brickman ◽

Jennifer J. Manly ◽

Nicole Schupf ◽

Richard P. Mayeux ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Daily Intake ◽

Apoe Genotype ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Race Ethnicity ◽

Reduced Risk

Objective: This study aimed to investigate the association between dietary prebiotic intake and risk for Alzheimer’s disease (AD). Methods: This longitudinal study includes 1,837 elderly (≥65 years) participants of a multi-ethnic community-based cohort study who were dementia-free at baseline and had provided dietary information from food frequency questionnaires. Total daily intake of fructan, one of the best-known prebiotics, was calculated based on consumption frequency and fructan content per serving of 8 food items. The associations of daily fructan intake with AD risk were examined using a Cox proportional hazards model, adjusted for cohort recruitment wave, age, gender, race/ethnicity, education, daily caloric intake, and APOE genotype. Effect modification by race/ethnicity, APOE genotype, and gender was tested by including an interaction term into the Cox models, as well as by stratified analyses. Results: Among 1,837 participants (1,263 women [69%]; mean [SD] age = 76 [6.3] years), there were 391 incident AD cases during a mean follow-up of 7.5 years (13736 person-years). Each additional gram of fructan intake was associated with 24% lower risk for AD ((95% CI)=0.60-0.97; P =0.03). Additional adjusting for smoking, alcohol consumption, and comorbidity index did not change results materially. The associations were not modified by race/ethnicity, gender, and APOE genotype, although stratified analyses showed that fructan intake was significantly associated with reduced AD risk in Hispanics but not in non-Hispanic Blacks or Whites. Conclusion: Higher dietary fructan intake is associated with a reduced risk of clinical Alzheimer’s disease among older adults.

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