Krystle E. Zuniga

Lycopene and Apo-12′-Lycopenal Reduce Cell Proliferation and Alter Cell Cycle Progression in Human Prostate Cancer Cells

Lycopene is associated with a reduced risk of prostate cancer. However, lycopene may not be wholly responsible for the effects seen in vivo or in cell culture systems. Apo-lycopenals or other lycopene metabolites, whether produced by cleavage enzymes within the body or consumed with tomato products, can be found in tissues at concentrations equivalent to physiological retinoid concentrations. Therefore, it is plausible that lycopenoids, like retinoids, are bioactive within tissues. Androgen-independent DU145 prostate cancer cells were treated with lycopene, apo-8′-lycopenal, or apo-12′-lycopenal. DU145 cell proliferation was significantly reduced by supra-physiological levels of lycopene and apo-12′-lycopenal, in part, through alteration of the normal cell cycle. Levels of the gap junction protein, connexin 43, were unaltered by lycopene or apo-lycopenal treatment while cell apoptosis rates significantly decreased. We further confirmed that connexin 43 protein levels were unaltered by lycopene treatment in mouse embryonic fibroblasts, or in Dunning R3327-H rat prostate tumor. The present data indicate that lycopene and apo-12′-lycopenal reduce the proliferation of prostate cancer cells, in part, by inhibiting normal cell cycle progression.

The interactions of dietary tomato powder and soy germ on prostate carcinogenesis in the TRAMP model.

The interactions between bioactive-rich food components within a complex human diet for the inhibition of prostate carcinogenesis are largely unknown and difficult to quantify in humans. Tomato and soy products have each shown anti-prostate cancer (PCa) activity in laboratory studies. The objective of this study was to determine the efficacy of dietary tomato and soy germ, alone and in combination, for the inhibition of PCa in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model. At 4 weeks of age, male C57BL/6 × FVB TRAMP mice (n = 119) were randomized to consume: AIN-93G control, 10% whole tomato powder (TP), 2% soy germ powder (SG), or 10% tomato powder with 2% soy germ powder (TP+SG) for 14 weeks. One hundred percent of mice fed the control diet had PCa, whereas PCa incidence was significantly lower in mice consuming TP (61%, P < 0.001), SG (66%, P < 0.001), and TP+SG (45%, P < 0.001). Although the protection offered by the combination of TP and SG was not synergistic, it was the most effective intervention. TP, SG, and TP+SG increased apoptotic index (AI) and modestly reduced the proliferative index (PI) in the prostate epithelium of TRAMP mice exhibiting primarily prostatic intraepithelial neoplasia. The dramatic reduction in the PI/AI ratio by the dietary interventions suggests that the control mice experience a stronger stimulus for malignant progression in the prostate microenvironment. Maximally effective and safe strategies for PCa prevention may result from optimizing combinations of nutrients and bioactives through an orchestration of dietary patterns. Cancer Prev Res; 6(6); 548–57. ©2013 AACR.

Subjective memory impairment and well-being in community-dwelling older adults

The relationship between subjective memory impairment (SMI), future cognitive decline, and negative health status provides an opportunity for interventions to reduce memory complaints in high‐risk groups. This study aimed to examine the relationship between SMI and indicators of well‐being in older adults enrolled in an exercise trial. Additionally, the study examined whether two different modes of exercise training, aerobic walking and non‐aerobic flexibility, toning, and balance, differentially influenced subjective memory across the trial.

Considerations in selection of diet assessment methods for examining the effect of nutrition on cognition

Older adults are the most rapidly growing age group in the United States, and it is estimated that 22.2% of U.S. adults over 71 years of age have cognitive impairments without dementia and 13.9% have dementia. Cognitive impairment is associated with reduced quality of life, increased risk of hospitalization, inability to live independently, and increased health care costs; therefore, identification of modifiable risk factors for prevention and delay of cognitive decline is of increasing importance. There is a growing body of research and interest in the relationship between diet and cognitive function. Epidemiologic studies suggest that cognitive function may be improved and cognitive decline prevented as a function of a particular nutrient, food group or dietary pattern; however, results from these trials have failed to be replicated in randomized controlled trials. One possible reason for the equivocality of findings in the diet and cognitive function literature may be the methodological issues and limitations in the assessment of dietary patterns and nutritional intake. Self-reported dietary data can be biased by many factors such as age, gender, socioeconomic status, and education; yet, there is limited research on the impact of cognitive function on the integrity of self-reported dietary data. Cognitive function itself may bias diet assessment methods, subsequently obscuring the evaluation of the nutrition-cognition relationship. The present review summarizes methodological validation studies that provide insight into potential errors of diet assessment methods due to cognitive function, identifies research gaps and provides recommendations for improving diet assessment accuracy in studies of individuals with cognitive impairments.

Associations between Physical Fitness Indices and Working Memory in Breast Cancer Survivors and Age-Matched Controls

BACKGROUND This study examined the effects of cardiorespiratory fitness, heart rate recovery, and physical activity on working memory in breast cancer survivors and age-matched controls. METHOD Using a case-control design, 32 women who had received a breast cancer diagnosis and completed primary treatment within the past 36-months (11 radiation only; 21 chemotherapy) and 30 age-matched women with no previous cancer diagnosis completed a n-back continuous performance task commonly used as an assessment of working memory. In addition, cardiorespiratory fitness and heart rate recovery were measured during a submaximal graded exercise test and physical activity was measured using 7-days of accelerometer monitoring. RESULTS Breast cancer survivors who had received chemotherapy had poorer heart rate recovery (p = .010) and engaged in less physical activity than women who had received radiation only (p = .004) or non-cancer controls (p = .029). Cancer treatment (radiation; chemotherapy) predicted differences in reaction times on the 1-back working memory task (p = .029). However, more rapid heart rate recovery predicted shorter reaction times on the 1-back task in the age-matched control group (p = .002). All participants with greater cardiorespiratory fitness displayed greater accuracy independent of disease status on the 1-back task (p = .017). No significant group differences in reaction times were observed for 2-back target trials between breast cancer survivors and controls. However, greater total physical activity predicted shorter reaction times in breast cancer survivors (radiation, chemotherapy) on the 2-back task (p = .014). In addition, all participants who exhibited more rapid heart rate recovery demonstrated better greater accuracy regardless of disease status (p = .013). CONCLUSION These findings support differences in physical activty participation, heart rate recovery, and 1- and 2-back working memory reaction times between breast cancer survivors and age-matched controls. Greater cardiorespiratory fitness, heart rate recovery, and physical activity were positively associated with better working memory performance across conditions.

Higher cardiorespiratory fitness levels are associated with greater hippocampal volume in breast cancer survivors.

As breast cancer treatment is associated with declines in brain and cognitive health, it is important to identify strategies to enhance the cognitive vitality of cancer survivors. In particular, the hippocampus is known to play an important role in brain and memory declines following cancer treatment. The hippocampus is also known for its plasticity and positive association with cardiorespiratory fitness (CRF). The present study explores whether CRF may hold promise for lessening declines in brain and cognitive health of a sample of breast cancer survivors within 3 years of completion of primary cancer treatment. We explored the role of cardiovascular fitness in hippocampal structure in breast cancer survivors and non-cancer female controls, as well as performed a median split to compare differences in hippocampal volume in relatively higher fit and lower fit cancer survivors and non-cancer controls. Indeed, CRF and total hippocampal volume were positively correlated in the cancer survivors. In particular, higher fit breast cancer survivors had comparable hippocampal volumes to non-cancer control participants (Cohen’s d = 0.13; p > 0.3), whereas lower fit breast cancer survivors showed significantly smaller hippocampal volumes compared to both lower fit and higher fit control participants (Cohen’s d = 0.87, p < 0.05). These results are the first to identify that CRF may protect the brain health of breast cancer survivors within 3 years of treatment. The present study uniquely contributes to the field of cancer and cognition and emphasizes the importance of investigating how individual differences in CRF play a role in brain changes of breast cancer survivors.

Moderate Physical Activity Mediates the Association between White Matter Lesion Volume and Memory Recall in Breast Cancer Survivors

Increased survival rates among breast cancer patients have drawn significant attention to consequences of both the presence of cancer, and the subsequent treatment-related impact on the brain. The incidence of breast cancer and the effects of treatment often result in alterations in the microstructure of white matter and impaired cognitive functioning. However, physical activity is proving to be a successful modifiable lifestyle factor in many studies that could prove beneficial to breast cancer survivors. This study investigates the link between white matter lesion volume, moderate physical activity, and cognition in breast cancer survivors following treatment compared to non-cancer age-matched controls. Results revealed that brain structure significantly predicted cognitive function via mediation of physical activity in breast cancer survivors. Overall, the study provided preliminary evidence suggesting moderate physical activity may help reduce the treatment related risks associated with breast cancer, including changes to WM integrity and cognitive impairment.

Latent Profiles of Macronutrient Density and their Association with Mobility Limitations in an Observational Longitudinal Study of Older U.S. Adults

ObjectivesOur first objective was to estimate empirically-derived subgroups (latent profiles) of observed carbohydrate, protein, and fat intake density in a nationally representative sample of older U.S. adults. Our second objective was to determine whether membership in these groups was associated with levels of, and short term change in, physical mobility limitations.Design and SettingMeasures of macronutrient density were taken from the 2013 Health Care and Nutrition Study, an off-year supplement to the Health and Retirement Study, which provided indicators of physical mobility limitations and sociodemographic and health-related covariates.Participants3,914 community-dwelling adults age 65 years and older.MeasurementsPercent of daily calories from carbohydrate, protein, and fat were calculated based on responses to a modified Harvard food frequency questionnaire. Latent profile analysis was used to describe unobserved heterogeneity in measures of carbohydrate, protein, and fat density. Mobility limitation counts were based on responses to 11 items indicating physical limitations. Poisson regression models with autoregressive controls were used to identify associations between macronutrient density profile membership and mobility limitations. Sociodemographic and health-related covariates were included in all Poisson regression models.ResultsFour latent subgroups of macronutrient density were identified: “High Carbohydrate”, “Moderate with Fat”, “Moderate”, and “Low Carbohydrate/High Fat”. Older adults with the lowest percentage of daily calories coming from carbohydrate and the greatest percentage coming from fat (“Low Carbohydrate/High Fat”) were found to have greater reported mobility limitations in 2014 than those identified as having moderate macronutrient density, and more rapid two-year increases in mobility limitations than those identified as “Moderate with Fat” or “Moderate”.ConclusionOlder adults identified as having the lowest carbohydrate and highest fat energy density were more likely to report a greater number of mobility limitations and experience greater increases in these limitations than those identified as having moderate macronutrient density. These results suggest that the interrelation of macronutrients must be considered by those seeking to reduce functional limitations among older adults through dietary interventions.

Recent cancer treatment and memory decline in older adults: An analysis of the 2002–2012 Health and Retirement Study

OBJECTIVE Few studies have examined the impact of cancer treatment on cognitive trajectories in the growing population of older adults diagnosed with and surviving cancer. This study examined whether recent cancer and its treatment accelerated memory decline in older adults. MATERIALS AND METHODS We conducted a secondary analysis of observations drawn from the Health and Retirement Study (2002-2012), a population-based sample of older adults in the United States. Changes in immediate (IWR) and delayed word recall (DWR) scores were estimated by latent growth modeling in individuals who never had cancer (n=10,939) or had been diagnosed with cancer between 2000 and 2002 and received treatment with some combination of radiation and/or surgery (n=240), chemotherapy only (n=34), or chemotherapy and some combination of radiation and/or surgery (n=64). RESULTS In the period immediately following treatment, individuals reporting a recent cancer treated with chemotherapy and surgery/radiation experienced significantly more rapid decline in IWR (b =-0.34, SE =0.17, p=0.047) and DWR (b=-0.38, SE=0.19, p=0.049) than the non-cancer group. Sensitivity analyses addressing mortality selection and memory-related disease at baseline attenuated the strength of these associations. There were no other statistically significant differences in estimated linear or quadratic slope by cancer status or treatment. CONCLUSION Our results support a potential association between recent cancer treatment and trajectories of memory decline in older adults and provide guidance on the interpretation of statistical estimates from panel studies of health and aging.

Cognitive Impairment in Breast Cancer Survivors

An increasing population of breast cancer patients and survivors is living with treatment-related side effects including cancer-related cognitive impairment (CRCI). Neuropsychological and neuroimaging studies suggest changes in cognitive function and brain structure and function during and after treatment. CRCI has proven difficult to treat due to a lack of understanding of the precise underlying mechanisms and lack of consensus on the appropriate assessments to diagnose the presence and severity of cognitive dysfunction. Using the aging literature as a model, physical activity, cardiorespiratory fitness, and exercise training may protect against CRCI or restore declines in cognitive function. Preliminary studies with breast cancer survivors suggest physical activity interventions may improve cognitive function. Standardized objective assessments and normative values for the measurement of CRCI and physical activity-related factors are needed. The relationship between physical activity, exercise training, cardiorespiratory fitness, and CRCI needs to be further investigated to explore the potential for therapeutic improvement.