MedicalResearch.com Interview with:
Lewis J. Smith, MD
Professor of Medicine and Associate Vice President for Research
Northwestern University and the Feinberg School of Medicine
Chicago, IL 60611
Medical Research: What is the background for this study? What are the main findings?
Dr. Smith: We previously observed in a survey of more than 1,000 patients with asthma that those consuming soy isoflavones in their diet had better lung functioning than their counterparts who consumed little or none. Using a more detailed soy questionnaire, we confirmed the observation in a different group of patients with asthma, and followed that up with laboratory studies. In cell culture studies, we saw that genistein, the major soy isoflavone, at levels that are achieved in individuals consuming a high soy diet, reduces eosinophilic inflammation, a key feature in asthma. In addition, people who consume more soy products, mostly in Japan and parts of China, generally have less asthma than in western countries. Although these data indicate a potential beneficial effect of soy isoflavones in patients with asthma and nutritional supplements are commonly used by people to treat and prevent disease and improve their health, there was little direct data to prove that the supplement is actually effective. As a result, we explored the effects of a soy isoflavone supplement in 386 adults and children aged 12 or older with poorly controlled asthma. All were taking medicine to treat their asthma – either corticosteroids or leukotriene modifiers – but none consumed soy more than once a week. In the randomized, double-blind study, half of the participants took a soy isoflavone supplement twice daily for six months, and the other half took a placebo. We found that the supplement, though able to increase blood levels of genistein, did not improve lung function, symptoms or measures of inflammation in these individuals.
MedicalResearch.com Interview with:
Gabriel Popescu PhD Associate Professor and
Shamira Sridharan, Ph.D. candidate
Quantitative Light Imaging Laboratory, Department of Bioengineering, Beckman Institute for Advanced Science and Technology University of Illinois at Urbana
Champaign Urbana, IL
Medical Research: What is the background for this study? What are the main findings?
Dr. Popescu: We developed a new optical tool that can identify patients at high risk for recurrence of prostate cancer after undergoing radical prostatectomy as treatment. Early identification of risk for recurrence can allow early treatment of disease.
Our main finding was that among individuals with worse disease outcomes, the tissue is more disorganized. This manifests as a decrease in anisotropy, or light scattering angle, which reports on nano-scale differences in tissue architecture.
MedicalResearch.com Interview with:
Dr. Michael Bailey, Ph.D.
Senior Principal Engineer
Assistant Professor, Mechanical Engineering
and Adjunct Assistant Professor, Urology
University of Washington
Medical Research: What is the background for this study? What are the main findings?
Dr. Bailey: Ultrasonic propulsion is a new technology that uses focused ultrasound energy to reposition kidney stones transcutaneously. We report the findings from the first human investigational trial of ultrasonic propulsion toward the applications of expelling small stones and dislodging large obstructing stones. Subjects underwent ultrasonic propulsion either awake without sedation or during ureteroscopy while anesthetized. A pain questionnaire was completed before, during, and after propulsion for awake subjects. Potential adverse events were assessed weekly for 3 weeks after propulsion for all subjects.
The primary outcome was to reposition stones in the collecting system. Secondary outcomes included safety, controlled movement of stones, and movement of stones < 5 mm and ≥ 5 mm. Stones were localized and repositioned in 14 of 15 enrolled subjects. Of the 43 targets, 28 (65%) showed some level of movement while 13 (30%) were displaced to a new location > 3 mm. No adverse events were reported. Mild discomfort during the procedure was rare, brief, and self-limited. Stones were moved in a controlled direction with over 30 fragments being passed by most patients who previously had a lithotripsy procedure. The largest stone moved was 10 mm. One patient experienced pain relief during treatment of an obstructing stone. In 4 subjects a seemingly large stone, which might have required surgery, was determined to be a cluster of small passable stones.
MedicalResearch.co Interview with: Katherine Ornstein, PhD MPH Assistant Professor Brookdale Department of Geriatrics and Palliative Medicine Institute for Translational Epidemiology Icahn School of Medicine at Mount Sinai New York, NY 10029 Medical Research: What is the background for this study? What are the main findings? Dr. Ornstein: Although we are rapidly expanding services to support the medically complex...
MedicalResearch.com Interview with:
David S. Lopez, Dr.P.H., M.P.H.
Assistant professor
University of Texas Health School of Public Health
Medical Research: What is the background for this study? What are the main findings?
Dr. Lopez: Coffee, and its most studied component, caffeine, have been implicated in potential health benefits due to the rich sources of antioxidants and anti-inflammatory compounds contained in this beverage.
Caffeine intake reduced the odds of prevalent erectile dysfunction, especially an intake equivalent to approximately 2-3 daily cups of coffee (170-375 mg/day). This reduction was also observed among overweight/obese and hypertensive men, but not among diabetic men. These associations are warranted to be investigated in prospective studies.
Medical Research: What are the main findings?
Dr. Lopez: Caffeine intake reduced the odds of prevalent erectile dysfunction, especially an intake equivalent to approximately 2-3 daily cups of coffee (170-375 mg/day). This reduction was also observed among overweight/obese and hypertensive men, but not among diabetic men. These associations are warranted to be investigated in prospective studies.
MedicalResearch.com Interview with:
Robert E Kalb, M.D.
Clinical Professor of Dermatology
State University of New York at Buffalo School of Medicine and Biomedical Sciences
Buffalo Medical Group, P.C.
Buffalo, NY 14221
Medical Research: What is the background for this study? What are the main findings?
Dr. Kalb: It's important to evaluate the safety of biologics in the real world post-marketing setting, and in particular with respect to serious infections. We studied patients with psoriasis in the PSOLAR registry and evaluated the risk of various biologic therapies. We found that infliximab and adalimumab were associated with increased risk of serious infections when compared with non-biologic/non-methotrexate therapies, while ustekinumab and etanercept were not associated with increased risk.
MedicalResearch.com Interview with:
Wei Zhang, Ph.D., Professor
Department of Pathology
Director, Cancer Genomics Core Lab
University of Texas MD Anderson Cancer Center
Houston, Texas 77030
Medical Research: What is the background for this study? What are the main findings?
Dr. Zhang: Epithelial ovarian cancer remains the most lethal gynecological malignancy. The 5-year survival rate for patients with advanced ovarian cancer is only 30-40%, and acquired resistance to platinum is considered a major factor in disease relapse. A major challenge in cancer treatment is the resilient ability of cancer cells to repair DNA damage caused by chemotherapy agents. In this study, we found that adding a molecule called miR-506 to standard chemotherapy can help cells overcome drug resistance, so that the chemotherapy drugs remain effective against ovarian cancer. This research supports a new combination approach, which may substantially benefit patients with this deadly disease.
MedicalResearch.com Interview with:
Ulka Agarwal, M.D.
California State University, East Bay
Student Health and Counseling Services
Hayward, CA
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Agarwal: Diabetic peripheral neuropathy affects 60 percent of patients with type 2 diabetes and can come with painful symptoms but limited treatment options. We thought a dietary intervention may help alleviate these symptoms since glycemic control plays a role in diabetes complications.
To get started with the pilot, we put 17 adults on a low-fat vegan diet for 20 weeks and prescribed weekly nutrition classes. We found significant improvements in pain, measured by the Short Form McGill Pain questionnaire, the Michigan Neuropathy Screening Instrument physical assessment, and through electrochemical skin conductance in the foot. The participants also lost an average of 14 pounds.
MedicalResearch.com Interview with :
Prof. Alexandre Reymond
Director, Center for Integrative Genomics
University of Lausanne
Lausanne Switzerland
MedicalResearch : What is the background for this study?
Prof. Reymond: Though a subset of recurrent DNA copy number variants (differing numbers of copies of genetic sequence at locations in the genome; CNVs) with rare population prevalence are known to have strong impact on carrier’s health, up to now their association with phenotypes such as intellectual disability has been almost exclusively evaluated in clinical context using individuals ascertained for diagnostics of developmental disorders. Thus the contribution of these genetic variants to health, cognition and life quality in the general population remains unclear. We used a population biobank, that of Estonia (Estonian Genome Center, University of Tartu), which contains samples from 52,000 adult participants (representative 5% of the country’s adult population), a British birth cohort (The Avon Longitudinal Study of Parents and Children; ALSPAC) and two more population-based cohorts from the USA and Italy to explore the consequences of CNVs in presumptively healthy populations.
MedicalResearch : What are the main findings?
Prof. Reymond: Rare recurrent CNVs known to be causative for specific syndromes (termed genomic disorders) have a global population prevalence of around 1%. Contrary to popular assumption that carriers of these syndromic CNVs identified in unselected, but assumed to be healthy, adult population cohorts are asymptomatic, we found that they are associated with unrecognized, but serious clinical sequelae.
Additionally our results showed that individually rare (less than 1 in 2000 individuals) but collectively common (around 10% of population) intermediate-size CNVs are negatively associated with carriers’ educational attainment. Altogether our results suggest that the life quality of at least 1 of 40 people might be negatively affected by rare CNVs.
MedicalResearch.com Interview with:
Professor Ramsey Cutress
Associate Professor in Breast Surgery
University of Southampton
Medical Research: What is the background for this study? What are the main findings?
Response: The main finding is that in young women with breast cancer, a breast cancer family history of breast cancer did not affect recurrence rates.
This work forms part of the Prospective Outcomes in Sporadic versus Hereditary breast cancer (POSH) study, which included 2850 women under age 41 years who were diagnosed with breast cancer and treated in the UK. The study, led by principal investigator Professor Diana Eccles, recorded patients’ personal characteristics, tumour characteristics, treatment, and family history of breast/ovarian cancer over a 15-year period.
MedicalResearch.com Interview with:
Dr. Michael Eriksen Benrós
Mental Health Centre Copenhagen
University of Copenhagen Faculty of Health Sciences
Copenhagen NV, Denmark,
National Centre for Register-based Research
Aarhus University Denmark
Medical Research: What is the background for this study?
Response: It is increasingly recognized that infections and immune responses can affect the brain and activate immunocompetent cells within the brain, influencing on neuronal signal transduction and possibly cognition. Impaired cognition has been observed in association with several infections and with elevated levels of CRP in smaller studies. Furthermore, experimental activation of inflammatory reactions in healthy volunteers has been shown to induce short-term reduced cognitive performance. Moreover, particularly patients with infection in the brain or sepsis have been shown to have affected cognition in long time periods after the infection has been cleared, thus infections might also have a longer lasting effect on cognition. However, large-scale longitudinal studies had been lacking on the association between infections and cognitive ability in the general population.
Medical Research: What are the main findings?
Response: Our study is the first large-scale study utilizing the extensive Danish registers to follow 190,000 males that had their IQ assessed at conscription, out of which 35% had a previous hospital contact with infection before the IQ testing was conducted. Our research shows a correlation between severe infections with a hospital contact and subsequent impaired cognition corresponding to an IQ score of 1.76 lower than the average. People with five or more hospital contacts with infections had an IQ score of 9.44 lower than the average. The study thus shows a clear dose-response relationship between the number of infections. Furthermore the effect on cognitive ability increased with the temporal proximity of the last infection and with the severity of the infection. Infections in the brain affected the cognitive ability the most, but many other types of infections severe enough to require a hospital contact where also associated with impairment of the cognitive ability.
MedicalResearch.com Interview with:
Enayet Karim Chowdhury, Research Fellow
Department of Epidemiology and Preventive Medicine
School of Public Health and Preventive Medicine
Monash University The Alfred Centre
Melbourne VIC 3004
Medical Research: What is the background for this study? What are the main findings?
Dr. Chowdhury: The study was conducted on elderly treated hypertensive population. Australia is currently undergoing a demographic transition towards having increasing number of older people. As age advances quality of life becomes increasingly affected by a variety of chronic diseases including poor renal function. Therefore early detection and management of the risk associated with these chronic diseases is crucial. Managing hypertension, even though challenging, can significantly improve quality of life of a person by reducing risk of having cardiovascular events. The main finding of the study is that in elderly treated hypertensive people, a rapid decline in renal function was associated with a higher risk of having cardiovascular events irrespective of having chronic kidney disease or not.
MedicalResearch.com Interview with:
Dr. Simon Cheng PhD.
Department of Sociology
University of Connecticut, Storrs, CT
Medical Research: What is the background for this study? What are the main findings?
Dr. Cheng: Our research is an empirical response to the Regnerus study, one of the most visible and controversial articles ever published in the social sciences. His study concluded that individuals raised by a gay or lesbian parent display less favorable adulthood outcomes than those who grew up in intact biological families. There have been many debates about the study’s conclusion and analysis, but we (Cheng and Powell) are the first to reassess Regnerus’s findings by analyzing his own data. Our reanalysis seriously calls into question his conclusions. We find that a large number of the people studied in the Regnerus study likely were misclassified as living with gay/lesbian parents. The misclassifications took several forms:
MedicalResearch.com Interview with:
Marie Crandall, MD, MPH, FACS
Associate Professor of Surgery
Northwestern University Feinberg School of Medicine
Chicago, IL 60611
Medical Research: What is the background for this study? What are the main findings?
Dr. Crandall: While the association between alcohol and interpersonal violence has been well established, research has been divided with respect to the direct effect of proximity to an establishment with a liquor license and violence. We used geographic regression analysis, which is a type of multivariate regression including geography as a variable, to examine the association between proximity to an establishment with a liquor license, such as a liquor store or tavern, and gun violence in Chicago.
We utilized our state trauma registry and geocoded 11,744 gunshot wounds that occurred between 1999-2009. On the assumption that different neighborhoods might experience risk differently, we used a combination of ordinary least squares and geographic regression analysis to identify homogenous areas with similar risk. We used sociodemographic variables as covariates in the analysis.
We found that the impact of proximity to an establishment with a liquor license and occurrence of gunshot wounds varied markedly by neighborhood. The areas of highest risk were found to have enormous associations, Odds Ratios (OR) greater than 500. These areas also tended to be more socioeconomically distressed areas of the city.
MedicalResearch.com Interview with:
Katherine Jones, M.A.
Research Associate, Department of Research
The American College of Obstetricians and Gynecologists
Department of Psychology, American University
Medical Research: What is the background for this study? What are the main findings?
Response: It is well evidenced that breastfeeding is highly advantageous for the mother, child, and society. Benefits to breastfeeding may be significantly larger for minority women as they are disproportionately affected by numerous adverse health outcomes. The benefits of breastfeeding may help mitigate some of these negative health consequences, and thus, also bridge larger gaps in racial and ethnic health disparities. This article aimed to review the literature on racial and ethnic disparities in breastfeeding rates and practices, conduct a systematic review of breastfeeding interventions, address barriers to breastfeeding among minority women, and provide obstetrician-gynecologists (ob-gyns) with recommendations on how they can help improve rates among minority women.
Overall, racial and ethnic minority women continue to have lower breastfeeding rates than white women in the United States, with African American women having the lowest rates of breastfeeding initiation and continuation among to all women. Minority women report several unique barriers to breastfeeding, including lack of access to information that promotes and supports breastfeeding, lack of work and cultural acceptance and support, language and literacy barriers, acculturation, and historical, sociopolitical, and economic challenges. Results from the systematic review of breastfeeding interventions among minority women indicated that breastfeeding-specific clinic appointments, enhanced breastfeeding programs, group prenatal education, peer counseling, and hospital policy changes significantly improve breastfeeding initiation, duration, and exclusivity.
MedicalResearch.com Interview with:
Dr. Jeanne Tie
Medical Oncologist | Royal Melbourne and Western Hospital
Research Fellow
Walter and Eliza Hall Institute of Medical Research
Parkville, VIC
Medical Research: What is the background for this study?
Dr. Tie: The increasing number of active agents available to treat metastatic colorectal cancer has resulted in an ever-improving life expectancy in this group of patients. However, the ability to expose patients with metastatic colorectal cancer to all effective anti-cancer treatment, particularly 3rd line treatment and beyond, is increasingly challenging in routine practice as some patients’ condition deteriorate too rapidly and do not live long enough to enjoy the benefit of these additional therapies. This is partly due to the current imaged-based method of assessing treatment response with the Response Evaluation Criteria in Solid Tumors (RECIST), which is usually performed every 8-12 weeks during the course of treatment. This means that for non-responders to treatment, several weeks to months will elapse before a switch to alternative therapy will be made. Conceptually, if a patient’s response to treatment could be made earlier, such as with a blood test, then an earlier switch to an alternative treatment can be made, minimizing the side-effects of the ineffective therapy and providing the opportunity for a more effective one. Currently, blood biomarkers add little to imaging-based assessment, with CEA lacking sensitivity and specificity.
Colorectal cancer is characterised by several recurrently mutated genes and advances in genomics and molecular technologies have now enabled rapid detection and quantification of these cancer-specific mutations in patient’s circulation (circulating tumor DNA - ctDNA). Previous studies have demonstrated that ctDNA can be detected in a high proportion of patients with advanced cancer. In this study, we describe the potential role of ctDNA as an early predictor of treatment response in patients with treatment naïve metastatic colorectal cancer (mCRC) undergoing chemotherapy and as a marker of disease bulk that could complement RECIST measurement.
MedicalResearch.com Interview with:
Perry N Halkitis, Ph.D., M.S., MPH
Professor of Applied Psychology
Global Public Health, and Population Health/Medicine
New York University.
Medical Research: What is the background for this study?
Dr. Halkitis: The P18 Cohort Study is a prospective cohort study of gay, bisexual and other young men who have sex with men (YMSM) which seeks to examine the development of health behaviors as these young men transition from adolescent to adulthood. Officially named “Syndemic Production among Emergent Adult Men”, this study was funded by the National Institute on Drug Abuse from 2009-2014 and renewed on March 1, 2014 for an additional five years.
The original aims of the study were as follows:
MedicalResearch.com Interview with:
Michelle Schmiegelow, MD, PhD-student
Hjertemedicinsk Forskning
Gentofte Universitetshospital
Hellerup
Medical Research: What is the background for this study?
Dr. Schmiegelow: Obesity has become a worldwide epidemic, but the excess cardiovascular risk observed in obese individuals may primarily be attributable to metabolic mediators, rather than obesity per se. Several studies conducted in primarily non-Hispanic white populations suggest that obese individuals without the metabolic syndrome, defined as metabolically healthy obese, have a cardiovascular risk similar to that of normal weight metabolically healthy individuals.
We used prospectively collected data from the Women’s Health Initiative studies to evaluate whether obesity unaccompanied by metabolic abnormalities was associated with increased risk of cardiovascular disease (CVD) across racial/ethnic subgroups in postmenopausal women. Additionally, we examined whether the use of the metabolic syndrome to define the metabolically healthy obese applied to the various racial/ethnic subgroups by quantifying the number and type of metabolic syndrome components.
All women were classified by obesity level and metabolic health status at baseline. The women were thus categorized according to body mass index (BMI, kg/m2) into normal weight (BMI 18.5-24.9 kg/m2), overweight (25-29.9 kg/m2) and obese (30.0 kg/m2) women. Metabolic health status was first defined by presence of the metabolic syndrome (yes/no), and second by number of metabolic syndrome components. In accordance with the International Diabetes Federation and the American Heart Association/National Heart, Lung, and Blood Institute we defined the metabolic syndrome as any two of the following (criteria for women): increased waist circumference ≥80 cm; increased level of triglycerides ≥150 mg/dL (≥1.7 mM); decreased level of HDL-C <50 mg/dL (<1.3 mM); increased blood pressure with either systolic blood pressure ≥130 mmHg or diastolic blood pressure ≥85 mmHg, or treatment with antihypertensive drugs; and impaired fasting serum glucose ≥100 mg/dL (6.1 mM).
Medical Research: What are the main findings?
Dr. Schmiegelow: The study population comprised 14,364 women without diabetes or prior cardiovascular disease. The women had a median age of 64 years (interquartile range 57–69), and 47% were white, 36% were black and 18% were Hispanic. Over a median follow-up of 13 years (interquartile range 12–14 years), 1,101 women (7.7%) had a first cardiovascular event.
The main findings of this study were that metabolic abnormalities appeared to confer more cardiovascular risk among black women than among white women. Consistent with other studies, among white women without the metabolic syndrome, obesity was not associated with increased cardiovascular risk compared with normal weight women. Conversely, black overweight and black obese women had increased cardiovascular risk compared with normal weight black women without the metabolic syndrome, even in absence of the metabolic syndrome.
According to number of metabolic syndrome components, black overweight or obese women with just two metabolic abnormalities had increased risk of cardiovascular disease, although they would be considered “metabolically healthy” based on the standard definition, particularly since one of these abnormalities were abdominal obesity for 79% of overweight and 98% of obese women, irrespective of race/ethnicity. White obese women with three metabolic abnormalities did not have a statistically significantly increased cardiovascular risk compared with normal weight metabolically healthy women. Thus, cardiovascular disease risk appeared to be elevated in black women by the presence of only two or three metabolic abnormalities to a degree that would require four or more metabolic abnormalities among white women. These findings did not appear to be driven by any particular combination of metabolic abnormalities.
MedicalResearch.com Interview with:
Dr. Hope M. Tiesman MSPH, PhD
CDC, Atlanta
Medical Research: What is the background for this study? What are the main findings?
Dr. Tiesman: The authors regularly monitor non-occupational injury trends, including the recent and significant increase in suicide rates. This finding led the authors to consider how these non-occupational trends impacted the workplace. We used data for two large national surveillance systems. We obtained data on workplace suicides from the Bureau of Labor Statistics' Census of Fatal Occupational Injury (CFOI) which compiles data on all fatal work-related injuries in the US. We obtained data on non-workplace suicides from the CDC's Web-Based Injury Statistics Query and Reporting System or WISQARS. WISQARS data are compiled using national death certificate data. From here we calculated suicide rates and compared trends across workplace and non-workplace suicides as well as examined the socio-demographics and occupational characteristics of those who chose suicide in the workplace.
Several important findings to highlight. Across the 8-yr timeframe, we found that workplace suicide rates remained relatively stable, even somewhat decreasing that it is until 2007 when a large and significant jump in rates was found. This was in contrast with non-workplace suicide rates which increased over the entire study period. Men had signifıcantly higher workplace suicide rates compared to women and generally, as age increased, so did workplace suicide rates. Those aged between 65 and 74 years had the highest suicide rate of all workers which was also a bit different from non-workplace suicide rates. Finally, we found that those in protective service occupations, such as police and firefighters, had the highest workplace suicide rates, followed closely by those in farming/fishing/and forestry occupations. These occupations have been associated with higher overall suicide rates in prior studies. A somewhat novel finding was that those in automotive maintenance and repair occupations also had significantly higher workplace suicide rates.
MedicalResearch.com Interview with:
David F. Penson, MD, MPH
Hamilton and Howd Chair in Urologic Oncology
Professor and Chair, Department of Urologic Surgery
Director, Center for Surgical Quality and Outcomes Research
Vanderbilt University Medical Center
Nashville, TN 37232-2765
Medical Research: What is the background for this editorial? What are the main findings?
Response: This editorial discusses the implication of the recent removal of the PSA data from the seer-medicare dataset. It reviews the significance of the action: specifically what it means for prior publications that used this information to address clinical research questions in prostate cancer. It makes the point that, while these datasets are powerful, researchers have stretched the limits of what they can do too far. Simply put, we cant always guarantee that the clinical data collected in administrative datasets will necessarily be accurate so we need to be more selective in how we use these data and not simply run analyses on the data just because it is easy.
MedicalResearch.com Interview with:
Thomas M. Gill, M.D
Humana Foundation Professor of Medicine (Geriatrics)
Professor of Epidemiology and of Investigative Medicine
Director Yale Program on Aging and Yale Center for Disability and Disabling Disorders
Director, Yale Training Program in Geriatric Clinical Epidemiology and Aging-Related Research
Medical Research: What is the background for this study? What are the main findings?h
Response: Understanding the disabling process at the end of life is essential for informed decision-making among older persons, their families, and their physicians.
We know from prior research that the course of disability at the end of life does not follow a predictable pattern for most older persons. This raises the question about what is driving the development and progression of disability at the end of life.
We identified six distinct trajectories of disability in the last year of life, ranging from the least disabled to most disabled. We found that the course of disability in the last year of life closely tracked the monthly prevalence of hospitalization for each of the six trajectories.
MedicalResearch.com Interview with:
Wendong Li, Ph.D.
Assistant professor of psychological sciences
Department of Psychological Sciences
Kansas State University
Manhattan, KS
Medical Research: What is the background for this study? What are the main findings?
Dr. Wen-Dong Li: There has been a "nature versus nurture" debate in leadership: Are leaders born or made? In academia, research on trait theories of leadership has shown that important individual characteristics such as personality traits are predictive of whether one is a leader or not (leadership role occupancy or emergence). One author of this paper, Dr. Arvey conducted twin studies showing that about 30% of the individual differences in leadership is attributable to individual differences in their genetic makeup. But so far, little research has examined whether specific genes are involved and no research has examined the pathways linking genes to leadership.
This is where this research came in. We found that a dopamine transporter gene, DAT1 was involved in genetic influences on leadership role occupancy, but through two opposing pathways. One pathway is through proactive personality: DAT1 10-repeat allele was negatively related to proactive personality, which in turn was positively associated with leadership role occupancy. The negative indirect effect was significant. On the other hand, DAT1 was positively related to (moderate) rule breaking, which was positively associated with leadership role occupancy. The overall relationship between DAT1 and leadership was not significant. Thus we call it a mixed blessing because the two opposing mechanisms offset each other.
MedicalResearch.com Interview with:
Rik Ossenkoppele PhD.
Postdoctoral researcher
UCSF Memory and Aging Center
MedicalResearch: What is the background for this study?
Dr. Ossenkoppele: Since 2004, several PET tracers have been developed that measure fibrillar amyloid-β plaques, a neuropathological hallmark of Alzheimer’s disease (AD). Through visual assessment by a nuclear medicine physician or quantitative cut-points, the presence or absence of amyloid-β pathology can be determined in the living human brain. The FDA, in support of the clinical application of amyloid imaging, has recently approved three of these PET tracers. A proportion of patients with other types of dementia then Alzheimer’s disease that harbor cerebral amyloid-β pathology, however, potentially limits the clinical utility of amyloid imaging. When ordering clinical amyloid PET scans and correctly interpreting the significance of amyloid PET results, clinicians need to understand the prevalence of amyloid-positivity across different types of dementia. It is also important to be aware of the relationships of amyloid-positivity prevalence and demographic (e.g. age and sex), cognitive and genetic (e.g. presence of the AD-risk allele apolipoprotein E [APOE] ε4) factors. Most amyloid PET studies to date come from single centers with modest sample sizes. We therefore conducted a meta-analysis with individual participant data from 29 cohorts worldwide, including 1359 patients with clinically diagnosed Alzheimer’s disease and 538 patients with non-AD dementia. We also included 1849 healthy controls with amyloid PET data, and an independent sample of 1369 AD patients with autopsy data from the NACC database.
MedicalResearch: What are the main findings?
Dr. Ossenkoppele: In patients clinically diagnosed with Alzheimer’s disease, the prevalence of amyloid-positivity decreased from 93% at age 50 to 79% at age 90. The drop in amyloid-positivity was most prominent in older Alzheimer’s disease patients who did not carry an APOE ε4 allele (~1/3 of these patients had a negative amyloid PET scan). This most likely reflects a mix of
1) clinical misdiagnoses (i.e. non-AD pathology causing an AD phenotype),
2) false negative PET scans (i.e. abundance of cerebral amyloid pathology that is not detected by PET), and
3) possibly elder patients need less amyloid pathology (sub-threshold levels for PET) to reach the stage of dementia due to age-related reductions in cognitive resilience (“cognitive reserve theory”) or simultaneous presence of multiple pathologies (“double-hit theory”).
The relatively high rate of amyloid-negative Alzheimer’s disease patients highlights the necessity of biomarker-informed patient selection for Alzheimer’s disease clinical trials.
In most patients clinically diagnosed with non-AD, the prevalence of amyloid-positivity increased with aging and was ~18% higher in APOE ε4 carriers. Presence of amyloid pathology in non-AD dementia may reflect
1) clinical misdiagnosis (i.e. AD pathology is the causative pathology), or
2) comorbid pathologies, where amyloid may be secondary to other pathologies that are actually driving the clinical presentation. Interestingly, patients with a clinical diagnosis of non-AD dementia who harbored cerebral amyloid pathology showed lower Mini-Mental State Examination scores (measure of global cognition), suggesting that amyloid-β is not just an innocent bystander.