Alzheimer's - Dementia, Author Interviews, Genetic Research, Race/Ethnic Diversity, Stanford / 21.02.2023
Stanford Study Identifies Genetic Variant Linked to Alzheimer’s in African Americans
MedicalResearch.com Interview with:
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Dr. Yann Le Guen[/caption]
Yann Le Guen, Ph.D.
Assistant Director, Computational Biology
Quantitative Sciences Unit
Stanford Medicine
MedicalResearch.com: What is the background for this study?
Response: Apart from aging, the strongest contributing factor for late-onset Alzheimer’s disease is a specific allele of the APOE gene, which has three common alleles E2, E3, and E4. While E3 is the most common and considered as the reference, E2 is associated with decreased Alzheimer’s disease risk and E4 is associated with increased Alzheimer’s disease risk. Notably the prevalence of E4 among Alzheimer’s patient is high with about 60% of these carrying at least one E4 allele, while solely about 30% Americans carry one E4 allele. It’s worth emphasizing that individuals with an E4/E4 genotype have an exponential increased in their risk to develop AD (10 times as likely than the reference E3/E3 genotype), and individuals with an E3/E4 genotype have an intermediate risk.
Though, most studies of Alzheimer’s disease genetic have been focused on European ancestry, this is beginning to change thanks to NIH’s efforts to fund more studies in non-European ancestry individuals. Our study built on these recent efforts to assess the Alzheimer disease risk associated with an APOE variant (R145C) present in about ~4% African Americans, but extremely rare in Europeans.
Dr. Yann Le Guen[/caption]
Yann Le Guen, Ph.D.
Assistant Director, Computational Biology
Quantitative Sciences Unit
Stanford Medicine
MedicalResearch.com: What is the background for this study?
Response: Apart from aging, the strongest contributing factor for late-onset Alzheimer’s disease is a specific allele of the APOE gene, which has three common alleles E2, E3, and E4. While E3 is the most common and considered as the reference, E2 is associated with decreased Alzheimer’s disease risk and E4 is associated with increased Alzheimer’s disease risk. Notably the prevalence of E4 among Alzheimer’s patient is high with about 60% of these carrying at least one E4 allele, while solely about 30% Americans carry one E4 allele. It’s worth emphasizing that individuals with an E4/E4 genotype have an exponential increased in their risk to develop AD (10 times as likely than the reference E3/E3 genotype), and individuals with an E3/E4 genotype have an intermediate risk.
Though, most studies of Alzheimer’s disease genetic have been focused on European ancestry, this is beginning to change thanks to NIH’s efforts to fund more studies in non-European ancestry individuals. Our study built on these recent efforts to assess the Alzheimer disease risk associated with an APOE variant (R145C) present in about ~4% African Americans, but extremely rare in Europeans.
Dr. Pierce[/caption]
Karen Pierce, Ph.D.
Professor, Department of Neurosciences, UCSD
Co-Director, Autism Center of Excellence, UCSD
MedicalResearch.com: What is the background for this study?
Response: The mean age of ASD diagnosis and eventual treatment remains at ~52 months in the United States1 - years beyond the disorder’s prenatal origins2, and beyond the age when it can be reliably diagnosed in many cases3.
Currently the only way to determine if a child has autism spectrum disorder (ASD) is to receive a developmental evaluation from an experienced clinician (usually a licensed clinical psychologist). There are often long waiting lists, and only a small number of clinicians have the experience required to make early-age (i.e., between 12-36 months) diagnoses of ASD. Thus, there are many places in the country as well as world wide wherein children wait months or years to receive a formal diagnosis due to a lack of available expertise. Moreover, diagnostic evaluations are expensive and usually cost the parent and/or insurance approximately ~$2,000 or more per evaluation. Finally, clinical evaluations usually take between 2-3 hours to complete and result in fatigue for both the parent and toddler.
Eye-tracking, which generates biologically-relevant, objective, and quantifiable metrics of both visual and auditory preference profiles in babies and toddlers in just minutes, is a technology that can dramatically change how ASD is diagnosed.
Dr. Zhongshang Yuan[/caption]
Yuan, Zhongshang PhD
Department of Biostatistics
School of Public Health
Shandong University
Jinan, Shandong, China
What is the background for this study?
Response: Comorbidities and genetic correlations between gastrointestinal tract diseases and psychiatric disorders have been widely reported, with the gut-brain axis (GBA) hypothesized as a potential biological basis. However, it is unclear the degree to which the shared genetic determinants contribute to these associations underlying GBA.
Dr. Harris[/caption]
MedicalResearch.com Interview with:
Rebecca Arden Harris, MD, MSc
Assistant Professor of Family Medicine and Community Health at the Hospital of the University of Pennsylvania
Senior Fellow, Leonard Davis Institute of Health Economics
Perelman School of Medicine, University of Pennsylvania
MedicalResearch.com: What is the background for this study?
Response: The impact of the nationwide overdose epidemic on Black women has received little attention from policy-makers, researchers, or the press.
MedicalResearch.com: What are the main findings?
Response: Over the 7-year study period, preventable overdose deaths among Black women resulted in nearly 0.75 million years of life lost (YLL). Women aged 25-34 have suffered a rising proportion of this burden.
Dr. Holland[/caption]
Thomas M Holland, MD, MS
Assistant Professor
Rush Institute for Health Aging
Rush College of Medicine & Rush College of Health Sciences
Response: We started many years ago by studying some natural and synthetic molecules that were able to counteract the early stages of this disease. With a view to early prevention, we wondered if these molecules could be routinely taken with the diet or dietary supplements. So our studies focused on the search for bioactive molecules present in food and edible plants.
Hops are very rich in polyphenolic compounds, and for this reason it is historically used for the production of beer, but also for the preparation of herbal teas and infusions, and its uses in traditional medicine are known. In recent years we have also collected interesting results on Coffee, Sage, Radix Imperatoriae, Cocoa and Cinnamon extracts.
Clare Jensen[/caption]
Clare Jensen
O’Haire Research Team
Center for the Human-Animal Bond
Purdue University College of Veterinary Medicine
MedicalResearch.com: What is the background for this study?
Response: Service dogs for PTSD are becoming more common and the evidence shows they can help improve mental health and quality of life for many veterans with PTSD. However, some veterans benefit more than others. Our research goal was to ask for the very first time: Why?
Dr. Stern[/caption]
Robert A. Stern, Ph.D.
Professor of Neurology, Neurosurgery, and Anatomy & Neurobiology
Director of Clinical Research, BU CTE Center
Senior Investigator, BU Alzheimer’s Disease Research Center
Boston University School of Medicine
MedicalResearch.com: What is the background for this study?
Response: The link between playing American football at the professional level and later-life brain disorders like chronic traumatic encephalopathy – or CTE -- and ALS has received increasing attention over the past 15 years. Previous research has shown that former NFL players are more likely to die from CTE and amyotrophic lateral sclerosis (ALS) and more likely to report cognitive impairment, behavioral changes, and dementia during life. Despite previous research focusing on the later-life effects of playing American football at the professional level, the long-term effects of college football participation remain largely unknown.
We had two goals for this new investigation. The first was to conduct a survey of the current overall health status, including cognitive and other neurological disorders, of older former college American football players compared with men in the general population. The second goal was to examine the mortality rate and causes of death in a cohort of older former college football players. The target population for this study was all 447 former Notre Dame football players who were listed as seniors on the varsity rosters during the 1964-1980 seasons. This was the era of legendary coaches Ara Parseghian and Dan Devine. I should add that this study was fully independent of the University of Notre Dame.
Dr. Launer[/caption]
Lenore J. Launer, Ph.D.
Chief, Laboratory of Epidemiology and Population Sciences
Intramural Research Program, National Institute on Aging.
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Identifying early risk factors and early changes in the brain will have a major impact on future clinical and public health priorities related to the looming epidemic of dementia. Several studies based on older populations suggest mid-life is an important period to start prevention measures. To date control of blood pressure levels has been the most robust and promising candidate to target for prevention of future cognitive impairment. Although several studies have looked at levels of blood pressure and risk for cognitive impairment, it was not known whether trajectories from young adulthood to middle age studies provided additional information about risk. To investigate possible biomarkers of future risk, we chose to examine the association of the mean arterial blood pressure trajectories to indicators of pathology seen on MRI and that are associated with cognition.
We highlight the results of the mean arterial blood pressure (MAP) measure, which is an integrated measure of systolic and diastolic blood pressure.
Sneha Vaddadi[/caption]
Sneha Vaddadi, BS
Department of Medical Education
Geisinger Commonwealth School of Medicine
Scranton, Pennsylvania
MedicalResearch.com: What is the background for this study?
Response: The prescription stimulants methylphenidate, amphetamine, and lisdexamfetamine, classified as Schedule II substances, are sympathomimetic drugs with therapeutic use widely used in the US for Attention Deficit Hyperactivity Disorder. Changes in criteria for diagnosis of Attention Deficit Hyperactivity Disorder in 2013 and approval of lisdexamfetamine for binge eating disorder in 2015 may have impacted usage patterns.
The goal of this study1 was to extend upon past research2 to compare the pharmacoepidemiology of these stimulants in the United States from 2010–2017, including consideration to variation within geographic regions, the Hispanic population, and the Medicaid population.
Sean C. Rose, MD
Child Neurology
Nationwide Children’s Hospital
The Ohio State University, Columbus
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: There is conflicting evidence regarding the association between repetitive head impacts during youth contact sports and worse neurocognitive outcomes. Most research has been conducted in older adults, while the research in children is mostly limited to 1-2 sports seasons.
Dr. van Dalen[/caption]
Jan Willem van Dalen, PhD
Department of Neurology
Donders Institute for Brain, Behaviour and Cognition
Radboud University Medical Centre Nijmegen
Department of Neurology
The Netherlands3Department of Public and Occupational Health
Amsterdam UMC, University of Amsterdam, Amsterdam
MedicalResearch.com: What is the background for this study?
Response: Although high systolic blood pressure in midlife has consistently been reported as a condition that increases the risk of developing dementia in old age, reports regarding this relationship in older people have been inconsistent. One potential reason for this, is that the relationship between systolic blood pressure and dementia in later life may be U-shaped, meaning that both individuals with low and with high systolic blood pressure are at increased incident dementia risk.
This study combined data from several longitudinal cohort studies specifically designed to study incident dementia in older people, to investigate whether these U-shaped relationships exist, and in which age ranges they appear. We included more than 16,500 people aged 60 and older, with over 2,700 incident dementia cases.
Also, we aimed to investigate whether these observational associations might be caused by confounding, differences in mortality, or result from opposite relationships between certain subgroups of individuals.