Alzheimer's - Dementia, Author Interviews, JAMA / 22.06.2024
Alzheimer’s Patients: Elevated Amyloid Detected on PET Scans of Family Members
MedicalResearch.com Interview with:
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Dr. Seto[/caption]
Mabel Seto, PhD
Harvard Aging Brain Study, Department of Neurology
Massachusetts General Hospital, Center for Alzheimer Research and Treatment
Department of Neurology
Brigham and Women’s Hospital
Harvard Medical School, Boston, Massachusetts
Vanderbilt Memory and Alzheimer’s Center
Vanderbilt University Medical Center
Nashville, Tennessee
MedicalResearch.com: What is the background for this study?
Response: The background for this study is that individuals with a family history of Alzheimer’s disease (i.e., one or more first-degree relatives) have a higher risk for the disease than individuals that don’t have a family history. Previous studies suggested a preferential maternal inheritance of AD, though they were limited in sample size and statistical power.
In our study, we wanted to focus on a larger, cognitively unimpaired sample. Using data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) study, a randomized clinical trial aimed at AD prevention, we examined the relationship between a parental history of significant memory impairment as a proxy for AD (as some individuals may not have pursued formal diagnosis) and amyloid-beta burden in the offspring.
Dr. Seto[/caption]
Mabel Seto, PhD
Harvard Aging Brain Study, Department of Neurology
Massachusetts General Hospital, Center for Alzheimer Research and Treatment
Department of Neurology
Brigham and Women’s Hospital
Harvard Medical School, Boston, Massachusetts
Vanderbilt Memory and Alzheimer’s Center
Vanderbilt University Medical Center
Nashville, Tennessee
MedicalResearch.com: What is the background for this study?
Response: The background for this study is that individuals with a family history of Alzheimer’s disease (i.e., one or more first-degree relatives) have a higher risk for the disease than individuals that don’t have a family history. Previous studies suggested a preferential maternal inheritance of AD, though they were limited in sample size and statistical power.
In our study, we wanted to focus on a larger, cognitively unimpaired sample. Using data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) study, a randomized clinical trial aimed at AD prevention, we examined the relationship between a parental history of significant memory impairment as a proxy for AD (as some individuals may not have pursued formal diagnosis) and amyloid-beta burden in the offspring.
Dr. Traverso[/caption]
Giovanni Traverso MD PhD
Karl Van Tassel (1925) Career Development Professor
Department of Mechanical Engineering
Koch Institute of Integrative Cancer Research
Division of Gastroenterology
Brigham and Women’s Hospital
Harvard Medical School, Boston, MA, USA
MedicalResearch.com: What is the background for this study?
Response: I think its always important to acknowledge that this is a big team effort. We have the teams from MIT, Celero Systems, West Virgnia University (WVU) and Brigham and Women’s Hospital (BWH) all working together on this. For this study, Celero prototyped the devices that we tested in pre-clinical (Swine) models and in a first-in-human study with the team at WVU.
Our lab focuses on the development of ingestible devices for drug delivery and sensing and these have informed the development of these efforts as you can see.
Dr. GALBIATI[/caption]
Francesca Galbiati, MD
Clinical/Research fellow in Endocrinology
Massachusetts General Hospital
MedicalResearch.com: What is the background for this study?
Response: Arginine-vasopressin (AVP) is a neurohormone well known for its role in water balance regulation. It promotes renal water absorption in the kidney, to maintain normal sodium levels in the blood via a tightly controlled osmotic regulation. Besides AVP classical role, data have shown that AVP effects extend beyond water balance regulation. Animal studies have shown that AVP has metabolic effects, including reducing food intake, inducing lipolysis, and promoting muscle regeneration in male mice.
Furthermore, AVP is regulated differently in males and females, and affects cognition differently across sexes, a phenomenon called sexual dimorphism. However, it is unknown whether its dimorphism translates to metabolism. Also, findings on AVP metabolic role are inconsistent, possibly due to the opposing effects of AVP at different receptor subtypes, which regulation is still largely unknown. We performed this study to better investigate AVP metabolic role, and explore sex differences. We hypothesized that AVP would be positively associated with BMI, adiposity, and lean mass (acting as a signal of energy availability). We also predicted that relationships between AVP and body composition measures would differ by sex. We used the AVP area under the curve around a standardized meal to better capture repeated measures in response to food intake (that directly impacts energy availability). This also allowed to avoid the possible risk of fluctuating AVP levels due to possible pulsatile secretion.
Dr. Orkaby[/caption]
Ariela Orkaby, MD, MPH
Geriatrics & Preventive Cardiology
Associate Epidemiologist
Division of Aging, Brigham and Women's Hospital
Assistant Professor of Medicine, Harvard Medical School
MedicalResearch.com: What is the background for this study?
Response: As the population is living longer, there is increased risk of frailty and vulnerability. Frailty is defined as reduced physiological reserve and decreased ability to cope with even an acute stress. Up to half of adults over the age of 85 are living with frailty and preventative measures are greatly needed. We tested the effect of vitamin D and marine omega-3 fatty acid supplementation on the risk of developing frailty in healthy older adults in the US enrolled in the VITamin D and OmegA-3 TriaL (VITAL) trial.
Dr. Orkaby[/caption]
Ariela Orkaby, MD, MPH
Geriatrics & Preventive Cardiology
Associate Epidemiologist
Division of Aging, Brigham and Women's Hospital
Assistant Professor of Medicine, Harvard Medical School
MedicalResearch.com: What is the background for this study?
Response: As the population is living longer, there is increased risk of frailty and vulnerability. Frailty is defined as reduced physiological reserve and decreased ability to cope with even an acute stress. Up to half of adults over the age of 85 are living with frailty and preventative measures are greatly needed. We tested the effect of vitamin D and marine omega-3 fatty acid supplementation on the risk of developing frailty in healthy older adults in the US enrolled in the VITamin D and OmegA-3 TriaL (VITAL) trial.
Dr. LeBoff[/caption]
Meryl S. LeBoff, MD
Dr. Manson[/caption]
JoAnn E. Manson, MD, DrPH
Professor, Epidemiology, Harvard T.H. Chan School Of Public Health
Michael and Lee Bell Professor of Women's Health, Medicine, Harvard Medical School
Chief, Preventive Medicine, Brigham And Women's Hospital
Co-Director, Womens Health, Brigham And Women's Hospital
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Osteoporosis is a major public health problem. Although supplemental vitamin D has been widely used to reduce the risk of fractures in the general population, studies of the effects of vitamin D on fractures, the most important bone health outcome, have been conflicting.
Randomized controlled trials, the highest quality studies, from around the world have shown benefit, no effect, or even harm of supplemental vitamin D on risk of fractures. Some of the trials used bolus dosing, had small samples sizes or short study duration, and co-administered calcium. No large RCTS of this scale tested whether daily supplemental vitamin D (without co-administration with calcium) prevented fractures in the US population.
To fill these knowledge gaps, we tested the hypothesis in this ancillary study to VITAL, whether daily supplemental vitamin D3 reduced the risk of incident total, non-spine and hip fractures in women and men in the US.
