Alzheimer's - Dementia, Author Interviews, Blood Pressure - Hypertension, NIH / 03.02.2016
Some Blood Pressure Medications May Be Protective Against Alzheimer’s Disease
MedicalResearch.com Interview with:
Dr. Juan M. Saavedra, MD and
Dr. Abdel Elkahloun PhD
Comparative genomics and Cancer Genetics Branch
National Human Genome Research Institute,
National Institutes of Health, Bethesda, MD
MedicalResearch: What is the background for this study? What are the main findings?
Response: Alzheimer’s disease is the most frequent age-related dementia, a progressing, devastating illness without effective treatment. By the time it is diagnosed, major and irreversible cell injury has already occurred. It is therefore imperative to identify therapeutic agents effective against early, pre-symptomatic injury mechanisms and risk factors increasing vulnerability the disease.
We focused on a class of compounds blocking receptors for Angiotensin II, the Angiotensin Receptor Blockers (ARBs). These compounds are commonly used for the treatment of hypertension, a major risk factor for Alzheimer’s disease.
We and others have found that in addition to their cardiovascular benefits, ARBs are strongly neuroprotective. The present study was designed to explore in depth the neuroprotective effects of one member of the ARB class, candesartan. To this effect we cultured neurons extracted from the rat brain. These neurons were exposed to high concentrations of glutamate, a recently identified early injury mechanism in Alzheimer’s disease. We found that candesartan prevented glutamate-induced neuronal injury.
We conducted in-depth examination of our results by genome-wide expression profile analysis. We found that candesartan normalized glutamate-induced alterations in expression of hundreds of genes, including many involved in neuronal inflammation, cardiovascular disease, diabetes and alterations in amyloid metabolism a hallmark for Alzheimer’s disease. This was evidence of direct neuroprotective effects of relevance for this disorder.
When we compared our results with published databases obtained from autopsy samples from Alzheimer’s disease patients, we found impressive correlations. The expression of more than 400 genes altered by glutamate and normalized by candesartan in our cultures was similarly changed in the Alzheimer’s databases.
The conclusion was that our cell culture results represented alterations found in the human condition. Our observations provide novel evidence of neuroprotection from early mechanisms of injury in Alzheimer’s disease and support testing candesartan in controlled clinical studies including individuals at the early stages of the illness, to unequivocally demonstrate their therapeutic effect.
Dr. Richard Deth[/caption]
MedicalResearch.com Interview with:
Dr. Richard Deth PhD
Professor of Pharmacology
Department of Pharmaceutical Sciences
Nova Southeastern University
Medical Research: What is the background for this study?
Dr. Deth: Vitamin B12 plays a crucial role in regulating and promoting methylation reactions (the attachment of a carbon atom to molecules), including DNA methylation. Recent research has identified methylation of DNA and consequential changes in gene expression as crucial factors in brain development, as well as in memory formation and maintenance of brain function during aging. More specifically, the cause(s) of neurodevelopmental disorders such as autism remain obscure, although numerous studies have demonstrated oxidative stress and low plasma levels of the antioxidant glutathione (GSH) in autism.
Medical Research: What are the main findings?
Dr. Deth: We found that brain levels of vitamin B12, especially the methylation-regulating form known as methylB12, decrease significantly with age, even though blood levels don’t show a similar decrease. Importantly, much lower levels of methylB12 were found in subjects with autism and schizophrenia compared to normal subjects of a similar age. Animal studies showed that impaired GSH formation is associated with decreased brain B12 levels.
Dr. Christoph Correll[/caption]
More on Mental Health on MedicalResearch.com
MedicalResearch.com Interview with:
Christoph U. Correll, MD
Professor of Psychiatry and Molecular Medicine
Hofstra Northwell School of Medicine
Hempstead, New York, USA
Investigator, Center for Psychiatric Neuroscience
Feinstein Institute for Medical Research
Manhasset, New York,
Medical Director, Recognition and Prevention
The Zucker Hillside Hospital,
Department of Psychiatry
Medical Research: What is the background for this study?
Dr. Correll: Antipsychotics have been used increasingly for psychotic, but also for many non-psychotic conditions, including for disorders and conditions for which they have not received regulatory approval. Moreover, antipsychotics have been associated with weight gain and abnormalities in blood fat and blood glucose levels. Although data in youth have been less available than in children and adolescents, youth appear to be more sensitive to the cardiometabolic adverse effects of antipsychotics than adults in whom significant weight gain might have already occurred due to long-term prior antipsychotic treatment. Nevertheless, type 2 diabetes, which is related to weight gain, overweight and obesity, seemed to be more common in adults than youth, likely due to the fact that it takes a long time for the body to develop diabetes. Recently, several individual epidemiologic or database studies with sufficient long-term follow-up durations suggested that the type 2 diabetes risk was higher in youth exposed to antipsychotics than healthy control youth and, possibly, even compared to psychiatrically ill patients treated with non-antipsychotic medications. However, a meta-analytic pooling of all available data has not been available to estimate the absolute and relative risk of type 2 diabetes in youth receiving antipsychotic treatment.
Medical Research: What are the main findings?
Dr. Correll: The main findings of the study that meta-analyzed data from 13 studies with 185,105 youth exposed to antipsychotics (average age 14.1 and 59.5 percent male) are that the absolute rates of type 2 diabetes are fortunately still relatively low, i.e. a cumulative type 2 diabetes risk of 5.7/1,000 patients and an exposure adjusted incidence rate of 3.1/1,000 patient-years. Nevertheless, the cumulative risk of 
Prof. Dimitrios Karussis[/caption]
MedicalResearch.com Interview with:
Prof. Dimitrios Karussis M.D., Ph.D.
Professor of Neurology
Head, Multiple Sclerosis Center
Hadassah BrainLabs
Medical Research: What is the background for this study? What are the main findings?
Prof. Karussis: BrainStorm Cell Therapeutics is developing innovative, autologous stem cell therapies for highly debilitating neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), and Parkinson’s Disease (PD). Our technology, NurOwn™ is a first-of-its-kind approach that induces autologous bone marrow-derived Mesenchymal Stem Cells (MSCs) to secrete Neurotrophic Growth Factors (NTFs). These MSC-NTF cells have been shown to be protective in several animal models of neurodegenerative diseases.
Data from the clinical trials described in the recent issue of the Journal of American Medicine – Neurology (JAMA Neurology), suggest that NurOwn can help patients with 
Dr. Aaron Dawes[/caption]
MedicalResearch.com Interview with:
Aaron J. Dawes, MD
Fellow, VA/RWJF Clinical Scholars Program
Division of Health Services Research
University of California Los Angeles
Los Angeles, CA 90024
Medical Research: What is the background for this study? What are the main findings?
Dr. Dawes: We reviewed the published literature to answer three basic questions about bariatric surgery and mental health conditions.
First, how common are mental health conditions among patients being referred for or undergoing bariatric surgery?
Dr. Diana Schendel[/caption]
MedicalResearch.com Interview with:
Diana Schendel, Professor MSO
Department of Public Health
Institute of Epidemiology and Social Medicine and
Department of Economics and Business National Centre for Register-based Research
Aarhus University
Denmark
Medical Research: What is the background for this study? What are the main findings?
Dr. Schende: Elevated mortality has been reported in persons with autism spectrum disorder (ASD), especially with comorbid epilepsy and intellectual disability. The effect of comorbidity on the risk for mortality in ASD, however, has not been rigorously examined in large, population-based studies. Our study aim was to investigate ASD mortality patterns overall and to assess the specific effects of comorbid mental, behavioral, and neurologic disorders on ASD mortality into young adulthood. Our study comprised a nation-wide Danish cohort of 1.9 million children of whom 20,492 were diagnosed with ASD. We observed 68 deaths in persons with ASD; 83% of the persons with ASD who died had comorbid mental/behavioral or neurologic disorders. The risk for mortality was two-fold higher in persons with 
Dr. Mayur Patel[/caption]
MedicalResearch.com Interview with:
Mayur Patel, MD, MPH, FACS
Assistant Professor of Surgery & Neurosurgery
Vanderbilt University Medical Center
Staff Surgeon and Surgical Intensivist
Nashville VA Medical Center
Medical Research: What is the background for this study?
Dr. Patel: Post-traumatic stress disorder (PTSD) can occur in patients after the traumatizing events of critical illness. Survivors of critical illness have reported PTSD symptoms months to even years after critical illness, possibly related to nightmare-like experiences, safety restraints creating communication barriers, and protective mechanical ventilation causing feelings of breathlessness and fear of imminent death. But, the epidemiology of PTSD after critical illness is unclear with wide ranging estimates (0-64%) and largely fails to distinguish past PTSD from new PTSD specifically resulting from the critical care experience.
Our study provides estimates on new cases of 
Dr. Silvia Sara Canetto[/caption]
MedicalResearch.com Interview with:
Silvia Sara Canetto, Ph.D., Professor
Faculty in the Department of Psychology, and
Affiliate Faculty in the
Center for Women's Studies and Gender Research,
Department of Ethnic Studies, and in the
Human Development and Family Studies Department
Colorado State University
Medical Research: What is the background for this study?
Dr. Canetto: In the United States, older men of European descent (so called white men) have significantly higher suicide rates than any other demographic group. For example, their suicide rates are significantly higher than those of older men of African, Latino or Indigenous descent, as well as relative to older women across ethnicities.
Behind these facts there is a cultural story, not just individual journeys of psychological pain and despair. Colorado State University’s Silvia Sara Canetto has spent a large portion of her research career seeking to uncover cultural stories of suicide.
A professor in the College of Natural Sciences’ Department of Psychology, Canetto adds a new chapter to that story in an article recently published in the journal Men and Masculinities. The article features a critical review of theories and research on suicide among older men.
Dr. Anick Bérard[/caption]
MedicalResearch.com Interview with:
Anick Bérard PhD FISPE
Research chair FRQ-S on Medications and Pregnancy
and Director, Réseau Québécois de recherche sur le médicament (RQRM)
and Professor, Research Chair on Medications, Pregnancy and Lactation
Faculty of Pharmacy University of Montreal
and Director, Research Unit on Medications and Pregnancy
Research Center
CHU Ste-Justine
Medical Research: What is the background for this study? What are the main findings?
Dr. Bérard: Paroxetine (one of the most used antidepressant during pregnancy) has been studied extensively over the past 10-12 years. In 2005, a black box warning was put on the Paxil label to caution against use during pregnancy due to the increased risk of cardiac defects. The ACOG 2010 guidelines also suggested switching to other antidepressants during pregnancy. Over the past decade, many studies, including meta-analyses, were performed on on paroxetine use during pregnancy and the risk of cardiac malformations - but results were sometimes statistically significant or not, although a consistent increased risk was observed. It was thought that these variations could be explained by different study designs, patient populations, and because maternal depression was not always taken into account correctly. Hence, we undertook another meta-analysis (the most recent and updated) to quantify the risk of cardiac defects overall as well as specific cardiac defects associated with paoxetine use during pregnancy and to assess the impact of study designs, maternal depression and patient population on the effect of the risk.
We found that women using paroxetine during the first trimester of pregnancy (critical time-window for malformations) were 23% more at risk of having a child with malformations (15 studies combined) - baseline risk of malformation is 3-5% and thus a 23% increased risk is 3.69-6.15% absolute risk; women using paroxetine during the first trimester of pregnancy were 28% more at risk of having a child with cardiac malformations (18 studies combined) - baseline risk of cardiac malformation is 1% and thus a 28% increased risk is 1.28% absolute risk. We found that paroxetine was increasing the risk of many specific cardiac defects as well. Although the estimates varied depending on the comparator group, study design, and malformation detection period, a trend towards increased risk was observed.
Josephine Mollon[/caption]
MedicalResearch.com Interview with:
Josephine Mollon MSc
Department of Psychosis Studies
Institute of Psychiatry, Psychology, and Neuroscience
King’s College London
London, England
Medical Research: What is the background for this study? What are the main findings?
Dr. Mollon: Psychotic symptoms, such as hallucinations and delusions, are core features of psychotic disorders. A significant minority of the general population also reports subclinical psychotic experiences. Evidence suggests that these experiences may lie on a continuum with clinically significant psychotic symptoms. For example, cognitive deficits, which are a hallmark of psychotic disorders, are also seen in people with subclinical psychotic experiences. We used population-based survey data to characterize cognitive functioning in adults with psychotic experiences while adjusting for important sociodemographic characteristics and investigating the effect of age.
The 171 (9.7%) adults with psychotic experiences showed significant memory and verbal deficits, but not IQ or processing speed deficits. Only participants 50 years and older with psychotic experiences showed medium to large impairments in general IQ, verbal knowledge, working memory and memory after adjusting for socioeconomic status, cannabis use, and common mental disorders.
Dr. Chugani[/caption]
MedicalResearch.com Interview with:
Diane C. Chugani, PhD
Director, Nemours Neuroscience Research
Nemours—AI DuPont Hospital for Children
Wilmington, DE 19803
Medical Research: What is the background for this study? What are the main findings?
Dr. Chugani: This clinical trial was performed at 5 sites throughout the country and was lead by our team at Wayne State University and Children’s Hospital of Michigan in Detroit. The study was sponsored by the National Institutes of Health through an Autism Centers of Excellence Network grant. Based upon our previous PET scanning studies showing low serotonin synthesis in the brains of young children with autism, we tested whether the serotonin-like drug buspirone would be beneficial in treating young children with Autism Spectrum Disorder. We found that low doses of buspirone were effective in reducing repetitive behaviors with no significant side effects in this group of children.
Dr. Zoltan Sarnyai[/caption]
MedicalResearch.com Interview with:
Zoltan Sarnyai, M.D., Ph.D.
Associate Professor of Pharmacology
Head, Laboratory of Psychiatric Neuroscience
Australian Institute of Tropical Health and Medicine (AITHM)
Comparative Genome Centre
Centre for Biodiscovery and Molecular Development of Therapeutics
James Cook University
Townsville, Australia
Medical Research: What is the background for this study?
Dr. Sarnyai: Schizophrenia has long been conceptualized as a disease contributed by the increased activity of the neurotransmitter system that provides dopamine for the brain. All clinically used antipsychotic drugs inhibit dopamine transmission in the brain by blocking dopamine receptors. These drugs have only a limited efficacy on a certain set of symptoms associated with schizophrenia. More recent research has uncovered that abnormal glucose and energy metabolism in the brain may contribute in the development of schizophrenia. This is not altogether surprising considering that our brain is using a disproportionately high amount of glucose to fuel neurotransmission (cell-to-cell communication in the brain), to maintain normal electrical activity of nerve cells and to deal with damaging free oxygen radicals. Therefore, even relatively small changes in the machinery that is required to provide energy for the brain cells can have very significant impact on brain function. In fact, recent studies have identified altered expression of genes and proteins that are responsible for enzymatic breakdown of glucose and proper handling of the metabolites to create the energy-rich molecule ATP. In addition, recent research shows decreased number and impaired function of the mitochondria, the powerhouses of the cell, in the brain of individuals with schizophrenia.
These recent results that show abnormal energy metabolism in schizophrenia raise the possibility of targeting metabolic pathways for therapeutic benefit in this condition. Ketogenic diet provides and alternative source of energy to the brain through fatty acids. Furthermore, since this diet is very low in carbohydrates, almost all the energy needs of the cells comes from breaking down fat (fatty acids) as opposed to glucose. This can circumvent the classic glucose metabolic pathways that maybe impaired in the disease. Also, breaking down fatty acids produces 40% more of the energy-rich molecule ATP than breaking down the carbohydrate glucose. Altogether, ketogenic diet may provide extra energy and can help neurotransmission in the brain, leading to the improvement of neurobiological processes underlying schizophrenia.
Dr. Rashmi Patel[/caption]
MedicalResearch.com Interview with:
Dr. Rashmi Patel
MA (Cantab) MA BM BCh PGDip (Oxon) MRCPsych
Psychiatry
King's College Londo
Dr. Martin[/caption]
MedicalResearch.com Interview with:
Dr Anne Martin PhD
Research Associate/Research Fellow
Physical Activity for Health Research Centre (PAHRC)
Institute for Sport, PE & Health Sciences
University of Edinburgh
TeleScot Research Group
Usher Institute for Population Health Sciences and Informatics
Edinburgh
Medical Research: What is the background for this study? What are the main findings?
Dr. Martin: Impairments in cognitive development during childhood can have detrimental effects on health behaviour, educational attainment, and socio-economic status later in life. Epidemiological evidence indicates an association between childhood obesity and cognition and educational attainment. Knowledge of when obesity related deficits in cognition and attainment emerge, and how large the deficits are at various ages, may be useful to support arguments for school-based obesity prevention initiatives and in translating evidence on this topic into policy aimed at preventing obesity.
In this study we explored whether the adverse association between obesity and cognition emerges in early childhood. Measures of cognitive abilities included visuo-spatial skills, expressive language skills and reasoning skills. Our findings indicated that obesity in the pre-school years may be weakly associated with some poorer cognitive outcomes at age 5 years in boys, independently of socioeconomic status.
Stronger relationships between obesity and