MedicalResearch.com Interview with:
Dr. Rebecca E. Amariglio Ph.D.
Massachusetts Alzheimers Disease Research Center
Massachusetts General Hospital
Medical Research: What is the background for this study? What are the main findings?
Dr. Amariglio: As the field of Alzheimer’s disease moves towards early detection and treatment, new tests that can measure very subtle changes in cognitive functioning are needed. A new instrument developed by the Alzheimer’s Disease Cooperative Study that measures subjective report of memory changes of both the study participant and a study partner (usually a family member) was associated with cognitive decline over four years. Specifically, greater report of memory concerns was associated with worse memory performance over time.
V. Zlokovic, MD, PhD
Professor and Chair
Department of Physiology and Biophysics
Keck School of Medicine of USC.
Medical Research: What is the background for this study? What are the main findings?
Dr. Zlokovic: Our team used high-resolution imaging of the living human brain to show for the first time that the brain’s protective blood barrier becomes leaky with age, starting at the hippocampus, a critical learning and memory center that is damaged by Alzheimer’s disease.
MedicalResearch.com Interview with:
Christian Benedict PhD
Associate Professor of Neuroscience
Uppsala University Dept. of Neuroscience
Medical Research: What is the background for this study?
Answer: Our study involved ~1500 men who were followed from 1970 to 2010. All participants were 50 years old at the start of study.
Medical Research: What are the main findings?
Answer: Men with reports of sleep disturbances had a 50%-higher risk to develop Alzheimer's disease during the 40-year follow-up period, than men without reports of sleep disturbances.
MedicalResearch.com Interview with:
Lena Johansson, PhD, MSc, RN
Institute of Neuroscience and Physiology
Department of Psychiatry and Neurochemistry
Sahlgrenska Academy at Gothenburg University
Medical Research: What are the main findings of the study?
Dr. Johansson: We found that a higher degree of neuroticism in midlife was associated with increased risk of Alzheimer’s disease over 38 years. On the 24 point scale, the risk increased with 4% per each step. Women who score high on the neuroticism scale were more likely to experience feelings such as anxiety, nervousness, worry, and irritability, and they were more moodiness and stress-prone.
The association between neuroticism and Alzheimer’s disease diminished after adjusting for longstanding perceived distress symptoms, which suggest that the associations was at least partly depended on long-standing distress symptoms.
When the two personality dimensions were combined, women with high neuroticism/low extraversion had a double risk of Alzheimer’s disease compared to those with low neuroticism/high extraversion.
MedicalResearch.com Interview with:
Sophie Billioti de Gage PharmD
University of Bordeaux Segalen
France
Medical Research: What are the main findings of the study?
Answer: The risk of Alzheimer’s disease was found increased by 43-51% in persons (>65) having initiated a treatment with benzodiazepines in the past (>5 years before). Risk increased with the length of exposure and when long acting benzodiazepines were used.
MedicalResearch.com Interview with:
Chuanhai Cao Ph.D.
Neuroscientist at the Byrd Alzheimer's Institute
and the USF College of Pharmacy.
Medical Research: What are the main findings of the study?
Dr. Cao: The major goal of this study was to investigate the effect of Ä9-tetrahydrocannabinol (THC), a major component of marijuana, on Alzheimer’s disease (AD) pathology. THC has long been known to have anti-inflammatory effects, but we were looking to determine whether THC directly affected amyloid beta (Aâ). Aâ aggregation is considered one of the key pathological hallmarks of Alzheimer’s disease. Our study showed that extremely low doses of THC were able to decrease Aâ production, inhibit Aâ aggregation, and enhance mitochondrial function in a cellular model of AD. Decreased levels of amyloid beta, coupled with THC’s inhibitory effect on aggregation may protect against the progression of Alzheimer’s disease.
MedicalResearch.com Interview with:
Dr. Caroline E Stephens PhD
Department of Community Health Systems
University of California, San Francisco
Medical Research: What are the main findings of the study?
Dr. Stephens: In our national random sample of nursing home residents, we found that mild cognitive impairment (CI) predicted higher rates of ED visits compared to no CI, but interestingly, ED visit rates decreased as severity of cognitive impairment increased. However, after nursing home residents were evaluated in the ED, severity of CI was not significantly associated with higher odds of hospitalization.
Another important finding was that the proportion of nursing home residents using feeding tubes more than tripled in advanced or end-stage dementia, from 9.9% to 33.8%. Moreover, tube-fed nursing home residents had 73% higher rates of total ED visits, but once evaluated in the ED, they were no more likely to be hospitalized than those without feeding tubes. This finding is particularly striking given the numerous existing studies that have questioned the utility and appropriateness of using feeding tubes in people with advanced dementia.
MedicalResearch.com Interview Invitation
Dr. Bryan K. Woodruff
Assistant Professor of Neurology
Mayo Clinic, Arizona
Medical Research: What are the main findings of the study?
Dr. Woodruff: There is evidence in the medical literature supporting a negative impact of losing a spouse for health conditions such as cancer or cardiovascular disease, but this has not been evaluated in terms of the impact of widowhood on the development of dementia. We used the National Alzheimer’s Disease Coordinating Center (NACC) database, which pools data gathered by multiple federally-funded Alzheimer’s disease research centers to try to answer this question. Specifically, we looked at the age at which individuals ultimately developed dementia in both individuals who lost their spouse and in those who remained married over the course of the study. Surprisingly, the data we analyzed did not support a negative impact of losing a spouse in individuals who had no cognitive difficulties when they entered the study, and we saw a paradoxical effect of widowhood in those with mild cognitive impairment (MCI).
MedicalResearch.com Interview with:
Susan Farr, Ph.D.
Research Professor of Geriatrics
Saint Louis University
MedicalResearch: What are the main findings of the study?
Dr. Farr: We found that reducing the conversion of amyloid precursor protein (APP) to beta amyloid with an antisense targeting the beta amyloid portion of amyloid precursor protein in the Tg2576 mouse which overexpresses human beta amyloid, improves learning and memory and reduces neuroinflammatory cytokine (inflammation in the brain).
MedicalResearch.com Interview with:
Yvette I. Sheline, M.D.
Professor of Psychiatry, Radiology, Neurology
Director, Center for Neuromodulation in Depression and Stress (CNDS)
University of Pennsylvania Perelman School of Medicine
Philadelphia, PA 19104
MedicalResearch: What are the main findings of this study?
Prof. Sheline: The main findings were that in transgenic mice who are genetically altered to develop Alzheimer's amyloid plaques, citalopram dramatically slowed the growth of plaques but did not cause existing plaques to shrink. In normal young people, it decreased the production of amyloid.
MedicalResearch.com Interview with: Niklas Mattsson MD, PhD University of California San Francisco Center for Imaging of Neurodegenerative Diseases VA Medical Center San Francisco, CA 94121,...
MedicalResearch.com Interview with:
Ziad Nasreddine MD FRCP(C)
Professeur adjoint
Université de Sherbrooke et McGill University
Neuro Rive-Sud/CEDRA: Centre Diagnostique et Recherche sur la Maladie d'Alzheimer Québec, Canada
MedicalResearch.com: What are the main findings of this study?
Dr. Nasreddine: The Montreal Cognitive Assessment (MoCA) total score (MoCA-TS) and Memory Index Score (MoCA-MIS) are useful in predicting conversion to Alzheimer’s disease (AD) in individuals with mild cognitive impairment (MCI). Identifying individuals with MCI at high of conversion to Alzheimer’s disease is important clinically and for selecting appropriate subjects for therapeutic trials.
MedicalResearch.com Interview with: Julian Benito-Leon University Hospital “12 de Octubre”, Madrid, Spain MedicalResearch.com: What are the main findings of the study? Dr. Benito-León: It...
MedicalResearch.com Interview with:
Ioannis Tarnanas M.Sc
Senior Researcher
Gerontechnology and Rehabilitation Research Group,
ARTORG Centre for Biomedical Engineering,
University of Bern, 3010 Bern, Switzerland
MedicalResearch.com: What are the main findings of the study?
Answer: We examined 75 healthy older people and 134 patients with mild cognitive impairment. Our aim was to collect neuropsychological, neurophysiological, neuroimaging and behavioural data by means of a virtual reality serious game, in order to model the profile of the patients who will progress to dementia within the next 2-4 years. We found that the prediction based on the performance at the virtual reality based computerized assessment instrument is comparable to that of more established and widely accepted biomarkers, such as ERP and MRI. This can be explained by the cognitive fidelity and richness of behavioural data collected with virtual reality based measures, which directly reflect neurocognitive processes affected at a very early stage.
MedicalResearch.com Interview with:
Prof. Dr. med. Piotr Lewczuk
Head,Lab for Clinical Neurochemistry
and Neurochemical Dementia Diagnostics,
Universitätsklinikum Erlangen,
Department of Psychiatry and Psychotherapy,
91054 Erlangen, Germany
MedicalResearch.com: What are the main findings of the study?
Prof. Dr. med. Piotr Lewczuk: In our study, we investigated the concentrations of four isoforms of amyloid beta peptides in the blood of healthy young volunteers without memory complains. The participants were stratified into three groups according to their apolipoprotein E (APOE) genotype, which is the mostly investigated and generally accepted genetic risk factor for sporadic Alzheimer’s Disease (AD). It is known that the alterations of the amyloid beta metabolism are the earliest changes in the course of AD, occurring many years (or even decades) before the onset of the clinical symptoms, but it is actually not known how early these alterations start. Correspondingly, we wanted to investigate if healthy persons with genetic risk factor show changes in their amyloid beta metabolism already 30-40 years before the age when AD is usually diagnosed. We did not find any differences between the groups with and without APOE-driven risk, which might be carefully interpreted as no signs of Alzheimer’s Disease pathology in persons at risk at such an early life stage. Taken together, we think that the Alzheimer’s Disease pathology starts some 10-20 years before the beginning of the clinical symptoms, but not earlier.
MedicalResearch.com Interview with:
Prof. Dr. Christa E. Müller
University of Bonn Pharmaceutical Institute Pharmaceutical
Chemistry I An der Immenburg 4 D-53121 Bonn (Endenich) Germany
MedicalResearch.com: What are the main findings of the study?
Prof. Dr. Christa E. Müller: Genetically altered mice which show an aggregation of Tau protein and many symptoms of Alzheimer's Disease which progressively worsen with time was used.
Caffeine was given to one group of mice at an early stage, when the symptoms were still moderate.
The caffeine-treated mice showed better memory and less inflammation and brain damages in comparison to the non-treated control mice. This means that caffeine protected the mice to some extent. The side effects were moderate.
MedicalResearch.com Interview with:
Rosebud O Roberts, M.B., Ch.B.
Professor of Epidemiology
Professor of Neurology
Mayo Clinic
MedicalResearch.com: What are the main findings of the study?
Dr. Roberts: We found that among persons 70 years and older, people with type 2 diabetes had a reduced glucose uptake (hypometabolism) in brain cells. We also found a similar association for people without type 2 diabetes but who had elevated hemoglobin A1c levels levels at the time of enrollment (HBA1c is a measure of glucose control, and represents the average blood glucose levels over a 3 month period). However, we did not find an association of diabetes with increased brain amyloid accumulation. Our findings were based on an investigation of the association of type 2 diabetes with markers of brain pathology: brain hypometabolism was assessed by 18F-fluorodeoxyglucose positron emission tomography [PET] and amyloid accumulation was assessed by 11-C Pittsburgh Compound B PET imaging.
Timothy Hughes, PhD, MPH
Roena B. Kulynych Center for Memory & Cognition Research
Department of Internal Medicine
Division of Gerontology and Geriatric Medicine
Wake Forest School of Medicine
Medical Center Boulevard, Winston-Salem, NC 27157-1207
MedicalResearch.com: What are the main findings of the study?
Dr. Hughes: This study is a follow-up to our recent paper that showed a novel relationship between arterial stiffness (commonly measured by pulse wave velocity) and the presence and extent of amyloid deposition in the brain, a hallmark of Alzheimer’s disease. For this study, we repeated brain amyloid imaging (using the Pittsburgh Compound B during PET imaging) in order to look for predictors of change in amyloid over two years in n=81 elderly adults aged 80+ and free from dementia. We observed that measures of systemic arterial stiffness (e.g. brachial ankle pulse wave velocity) was strongly associated with the extent of amyloid deposition in the brain at both baseline and follow-up. The change in brain amyloid accumulation over two years resulted in an increase in in the number of participants with Alzheimer’s-like (amyloid-positive) from 45% at baseline to a surprising 75% after just two years. This change in brain amyloid accumulation over two years was strongly related to having greater central stiffness (as measured by carotid femoral pulse wave velocity). These relationships between arterial stiffness and brain amyloid deposition were independent of the effects of age, gender, body mass index, antihypertensive medication use and even current blood pressure.
MedicalResearch.com Interview with:
Yanzhuang Wang, PhD
Associate professor
Dept. of Molecular, Cellular and Developmental Biology and Dept. of Neurology University of Michigan
Ann Arbor, MI 48109-1048
MedicalResearch.com: What are the main findings of the study?
Dr. Wang: We learned how to repair a cellular structure called the Golgi apparatus that is broken in Alzheimer’s disease. This helps us understand how to reduce the formation of the toxic plaques that kill cells in the brain of Alzheimer's patients. The formation of amyloid plaques is a hallmark of Alzheimer’s disease; but exactly how much the plaques contribute to the disease is still not known. Our study found that the broken Golgi in the disease may be a major source of the toxicity of amyloid plaques. We showed in this study that repairing the Golgi can reduce the formation of the toxic plaques and thus may delay the disease development.
MedicalResearch.com Interview with:
Dr. Erin Abner Ph.D.
Assistant Professor of Epidemiology
University of Kentucky College of Public Health
Lexington, Kentucky
MedicalResearch.com: What are the main findings of the study?
Dr. Abner: The findings from this study are preliminary results from The Prevention of Alzheimer’s Disease with Vitamin E and Selenium Study. This early look at the data indicates that very simple measures of memory change, in this case asking older men with no cognitive impairment about changes in their memory over the past year, and whether they believe those changes are a problem, can be used to predict cognitive impairment years later. Men who said at study baseline that the changes in their memory represented problems to them were over twice as likely as men who did not complain to develop clinically detectable cognitive impairment during follow-up. This is exciting because the field of Alzheimer’s research is moving toward earlier intervention in the disease process. As of now, our best methods for identifying individuals without cognitive impairment who are likely to develop Alzheimer’s disease in the future are procedures that many people find intimidating, like lumbar puncture and PET scanning. Identifying older adults at high risk for future cognitive impairment with low-cost, non-invasive screening techniques would help researchers to target potential therapies to the people who stand to benefit the most.
MedicalResearch.com Interview with:
Anton P. Porsteinsson M.D.
William B. and Sheila Konar Professor of Psychiatry
Director, Alzheimer's Disease Care, Research and Education Program (AD-CARE)
University of Rochester School of Medicine and Dentistry
Rochester, N.Y. 14620
MedicalResearch.com: What are the main findings of the study?
Dr. Porsteinsson: Identifying drugs outside the antipsychotic class with targeted anti-agitation effects that provide greater benefit or lower risk among patients with Alzheimer’s disease is a research priority. Citalopram, a selective serotonin reuptake inhibitor (SSRI), is frequently used in older individualsand has been suggested as an alternative to antipsychotic drugs for agitation and aggression in dementia. Among 186 patients with probable Alzheimer’s disease and agitation receiving psychosocial intervention, the addition of citalopram compared with placebo robustly and significantly reduced agitation and caregiver distress, but modest cognitive and cardiac adverse effects of citalopram may limit its practical application at the 30 mg/d dose studied in this trial. There are insufficient data on efficacy for agitation at lower doses of citalopram.
MedicalResearch.com Interview with:
Rachelle S. Doody, M.D.,Ph.D.
Effie Marie Cain Chair in Alzheimer's Disease Research
Director, Alzheimer's Disease and Memory Disorders Center
Baylor College of Medicine-Department of Neurology
Houston, Texas 77030: MedicalResearch.com
MedicalResearch.com: What are the main findings of the study?
Dr. Doody: The study set out to see whether the antibody infusion treatment, Solanezumab, would improve the course of mild to moderate Alzheimer's disease in the ways necessary to gain drug approval. Unfortunately, the results did not support an approvable treatment for this purpose.
MedicalResearch.com Interview with: Jason R. Richardson MS, PhD, Associate Professor Department of Environmental and Occupational Medicine Robert Wood Johnson Medical School and Resident...
MedicalResearch.com Interview with: Stephen Salloway, MD, MS Director of Neurology and the Memory and Aging Program, Butler Hospital Professor of Neurology and...
MedicalResearch.com Interview Invitation
Maurice Dysken, MD
Professor, School of Medicine
Department of Psychiatry
Minneapolis VA Health Care System,
Minneapolis, Minnesota
MedicalResearch.com: What are the main findings of the study?
Dr. Dysken: In patients with mild-to-moderate Alzheimer’s disease who were taking an acetylcholinesterase inhibitor, a dosage of 2000 IU/d of vitamin E significantly slowed functional decline compared to placebo by 6.2 months over the mean follow-up period of 2.27 years. Over this period of time caregiver time increased least in the vitamin E group compared to the other three groups (memantine alone, vitamin E plus memantine, and placebo) although the only statistically significant difference was between vitamin E alone and memantine alone. There were no significant safety concerns for vitamin E compared to placebo and mortality was lowest in the vitamin E alone group. It should be noted that patients who were on warfarin were excluded from the study because of a possible interaction with vitamin E that could have possibly increased bleeding events.
Dr. Bruce Reed PhD
Professor of Neurology,
Associate Director UC Davis Alzheimer's Disease Center
Davis, CA 95616
MedicalResearch.com: What are the main findings of the study?
Dr. Reed: We found that high LDL cholesterol and low HDL cholesterol in blood were both associated with higher amyloid deposition in the brain. This is potentially very important because the deposition of amyloid seems to be a critical step that kicks off a whole chain of events that eventually lead to Alzheimer's disease. It is widely believed (although not proven) that if this deposition of amyloid could be blocked that we could greatly decrease the incidence of Alzheimer's. The connection to cholesterol is exciting because we know a fair amount about how to change cholesterol levels. A great deal more research needs to be done, but this does suggest a potential new path toward trying to prevent AD.
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