Alzheimer's - Dementia, Author Interviews, Cognitive Issues, Memory, University Texas / 28.06.2016

MedicalResearch.com Interview with: Timothy Q. Duong, Ph.D Stanley I. Glickman MD Professor of Ophthalmology, Radiology, and Physiology South Texas Veterans Health Care System, VA Southwest National Primate Research Center University of Texas Health Science Center San Antonio, Texas MedicalResearch.com: What is the background for this study? What are the main findings? Response: A single oral dose of methylene blue increased fMRI response in the bilateral insular cortex during a task that measured reaction time to a visual stimulus. The fMRI results also showed an increased response during short-term memory tasks involving the brain’s prefrontal cortex, which controls processing of memories. Methylene blue was also associated with a 7 percent increase in correct responses during memory retrieval. The findings suggest that methylene blue can regulate certain brain networks related to sustained attention and short-term memory after a single oral low dose. (more…)
Alzheimer's - Dementia, Author Interviews, Cost of Health Care, Geriatrics / 22.06.2016

MedicalResearch.com Interview with: Pei-Jung Lin, Ph.D. Assistant Professor Center for the Evaluation of Value and Risk in Health Institute for Clinical Research and Health Policy Studies Tufts Medical Center Boston, MA 02111 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Alzheimer’s disease (AD) is a slow, progressive disease. Many people with AD may live for years with the disease left unrecognized or untreated, in part because the early symptoms are mild and often mistaken as part of normal aging. In this study, we found that Alzheimer’s patients may use more health care services and incur higher costs than those without dementia even before they receive a formal diagnosis. For example, total Medicare expenditures were 42% higher among Alzheimer’s patients than matched controls during the year prior to diagnosis ($15,091 vs. $10,622), and 192% higher in the first year immediately following diagnosis ($27,126 vs. $9,274). We also found similar trends among Medicare patients with mild cognitive impairment (MCI)— a prodromal stage of AD and associated with higher dementia risk. Our study suggests that an Alzheimer’s disease or MCI diagnosis appears to be prompted by other health problems such as cardiovascular and cerebrovascular diseases, pneumonia, renal failure, urinary tract infections, and blood and respiratory infections. This finding likely reflects a failure of ambulatory care related to the impact of cognitive impairment on other chronic conditions. (more…)
Alzheimer's - Dementia, Author Interviews, Brigham & Women's - Harvard, JAMA, Stroke / 14.06.2016

MedicalResearch.com Interview with: Alessandro Biffi, MD Behavioral Neurology and Neuropsychiatry Departments of Neurology and Psychiatry Massachusetts General Hospital / Harvard Medical School MedicalResearch.com: What is the background for this study? Dr. Biffi: Intracerebral Hemorrhage (ICH) is the most severe form of stroke. It is a form of hemorrhagic (i.e. bleeding) stroke that accounts for ~ 15% of all acute cerebrovascular conditions, affecting ~ 70,000 Americans every year. However, because of its severity it is responsible for almost half of all stroke-related disability worldwide. Survivors of ICH are at very high risk for cognitive impairment (up to and including dementia) following the acute cerebral bleeding event. However, we possess very limited understanding of the time dynamics and risk factors for post-ICH dementia. In particular, prior to our study it was unclear whether the acute cerebral injury due to ICH would be the only mechanism potentially responsible for subsequent development of dementia. This question is motivated by prior observations suggesting that Intracerebral Hemorrhage represents the acute manifestation of cerebral small vessel disease, a progressive degenerative disorder of small caliber arteries of the central nervous system. There exist two major subtypes of small vessel disease: 1) cerebral amyloid angiopathy, caused by the deposition of a toxic protein product, beta-amyloid, in the blood vessels (in a process similar to the formation of beta-amyloid plaques that cause Alzheimer's disease); 2) arteriolosclerosis, caused by long-standing elevated blood pressure. ICH survivors have been previously shown to harbor very severe small vessel disease, which has been linked to dementia in patients without cerebral bleeding. Our hypothesis was that early-onset dementia (occurring in the first 6 months after ICH) is a manifestation of the acute neurological damage associated with cerebral bleeding, whereas delayed onset dementia (developing beyond 6 months from the acute ICH event) is associated with known markers of small vessel disease, including imaging findings on CT/MRI and genetic markers (such as the APOE gene). (more…)
Aging, Alzheimer's - Dementia, Antioxidants, Author Interviews, Nutrition, Supplements / 04.06.2016

MedicalResearch.com Interview with: Jennifer Lemon, PhD Research Associate Medical Radiation Sciences McMaster University MedicalResearch.com: What is the background for this study? Dr. Lemon: Research with the supplement began in 2000, as part of my doctoral degree; we developed the supplement to try to offset the severe cognitive deterioration and accelerated aging in a mouse model we were working with in the lab. Based on aging research, five mechanisms appeared to be key contributors to the process of aging; those include oxidative stress, inflammation, mitochondrial deterioration, membrane dysfunction and impaired glucose metabolism. The criteria we used for including components in the supplement were as follows: each one of the 30 components had scientific evidence to show they acted on one or more of the above mechanisms were able to be taken orally, and were available to humans over-the-counter. Even then the hope was that if the formulation was successful, this would make it more available to the general public. (more…)
Alzheimer's - Dementia, Author Interviews, Geriatrics, Johns Hopkins / 03.06.2016

MedicalResearch.com Interview with: Halima Amjad, MD, MPH Post-doctoral Fellow Johns Hopkins University School of Medicine Division of Geriatric Medicine and Gerontology MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Amjad: Safety is an important aspect of dementia care. Dementia is underdiagnosed, however, and there is limited understanding of safety issues in people with undiagnosed dementia. We wanted to better understand potentially unsafe activities and living conditions in all older adults with dementia and specifically examine these activities in undiagnosed dementia. We found that in all study participants with probable dementia, the prevalence of driving, cooking, managing finances, managing medications, or going to physician visits alone was over 20%. The prevalence was higher in older adults with probable dementia without a diagnosis, and even after accounting for sociodemographic, medical, and physical impairment factors, the odds of engaging in these activities was over 2.0 in undiagnosed versus diagnosed probable dementia. Potentially unsafe living conditions including unmet needs and performance on cognitive tests were similar between these groups. (more…)
Alzheimer's - Dementia, Author Interviews / 01.06.2016

MedicalResearch.com Interview with: Prof. Margitta Elvers, PhD Institute of Hemostasis, Hemotherapy and Transfusion Medicine University Clinic of the Heinrich-Heine-University Düsseldorf Düsseldorf Germany MedicalResearch.com: What is the background for this study? What are the main findings? Prof. Elvers: Platelets are the main players in hemostasis and thrombosis, but are also recognized to be involved in the pathology of different neurodegenerative diseases. It is well known that amyloid-beta is able to activate platelets and to induce platelet activation. In Alzheimer’s Disease (AD) patients, platelet activation is enhanced and a correlation between AD and vascular diseases such as stroke and atherosclerosis was shown in different studies However, a direct contribution of platelets to the progression of Alzheimer’s disease (AD) was an open question for many years. In the last years our group in Düsseldorf, Germany, provided strong evidence for platelets to play a relevant role in the progression of AD, because AD transgenic mice showed enhanced platelet signaling that translated into almost unlimited thrombus formation in vitro and accelerated carotid artery occlusion in vivo suggesting that these mice are at high risk of arterial thrombosis leading to cerebrovascular and unexpectedly to cardiovascular complications that might be also relevant in AD patients. In the recent study, we analyzed the contribution of platelets, which accumulate at vascular Abeta deposits, to cerebral amyloid angiopathy (CAA), a vascular dysfunction in most of  Alzheimer’s disease patients, characterized by deposits of Abeta in the wall of cerebral vessels. We found that synthetic monomeric Abeta is able to bind to integrin alphaIIbbeta3 via its RHDS (Arg-His-Asp-Ser) sequence thereby stimulating the release of adenosine diphosphate (ADP) and clusterin from platelets. ADP enhanced integrin activation via the ADP receptors P2Y1 and P2Y12 and further increased platelet clusterin release and Abeta fibril formation. Clopidogrel, an antiplatelet drug which irreversible inhibits P2Y12, inhibited Abeta aggregation in human and murine platelet cell cultures. Treatment of AD transgenic mice with clopidogrel for three months reduced clusterin plasma levels and the incidence of CAA. (more…)
AHA Journals, Alzheimer's - Dementia, Author Interviews, Blood Pressure - Hypertension, Cognitive Issues, Stroke / 23.05.2016

MedicalResearch.com Interview with: Kazem Rahimi, DM, MSc Oxford Martin School University of Oxford United Kingdom MedicalResearch.com: What is the background for this study? Dr. Rahimi: Vascular dementia is the second most common cause of dementia and is increasing in prevalence worldwide. Vascular dementia often occurs after stroke and can cause apathy, depression, and a decline in cognitive function, and can eventually result in death. High blood pressure (BP) has been identified as a potential risk factor for the development of vascular dementia. However, previous studies, which have been small in size, have reported conflicting results on the relationship between blood pressure and vascular dementia. (more…)
Alzheimer's - Dementia, Author Interviews, Rheumatology / 16.05.2016

MedicalResearch.comcom Interview with: Hui-Wen Lin MD, PHD Department of Mathematics, Soochow University Evidence-Based Medicine Center, Wan Fang Hospital, Taipei Medical University Taipei, Taiwan MedicalResearch.com: What is the background for this study? Dr. Hui-Wen Lin: Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder that affects multiple organ systems and it predominantly affects women aged 20 to 40 years, and clinical symptoms caused by autoantibody deposition that triggers subsequent inflammatory reactions vary between individuals. There were 30~80% of SLE patients present neurological symptoms, and it is referred to as neuropsychiatric SLE (NPSLE). However there is no research about risk of dementia for SLE patients. Therefore we investigated this issue by analyzing the National Health Insurance Research Database in Taiwan. (more…)
ALS, Alzheimer's - Dementia, Author Interviews, Nature / 07.05.2016

MedicalResearch.com Interview with: Ana Pereira, MD Instructor in Clinical Medicine Bruce McEwen's laboratory Rockefeller University  MedicalResearch.com: What is the background for this study? Dr. Pereira: The neurons most susceptible to dying in Alzheimer’s disease are the ones that use glutamate as a neurotransmitter (chemical messengers that enable neurotransmission). Glutamate is the major excitatory neurotransmitter in the brain and its regulation is critical for learning and memory. When glutamate is not located in the correct place and amount, it causes several deleterious effects to neurons that can ultimately lead to cell death. Importantly, the glutamate transporter EAAT2 is the dominant regulator of glutamate levels and it is highly depressed in Alzheimer’s disease. Furthermore, glutamatergic dysregulation is implicated in several pathological mechanisms in Alzheimer’s disease including the release and toxicities of the proteins implicated in Alzheimer’s disease: amyloid-beta (which form amyloid plaques) and tau (which form neurofibrillary tangles). Better regulation of glutamatergic neural circuits is critically important to effectively treat age-related cognitive decline and Alzheimer’s disease. (more…)
Alzheimer's - Dementia, Author Interviews, Heart Disease / 06.05.2016

MedicalResearch.com Interview with: T. Jared Bunch, MD Director of Heart Rhythm Research Medical Director for Heart Rhythm Services Intermountain Healthcare System MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Bunch: Approximately 6 years ago we found that patients with atrial fibrillation experienced higher rates of all forms of dementia, including Alzheimers disease.  At the time we started to ask the questions of why this association existed.  We know that atrial fibrillation patients experience higher rates of stroke.  These patients are placed on blood thinners, most commonly warfarin, to lower risk of stroke which at the same time expose that patient to a higher risk of intracranial bleeding.  One possibility to explain the association was that perhaps dementia in the manifestation of many small clots or bleeds in the brain that in total lead to cognitive decline.  If this is the case, then the efficacy and use of anticoagulation is very important in atrial fibrillation patients. We conducted additional studies that showed this to be the case.  In patients with no history of dementia, managed long-term with warfarin anticoagulation, those that had levels that were frequently too higher or too low that resulted in poor times in therapeutic range, experienced significantly higher rates of dementia.  The risk was highest in younger atrial fibrillation patients that were less than 80 years of age.  We then found that in atrial fibrillation patients that were frequently over anticoagulated and also use an antiplatelet agent, aspirin or plavix, the dementia rates nearly doubled.  At this point we raised the question if atrial fibrillation increased the risk beyond anticoagulation, or does anticoagulation efficacy drive most of the risk.  This question formed the background of the current study. (more…)
Alzheimer's - Dementia, Author Interviews, Depression, Lancet / 02.05.2016

MedicalResearch.com Interview with: Saira Saeed Mirza, MD, PhD Department of Epidemiology Erasmus MC, Rotterdam MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Mirza: Depressive symptoms appearing in late-life have been extensively studied for their relationship with dementia. They not only very frequently occur in demented patients, but also predict dementia. In this context, depressive symptoms have largely been assessed at a single time point only. However, depression is a disorder which remits and relapses, and symptoms do not remain same over the years. Given this pattern of disease progression, it is more important to study the course of depression over time in relation to long-term health outcomes such as dementia, rather than assessing it at a single time-point, which will neglect the course of depression. This is important as people follow different courses of depression, and different courses of depression might carry different risks of dementia. When we studied the course of depressive symptoms over 11 years in community dwelling older adults in Rotterdam, and the subsequent risks of dementia, we observed that only those who had increasing or worsening depressive symptoms were at a higher risk of dementia. In this group of people, about one in five persons developed dementia. Interestingly, people suffering from high depressive symptoms at a single time point were not at a higher dementia risk than those without depressive symptoms. (more…)
Alzheimer's - Dementia, Author Interviews, Dermatology / 01.05.2016

MedicalResearch.com Interview with: Alexander Egeberg, MD PhD National Allergy Research Centre, Departments of Dermato-Allergology and Cardiology Herlev and Gentofte University Hospital University of Copenhagen Hellerup, Denmark  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Egeberg: Certain proteins and inflammatory processes have been found in increased levels in the skin of patients with rosacea, and these have also been linked to dementia, in particular Alzheimer's disease. While this may be one potential explanation, we cannot say for sure that this is the cause. Our team have recently shown a link between rosacea and other neurological diseases, and single-case reports have previously described a possible association between rosacea and Alzheimers disease. However, this is the first comprehensive investigation of Alzheimer's disease in a large population of patients with rosacea. We found a slightly increased risk of dementia, in particular Alzheimer's disease in patients with rosacea. (more…)
Alzheimer's - Dementia, Author Interviews, Biomarkers / 27.04.2016

MedicalResearch.com Interview with: Dr Anne Poljak Leader of the Proteomics Group Centre for Healthy Brain Ageing (CHeBA) UNSW, Australia  MedicalResearch.com: What is the background for this study?  Dr Poljak: Amyloid-beta (Aβ) peptides are found in abundance in the plaque particles which build up in the Alzheimer’s brain and small blood vessels of the brain, and are therefore considered hallmark features of Alzheimer’s disease. However they are also found in blood which is a convenient body fluid for sampling purposes. We therefore wished to assay them in plasma samples from one of our longitudinal population based studies of older age individuals (70 – 90 years) – the Centre for Healthy Brain Ageing’s Sydney Memory and Ageing Study. Other research groups had previously measured these peptides in plasma, but there was controversy in the area because of differences in outcomes across laboratories. So one of the main questions was whether plasma levels of Aβ peptides have any relationship with what is happening in the brain, or are they a red-herring? We wanted to see how the levels we found would compare with the findings of others in relation to Alzheimer’s disease and mild cognitive impairment. A further question was how our plasma levels would relate to other clinical measures including cognition and brain volumetrics. One of the precautions we took was to use an assay kit with very well characterized antibodies, so we could be confident that our method was specific for the two full length Aβ peptides (Ab1-40 and Ab1-42). (more…)
Alzheimer's - Dementia, Author Interviews, JAMA, UCSF / 20.04.2016

MedicalResearch.com Interview with: Jennifer S. Yokoyama, PhD Assistant Professor, Memory and Aging Center University of California, San Francisco MedicalResearch.com: What is the background for this study? Dr. Yokoyama: Alzheimer’s disease is a common neurodegenerative disease that occurs in older adults. Clinically, Alzheimer’s disease is primarily associated with changes in cognition (e.g., declines in memory, language and visuospatial functioning). Pathologically, Alzheimer’s disease is associated with misfolded amyloid beta and tau proteins and can only be definitively diagnosed at autopsy. It has long been appreciated that there is a link between the immune system and Alzheimer’s disease, and there are multiple sources of evidence that suggest that immune activity may be increased in patients with Alzheimer’s. Although there is strong evidence for an association between immune activity and Alzheimer’s disease there has always been a chicken-egg problem because we don’t know whether the Alzheimer’s disease process triggers the immune response or whether altered immune function promotes the Alzheimer’s disease process. Genetic information can offer important clues about the role of the immune system in Alzheimer’s disease. Each person has a unique genetic fingerprint, and different combinations of gene changes (“variants”) put individuals at higher or lower risk for different diseases. Genetic data enables us to test whether having a certain genetic variant puts people at greater risk for both Alzheimer’s disease and autoimmune diseases, immune system diseases in which the immune system is overactive (e.g., Crohn's disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes, Celiac's disease, and psoriasis). Rather than only responding to foreign objects such as bacteria and viruses, in autoimmune diseases the immune system also responds to the body’s own material, which do not ordinarily create an immune response, thereby leading to symptoms associated with higher levels of inflammation and other long-term problems. A variant that increases risk for both Alzheimer’s disease and autoimmune diseases would suggest a common biological pathway. MedicalResearch.com: What are the main findings? Dr. Yokoyama: In our study we tested whether there are genetic variants that put people at increased risk for both Alzheimer's disease and autoimmune diseases. We found eight genetic variants that influence people’s risk for both Alzheimer's disease and autoimmune disease. Some of these variants were associated with lower risk of autoimmune disease and Alzheimer’s disease, but two variants were associated with greater risk for both.   (more…)
Alzheimer's - Dementia, Author Interviews / 12.04.2016

MedicalResearch.com Interview with: Dr. Sven Joubert, PhD Département de psychologie, Université de Montréal Centre de recherche Institut universitaire de gériatrie de Montréal (CRIUGM) Montréal, Canada MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Joubert: Difficulties in recognizing familiar people in Alzheimer's disease have typically been attributed to the underlying memory impairment. There is evidence however that people with Alzheimer's disease also have difficulties in visual perception. The aim of this study was to determine if people with Alzheimer's were specifically impaired at face perception. In the current study, people with Alzheimer's along with healthy seniors were asked to process pictures of faces and cars at both upright and inverted orientation. Results showed that persons with Alzheimer's disease had a reduced face inversion effect, in other words they had a disproportionate impairment in processing upright relative to inverted faces. This reduced inversion effect in Alzheimer's disease, which was specific to faces, may reflect a reduced ability in "holistic" processing of faces, in other words the ability to form intergrated and individualized representations of faces based on their local features. (more…)
Alzheimer's - Dementia, Author Interviews, Depression, JAMA, UCSF / 18.03.2016

MedicalResearch.com Interview with: Allison R. Kaup, PhD Assistant Adjunct Professor, UCSF Department of Psychiatry Clinical Research Psychologist / Clinical Neuropsychologist and Kristine Yaffe MD Professor of Psychiatry, Neurology and Epidemiology Chief of Geriatric Psychiatry and Director of the Memory Evaluation Clinic San Francisco VA Medical Center  MedicalResearch.com: What is the background for this study? Response: Previous research has shown that older adults with depression are more likely to develop dementia.  But, most studies have only examined an older adult’s depressive symptoms at one point in time.  This is an important limitation because we know that depressive symptoms change over time and that older adults show different patterns of depressive symptoms over time.  For the present study, older adults were followed for several years.  We assessed what patterns of depressive symptoms they tended to have during the early years of the study, and then investigated whether these different patterns were associated with who developed dementia during the later years of the study. MedicalResearch.com: What are the main findings? Response: Older adults in this study tended to show one of 3 different patterns of depressive symptoms.  Most tended to have few, if any, symptoms over time.  Some tended to have a moderate level of depressive symptoms at the beginning of the study, which increased over time.  And others tended to have a high level of depressive symptoms at the beginning of the study, which increased over time. We found that older adults with the high-and-increasing depressive symptoms pattern were almost twice as likely to develop dementia than those with minimal symptoms, even when accounting for other important factors.  While older adults with the moderate-and-increasing depressive symptom pattern were also somewhat more likely to develop dementia, this association was not as strong and did not hold up in our statistical models when we accounted for what individuals’ cognitive functioning was like during the early years of the study. (more…)
Alzheimer's - Dementia, Author Interviews, Exercise - Fitness, Lifestyle & Health / 14.03.2016

MedicalResearch.com Interview with: Cyrus A. Raji, MD, PhD Resident in Diagnostic Radiology UCLA Health System  MedicalResearch.com: What is the background for this study? What are the main findings? Dr. Raji: The purpose of this study was to investigate the relationship between caloric expenditure from leisure physical activities (15 different ones were assessed from walking to gardening to dancing to swimming etc.). Increased caloric expenditure from these physical activities were related to larger gray matter volumes in key brain areas for memory and learning (hippocampus, precuneus) that are also affected by Alzheimer's. These findings were demonstrated in 876 persons who had MRI scans and caloric expenditure assessed. Five years after the scan a subset of 326 persons from the larger group of 876 were followed cognitively and it was found that those with larger gray matter volumes associated with physical activity in the orbital frontal cortex and precuneus had a 2 fold reduction in the risk for cognitive decline to mild cognitive impairment and Alzheimer's dementia.  (more…)
Alzheimer's - Dementia, Author Interviews, Cognitive Issues, Education, Mayo Clinic, Neurology / 25.02.2016

MedicalResearch.com Interview with: Prashanthi Vemuri, PhD Mayo Clinic Rochester, Minnesota  Medical Research: What is the background for this study? What are the main findings? Dr. Vemuri: Lifetime Intellectual enrichment has been found to delay the symptoms of dementia but the impact on brain changes due to Alzheimer’s disease has been poorly understood. In this study we studied the impact of lifetime intellectual enrichment (education, occupation, and midlife cognitive activities) on the brain changes related to Alzheimer’s disease. We obtained serial imaging on 393 individuals from a population based sample. We found that in majority of the individuals, there were minimal effects of intellectual enrichment on brain changes due to Alzheimer’s disease. However in those with higher genetic risk of Alzheimer’s, lifetime intellectual enrichment had a protective effect on the brain. (more…)
Alzheimer's - Dementia, Author Interviews, Dental Research, Infections, Stroke / 18.02.2016

MedicalResearch.com Interview with: Dr. Robert Friedland MD Mason C. and Mary D. Rudd Endowed Chair In Neurology Professor, Dept. of Neurology University of Louisville Health Care Outpatient Center Louisville, KY 40292 Medical Research: What is the background for this study? What are the main findings? Dr. Robert Friedland: Oral infectious diseases are associated with stroke. Previous research by this group has shown that oral bacteria, cnm-positive Streptococcus mutans, was associated with cerebral microbleeds and intracerebral hemorrhage. We developed this study to investigate the roles of this bacteria in patients entering the hospital for all types of stroke. Among the patients who experienced intracerebral hemorrhage (ICH), 26 percent were found to have a specific bacterium in their saliva, cnm-positive S. mutans. Among patients with other types of stroke, only 6 percent tested positive for the bacterium. We also evaluated MRIs of study subjects for the presence of cerebral microbleeds (CMB), small brain hemorrhages which may cause dementia and also often underlie ICH. We found that the number of CMBs was significantly higher in subjects with cnm-positive S. mutans than in those without. (more…)
Alzheimer's - Dementia, Author Interviews, JAMA, Pharmacology / 15.02.2016

MedicalResearch.com Interview with: Dr. Britta Haenisch PhD German Center for Neurodegenerative Diseases (DZNE)  Medical Research: What is the background for this study? Dr. Haenisch: Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal diseases, but have also been shown to be potentially involved in cognitive decline: There were hints from recent other studies that PPIs might affect cognition, e.g. Lam et al. (2013) report a significant association of PPI use with vitamin B12 deficiency in a population-based sample. Vitamin B12 deficiency has been shown to be associated with cognitive decline. In another study, PPIs were observed to enhance amyloid beta peptide (Aβ) levels in mouse brain by affecting the enzymes β- and γ-secretase which leads to increased Aβ levels in mice. Medical Research: What are the main findings? Dr. Haenisch: The current study provides a statistical association (applying a time-dependent analysis) between proton pump inhibitors prescription and occurrence of dementia with a focus on long-term regular PPI prescription in patients aged 75 years and older. In our analysis we focused on long-term regular PPI prescription for at least 18 months. It does not prove that proton pump inhibitors cause dementia. References -Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-2442. -Badiola N, Alcalde V, Pujol A, et al. The proton-pump inhibitor lansoprazole enhances amyloid beta production. PLoS One. 2013;8(3):e58837 (more…)
Alzheimer's - Dementia, Author Interviews, Blood Pressure - Hypertension, NIH / 03.02.2016

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. (more…)
Alzheimer's - Dementia, Author Interviews, Diabetes / 27.01.2016

MedicalResearch.com Interview with: Dr. Erin L. Abner PhD Sanders-Brown Center on Aging and Alzheimer's Disease Center College of Public Health, University of Kentucky Lexington, KY  Medical Research: What is the background for this study? What are the main findings? Dr. Abner: Diabetes is an important public health concern, and it has been linked to cognitive impairment and dementia, including dementia due to Alzheimer’s disease, in multiple studies of aging and cognition. Diabetes is considered by many to be a risk factor for Alzheimer’s disease, and there are many good reasons for scientists to have come to this conclusion. But, there are many brain diseases other than Alzheimer’s that cause dementia, and correctly identifying Alzheimer’s in a clinical patient can be deceptively difficult. When we looked at a very large sample of autopsied research volunteers (>2000 persons), we found that brain infarcts were more common among people with diabetes compared to people without, but Alzheimer’s pathology was about the same in both groups. Others have made this observation before, but in much smaller samples. Replicating this finding in a large sample is strong evidence that it is in fact cerebrovascular disease and not Alzheimer’s pathology that should be the primary concern among people with diabetes. In addition, we found that having diabetes was predictive of worsened global cognition at the end of life. (more…)
Alzheimer's - Dementia, Author Interviews, Cognitive Issues, Memory / 26.01.2016

MedicalResearch.com Interview with: Dr. Brian K. Lebowitz, PhD ABPP-CN DIRECTOR OF NEUROPSYCHOLOGY TRAINING Clinical Neuropsychologist Clinical Assistant Professor, Neurology Stony Brook University Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Lebowitz: As a lifespan neuropsychologist, my clinical work involves evaluating cognitive concerns in both children and adults.  We know that children with learning disorders, such as dyslexia, often demonstrate difficulties on neuropsychological tests that are seemingly unrelated to reading.  For example, children with dyslexia may have difficulty with auditory processing and short-term memory.  We also know that, for many individuals, learning disorders remain present throughout the lifespan.  Despite awareness of the relationship between reading disorder and other areas of cognitive weakness, many clinicians who work with older adults do not routinely ask about academic/neurodevelopmental history.  Further, little research has assessed the potential impact of lifelong learning disorder on later life neuropsychological test performance. Our study attempted to assess whether or not a history of possible reading disorder increased the likelihood that an individual's performance would fall at a level suggestive of possible Mild Cognitive Impairment MCI), a diagnosis associated with increased risk for Alzheimer’s disease.  Individuals with MCI continue to function normally in everyday life but experience subjective memory problems and identified weaknesses on neuropsychological tests.  Our study found a strong relationship between poor reading ability and low memory test scores on two tests commonly used to evaluate memory complaints in older adults.  Depending on the test, individuals with a suspected reading disorder were two to three-and-one-half times more likely than their peers to score at a level indicative of Mild Cognitive Impairment. (more…)
ALS, Alzheimer's - Dementia, Author Interviews, JAMA, Multiple Sclerosis, Neurological Disorders, Stem Cells / 12.01.2016

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 ALS.  The two trials featured in the article, a phase 1/2 and a phase 2a, studied the transplantation NurOwn cells in ALS patients.  These trials confirmed the excellent safety profile of NurOwn and suggest a clinically meaningful effect. The investigators used two well established clinical endpoints that measure disease activity in ALS, the Revised ALS Functional Rating Scale and Forced Vital Capacity, and were able demonstrate a slowing of disease activity in the period following treatment. (more…)
Alcohol, Alzheimer's - Dementia, Author Interviews, BMJ / 11.12.2015

MedicalResearch.com Interview with:

Professor, Frans Boch Waldorff General Practitioner Research Unit of General Practice Denmark

MedicalResearch: What is the background for this study? What are the main findings? Prof. Waldorff: While there are numerous studies focusing on alcohol as a risk factor for dementia and mortality in healthy subjects, virtually no attention has been paid to the effect of alcohol consumption in patients with Alzheimer’s disease (AD). Considering that AD is a neurodegenerative disorder and that alcohol has known neurotoxic effects, one could easily jump to the conclusion that alcohol is damaging for patients with AD. The aim of this study was to investigate whether the positive association between moderate alcohol intake and mortality shown in population-based studies on healthy subjects can be transferred to patients with mild AD. In our study we found that patients with mild  Alzheimer’s disease , moderate alcohol consumption (two to three units per day) was associated with a significantly lower risk of death compared with those who only had alcohol occasionally (one or less than one unit per day), and with those who had high alcohol intake (more than 3 units per day). Abstinence or high alcohol intake did not significantly raise mortality compared with those drinking only occasionally. (more…)
Alzheimer's - Dementia, Author Interviews, Journal Clinical Oncology, Prostate Cancer, Testosterone, University of Pennsylvania / 10.12.2015

MedicalResearch.com Interview with: Kevin T. Nead, MD, MPhil Dept. of Radiation Oncology Perelman School of Medicine University of Pennsylvania MedicalResearch: What is the background for this study? What are the main findings? Dr. Nead: There are a growing number of studies suggesting that the use of  Androgen Deprivation Therapy (ADT)  may be associated with cognitive changes and some of these changes overlap with characteristic features of Alzheimer’s disease. In addition, low testosterone levels have been associated with Alzheimer’s disease risk and ADT lowers testosterone levels. Despite these findings, we could not identify any studies examining the association between ADT and Alzheimer’s disease risk. We therefore felt this study could make an important contribution in guiding future research to fully understand the relative risks and benefits of ADT. We examined electronic medical record data from Stanford University and Mt. Sinai hospitals to identify a cohort of 16,888 patients with prostate cancer. We found that men with prostate cancer who received Androgen Deprivation Therapy were more likely to develop Alzheimer’s disease than men who did not receive  Androgen Deprivation Therapy. We also found that this risk increased with a longer duration of ADT. These results were consistent using multiple statistical approaches and separately at both Stanford and Mr. Sinai. (more…)
Alzheimer's - Dementia, Author Interviews, Nature, UCSF / 03.12.2015

MedicalResearch.com Interview with: Elsa Suberbielle, DVM, PhD Research Scientist Gladstone Institute of Neurological Diseases San Francisco, CA 94158 Medical Research: What is the background for this study? Dr. Suberbielle: BRCA1 is a key protein involved in DNA repair, and mutations that impair its function increase the risk for breast and ovarian cancer. Research into DNA repair mechanisms in dividing cells recently was recently rewarded by the Nobel Prize in Chemistry. In such cells, BRCA1 helps repair a type of DNA damage known as double-strand breaks that can occur when cells are injured. In neurons, though, such breaks can occur even under normal circumstances, for example, after increased brain activity, as shown by the team of Gladstone scientists in an earlier study. The researchers speculated that in brain cells, cycles of DNA damage and repair facilitate learning and memory, whereas an imbalance between damage and repair disrupts these functions. Medical Research: What are the main findings? Dr. Suberbielle In a new study published in Nature Communications, Researchers from the Gladstone Institutes demonstrates that Alzheimer’s disease is associated with a depletion of BRCA1 in neurons and that BRCA1 depletion can cause cognitive deficits. The researchers experimentally reduced BRCA1 levels in the neurons of mice. Reduction of the DNA repair factor led to an accumulation of DNA damage and to neuronal shrinkage. It also caused learning and memory deficits. Because Alzheimer’s disease is associated with similar neuronal and cognitive problems, the scientists wondered whether they might be mediated by depletion of BRCA1. They therefore analyzed neuronal BRCA1 levels in post-mortem brains of Alzheimer’s patients. Compared with non-demented controls, neuronal BRCA1 levels in the patients were reduced by 65-75%. To determine the causes of this depletion, the investigators treated neurons grown in cell culture with amyloid-beta proteins, which accumulate in Alzheimer brains. These proteins depleted BRCA1 in the cultured neurons, suggesting that they may be an important cause of the faulty DNA repair seen in Alzheimer brains. Further supporting this conclusion, the researchers demonstrated that accumulation of amyloid-beta in the brains of mice also reduced neuronal BRCA1 levels. They are now testing whether increasing BRCA1 levels in these mouse models can prevent or reverse neurodegeneration and memory problems. (more…)
Alzheimer's - Dementia, Author Interviews, Cleveland Clinic, JAMA / 22.09.2015

Jeffrey L. Cummings, M.D., Sc.D. Director, Lou Ruvo Center for Brain Health Camille and Larry Ruvo Chair for Brain Health Cleveland Clinic Las Vegas, NV 89106MedicalResearch.com Interview with: Jeffrey L. Cummings, M.D., Sc.D. Director, Lou Ruvo Center for Brain Health Camille and Larry Ruvo Chair for Brain Health Cleveland Clinic  Las Vegas, NV 89106  Medical Research: What is the background for this study? What are the main findings? Dr. Cummings: Agitation is a common problem in Alzheimer’s disease (AD); approximately 70% of patients with AD will experience periods of agitation.  This difficult behavior challenges patients and caregivers, adversely affects quality of life, and may precipitate institutionalization.  There are not drugs approved for treatment of agitation in Alzheimer’s disease. The study reported in JAMA showed that a drug based on a combination of dextromethorphan and quinidine (DM/Q) produced statistically significant and clinically meaningful reduction in agitation in Alzheimer’s disease patients.  The study met its primary outcome (decline in the Neuropsychiatric Inventory agitation scale in drug compared to placebo) and many of its secondary outcomes (e.g, decreases in caregiver stress).  The agent was safe and well tolerated. (more…)