Alzheimer's - Dementia, Annals Internal Medicine, Author Interviews, Critical Care - Intensive Care - ICUs, Health Care Systems, University of Pittsburgh / 12.12.2016

MedicalResearch.com Interview with: Joshua M. Thorpe, PhD, MPH From the Center for Health Equity Research and Promotion Veterans Affairs Pittsburgh Healthcare System Pittsburgh Pennsylvania, and Center for Health Services Research in Primary Care Department of Pharmacy and Therapeutics University of Pittsburgh School of Pharmacy MedicalResearch.com: What is the background for this study? Response: Care coordination for persons with dementia is challenging for health care systems under the best of circumstances. These coordination challenges are exacerbated in Medicare-eligible veterans who receive care through both Medicare and the Department of Veterans Affairs (VA). Recent Medicare and VA policy changes (e.g., Medicare Part D, Veteran’s Choice Act) expand veterans’ access to providers outside the VA. While access to care may be improved, seeking care across multiple health systems may disrupt care coordination and increase the risk of unsafe prescribing - particularly in veterans with dementia. To see how expanded access to care outside the VA might influence medication safety for veterans with dementia, we studied prescribing safety in Veterans who qualified for prescriptions through the VA as well as through the Medicare Part D drug benefit. (more…)
Alzheimer's - Dementia, Author Interviews, Cognitive Issues, Depression, JAMA / 03.12.2016

MedicalResearch.com Interview with: Zahinoor Ismail MD FRCPC Clinical Associate Professor, Hotchkiss Brain Institute University of Calgary MedicalResearch.com: What is the background for this study? What are the main findings? Response: Depression and depressive symptoms are common in mild cognitive impairment (MCI). Evidence suggests that depression in MCI increases the likelihood of progression from MCI to dementia, compared to non-depressed people with MCI. In the newer construct of mild behavioural impairment (MBI), which describes the relationship between later life onset of sustained and impactful neuropsychiatric symptoms and the risk of cognitive decline and dementia, depression is an important subdomain (in addition to apathy, impulse control, social cognition and psychotic symptoms). Thus, depression and depressive symptoms are a significant risk factor for cognitive, behavioural and functional outcomes in older adults who have at most mild cognitive impairment. As the importance of neuropsychiatric symptoms in older adults emerges, good prevalence estimates are required to inform clinicians and researchers as well as public health policy and decision makers. We performed a systematic review and meta-analysis to determine the best estimate of prevalence of depression in  mild cognitive impairment. We included 57 studies, representing 20,892 participants in the analysis. While we determined that the omnibus prevalence estimate was 32%, there was significant heterogeneity in this sample based on setting. In community samples, the rate was 25%, but in clinical samples this was higher at 40%. Additionally, different case ascertainment methods for depression (self report, clinician administered or caregiver report) and different MCI criteria didn't change the prevalence estimates. (more…)
Alzheimer's - Dementia, Author Interviews, JAMA, Neurological Disorders / 20.10.2016

MedicalResearch.com Interview with: Dr David Lynch MB, MRCPI Leonard Wolfson Clinical Fellow UCL Institute of Neurology Queen Square, London MedicalResearch.com: What is the background for this study? What are the main findings? Response: In 2011 it was discovered that mutations in a gene called CSF1R cause a rare syndrome of early onset dementia often accompanied by movement disorders, spasticity and seizures, which is named adult onset leukoencephalopathy with axonal spheroids (ALSP). The hallmarks of ALSP are a characteristic appearance on MRI imaging and findings in brain pathological specimens - axonal swellings or 'spheroids'. We manage a multidisciplinary group with expertise in leukoencephalopathies and have previously identified patients with mutations in CSF1R. However, we also found patients with a syndrome typical of ALSP who did not carry mutations in CSF1R. In this study, we showed that some of these patients carry recessive mutations in a different gene, AARS2. This included a patient with characteristic axonal spheroids in brain tissue and typical ALSP clinical and imaging features. (more…)
Alzheimer's - Dementia, Author Interviews, Hormone Therapy, JAMA, Prostate Cancer, University of Pennsylvania / 15.10.2016

MedicalResearch.com Interview with: Kevin T. Nead, MD, MPhil Resident, Radiation Oncology Perelman School of Medicine Hospital of the University of Pennsylvania. MedicalResearch.com: What is the background for this study? Response: Androgen deprivation therapy is a primary treatment for prostate cancer and works by lowering testosterone levels. There is a strong body of research suggesting that low testosterone can negatively impact neurovascular health and function. We were therefore interested in whether androgen deprivation therapy is associated with dementia through an adverse impact on underlying neurovascular function. (more…)
Alzheimer's - Dementia, Author Interviews, Critical Care - Intensive Care - ICUs, End of Life Care, Geriatrics, JAMA / 12.10.2016

MedicalResearch.com Interview with: Joan M. Teno, MD, MS Department of Gerontology and Geriatrics, Cambia Palliative Care Center of Excellence University of Washington Medicine Seattle, Washington MedicalResearch.com: What is the background for this study? Response: An important challenge for our health care system is effectively caring for persons that high-need, high-cost — persons afflicted with advanced dementia and severe functional impairment are among these persons, with substantial need and if hospitalized in the ICU and mechanically ventilated are high cost patients, who are unlikely to benefit from this level of care and our best evidence suggest the vast majority of persons would not want this care. In a previous study, we interviewed families of advance dementia with 96% starting the goals of care are to focus comfort. Mechanical ventilation in some cases may be life saving, but in cases such as those with advanced dementia and severe functional impairment, they may result in suffering without an improvement in survival. (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research, PNAS / 12.10.2016

MedicalResearch.com Interview with: Dr. Magdalena Sastre PhD Faculty of Medicine, Department of Medicine Senior Lecturer Imperial College London MedicalResearch.com: What is the background for this study? Response: Alzheimer’s disease is the most common neurodegenerative disorder, affecting over 45 million people around the world. Currently, there are no therapies to cure or stop the progression of the disease. Here, we have developed a gene therapy approach whereby we delivered a factor called PGC-1α, which regulates the expression of genes involved in metabolism, inflammation and oxidative stress in the brain of transgenic mice. This factor is also involved in the regulation of energy in the cells, because it controls the genesis of mitochondria and in the generation of amyloid-β, the main component of the neuritic plaques present in the brains of Alzheimer’s disease patients. We have found that the animals with Alzheimer’s pathology treated with PGC-1α develop less amyloid plaques in the brain, perform memory tasks as well as healthy mice and do not have neuronal loss in the brain areas affected by the disease. (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research, JAMA, Race/Ethnic Diversity / 10.10.2016

MedicalResearch.com Interview with: Dr Tamara Shiner MD PhD Specialist in Neurology Neurology Division Tel Aviv Sourasky Medical Centre MedicalResearch.com: What is the background for this study? What are the main findings? Response: Although in the past believed to be sporadic, there is much emerging evidence for a significant genetic contribution to Dementia with Lewy bodies (DLB). Hetrozygosity for common mutations in the GBA gene have been shown to be more frequent among DLB patients and Parkinson's disease patients than in the general population. We found that GBA mutations are in fact exceptionally frequent among Ashkenazi Jewish (AJ) patients with Dementia with Lewy bodies. Our results indicate that one in three of all Ashkenazi DLB patients carry mutations in this specific gene (compared to approximately 6% in the general Ashkenazi Jewish population). We also found that those who carry these mutations have a more severe disease phenotype. (more…)
Alzheimer's - Dementia, Author Interviews, Biomarkers / 01.09.2016

MedicalResearch.com Interview with: Professor B. Paul Morgan Director, Systems Immunity Research Institute Institute of Infection and Immunity School of Medicine Cardiff University MedicalResearch.com: What is the background for this study? Response: Inflammation is a normal response of the body to infection or injury; however, it is well known that inflammation also has a dark side and when it escapes normal controls can cause disease. Some illnesses, like rheumatoid arthritis, have been known for many years to be caused by rogue inflammation and most of the drugs used to treat work by suppressing the inflammation (anti-inflammatories). More recently, it has become clear that inflammation is behind many other diseases that were previously thought of as diseases of ageing caused by wear and tear and lifestyle - these include heart disease and some brain diseases, notably Alzheimer's disease the commonest cause of dementia. Evidence that inflammation is one of the drivers of disease has come from many sources, including some where it was noticed that people on long-term anti-inflammatory drugs for other reasons appeared to be protected from developing Alzheimer's disease. A problem is that Alzheimer's disease, despite the name, is not a single disease but rather a group of conditions with similar symptoms, and inflammation is likely to be a cause in only some of the patients; further, most of the inflammation might be occurring very early in the disease, even before symptoms are obvious. So, there is an urgent need for a simple test or set of tests that can be used in individuals with the very earliest hints of Alzheimer's disease - mild memory loss - that will pick out those who have brain inflammation and are most likely to develop Alzheimer's disease. It might then be possible to treat this select group with anti-inflammatory drugs that will reduce brain inflammation and slow or stop progression of the disease. (more…)
Alzheimer's - Dementia, Author Interviews, Immunotherapy, Nature / 01.09.2016

MedicalResearch.com Interview with: Roger M. Nitsch, MD Professor and Director Institute for Regenerative Medicine · IREM University of Zurich Campus Schlieren Switzerland MedicalResearch.com: What is the background for this study? What are the main findings? Response: The main finding is that treatment with aducanumab resulted in an unprecedented reduction of brain amyloid plaques in patients with Alzheimer's disease.  The removal of amyloid from patients brains were both dose- and time-dependent.  We also observed initial hints for stabilized brain functions in patients receiving aducanumab.  In contrast, patients in the placebo group continued to declined as usual in this stage of Alzheimer's disease. The main safety finding in 22% of all treated patients was ARIA - an Amyloid-Related Imaging Abnormality - suggestive of fluid shifts in the brains. In most cases, ARIA occurred in the absence of clinical signs and resolved spontaneously.  In one third of the ARIA cases, patients experienced transient headaches.  None of the patients had to hospitalized because of ARIA. (more…)
Alzheimer's - Dementia, Author Interviews, Brigham & Women's - Harvard, Education / 30.08.2016

MedicalResearch.com Interview with: Deborah Blacker MD, ScD Director of the Gerontology Research Unit Department of Psychiatry Massachusetts General Hospital MedicalResearch.com: What is the background for this study? What are the main findings Response: Many observational studies have found that those who are cognitively active have a lower risk of developing Alzheimer's disease or any type of dementia. However, we and others have been concerned that these findings might be spurious due to two potential biases:
  • 1) “confounding,” meaning that those who are cognitively active have lower rates of Alzheimer’s disease for another reason, in particular the effect of greater education, which is associated with both lower risk of Alzheimer’s and higher levels of cognitive activity; and
  • 2) “reverse causation,” meaning that theassociation could be due to a reduction in cognitive activity among those already in the long preclinical phase of cognitive decline before Alzheimer’s dementia (rather than the lack of cognitive activity causing the Alzheimer’s). Our study performed a systematic review of the literature on the association, and then a set of bias analyses to assess whether confounding or reverse causation could account for the observed associations.
(more…)
Alzheimer's - Dementia, Author Interviews, Nutrition / 28.08.2016

MedicalResearch.com Interview with: William B. Grant, Ph.D. Director, Sunlight, Nutrition, and Health Research Center San Francisco, CA www.sunarc.org MedicalResearch.com: What is the background for this study? What are the main findings? Response: The present study is the culmination of 20 years of investigating dietary links to Alzheimer's disease (AD). I am a physicist by training and spent my salaried career as an atmospheric scientist. In the 1990s while studying the effect of acid rain and ozone on eastern hardwood forests, I became familiar with the geographical ecological study approach. In this approach, populations are defined geographically, such as by state or country, and health outcomes are compared statistically with risk-modifying factors. Ecological studies are an efficient way to analyze the results of unplanned experiments. In 1996, I read that Japanese-American men living in Hawaii had two and a half times the prevalence of  Alzheimer's disease as native Japanese. I knew that AD patients often had higher concentrations of aluminum in their brains than other people, and that acid rain increased the concentration of aluminum in trees. It quickly occurred to me that the American diet must be the cause of the increased AD rate, and that by using the ecological approach, I could prove it. My first study, published in 1997, compared AD prevalence rates for 11 countries with macro-dietary factors of national diets. Total fat was found to have the highest correlation with AD, followed by total energy (calories), with fish reducing risk slightly, while countries such as China, Japan, and India, with large amounts of rice in the diet, had very low  Alzheimer's disease rates. This study was the first major study linking diet to risk of AD and led to observational studies that confirmed the findings five years later. (more…)
Alzheimer's - Dementia, Author Interviews, Calcium, Neurology / 19.08.2016

MedicalResearch.com Interview with: Silke Kern, MD, PhD Neuropsychiatric Epidemiology Unit and Clinical Neurochemistry Laboratory Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology Sahlgrenska Academy University of Gothenburg Gothenburg, Sweden MedicalResearch.com: What is the background for this study? What are the main findings? Response: Calcium has an important role in ischemic neuronal cell death and atherosclerosis. Several studies suggest that increased serum calcium increases the risk for vascular events and worsens the outcome after stroke. Widespread ischemic neuronal cell death and atherosclerosis might lead to dementia. We therefore examined if Calcium supplementation is associated with development of dementia. Our study is the first to show a relationship between Calcium supplementation and increased risk for dementia in older women. This risk is mainly confined to women with cerebrovascular disease (history of stroke or presence of white matter lesions). (more…)
Alzheimer's - Dementia, Author Interviews, Neurological Disorders / 05.08.2016

MedicalResearch.com Interview with: Auriel Willette, PhD Assistant Professor Departments of Food Science and Human Nutrition, and Psychology Iowa State University MedicalResearch.com: What is the background for this study? What are the main findings? Response: The Alzheimer's disease (AD) field continues to look for biological markers that can detect onset and progression of the disease, mainly memory decline and atrophy of medial temporal lobe where conscious memories are formed. The immune system has long been known to affect the onset and progression of Alzheimer's disease (AD), usually through a process called inflammation in the brain that causes damage to brain cells called neurons. We wished to examine all available immune system data in a large, well-established cohort across the AD spectrum and discover which immune markers best explained memory decline and medial temporal atrophy over 2 years. In essence, among dozens of candidate immune markers, we consistently found two to be most relevant: neuronal pentraxin 2 (NPTX2) and chitinase-3-like-protein-1 (C3LP1). NPTX2 is important for facilitating communication between neurons, whereas C3LP1 is related to activation of a part of the immune system that causes inflammation in the brain. To our surprise, higher NPTX2 levels at baseline were potently related to less memory loss and less medial temporal atrophy over 2 years. C3LP1, by contrast, was a relatively poor predictor. NPTX2 also better predicted levels of amyloid and tau in the brain, which are generally thought to help cause AD. Finally, we found that more years of education led to higher NPTX2 levels, suggesting that more formal learning leads to more stable, stronger connections between neurons that give rise to memory. (more…)
Alzheimer's - Dementia, Author Interviews, Endocrinology, Hormone Therapy, Mayo Clinic, Menopause / 13.07.2016

MedicalResearch.com Interview with: Kejal Kantarci, M.D. M.S. Professor of Radiology Division of Neuroradiology MedicalResearch.com: What is the background for this study? What are the main findings? Response: A rapid decline in estrogen with menopause may be associated with an increased risk of Alzheimer’s disease risk in women. This study was conducted in newly postmenopausal women who received 17β-Estradiol via a skin patch or conjugated equine estrogen orally or placebo. Those who received 17β-Estradiol patch had reduced β-amyloid deposits, the plaques found in the brains of people with Alzheimer’s disease, three years after the end of the hormone therapies. In the study, women with APOE e4 — one form of the most common gene associated with late-onset Alzheimer's disease — who received the 17β-Estradiol patch had lower levels of β-amyloid deposits than those who received placebo. (more…)
Alzheimer's - Dementia, Author Interviews, Chemotherapy, Parkinson's / 13.07.2016

MedicalResearch.com Interview with: Charbel Moussa MD. PhD Assistant Professor of Neurology Director- Laboratory for Dementia and Parkinsonism Clinical Research Director- National Parkinson's Foundation Center for Excellence Translational Neurotherapeutics Program Department of Neurology Georgetown University Medical Center Washington DC. MedicalResearch.com: What is the background for this study? What are the main findings? Response: We conducted a pilot open label proof-of-concept study to evaluate the safety and tolerability of Nilotinib in participants with advanced Parkinson’s disease (PD) with dementia (PDD) or dementia with Lewy bodies (DLB). Our primary objective is to demonstrate that low oral daily doses of 150mg or 300mg Nilotinib (compared to 600-800mg in cancer) are safe and tolerated. Our secondary objectives are that Nilotinib will cross the blood brain barier and may inhibit cerebral spinal fluid Abl. Based on preclinical data we also hypothesized that Nilotinib will increase DA levels. Motor and cognitive functions were also measured as exploratory clinical outcomes. Other exploratory outcomes are that Nilotinib may alter PD-related CSF biomarkers DJ-1 and α-synuclein. As most participants in this study had dementia we also explored the effects of Nilotinib on Alzheimer's Disease-related CSF biomarkers, including Aβ40 and Aβ42, total tau and phosphorylated tau (p-tau). (more…)
Alzheimer's - Dementia, Author Interviews, Brain Injury, JAMA, Parkinson's / 11.07.2016

MedicalResearch.com Interview with: Paul K. Crane, MD MPH Professor Department of Medicine Adjunct Professor Department of Health Services University of Washington MedicalResearch.com: What is the background for this study? Response: The background is that the most common experience of head injury with loss of consciousness is an apparent recovery. Sometimes this is very fast, sometimes it takes somewhat longer, but typically people return to their prior baseline. Nevertheless there is concern that the head injury may have set in motion processes that would lead to late life neurodegenerative conditions. This is bad enough for someone to deal with but it's made even worse if the head injury isn't even the victim's fault. Previous research has focused especially on Alzheimer's disease. A more limited research has focused on Parkinson's disease. We used data from three prospective cohort studies that included more than 7,000 people to study the relationship between head injury with loss of consciousness and subsequent risk of Alzheimer's and Parkinson's disease. We collected head injury exposure data at study enrollment, at a time when we administered cognitive tests and knew they did not have dementia, so our exposure data are not biased. Each of these studies also performed brain autopsies on people who died, and we evaluated data from more than 1500 autopsies. (more…)
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…)