Alzheimer's - Dementia, Author Interviews, Depression, JAMA / 18.05.2017

MedicalResearch.com Interview with: Archana Singh-Manoux, PhD Research Professor (Directeur de Recherche) Epidemiology of ageing & age-related diseases INSERM  France Honorary Professor University College London, UK  MedicalResearch.com: What is the background for this study? Response: Depressive symptoms are common in dementia patients. Previous studies, based on older adults, show depressive symptoms in late life to be associated with an increased risk of dementia. These studies do not allow conclusions to be drawn on the causal nature of the association between depressive symptoms and dementia. (more…)
Alzheimer's - Dementia, Author Interviews / 02.05.2017

MedicalResearch.com Interview with: Dr. Petr Kocis PhD Vice President Preclinical Development Alzheon, Inc. University of Oxford MedicalResearch.com: What is the background for this study? What are the main findings? Response: Researchers widely accept that amyloid plaques are the hallmark of Alzheimer’s disease. However, for many years, drug development has focused on the solid amyloid plaque as a primary disease culprit. Recent advances show that it is more likely that early stage soluble beta amyloid oligomers play a key role in the pathogenic process of Alzheimer’s disease. A paper recently published by Alzheon, a company developing medicines for Alzheimer’s disease and other neurological disorders, suggests a new therapeutic mechanism for targeting toxic amyloid beta oligomers with a small molecule, tramiprosate, the active agent in the drug candidate, ALZ-801. ALZ-801 is a Phase 3-ready drug candidate that is an optimized prodrug of tramiprosate, with a substantially improved pharmacokinetic and safety profile compared to tramiprosate. Alzheon scientists discovered that tramiprosate acts to inhibit the production of neurotoxic beta amyloid oligomers by ‘enveloping’ the amyloid peptide to prevent its misfolding into soluble amyloid aggregates. Beta amyloid oligomers are believed to be key drivers of the pathogenic process in Alzheimer’s disease (AD). This novel enveloping mechanism of tramiprosate prevents the self-assembly of misfolded proteins into beta amyloid oligomers that lead to amyloid aggregation and, subsequently, cause neuronal toxicity and clinical progression in Alzheimer’s disease. These results were published in the medical journal, CNS Drugs, and the paper is available through Open Access here. [“Elucidating the Aß42 Anti-Aggregation Mechanism of Action of Tramiprosate in Alzheimer’s Disease: Integrating Molecular Analytical Methods, Pharmacokinetic and Clinical Data”] (more…)
Alzheimer's - Dementia, Author Interviews / 11.04.2017

MedicalResearch.com Interview with: Emily Mason, Ph.D. Postdoctoral Associate Department of Neurological Surgery University of Louisville MedicalResearch.com: What is the background for this study? What are the main findings? Response: Alzheimer’s disease is a devastating neurodegenerative disease that currently affects one in eight Americans over the age of 65. Unfortunately, there is still no treatment that will halt or reverse the pathology associated with Alzheimer’s disease. One of the reasons for this may be that we still don’t fully understand what is happening in the very earliest stages of the disease. Previous studies have shown that one of the pathological hallmarks of the disease, called “tau tangles,” begins to accumulate in a specific area of the brain called the medial temporal lobe decades before people are typically diagnosed with Alzheimer’s disease. We wondered if we could use cognitive tests targeted to structures in the medial temporal lobe to pick up very subtle behavioral changes in people who were at increased risk for Alzheimer’s disease. We examined people who were in their 40s and 50s, which is a time when if any differences could be detected, it’s possible that pathology may be reversible. Using a cognitive task called “odd man out" that can be easily implemented using a computer, we found that subjects at risk for Alzheimer’s disease tended to do worse in identifying differences between objects called Greebles. These objects are highly visually similar, and most people have never seen them before. Those two things make this task very difficult. We believe that this study lays some of the groundwork in developing cognitive tests targeted at relatively young subjects who may be in the very earliest stages of the disease. (more…)
Aging, Alzheimer's - Dementia, Author Interviews, JAMA, Supplements / 21.03.2017

MedicalResearch.com Interview with: Richard J. Kryscio, Ph.D. Statistics and Chair, Biostatistics and Sanders-Brown Center on Aging Sanders-Brown Center on Aging University of Kentucky  MedicalResearch.com: What is the background for this study? Response: At the time the trial was initiated (2002), there was ample evidence that oxidative stress is an important mechanism in brain aging. Research showed that protein oxidation is linked to the brain’s response to the abnormal proteins seen in Alzheimer disease (amyloid beta plaques in particular) leading to inflammation, DNA repair problems, reduced energy production, and other cellular changes that are identified mechanisms in the Alzheimer brain. Both vitamin E and selenium are antioxidants. Antioxidants, either through food or supplements, are believed to reduce oxidative stress throughout the body. In the brain, they may reduce the formation of amyloid beta plaques, reduce brain inflammation, and improve other brain processes. Studies in humans support these hypotheses. The Rotterdam study in the Netherlands, as an example, showed that initial blood levels of vitamin E could predict dementia risk. Those people with higher vitamin E levels were 25% less likely to develop dementia. Also, selenium deficiency results in cognitive difficulties and several population-based studies have shown an association between selenium level and cognitive decline (lower selenium levels are linked to thinking changes in the elderly). (more…)
Aging, Alzheimer's - Dementia, Author Interviews, PLoS / 04.03.2017

MedicalResearch.com Interview with: Emma van Bussel MD, MSc Academic Medical Center | University of Amsterdam Amsterdam | The Netherlands  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Dementia forms a high social and economic burden on society. Since there is a growing number of older people, the occurrence of dementia is expected to increase over the years to come. For future planning of care, it is important to have reliable predictions on new dementia cases for the population at large. Studies in Western countries suggested that the incidence per 1000 person years is declining. We studied the incidence trend of dementia in the Netherlands in primary care registry data, in a population of over 800,000 older people (60 years and over) for the years 1992 to 2014. Our results indicate a small increase of 2.1% (95% CI 0.5% to 3.8%) per year in dementia incidence over the past decades. The trend did not change in the years after 2003, when a national program was developed to support dementia care and research, compared to the years prior to 2003. (more…)
Alzheimer's - Dementia, Author Interviews, Lancet, Vaccine Studies / 01.03.2017

MedicalResearch.com Interview with: Petr Novak, MD, PhD AXON Neuroscience Bratislava, Slovakia MedicalResearch.com: What is the background for this study? Response: Alzheimer’s disease is a complex, multifactorial disorder, with many-faceted neuropathology. A hallmark finding is the co-existence of neurofibrillary pathology (such as neurofibrillary tangles) composed of tau protein, and amyloid-β pathology (plaques) [1]. Neurofibrillary pathology is closely correlated with cognitive impairment in Alzheimer’s disease [2], while support for the role amyloid in the disease pathogenesis comes from the ability of certain mutations to induce AD in an autosomal-dominant fashion [3]. The field has explored various anti-amyloid therapies to great extent, and continues to do so with undiminished effort [4]; meanwhile, there is a noticeable paucity of investigated therapies aimed at neurofibrillary tau protein pathology, despite the ability of tau protein dysfunction to cause a multitude of neurodegenerative disorders, collectively named “tauopathies” [5]. AADvac1 is the first tau-targeted immunotherapy investigated in humans [6], a pioneering effort to target the component of AD neuropathology that is proximal to neuronal damage and cognitive loss, and thus to halt or slow the progression of Alzheimer’s disease. (more…)
Alzheimer's - Dementia, Author Interviews, Brigham & Women's - Harvard, Geriatrics, Heart Disease, Stroke / 26.02.2017

MedicalResearch.com Interview with: Ariela Orkaby, MD, MPH Geriatrics & Preventive Cardiology Associate Epidemiologist Division of Aging, Brigham and Women's Hospital Instructor in Medicine, Harvard Medical School MedicalResearch.com: What is the background for this study? What are the main findings? Response: Atrial Fibrillation is a common heart rhythm that affects 1 in 25 adults over age 60 and 1 in 10 adults over age 80. The feared consequence of atrial fibrillation is stroke, leading to the prescription of blood thinning medications (anticoagulants such as warfarin) to prevent strokes. However, there is an underutilization of these life-saving medications in older adults, and particularly in those who have dementia. In part, this is due to a lack of research and inclusion of older adults with dementia in prior studies. In this study, we used clinical Veterans Administration data, linked to Medicare, to follow 2,572 individuals over age 65 who had atrial fibrillation and until a diagnosis of dementia. The average age was 80 years, and 99% were male. We found that only 16% remained on warfarin. We used statistical methods to account for reasons why a patient would or would not be treated with warfarin and found that those who continued to take warfarin had a significantly lower risk of stroke (HR 0.74, 95% Confidence interval 0.54- 0.99, p=0.47) and death (HR 0.72, 95% CI 0.60-0.87, p<0.01) compared to those who did not continue to take warfarin, without an increased risk of bleeding. (more…)
Alzheimer's - Dementia, Author Interviews, Neurology, Sleep Disorders / 25.02.2017

MedicalResearch.com Interview with: Dr. Matthew P. Pase Sidney Sax NHMRC Fellow, Department of Neurology Boston University School of Medicine Investigator, Framingham Heart Study; Senior Research Fellow, Swinburne University of Technology. Boston MA 02118 MedicalResearch.com: What is the background for this study? Response: Sleep disturbances are common in dementia. However, most studies have focused on patients who already have dementia and so it is unclear whether disturbed sleep is a symptom or a cause of dementia. We studied 2,457 older participants enrolled in the Framingham Heart Study, a large group of adults sampled from the community in Framingham, Massachusetts. We asked participants to indicate how long they typically slept each night. Participants were then observed for the following 10-years to determine who developed dementia, including dementia due to Alzheimer’s disease. Over the 10 years, we observed 234 cases of dementia. Information on sleep duration was then examined with respect to the risk of developing dementia. (more…)
Alzheimer's - Dementia, Author Interviews / 17.02.2017

MedicalResearch.com Interview with: Shinsuke Ishigaki Department of Neurology Department of Therapeutics for Intractable Neurological Disorders Nagoya University Graduate School of Medicine Nagoya,Japan MedicalResearch.com: What is the background for this study? What are the main findings? Response: Frontotemporal lobar degeneration (FTLD) is a pathological process that has been characterized by personality changes, abnormal behaviors, language impairment, and progressive dementia. The genetic and pathological similarities in fused in sarcoma (FUS), transactive response (TAR) DNA-binding protein 43 (TDP-43), and C9orf72 in relation to FTLD and amyotrophic lateral sclerosis (ALS) have recently lead to the recognition that the two conditions represent points on a spectrum of a single disease entity. Additionally, Frontotemporal lobar degeneration has also been classified as a tauopathy, characterized by an accumulation of phosphorylated microtubule-associated protein tau (tau) in affected neurons. Our study demonstrated a biological link between FUS/SFPQ and the regulation of tau isoforms involved in the early phase of Frontotemporal lobar degeneration. (more…)
Alzheimer's - Dementia, Author Interviews, Cognitive Issues, Environmental Risks, Lancet / 05.01.2017

MedicalResearch.com Interview with: Hong Chen, PhD Scientist, Environmental Health Assessment Public Health Ontario | Santé publique Ontario Assistant Professor, Dalla Lana School of Public Health University of Toronto Adjunct Scientist, Institute for Clinical Evaluative Sciences Toronto, ON MedicalResearch.com: What is the background for this study? Response: Over the past several decades, there is unequivocal evidence that living close to major roadways may lead to various adverse health outcomes, such as cardio-respiratory related mortality and mortality. In the past decade, concern is growing that exposures associated with traffic such as air pollution and noise may also have an adverse impact on brain health. Several experimental studies show that air pollutants and diesel exhaust induce oxidative stress and neuroinflammation, activate microglia (which act as the first and main form of immune defense in the central nervous system), and stimulate neural antibodies. There are also a small number of epidemiological studies linking traffic-related noise and air pollution to cognitive decline and increased incidence of Parkinson’s disease and Alzheimer’s disease. Studies also showed that living near roads was associated with reduced white matter hyperintensity volume and cognition, but its effect on the incidence of dementia, Parkinson’s disease, and multiple sclerosis is unknown. Given hundreds of millions of people worldwide live close to major roads, we conducted this population-based cohort study to investigate the association between residential proximity to major roadways and the incidence of these three neurological diseases in Ontario, Canada. (more…)
Alzheimer's - Dementia, Author Interviews, Kidney Disease, Neurology / 19.12.2016

MedicalResearch.com Interview with: Kay Deckers, MSc PhD student School for Mental Health and Neuroscience Department of Psychiatry and Neuropsychology Maastricht University The Netherlands MedicalResearch.com: What is the background for this study? Response: In an earlier review (https://www.ncbi.nlm.nih.gov/pubmed/25504093), we found that renal dysfunction was one the new candidate risk factors of dementia and needed further investigation. MedicalResearch.com: What are the main findings? Response: Albuminuria is associated with an increased risk of developing cognitive impairment or dementia. (more…)
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…)