Alzheimer's - Dementia, Author Interviews, Obstructive Sleep Apnea / 26.07.2017

MedicalResearch.com Interview with: O. Michael Bubu, M.D., M.P.H., C.P.H Wheaton College MedicalResearch.com: What is the background for this study?
  • Obstructive Sleep Apnea (OSA) and Alzheimer’s disease (AD) are both chronic disease conditions that are highly prevalent, cause significant morbidity and mortality to those afflicted, and have an enormous socio-economic impact. Recent human and animal studies describe associations between Sleep Disordered Breathing (SDB) and Alzheimer's Disease (AD). However, whether OSA accelerates longitudinal increases in amyloid (Aβ) burden in MCI patients is presently unclear.
  • In this study, we examined the effect of Obstructive Sleep Apnea (OSA) on longitudinal changes in brain amyloid deposition, and Alzheimer’s disease (AD) Cerebrospinal fluid (CSF) biomarkers including CSF beta-amyloid 42 peptide (Aβ-42), CSF TAU protein, CSF phosphorylated TAU protein (PTAU) in Cognitive Normal (CN), Mild Cognitive Impairment (MCI) and AD elderly. Brain amyloid (Aβ) burden, CSF Abeta42 and tau proteins are biomarkers (measurable substances whose presence are indicative) of AD-associated pathologic changes in the brain.
  • Data from 1639 subjects (516 CN, 798 MCI and 325 AD, mean ages = 74.4 ± 5.8; 73.4 ± 7.4 and 75.1 ± 7.8 respectively), in the Alzheimer’s disease Neuroimaging Initiative (ADNI) database was used. OSA was self-reported and participants were labeled OSA positive, or OSA negative (mean ages = 72.3 ± 7.1; and 73.9 ± 7.3 respectively). Statistical analyses were conductedto examine whether OSA positive compared to OSA negative participants experienced significant differences in the rate of change of AD biomarkers over time (mean = 2.52 ± 0.51 years) in each group (CN, MCI and AD). Both OSA positives and negatives were similar in age, APOE e4 status, and history of cardiovascular disease. The final models controlled for sex, body mass index (BMI), and Continuous Pulmonary Airway Pressure (CPAP) use.
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Alzheimer's - Dementia, Author Interviews, Columbia, Nutrition / 24.07.2017

MedicalResearch.com Interview with: Yian Gu, PhD Assistant Professor of Neuropsychology (in Neurology and Taub Institute for Research on Alzheimer's Disease and the Aging Brain) Columbia University Medical Center MedicalResearch.com: What is the background for this study? What are the main findings? Response: We have previously shown that elderly individuals who consume healthier diet (certain foods, nutrients, and dietary patterns) have larger brain volume, better cognition, and lower risk of developing Alzheimer’s disease. The current study aimed to examine the biological mechanisms for the relationship between diet and brain/cognitive health.  (more…)
Alzheimer's - Dementia, Author Interviews, Radiology / 18.07.2017

MedicalResearch.com Interview with: Liana Apostolova, MD, MSc, FAAN Barbara and Peer Baekgaard Professor  in Alzheimer's Disease Research Professor in Neurology, Radiology. Medical and Molecular Genetics Indiana University School of Medicine Indiana Alzheimer's Disease Center Indianapolis, IN 46202 MedicalResearch.com: What is the background for this study? Response: While many studies have evaluated the diagnostic or prognostic implications associated with amyloid PET, few have explored its effects on the patient or caregiver. Amyloid imaging does not only help clinicians with their diagnosis and management. It also affects patient and caregiver decisions related to lifestyle, financial and long-term care planning, and at times also employment. Few studies to date have explored patient and caregiver views on the clinical use of amyloid PET and the potential benefits they could derive from having more precise diagnosis. (more…)
Alzheimer's - Dementia, Author Interviews, Cognitive Issues, Technology / 18.07.2017

MedicalResearch.com Interview with: Douglas W. Scharre MD Professor of Clinical Neurology and Psychiatry Director, Division of Cognitive Neurology Department of Neurology Director, Center for Cognitive and Memory Disorders Director, Memory Disorders Research Center Co-Director, Neuroscience Research Institute Ohio State University Wexner Medical Center Columbus, OH   MedicalResearch.com: What is the background for this study? What are the main findings? Response: Self-Administered Gerocognitive Examination (SAGE) is a pen-and paper, valid and reliable cognitive assessment tool for identifying individuals with mild cognitive impairment (MCI) or early dementia. We published age and education normative data on SAGE and determined that one point be added to the scores when age over 79 and one point be added when education level is 12 years or less. We evaluated the identical test questions in digital format (eSAGE) made for tablet use, adjusted with previously published age and education norms, and determined eSAGE’s association with gold standard clinical assessments. eSAGE is commercially known as BrainTest. (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research / 22.06.2017

MedicalResearch.com Interview with: Mikko Hiltunen, PhD Professor of Tissue and Cell Biology University of Eastern Finland School of Medicine, Institute of Biomedicine Kuopio,  Finland  MedicalResearch.com: What is the background for this study? What are the main findings? Response:  We wanted to assess among the population-based METSIM (METabolic Syndrome In Men) cohort whether protective variant in APP gene (APP A673T) affects the beta-amyloid levels in plasma. The rationale behind this was that previous genetic studies have discovered that the APP A673T variant decreases the risk of having Alzheimer’s disease (AD). However, the protective functional outcome measures related to this variant were lacking and thus we anticipated that the elucidation of plasma samples in terms of beta-amyloid levels would provide the much needed link between APP A673T variant and potential protective functions. (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research, Mental Health Research / 23.05.2017

MedicalResearch.com Interview with: Auriel Willette, M.S., Ph.D. 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: Translocase of Outer Mitochondrial Membrane 40 (TOMM40) is a gene that regulates the width of the outer mitochondrial pore, facilitating the transport of ribosomal pre-proteins into the inner mitochondrial matrix for translational modification into functional proteins. In 2010, Dr. Allen Roses, who discovered the Apolipoprotein E (APOE) gene, Dr. Michael Lutz, and other colleagues found that a variation in poly-T length at locus rs10524523 ('523) within intron 6 predicted Alzheimer's disease onset. Specifically, a "long" versus "short" poly-T length was related to earlier age of onset by 8 years. However, several multi-cohort studies either failed to replicate the findings or found the opposite relationship, where a "long" or "very long" poly-T length was related to later age of onset. The literature has remained mixed to this day. We were interested in testing factors that might change the relationship between TOMM40 and both cognitive decline and risk for having Alzheimer's disease. It is known that a family history (FH) of Alzheimer's disease has been associated with mitochondrial dysfunction. We reasoned, then, that FH may interact with TOMM40 to modulate how it was related to our outcomes of interest. We investigated this hypothesis in two separate cohorts: the Wisconsin Registry for Alzheimer's Prevention (WRAP), a late middle-aged cohort, and the Alzheimer's Disease Neuroimaging Initiative (ADNI), a well-characterized sample of aged participants from across the Alzheimer's spectrum. (more…)
Alzheimer's - Dementia, Author Interviews, Biomarkers / 18.05.2017

MedicalResearch.com Interview with: Ali Yilmaz, PhD Beaumont Research Institute Beaumont Health, Royal Oak, MI MedicalResearch.com: What is the background for this study? What are the main findings? Response: Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by the accumulation of β-amyloid plaques and tau tangles. Mild cognitive impairment (MCI) is progressive degree of impairment that is greater than might be attributed to normal age-related cognitive decline, but is not so severe as to merit a diagnosis of dementia. MCI is thought to be a transitional state between normal aging and AD sufferers phenotypically converting to AD at a rate of 10% per year. Currently there is no cure and few reliable diagnostic biomarkers for AD. As we live longer there is an ever increasing demand for valid and reliable biomarkers of Alzheimer's disease; not only because it will help clinicians recognize the disease in its earliest symptomatic stages but will also be important for developing novel treatment of AD. Using 1D H NMR metabolomics, we biochemically profiled saliva samples collected from healthy-controls (n = 12), mild cognitive impairment (MCI) sufferers (n = 8), and Alzheimer’s disease (AD) patients (n = 9). We accurately identified significant concentration changes in 22 metabolites in the saliva of MCI and AD patients compared to controls. (more…)
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.
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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…)