Alzheimer's - Dementia, Author Interviews, Diabetes / 27.01.2016

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

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

MedicalResearch.com Interview with: Prof. Dimitrios Karussis M.D., Ph.D. Professor of Neurology Head, Multiple Sclerosis Center Hadassah BrainLabs Medical Research: What is the background for this study? What are the main findings? Prof. Karussis: BrainStorm Cell Therapeutics is developing innovative, autologous stem cell therapies for highly debilitating neurodegenerative diseases such as Amyotrophic Lateral Sclerosis (ALS), Multiple Sclerosis (MS), and Parkinson’s Disease (PD).  Our technology, NurOwn™ is a first-of-its-kind approach that induces autologous bone marrow-derived Mesenchymal Stem Cells (MSCs) to secrete Neurotrophic Growth Factors (NTFs).  These MSC-NTF cells have been shown to be protective in several animal models of neurodegenerative diseases. Data from the clinical trials described in the recent issue of the Journal of American Medicine – Neurology (JAMA Neurology), suggest that NurOwn can help patients with ALS.  The two trials featured in the article, a phase 1/2 and a phase 2a, studied the transplantation NurOwn cells in ALS patients.  These trials confirmed the excellent safety profile of NurOwn and suggest a clinically meaningful effect. The investigators used two well established clinical endpoints that measure disease activity in ALS, the Revised ALS Functional Rating Scale and Forced Vital Capacity, and were able demonstrate a slowing of disease activity in the period following treatment. (more…)
Alcohol, Alzheimer's - Dementia, Author Interviews, BMJ / 11.12.2015

MedicalResearch.com Interview with:

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

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

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

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

Jeffrey L. Cummings, M.D., Sc.D. Director, Lou Ruvo Center for Brain Health Camille and Larry Ruvo Chair for Brain Health Cleveland Clinic Las Vegas, NV 89106MedicalResearch.com Interview with: Jeffrey L. Cummings, M.D., Sc.D. Director, Lou Ruvo Center for Brain Health Camille and Larry Ruvo Chair for Brain Health Cleveland Clinic  Las Vegas, NV 89106  Medical Research: What is the background for this study? What are the main findings? Dr. Cummings: Agitation is a common problem in Alzheimer’s disease (AD); approximately 70% of patients with AD will experience periods of agitation.  This difficult behavior challenges patients and caregivers, adversely affects quality of life, and may precipitate institutionalization.  There are not drugs approved for treatment of agitation in Alzheimer’s disease. The study reported in JAMA showed that a drug based on a combination of dextromethorphan and quinidine (DM/Q) produced statistically significant and clinically meaningful reduction in agitation in Alzheimer’s disease patients.  The study met its primary outcome (decline in the Neuropsychiatric Inventory agitation scale in drug compared to placebo) and many of its secondary outcomes (e.g, decreases in caregiver stress).  The agent was safe and well tolerated. (more…)
Alzheimer's - Dementia, Author Interviews, JAMA / 26.08.2015

Dr. Eric Reiman MD Executive Director, Banner Alzheimer’s Institute (BAI) Chief Executive Officer, Banner Research, Clinical Director of the Neurogenomics Division at the Translational Genomics Research Institute (TGen) Professor of Psychiatry, University of Arizona Director, Arizona Alzheimer’s ConsortiumMedicalResearch.com Interview with: Dr. Eric Reiman MD Executive Director, Banner Alzheimer’s Institute (BAI) Chief Executive Officer, Banner Research Clinical Director of the Neurogenomics Division at the Translational Genomics Research Institute (TGen) Professor of Psychiatry, University of Arizona Director, Arizona Alzheimer’s Consortium Phoenix Arizona   Medical Research: What is the background for this study? What are the main findings? Dr. Reiman: Beta-amyloid plaque deposition is a cardinal feature of Alzheimer’s disease. Recent positron emission tomography (PET) have suggested that about one-fourth of patients with the clinical diagnosis of mild-to-moderate Alzheimer’s dementia—and more than a third of those who had no copies of the APOE4 gene, the major genetic risk factor for Alzheimer’s—do not have appreciable amyloid plaque deposition. We wondered whether this finding reflected an absence of appreciable brain amyloid, particularly in APOE4 non-carriers, or instead an underestimation of amyloid plaques using PET. In those patients with minimal plaque deposition, we also wondered what percentages had neuropathological evidence of another dementia-causing disease, neurofibrillary tangle pathology (the other cardinal feature of Alzheimer’s, or no known pathological contribution. We surveyed data from the 100 APOE4 non-carriers and 100 APOE4 carriers who had the clinical diagnosis of mild-to-moderate Alzheimer’s dementia during their last visit at any of the nation’s Alzheimer’s Disease Centers and had an autopsy performed within the next 2 years. As we reported in JAMA Neurology, 37 percent of APOE4 non-carriers and 13 percent of APOE4 carriers with a clinical diagnosis of mild-to-moderate Alzheimer’s had minimal evidence of neuritic or diffuse amyloid plaques—and those for whom we had brain samples had no evidence of increased soluble amyloid. A proportion of individuals had a different neuropathological diagnosis. While nearly half of those patients with minimal amyloid or any other pathology had extensive tangle formation, a similar percentage was found in cognitively unimpaired persons in the same age range. Our findings suggest the PET findings are correct – that a quarter of all patients (and more than a third of APOE4 non-carriers) with the clinical diagnosis of Alzheimer’s dementia do not have appreciable amyloid pathology, and that about 10 to 15 percent of patients do not have a clear explanation for their dementia. (more…)
Alzheimer's - Dementia, Author Interviews, Diabetes, Diabetologia / 14.08.2015

Laura Ekblad, MD, researcher Turku PET CentreMedicalResearch.com Interview with: Laura Ekblad, MD, researcher Turku PET Centre Medical Research: What is the background for this study? What are the main findings? Dr. Ekblad: The background for our study is that the metabolic syndrome and diabetes have been shown to increase the risk for cognitive decline and dementia. Also, insulin resistance is thought to play a pivotal role in the pathophysiology of Alzheimer´s disease. In addition, intranasal insulin administration is being studied as a promising treatment for Alzheimer´s disease. Previous studies indicate that both gender and APOE epsilon 4 genotype modulate the effects of insulin on cognition. Our main findings are that insulin resistance is associated with poorer verbal fluency, but only in women. Our population-based study consisted of adults from 30-97 years of age and we had nearly 6000 participants. Age did not modulate the association of insulin resistance and cognition, which means that our results apply even to young adults. We also found that insulin resistance associated with poorer verbal fluency only in non-carriers of the APOE epsilon 4 genotype. (more…)
Alzheimer's - Dementia, Author Interviews, Sleep Disorders / 08.08.2015

Helene Benveniste, MD, PhD Professor of Anesthesiology and Radiology Vice Chair for Research, Department of Anesthesiology Stony Brook Medicine, Stony Brook NYMedicalResearch.com Interview with: Helene Benveniste, MD, PhD Professor of Anesthesiology and Radiology Vice Chair for Research, Department of Anesthesiology Stony Brook Medicine, Stony Brook NY Medical Research: What is the background for this study? Dr. Benveniste: The ‘glymphatic’ pathway is a part of the brain and is responsible for removal of waste products and excess fluid that built up especially during wakefulness. The concept was introduced by Nedergaard’s team in 2012 from University of Rochester. Importantly it has been shown to remove waste products such as soluble amyloid beta and tau protein which build up excessively in the brain of subjects afflicted with Alzheimer’s disease. The glymphatic system has been studied in detail in animal models (not yet humans) and actually is a brain-wide pathway which runs along (i.e. on the outside) of all vessels in the brain and connects to the space around the brain cells (referred to as the interstitial fluid (ISF) space). The outer part of the glymphatic network ‘tube’ is bordered by a certain type of brain cells so-called ‘astroglial’ cells which are arranged in a special way so that their endfeet cover >97% of the surface of all brain vessels. One can think of this as if the astroglial cell’s ‘endfeet’ are arranged as a donut shaped tube around all the vessels. On the astroglial endfeet there are special water channels (aquaporin-4 water channels) which are critical for how efficiently the glymphatic system can get rid of waste because it allows water to move fast through the brain tissue so as to ‘flush’ waste products out efficiently. The small gap between the astroglial endfeet also act like a ‘sieve’ so that only waste products of a certain size can access the entire pathway. Cerebrospinal fluid (CSF) circulates into the glymphatic pathway from the surface of the brain along the arteries which dives directly from the surface into the deeper part of the brain; and ultimately enters the space around the brain cells; and sweeps through it and thereby mixes with the interstitial fluid of the brain which contains waste products. The CSF-ISF mix with the waste products is then flushed out on the other ‘side’ along the veins and ultimately ends up in lymph vessels in the body and then in the blood. It has been shown that the glymphatic pathway removes brain waste more efficiently in a state of ‘unconsciousness’ e.g. sleep or anesthesia when compared to wakefulness. Given this intriguing finding i.e. that sleeps seems to affect the waste clearance from the brain we thought that the next to look at was sleeping positions. We did these studies in anesthetized rodents. (more…)
Alzheimer's - Dementia, Author Interviews, Diabetes, JAMA, Nutrition / 31.07.2015

Auriel A. Willette, M.S., Ph.D. Food Science and Human Nutrition Neuroscience Interdepartmental Graduate Program Gerontology Interdepartmental Graduate Program Iowa State University, AmesMedicalResearch.com Interview with: Auriel A. Willette, M.S., Ph.D. Food Science and Human Nutrition Neuroscience Interdepartmental Graduate Program Gerontology Interdepartmental Graduate Program Iowa State University, Ames Medical Research: What is the background for this study? What are the main findings? Response: Obesity is a major health concern around the world. Obesity causes insulin resistance, defined in this case as the inability of insulin to bind to its receptor and mediate glucose metabolism. Other researchers and I have recently found that higher insulin resistance is associated with less glucose metabolism in the brains of patients with Alzheimer's disease. This relationship is found primarily in medial temporal lobe, an area necessary for generating new memories of facts and events. This is important because Alzheimer's disease is characterized by progressive decreases in glucose metabolism over time, and partly drives worse memory performance. Insulin resistance in midlife also increases the risk of developing Alzheimer's disease. We wanted to determine if insulin resistance is linked to similar effects in cognitively normal, late middle-aged participants decades before Alzheimer's disease typically occurs. If so, insulin resistance might be an important biological marker to track from middle-age onwards. Thus, we examined the association between insulin resistance, regional glucose metabolism using FDG-PET, and memory function in 150 middle-aged participants, many of whom had a mother or father with Alzheimer's disease. We found that higher insulin resistance was strongly associated with less glucose metabolism throughout many brain regions, predominantly in areas that are affected by Alzheimer's disease. The strongest statistical effects were found in left medial temporal lobe, which again is important for generating new memories. This relationship, in turn, predicted worse memory performance, both immediately after learning a list of words and a 20-minute delay thereafter. The take-home message is that insulin resistance has an Alzheimer's-like association with glucose metabolism in middle-aged, cognitively normal people at risk for Alzheimer's, an association which is related to worse memory. (more…)
Alzheimer's - Dementia, Author Interviews, NYU / 21.07.2015

Fernando Goni, PhD MS Adjunct associate professor Department of Neurology, Center for Cognitive Neurology NYU School of Medicine NYU Langone Medical CenterMedicalResearch.com Interview with: Fernando Goni, PhD MS Adjunct associate professor Department of Neurology, Center for Cognitive Neurology NYU School of Medicine NYU Langone Medical Center Medical Research: What is the background for this study? What are the main findings? Dr. Goni: It has been established that most neurodegenerative diseases including Alzheimer's, Lewy Body and other dementias, Parkinson's and prion diseases develop and progress along similar paths. In each disease, a particular protein undergoes a change in its shape from a soluble, physiologically functional protein to a protein that has lost the ability to perform its required tasks in the brain, starting off a chain reaction of binding to each other with little control. These aggregates become toxic to brain cells. We raised antibodies in mice against the common beta-sheet structures present in toxic oligomers of many neurodegenerative diseases including amyloid and tau in Alzheimer's; oligomeric forms of prions and oligomerized alpha-synuclein in Parkinson's. From that response, we produced monoclonal antibodies of the same characteristics. At least three of the monoclonals recognize pathological structures in histological samples of human brains from Alzheimer's disease, Parkinson's disease and GSS (human prionosis). They also recognized in vitro the oligomeric forms particular for each disease. In old animals of a mouse model of Alzheimer's, that already had pathology, the monoclonal antibodies could rescue behavior and reduced significantly the oligomers of Tau and Abeta. (more…)
Alzheimer's - Dementia, Author Interviews, JAMA, Medical Imaging, UCSF / 20.05.2015

Rik Ossenkoppele PhD. Postdoctoral researcher UCSF Memory and Aging CenterMedicalResearch.com Interview with: Rik Ossenkoppele PhD. Postdoctoral researcher UCSF Memory and Aging Center MedicalResearch: What is the background for this study? Dr. Ossenkoppele: Since 2004, several PET tracers have been developed that measure fibrillar amyloid-β plaques, a neuropathological hallmark of Alzheimer’s disease (AD). Through visual assessment by a nuclear medicine physician or quantitative cut-points, the presence or absence of amyloid-β pathology can be determined in the living human brain. The FDA, in support of the clinical application of amyloid imaging, has recently approved three of these PET tracers. A proportion of patients with other types of dementia then Alzheimer’s disease that harbor cerebral amyloid-β pathology, however, potentially limits the clinical utility of amyloid imaging. When ordering clinical amyloid PET scans and correctly interpreting the significance of amyloid PET results, clinicians need to understand the prevalence of amyloid-positivity across different types of dementia. It is also important to be aware of the relationships of amyloid-positivity prevalence and demographic (e.g. age and sex), cognitive and genetic (e.g. presence of the AD-risk allele apolipoprotein E [APOE] ε4) factors. Most amyloid PET studies to date come from single centers with modest sample sizes. We therefore conducted a meta-analysis with individual participant data from 29 cohorts worldwide, including 1359 patients with clinically diagnosed Alzheimer’s disease and 538 patients with non-AD dementia. We also included 1849 healthy controls with amyloid PET data, and an independent sample of 1369 AD patients with autopsy data from the NACC database. MedicalResearch: What are the main findings? Dr. Ossenkoppele: In patients clinically diagnosed with Alzheimer’s disease, the prevalence of amyloid-positivity decreased from 93% at age 50 to 79% at age 90. The drop in amyloid-positivity was most prominent in older Alzheimer’s disease patients who did not carry an APOE ε4 allele (~1/3 of these patients had a negative amyloid PET scan). This most likely reflects a mix of 1) clinical misdiagnoses (i.e. non-AD pathology causing an AD phenotype), 2) false negative PET scans (i.e. abundance of cerebral amyloid pathology that is not detected by PET), and 3) possibly elder patients need less amyloid pathology (sub-threshold levels for PET) to reach the stage of dementia due to age-related reductions in cognitive resilience (“cognitive reserve theory”) or simultaneous presence of multiple pathologies (“double-hit theory”). The relatively high rate of amyloid-negative Alzheimer’s disease patients highlights the necessity of biomarker-informed patient selection for Alzheimer’s disease clinical trials. In most patients clinically diagnosed with non-AD, the prevalence of amyloid-positivity increased with aging and was ~18% higher in APOE ε4 carriers. Presence of amyloid pathology in non-AD dementia may reflect 1) clinical misdiagnosis (i.e. AD pathology is the causative pathology), or 2) comorbid pathologies, where amyloid may be secondary to other pathologies that are actually driving the clinical presentation. Interestingly, patients with a clinical diagnosis of non-AD dementia who harbored cerebral amyloid pathology showed lower Mini-Mental State Examination scores (measure of global cognition), suggesting that amyloid-β is not just an innocent bystander. (more…)
Alzheimer's - Dementia, Author Interviews, Diabetes, JAMA / 28.04.2015

MedicalResearch.com Interview with: Dimitry S. Davydow, MD, MPH Associate Professor Department of Psychiatry and Behavioral Sciences University of Washington School of Medicine Seattle, WA 98195 Dr, Davydow wishes to acknowledge Dr. Wayne Katon, the lead investigator of the study, who passed away on March 1, 2015. Medical Research: What is the background for this study? Dr. Davydow: The medical and public health communities have known for quite a while that diabetes and depression are both potential risk factors for developing dementia later in life. Dr. Wayne Katon previously published two articles detailing the results of two studies of relatively large groups of patients (one with nearly 4,000 patients and the other with 29,000 patients) with diabetes showing that those with diabetes and co-existing depression had a greater risk of developing dementia later in life than those patients with just diabetes. These initial studies were important since patients with diabetes are 3 to 4-times more likely to suffer from depression compared to the general population. However, it remained unclear when comparing to a population without either diabetes or depression, to what extent each independently raised the risk of developing dementia, and then to what extent having both conditions increased an individual’s subsequent risk of dementia. We sought to answer these questions with this study. In addition, with the growing obesity epidemic, which carries with it higher burdens of both diabetes and depression, there is reason to be concerned that the risk of dementia could be higher at even younger ages. To address this issue, we also wanted to see if there was a differential impact of the combination of diabetes and co-existing depression on dementia risk among those younger than 65 compared to individuals 65 or older. We were fortunate to be able to examine health data from all Danish citizens 50 or older over a 6 year period, a population numbering nearly 2.5 million people to be able to answer these questions. Medical Research: What are the main findings? Dr. Davydow: We found that compared to individuals without diabetes or depression, those with diabetes alone had about a 15% greater risk of developing dementia, those with depression alone had about an 83% greater risk of developing dementia, and those with both diabetes and co-existing depression had a 107% greater risk of developing dementia compared to those without either condition. We also found that of all of the cases of dementia diagnosed in Denmark among individuals 50 or older between 2007 through 2013, 6% were potentially due to combination of having both diabetes and depression. This was also true for those 65 or older, where 6% of all diagnosed dementia was potentially attributable to the combination of both diabetes and depression. However, among individuals under age 65, we found that 25% of all cases of dementia may have been directly attributable to the combination of diabetes and co-existing depression. (more…)
Alzheimer's - Dementia, Author Interviews, Mayo Clinic / 25.03.2015

Melissa Murray, Ph.D Assistant Professor of Neuroscience Mayo ClinicMedicalResearch.com Interview with: Melissa Murray, Ph.D Assistant Professor of Neuroscience Mayo Clinic   Medical Research: What is the background for this study? What are the main findings? Dr. Murray: Our study investigates two of the hallmark brain pathologies that underlie Alzheimer’s disease, abnormally accumulated tau and amyloid proteins.  While both are integral to diagnosing Alzheimer’s disease postmortem, their exclusive relationship with cognitive decline has been debated.  Using a large series from our brain bank we found that while an increase in abnormal accumulation of both proteins shares a close relationship with a decline in cognition, tau is the key driver of decline.  This was important for us to understand as the second part of our study investigated amyloid brain scanning. We found that amyloid brain scanning closely represents amyloid deposits and not tau in postmortem brain tissue.  One particular aspect we focused on is the cutoff for what would be a amyloid-positive brain scan that indicates Alzheimer’s disease.  Our study supports that currently available cutoffs correspond to a level of amyloid accumulation that occurs before Alzheimer’s disease has too far advanced. (more…)
Alzheimer's - Dementia, Author Interviews, Johns Hopkins, Medical Imaging / 20.03.2015

Arnold Bakker, Ph.D. Assistant Professor Division of Psychiatric Neuroimaging Department of Psychiatry and Behavioral Sciences The Johns Hopkins University School of Medicine Baltimore, MD 21287MedicalResearch.com Interview with: Arnold Bakker, Ph.D. Assistant Professor Division of Psychiatric Neuroimaging Department of Psychiatry and Behavioral Sciences The Johns Hopkins University School of Medicine Baltimore, MD 21287 Medical Research: What is the background for this study? What are the main findings? Dr. Bakker: Patients who are at increased risk for developing dementia due to Alzheimer’s disease show hyperactivity in an area of the brain called the hippocampus, which is critically important for memory function. This study investigated the functional significance of this hyperactivity and determined if, similar to animal studies, treatment with low dose levetiracetam would reduce this increased activation and improve memory function in these patients. Results showed that this overactivity is a dysfunctional condition that contributes to the memory impairment such that treatment with very low doses of levetiracetam both reduces this overactivity and improves memory function in these patients. (more…)
Alzheimer's - Dementia, Author Interviews, Karolinski Institute, Lancet / 13.03.2015

MedicalResearch.com Interview with: Miia Kivipelto MD, PhD, Professor Deputy Head, Senior Geriatrician Aging Research Center and Alzheimer Disease Research Center Karolinska Institutet Clinical Trials Unit, Memory Clinic Karolinska University Hospital Stockholm, Sweden Medical Research: What is the background for this study? What are the main findings? Dr. Kivipelto: Epidemiological studies have linked several modifiable risk factors to cognitive impairment and dementia but evidence from randomized controlled trials (RCT) has been lacking showing the efficacy of the interventions. Because cognitive impairment, dementia and Alzheimer’s disease are complex, multi-factorial disorders, multidomain interventions targeting several risk factors and disease mechanisms simultaneously could be needed for optimum preventive effect. The FINGER study is the first large, long-term RCT indicating that multi-domain intervention can improve and maintain cognitive functioning in at risk elderly people from the general population. We observed a significant intervention effects on the primary outcome (overall cognition), main secondary outcomes (executive functioning and processing speed) as well as on complex memory tasks and risk of cognitive decline. The multidomain lifestyle intervention was feasible and safe. (more…)
Alzheimer's - Dementia, Author Interviews, Brigham & Women's - Harvard, JAMA, Memory / 24.02.2015

Dr. Rebecca E. Amariglio Ph.D. Massachusetts Alzheimers Disease Research Center Massachusetts General HospitalMedicalResearch.com Interview with: Dr. Rebecca E. Amariglio Ph.D. Massachusetts Alzheimers Disease Research Center Massachusetts General Hospital Medical Research: What is the background for this study? What are the main findings? Dr. Amariglio: As the field of Alzheimer’s disease moves towards early detection and treatment, new tests that can measure very subtle changes in cognitive functioning are needed. A new instrument developed by the Alzheimer’s Disease Cooperative Study that measures subjective report of memory changes of both the study participant and a study partner (usually a family member) was associated with cognitive decline over four years.  Specifically, greater report of memory concerns was associated with worse memory performance over time. (more…)
Alzheimer's - Dementia, Author Interviews, Exercise - Fitness / 06.02.2015

MedicalResearch.com Interview with: Paula Iso-Markku, MD, Department of Clinical Physiology and Nuclear Medicine,  HUS Medical Imaging Center,  Helsinki University Central Hospital and University of Helsinki Helsinki , Finland MedicalResearch: What is the background for this study? What are the main findings? Dr. Iso-Markku : The social, financial and humane burden of the dementia is extensive as the worldwide prevalence of dementia is estimated around 35.6 million. Finding efficient prevention strategies for dementia is crucial. Within the past decade vascular risk factors have been recognized as very potential risk factors of dementia. As physical activity is known to affect vascular risk factors, it might also be a potential preventive tool against dementia. Few comprehensive epidemiological studies on physical activity in middle age and dementia occurrence later in life have been conducted. The comprehensive Finnish Twin Study offers a unique approach to the subjects as the shared growing up environment and genes can be taken into account. The study population is extensive and a good representation of the Finnish population. In this study the association of physical activity in adulthood and dementia mortality was investigated in a 29-year follow-up. The main finding in this study was that persistent vigorous (i.e. more strenuous than walking) physical activity was significantly associated with lower dementia mortality. The results in the paired analysis, comparing twins to co-twins, were similar but remained non-significant. The analyses of the volume of physical activity were, however, controversial. (more…)
Alzheimer's - Dementia, Author Interviews / 05.02.2015

MedicalResearch.com Interview with: V. Zlokovic, MD, PhD Professor and Chair Department of Physiology and Biophysics Keck School of Medicine of USC.V. Zlokovic, MD, PhD Professor and Chair Department of Physiology and Biophysics Keck School of Medicine of USC.   Medical Research: What is the background for this study? What are the main findings? Dr. Zlokovic: Our team used high-resolution imaging of the living human brain to show for the first time that the brain’s protective blood barrier becomes leaky with age, starting at the hippocampus, a critical learning and memory center that is damaged by Alzheimer’s disease. (more…)
Alzheimer's - Dementia, Author Interviews, Cognitive Issues / 26.01.2015

MedicalResearch.com Interview with: Craig S. Atwood Associate Professor, University of Wisconsin Madison, WI Richard L. Bowen, M.D. Private Practice, Charleston, SC Medical Research: What is the background for this study? Response: Currently, there is no treatment for Alzheimer’s disease that halts or slows its progression. Alzheimer’s disease is a neurodegenerative disorder resulting in memory loss and impairments of behavioral, language and visuo-spatial skills. A growing body of biological, preclinical and epidemiological data suggests that the age-related changes in hormones of the hypothalamic-pituitary-gonadal (HPG) axis are a major etiological factor in Alzheimer disease. The changes in these hormones include not only the decline in the sex steroids, (i.e. 17-estradiol and testosterone), but the elevations in gonadotropin-releasing hormone and luteinizing hormone. In particular there are encouraging epidemiological studies involving the use of Lupron Depot which suppresses these hormones. In one such study which included hundreds of thousands of patients it was found that men who had prostate disease and were treated with Lupron Depot had a 34 to 55 percent decreased risk of developing Alzheimer’s disease compared with prostate-cancer patients who didn’t receive the drug. (more…)
Alzheimer's - Dementia, Author Interviews, Sleep Disorders / 29.10.2014

Christian Benedict PhD Associate Professor of Neuroscience Uppsala University Dept. of NeuroscienceMedicalResearch.com Interview with: Christian Benedict PhD Associate Professor of Neuroscience Uppsala University Dept. of Neuroscience   Medical Research: What is the background for this study? Answer: Our study involved ~1500 men who were followed from 1970 to 2010. All participants were 50 years old at the start of study. Medical Research: What are the main findings? Answer: Men with reports of sleep disturbances had a 50%-higher risk to develop Alzheimer's disease during the 40-year follow-up period, than men without reports of sleep disturbances. (more…)
Alzheimer's - Dementia, Author Interviews, Neurology / 07.10.2014

Lena Johansson, PhD, MSc, RN Institute of Neuroscience and Physiology Department of Psychiatry and Neurochemistry Sahlgrenska Academy at Gothenburg UniversityMedicalResearch.com Interview with: Lena Johansson, PhD, MSc, RN Institute of Neuroscience and Physiology Department of Psychiatry and Neurochemistry Sahlgrenska Academy at Gothenburg University Medical Research: What are the main findings of the study? Dr. Johansson: We found that a higher degree of neuroticism in midlife was associated with increased risk of Alzheimer’s disease over 38 years. On the 24 point scale, the risk increased with 4% per each step. Women who score high on the neuroticism scale were more likely to experience feelings such as anxiety, nervousness, worry, and irritability, and they were more moodiness and stress-prone. The association between neuroticism and Alzheimer’s disease diminished after adjusting for longstanding perceived distress symptoms, which suggest that the associations was at least partly depended on long-standing distress symptoms. When the two personality dimensions were combined, women with high neuroticism/low extraversion had a double risk of Alzheimer’s disease compared to those with low neuroticism/high extraversion. (more…)
Alzheimer's - Dementia, Author Interviews, BMJ / 10.09.2014

Sophie Billioti de Gage PharmD University of Bordeaux Segalen FranceMedicalResearch.com Interview with: Sophie Billioti de Gage PharmD University of Bordeaux Segalen France   Medical Research: What are the main findings of the study? Answer: The risk of Alzheimer’s disease was found increased by 43-51% in persons (>65) having initiated a treatment with benzodiazepines in the past (>5 years before). Risk increased with the length of exposure and when long acting benzodiazepines were used. (more…)
Alzheimer's - Dementia, Author Interviews, Cannabis / 03.09.2014

Chuanhai Cao Ph.D. Neuroscientist at the Byrd Alzheimer's Institute and the USF College of Pharmacy.MedicalResearch.com Interview with: Chuanhai Cao Ph.D. Neuroscientist at the Byrd Alzheimer's Institute and the USF College of Pharmacy. Medical Research: What are the main findings of the study? Dr. Cao: The major goal of this study was to investigate the effect of Ä9-tetrahydrocannabinol (THC), a major component of marijuana, on Alzheimer’s disease (AD) pathology. THC has long been known to have anti-inflammatory effects, but we were looking to determine whether THC directly affected amyloid beta (Aâ). Aâ aggregation is considered one of the key pathological hallmarks of Alzheimer’s disease. Our study showed that extremely low doses of THC were able to decrease Aâ production, inhibit Aâ aggregation, and enhance mitochondrial function in a cellular model of AD. Decreased levels of amyloid beta, coupled with THC’s inhibitory effect on aggregation may protect against the progression of Alzheimer’s disease. (more…)
Alzheimer's - Dementia, Author Interviews, Emergency Care / 11.08.2014

Dr. Caroline E Stephens PhD Department of Community Health Systems University of California, San FranciscoMedicalResearch.com Interview with: Dr. Caroline E Stephens PhD Department of Community Health Systems University of California, San Francisco Medical Research: What are the main findings of the study? Dr. Stephens: In our national random sample of nursing home residents, we found that mild cognitive impairment (CI) predicted higher rates of ED visits compared to no CI, but interestingly, ED visit rates decreased as severity of cognitive impairment increased.  However, after nursing home residents were evaluated in the ED, severity of CI was not significantly associated with higher odds of hospitalization. Another important finding was that the proportion of nursing home residents using feeding tubes more than tripled in advanced or end-stage dementia, from 9.9% to 33.8%.  Moreover, tube-fed nursing home residents had 73% higher rates of total ED visits, but once evaluated in the ED, they were no more likely to be hospitalized than those without feeding tubes.  This finding is particularly striking given the numerous existing studies that have questioned the utility and appropriateness of using feeding tubes in people with advanced dementia. (more…)
Alzheimer's - Dementia, Author Interviews, Mayo Clinic / 25.07.2014

Dr. Bryan K. Woodruff Assistant Professor of Neurology Mayo Clinic, ArizonaMedicalResearch.com Interview Invitation Dr. Bryan K. Woodruff Assistant Professor of Neurology Mayo Clinic, Arizona Medical Research: What are the main findings of the study? Dr. Woodruff: There is evidence in the medical literature supporting a negative impact of losing a spouse for health conditions such as cancer or cardiovascular disease, but this has not been evaluated in terms of the impact of widowhood on the development of dementia.  We used the National Alzheimer’s Disease Coordinating Center (NACC) database, which pools data gathered by multiple federally-funded Alzheimer’s disease research centers to try to answer this question.  Specifically, we looked at the age at which individuals ultimately developed dementia in both individuals who lost their spouse and in those who remained married over the course of the study.  Surprisingly, the data we analyzed did not support a negative impact of losing a spouse in individuals who had no cognitive difficulties when they entered the study, and we saw a paradoxical effect of widowhood in those with mild cognitive impairment (MCI). (more…)
Alzheimer's - Dementia, Author Interviews, JAMA, Neurological Disorders, Stroke / 23.07.2014

MedicalResearch.com Interview with: Agustin Ibanez, PhD Laboratory of Experimental Psychology and Neuroscience Institute of Cognitive Neurology and the National Scientific and Technical Research Council and Sandra Baez, MS; Institute of Cognitive Neurology and Institute of Neuroscience, Favaloro University, Buenos Aires, Argentina Medical Research: What are the main findings of the study? Answer: Both patients with the behavioral variant of frontotemporal dementia (bvFTD) and patients with frontal strokes presented moral judgment abnormalities. Their deficits were related to impairments in the integration of intentions and outcomes. Specifically, both patient groups judged moral scenarios by focusing on the actions' outcomes instead of the protagonists' intentions. (more…)
Alzheimer's - Dementia, Author Interviews / 23.05.2014

Susan Farr, Ph.D. Research Professor of Geriatrics Saint Louis UniversityMedicalResearch.com Interview with: Susan Farr, Ph.D. Research Professor of Geriatrics Saint Louis University   MedicalResearch: What are the main findings of the study? Dr. Farr: We found that reducing the conversion of amyloid precursor protein (APP) to beta amyloid with an antisense targeting the beta amyloid portion of amyloid precursor protein in the Tg2576 mouse which overexpresses human beta amyloid, improves learning and memory and reduces neuroinflammatory cytokine (inflammation in the brain). (more…)