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…)
Author Interviews, Cognitive Issues, Weight Research / 26.11.2014

Nicolas Cherbuin PhD ARC Future Fellow - Director of the NeuroImaging and Brain Lab Centre for Research on Ageing, Health and Wellbeing Research School of Population Health - College of Medicine Biology and Environment Australian National UniversityMedicalResearch.com Interview with: Nicolas Cherbuin PhD ARC Future Fellow - Director of the NeuroImaging and Brain Lab Centre for Research on Ageing, Health and Wellbeing Research School of Population Health - College of Medicine Biology and Environment Australian National University Medical Research: What is the background for this study? What are the main findings? Dr. Cherbuin: A number of modifiable risk factors for cognitive aging dementia and Alzheimer’s disease have been identified with a high level of confidence by combining evidence from animal research and systematic reviews of the literature in humans that summarise the available findings without focusing on extreme findings that come about from time to time in research. One such risk factor is obesity for which we have previously conducted a systematic review (Anstey et al. 2011). This showed that obesity is associated with a two-fold increased risk of dementia and a 60% increased risk of Alzheimer’s disease. What was surprising is that this effect was only detectable for obesity in middle age but not old age. This might suggest that the obesity only has an adverse effects on brain health earlier in life and that this effect fades at older ages. This is unlikely because a number of animal studies have shown that the biological mechanisms linking obesity with brain pathology do not disappear with older age but in fact appear to increase. Moreover, human studies show that thinking abilities decline faster in obese individuals. An alternative explanation is that human epidemiological studies investigating this question in older individuals include participants who do not have clinical dementia but in whom the disease is developing. Since dementia and Alzheimer’s disease pathology is associated with weight loss it is possible that estimated effects in humans have been confounded by this issue. Another possible confounder is that older people tend to lose muscle mass (sarcopenia) this may lead to the paradoxical condition in aging where a person has a normal weight but has excessive fat mass. Since it is fat tissue that is linked to risk to cerebral health it may have led to the apparently contradictory findings that obesity may not be a risk in older age. It is therefore of great interest to clarify whether obesity in early old age in individuals free of dementia is associated with poorer cerebral health. The hippocampus is one of the structures most sensitive stressors. Because obesity is known to lead to a state of chronic inflammation which is deleterious to the hippocampus, it was a logical structure to investigate. Moreover, the hippocampus is needed for memory function and mood regulation and is directly implicated in the dementia disease process. This study investigated 420 participants in their early 60s taking part in a larger longitudinal study of aging taking place in Canberra, Australia and who underwent up to three brain scans over an 8-year follow-up. These individuals were free of dementia and other neurological disorders. Associations between obesity and shrinkage of the hippocampus were investigated with longitudinal analyses which controlled for major confounders. The main findings were that overweight and obese participants had smaller volume of the hippocampus at the start of the study. In addition, the hippocampus shrunk more in these individuals over the follow-up period. (more…)
Author Interviews, Memory, Nature / 23.11.2014

Vijay Ramanan, PhD Indiana University Center for Neuroimaging (CfN) Department of Radiology Indianapolis, IN 46202MedicalResearch.com Interview with: Vijay Ramanan, PhD Indiana University Center for Neuroimaging (CfN) Department of Radiology Indianapolis, IN 46202 Medical Research: What is the background for this study? What are the main findings? Dr. Ramanan: Impairment in episodic memory is one of the first clinical deficits in early Alzheimer’s disease, the most common cause of dementia.  Among other examples, this might be reflected as an inability to recall an article recently read or as difficulty remembering what one had for dinner last night.  Unfortunately, the genetic and environmental mechanisms underlying these deficits are not fully understood.  Our goal was to discover new genes and pathways underlying memory performance to help identify potential drug targets for protecting against and ultimately reversing memory loss in dementia and normal aging. Through studying a large representative sample of older Americans, we discovered a variant (single nucleotide polymorphism or SNP) in the FASTKD2 gene associated with better memory performance and replicated this finding in independent samples.  We then integrated additional data to extend our understanding of the effect of this SNP.  For example, we know that the hippocampus is a vital brain structure for encoding and retrieving memories and it is well-understood that decreased hippocampal volume is a key early marker of Alzheimer’s disease and one that can be measured noninvasively through magnetic resonance imaging (MRI).  We predicted that this new memory-protective SNP would be associated with increased hippocampal volume and this turned out to be true.  We also discovered that carriers of this memory-protective SNP exhibited lower levels of proteins involved in cell death in the cerebrospinal fluid bathing the brain and spinal cord, a striking finding given that FASTKD2 encodes a protein that appears to promote apoptosis (i.e., programmed cell death).  Together, these convergent findings are consistent with a neuroprotective effect of this novel SNP discovery.  More broadly, our results nominate FASTKD2 and its functional pathways as potential targets for modulating neurodegeneration to combat memory loss in older adults. (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 / 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…)
Alzheimer's - Dementia, Author Interviews, Genetic Research, NIH / 10.04.2014

Prof. Dr. med. Piotr Lewczuk Head,Lab for Clinical Neurochemistry and Neurochemical Dementia Diagnostics, Universitätsklinikum Erlangen, Department of Psychiatry and Psychotherapy, 91054 Erlangen, GermanyMedicalResearch.com Interview with: Prof. Dr. med. Piotr Lewczuk Head,Lab for Clinical Neurochemistry and Neurochemical Dementia Diagnostics, Universitätsklinikum Erlangen, Department of Psychiatry and Psychotherapy, 91054 Erlangen, Germany MedicalResearch.com: What are the main findings of the study? Prof. Dr. med. Piotr Lewczuk: In our study, we investigated the concentrations of four isoforms of amyloid beta peptides in the blood of healthy young volunteers without memory complains. The participants were stratified into three groups according to their apolipoprotein E (APOE) genotype, which is the mostly investigated and generally accepted genetic risk factor for sporadic Alzheimer’s Disease (AD). It is known that the alterations of the amyloid beta metabolism are the earliest changes in the course of AD, occurring many years (or even decades) before the onset of the clinical symptoms, but it is actually not known how early these alterations start. Correspondingly, we wanted to investigate if healthy persons with genetic risk factor show changes in their amyloid beta metabolism already 30-40 years before the age when AD is usually diagnosed. We did not find any differences between the groups with and without APOE-driven risk, which might be carefully interpreted as no signs of Alzheimer’s Disease pathology in persons at risk at such an early life stage. Taken together, we think that the Alzheimer’s Disease pathology starts some 10-20 years before the beginning of the clinical symptoms, but not earlier. (more…)
Alzheimer's - Dementia, Author Interviews, JAMA, University of Pittsburgh, Wake Forest / 31.03.2014

MedicalResearch.com Interview Invitation with: Timothy Hughes, PhD, MPH Roena B. Kulynych Center for Memory & Cognition Research Department of Internal Medicine Division of Gerontology and Geriatric Medicine Wake Forest School of Medicine Medical Center Boulevard, Winston-Salem, NC 27157-1207Timothy Hughes, PhD, MPH Roena B. Kulynych Center for Memory & Cognition Research Department of Internal Medicine Division of Gerontology and Geriatric Medicine Wake Forest School of Medicine Medical Center Boulevard, Winston-Salem, NC  27157-1207 MedicalResearch.com: What are the main findings of the study? Dr. Hughes: This study is a follow-up to our recent paper that showed a novel relationship between arterial stiffness (commonly measured by pulse wave velocity) and the presence and extent of amyloid deposition in the brain, a hallmark of Alzheimer’s disease. For this study, we repeated brain amyloid imaging (using the Pittsburgh Compound B during PET imaging) in order to look for predictors of change in amyloid over two years in n=81 elderly adults aged 80+ and free from dementia. We observed that measures of systemic arterial stiffness (e.g. brachial ankle pulse wave velocity) was strongly associated with the extent of amyloid deposition in the brain at both baseline and follow-up. The change in brain amyloid accumulation over two years resulted in an increase in in the number of participants with Alzheimer’s-like (amyloid-positive) from 45% at baseline to a surprising 75% after just two years. This change in brain amyloid accumulation over two years was strongly related to having greater central stiffness (as measured by carotid femoral pulse wave velocity). These relationships between arterial stiffness and brain amyloid deposition were independent of the effects of age, gender, body mass index, antihypertensive medication use and even current blood pressure. (more…)
Alzheimer's - Dementia, Author Interviews, PNAS, University of Michigan / 19.03.2014

Yanzhuang Wang, PhD Associate professor Dept. of Molecular, Cellular and Developmental Biology and Dept. of Neurology University of Michigan Ann Arbor, MI 48109-1048MedicalResearch.com Interview with: Yanzhuang Wang, PhD Associate professor Dept. of Molecular, Cellular and Developmental Biology and Dept. of Neurology University of Michigan Ann Arbor, MI 48109-1048  MedicalResearch.com: What are the main findings of the study? Dr. Wang: We learned how to repair a cellular structure called the Golgi apparatus that is broken in Alzheimer’s disease. This helps us understand how to reduce the formation of the toxic plaques that kill cells in the brain of Alzheimer's patients. The formation of amyloid plaques is a hallmark of Alzheimer’s disease; but exactly how much the plaques contribute to the disease is still not known. Our study found that the broken Golgi in the disease may be a major source of the toxicity of amyloid plaques. We showed in this study that repairing the Golgi can reduce the formation of the toxic plaques and thus may delay the disease development. (more…)
Alzheimer's - Dementia / 25.02.2014

Dr. Erin Abner Ph.D. Assistant Professor of Epidemiology University of Kentucky College of Public Health Lexington, KentuckyMedicalResearch.com Interview with: Dr. Erin Abner Ph.D. Assistant Professor of Epidemiology University of Kentucky College of Public Health Lexington, Kentucky MedicalResearch.com: What are the main findings of the study? Dr. Abner:  The findings from this study are preliminary results from The Prevention of Alzheimer’s Disease with Vitamin E and Selenium Study. This early look at the data indicates that very simple measures of memory change, in this case asking older men with no cognitive impairment about changes in their memory over the past year, and whether they believe those changes are a problem, can be used to predict cognitive impairment years later. Men who said at study baseline that the changes in their memory represented problems to them were over twice as likely as men who did not complain to develop clinically detectable cognitive impairment during follow-up. This is exciting because the field of Alzheimer’s research is moving toward earlier intervention in the disease process. As of now, our best methods for identifying individuals without cognitive impairment who are likely to develop Alzheimer’s disease in the future are procedures that many people find intimidating, like lumbar puncture and PET scanning. Identifying older adults at high risk for future cognitive impairment with low-cost, non-invasive screening techniques would help researchers to target potential therapies to the people who stand to benefit the most. (more…)
Alzheimer's - Dementia, Author Interviews, JAMA, Mental Health Research / 19.02.2014

Anton P. Porsteinsson M.D. William B. and Sheila Konar Professor of Psychiatry Director, Alzheimer's Disease Care, Research and Education Program (AD-CARE) University of Rochester School of Medicine and Dentistry Rochester, N.Y. 14620MedicalResearch.com Interview with: Anton P. Porsteinsson M.D. William B. and Sheila Konar Professor of Psychiatry Director, Alzheimer's Disease Care, Research and Education Program (AD-CARE) University of Rochester School of Medicine and Dentistry Rochester, N.Y. 14620 MedicalResearch.com: What are the main findings of the study? Dr. Porsteinsson: Identifying drugs outside the antipsychotic class with targeted anti-agitation effects that provide greater benefit or lower risk among patients with Alzheimer’s disease is a research priority.  Citalopram, a selective serotonin reuptake inhibitor (SSRI), is frequently used in older individualsand has been suggested as an alternative to antipsychotic drugs for agitation and aggression in dementia.  Among 186 patients with probable Alzheimer’s disease and agitation receiving psychosocial intervention, the addition of citalopram compared with placebo robustly and significantly reduced agitation and caregiver distress, but modest cognitive and cardiac adverse effects of citalopram may limit its practical application at the 30 mg/d dose studied in this trial. There are insufficient data on efficacy for agitation at lower doses of citalopram. (more…)
Alzheimer's - Dementia, Author Interviews, Baylor College of Medicine Houston, NEJM / 02.02.2014

Rachelle S. Doody, M.D.,Ph.D. Effie Marie Cain Chair in Alzheimer's Disease Research Director, Alzheimer's Disease and Memory Disorders Center Baylor College of Medicine-Department of Neurology Houston, Texas 77030: MedicalResearch.com MedicalResearch.com Interview with: Rachelle S. Doody, M.D.,Ph.D. Effie Marie Cain Chair in Alzheimer's Disease Research Director, Alzheimer's Disease and Memory Disorders Center Baylor College of Medicine-Department of Neurology Houston, Texas 77030: MedicalResearch.com MedicalResearch.com: What are the main findings of the study?  Dr. Doody: The study set out to see whether the antibody infusion treatment, Solanezumab, would improve the course of mild to moderate Alzheimer's disease in the ways necessary to gain drug approval.  Unfortunately, the results did not support an approvable treatment for this purpose. (more…)
Alzheimer's - Dementia, Author Interviews / 17.12.2013

MedicalResearch.com Interview with: Lieke Smits drs. L.L. Smits VU University Medical Center Department of Neurology - Alzheimer Center 1081 HV Amsterdam, The Netherlands MedicalResearch.com:  What are the main findings of the study? Answer: In this study we used two visual ratings scales to estimate atrophy of the medial temporal lobe (MTA) and posterior atrophy (PA) on MRI in patients with Alzheimer’s disease. We assessed associations between MTA and PA with cognitive impairment. We found that MTA was associated with worse performance in memory, language and attention, while PA was associated with worse performance in viuso-spatial functioning and executive functioning. Further stratification for age at diagnosis revealed that in late onset (>65 years old) MTA was associated with impairment in memory, language, visuo-spatial functioning and attention. In early onset patients (<65 years old), worse performance on visuo-spatial functioning almost reached significance. (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research, JAMA / 30.08.2013

Ekaterina Rogaeva, PhD Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, CanadaDepartment of Medicine, University of Toronto, Toronto, Ontario, CanadaCambridge Institute for Medical Research and Department of Clinical Neurosciences, University of Cambridge, Cambridge, EnglandMedicalResearch.com Interview with: Ekaterina Rogaeva, PhD Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, Canada Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, Ontario, CanadaDepartment of Medicine, University of Toronto, Toronto, Ontario, CanadaCambridge Institute for Medical Research and Department of Clinical Neurosciences, University of Cambridge, Cambridge, England MedicalResearch.com: What are the main findings of the study? Answer: We tested the hypothesis that late-onset Alzheimer disease (AD) might be in part explained by the homozygosity of unknown loci. In a genome-wide study of a Caribbean Hispanic population with noticeable inbreeding and high risk of AD we assessed the presence of long runs of homozygosity (ROHs) – regions where the alleles inherited from both parents are identical. Our results suggest the existence of recessive AD loci, since the mean length of the ROH per person was significantly longer in AD cases versus controls, and this association was stronger in familial AD. (more…)