Alzheimer's - Dementia, Author Interviews, Biomarkers, JAMA, MRI / 22.05.2023

MedicalResearch.com Interview with: Ruben Smith MD, PhD Associate professor at Clinical Memory Research Division of Neurology Lund University   MedicalResearch.com: What is the background for this study? Response: Since a few years it has become possible to visualize tau pathology in Alzheimer’s Disease (AD) using positron emission tomography (PET). The tau-PET radiotracer Flortaucipir (Tauvid) was recently approved by the US Food and Drug Administration as an AD diagnostic tool. Since PET imaging is costly and exposes the patient to radioactivity we wanted to study the added clinical value of tau-PET in the diagnostic work-up of patients with cognitive symptoms, before widespread implementation in clinical practice. (more…)
Author Interviews, Dental Research, Mental Health Research, NYU / 15.04.2021

MedicalResearch.com Interview with: ANGELA R. KAMER, DMD, MS, PhD Associate Professor Periodontology and Implant Dentistry NYU Dentistry MedicalResearch.com: What is the background for this study? Response: The accumulation of amyloid β plaques and neurofibrillary pathology in the brain are pathognomonic to Alzheimer's disease (AD). Brain amyloid deposition begins decades before cognitive dysfunction and is thought to be the first AD pathological feature followed by tau tangle accumulations and other pathologies. The mechanisms by which brain amyloid develops are incompletely understood although inflammation and bacterial imbalances (known as dysbiosis) of the gut and oral cavity may be involved. Periodontal disease affecting more than 50% of elderly is an inflammatory, chronic condition characterized by periodontal tissue destruction and bacterial imbalances. Using PET studies, we showed previously that measures of periodontal destruction were associated with brain amyloid retention in the brain [1]. In this study, we sought to investigate whether subgingival (under the gum line) bacteria associated with Alzheimer’s disease specific pathology, namely amyloidosis and tauopathy. (more…)
Alzheimer's - Dementia, Author Interviews, Eli Lilly, NEJM / 16.03.2021

MedicalResearch.com Interview with: Stephen Salloway, M.D., M.S. Director of Neurology and the Memory and Aging Program, Butler Hospital Martin M. Zucker Professor of Psychiatry and Human Behavior Professor of Neurology, Alpert Medical School of Brown University Providence, RI 02906  MedicalResearch.com: What is the background for this study? Response: This 78 week phase 2 study tested donanemab in patients with early Alzheimer’s disease. Donanemab is a an anti-amyloid monoclonal antibody that targets the N3 pyroglutamate epitope.  MedicalResearch.com: What are the main findings? Response: The drug produced a substantial lowering of amyloid plaques and showed a slowing in cognitive decline. Key innovations included using PET scans to ensure all patients were amyloid positive and had a moderate level of tau build-up and switching from drug to placebo once the amyloid level was below the expected cut-off for Alzheimer’s disease. There were no new safety signals. The main side-effect was amyloid-related imaging abnormalities (ARIA) that have been seen with other anti-amyloid treatments. ARIA is managed with regular safety MRI scans.  Donanemab is now being tested in a larger phase 3 trial that could lead to regulatory approval. (more…)
Alzheimer's - Dementia, Author Interviews, UCSD / 03.03.2021

MedicalResearch.com Interview with: Dr. Steven L. Wagner PhD University of California, San Diego Department of Neurosciences Professor in Residence School of Medicine, Medical Teaching Facility Room 150 La Jolla, California 92093-0624  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Amyloid plaques are pathological hallmarks of Alzheimer’s disease (AD)—clumps of misfolded proteins that accumulate in the brain, disrupting and killing neurons and resulting in the progressive cognitive impairment that is characteristic of the widespread neurological disorder.  Amyloid plaques are composed of small protein fragments called amyloid beta (Aβ) peptides. These peptides are generated by enzymes called β-secretase and γ-secretase, which sequentially cleave a protein called amyloid precursor protein on the surfaces of neurons to release Aβ fragments of varying lengths. Some of these fragments, such as Aβ42, are particularly prone to forming plaques, and their production is elevated in patients with mutations predisposing them to early-onset AD. Several attempts have been made to treat or prevent AD using drugs that inhibit either β-secretase or γ-secretase, but many of these drugs have proved to be highly toxic or unsafe in humans, likely because β-secretase and γ-secretase are required to cleave additional proteins in the brain and other organs. Instead, Wagner and colleagues investigated the therapeutic potential of drugs known as γ-secretase modulators or GSMs, which instead of inhibiting the γ-secretase enzyme, slightly alter its activity so that it produces fewer Aβ peptides that are prone to form plaques while continuing to duties cleaving other protein targets. “GSMs offer the ability to mitigate mechanism-based toxicities associated with γ-secretase inhibitors,” said Wagner.  (more…)
Alzheimer's - Dementia, Author Interviews, Cognitive Issues, Memory, Surgical Research / 23.01.2021

MedicalResearch.com Interview with: Pascual Sánchez-Juan, MD, PhD Servicio de Neurología Hospital Universitario "Marqués de Valdecilla" Unidad de Deterioro Cognitivo https://www.facebook.com/deteriorocognitivovaldecilla Director científico Biobanco Valdecilla Avda Marqués de Valdecilla s/n  MedicalResearch.com: What is the background for this study? Response: Alzheimer's disease is one of the greatest public health challenges. From the moment the first lesions appear in the brain to the clinical manifestations, up to 20 years can pass. Today we can detect the presence of these initial lesions through biochemical markers such as amyloid-β, which is one of the main proteins accumulated in the brains of Alzheimer's patients. The prevalence of cerebral amyloid-β pathology in cognitively asymptomatic individuals increases with age. It has been estimated that 21.1% of the population at the age of 65 will have a positive amyloid scan or a pathological cerebrospinal fluid (CSF) amyloid-β determination, and which will double by the age of 90. Due to the aging of our societies and advances made in medical care, an increasing number of elderly and more fragile people are considered candidates for major surgery. In preoperative screenings, respiratory and cardiovascular functions are routinely checked; however, it is not commonly assessed how the brain is going to cope with the intervention. In the clinic, the patient’s relatives frequently tell us that the memory problems began after a surgical procedure or a hospital admission. This posed us the following question: is this just a recall bias or has surgery triggered the appearance of the symptoms in a previously affected brain?” (more…)
Alzheimer's - Dementia, Author Interviews, Lipids, Mental Health Research, Microbiome / 18.11.2020

MedicalResearch.com Interview with: Moira Marizzoni, PhD Researcher, Fatebenefratelli Center in Brescia  MedicalResearch.com: What is the background for this study? Response: Alzheimer’s disease is the most common cause of dementia. Still incurable, it directly affects nearly one million people in Europe, and indirectly millions of family members as well as society as a whole. The gut microbiota could play a role in brain diseases including Alzheimer’s disease. Some gut bacteria components or products can reach the brain via the blood and might promote brain amyloidosis (one of the main pathological features in Alzheimer’s disease).   MedicalResearch.com: What are the main findings?  Response: This study evaluated a cohort of 89 people between 65 and 85 years of age composed of subjects suffering from Alzheimer’s disease or other neurodegenerative diseases causing similar memory problems, and of subjects with no memory problems. The study revealed that elevated levels of microbiota-products with known pro-inflammatory properties (i.e. lipopolysaccharides and the short chain fatty acids acetate and valerate) were associated with greater cerebral amyloid pathology while elevated levels of those with anti-inflammatory properties (i.e. the short chain fatty acid butyrate) were associated with lower amyloid pathology. (more…)
Alzheimer's - Dementia, Author Interviews, Biomarkers, Heart Disease / 25.02.2020

MedicalResearch.com Interview with: Prof. Konstantinos Stellos, MD, DM, MRCP, DSc, FAHA, FESC Professor of Medicine, Chair of Cardiovascular Medicine, Chair of Epitranscriptomics Lead, Vascular Biology & Medicine Theme Hon. Consultant Cardiologist, Newcastle Hospitals NHS Foundation Trust Biosciences Institute Faculty of Medical Sciences Newcastle University MedicalResearch.com: What is the background for this seminar? Can you tell us a little about how amyloid is made and stored? Response: Patients are afraid that they may die due to a heart attack - a major cause of death worldwide- or if they live long they may get dementia compromising severely their quality of life in their last years of life. Many years ago we asked the question whether there is a link between these two ageing-associated diseases. For this reason we studied the clinical value of amyloid-beta peptides in patients with coronary heart disease. We chose to study the amyloid-beta peptides, which are the cleavage product of the beta- and gamma-secretases of the mother protein amyloid precursor protein, because amyloid-beta plaques in brain is the hallmark of Alzheimer's disease. Following amyloid precursor protein (APP) gene transcription, APP is cleaved in the nonamyloidogenic pathway (plasma membrane) by α- and γ- secretases or in the amyloidogenic pathway (endosomes) by β- and γ- secretases. The later pathway generates amyloid beta (Αβ) peptides that are released extracellularly. Αβ accumulation in blood or tissues may result from enhanced production/cleavage or by impaired degradation and/or clearance. The related mechanisms are depicted in Figure 2 of our publication in JACC: http://www.onlinejacc.org/content/75/8/952  (more…)
Alzheimer's - Dementia, Author Interviews, Cognitive Issues, Duke, Neurology / 24.09.2019

MedicalResearch.com Interview with: Juan Helen Zhou, PhD, on behalf of the co-authors Associate Professor and Principal Investigator Neuroscience and Behavioural Disorders (NBD) Programme Duke-NUS Medical School, SingaporeJuan Helen Zhou, PhD, on behalf of the co-authors Associate Professor and Principal Investigator Neuroscience and Behavioural Disorders (NBD) Programme Duke-NUS Medical School, Singapore  MedicalResearch.com: What is the background for this study? Response: Alzheimer’s disease and cerebrovascular disease are among the leading disorders affecting the elderly, with up to 50 per cent of dementia patients showing co-occurrence of both disorders. It is therefore of great interest to understand the influence of co-occurring Alzheimer’s disease and cerebrovascular disease pathologies on brain changes, and examine if such changes are able to track early differential disease progression. Past cross-sectional studies have suggested that Alzheimer's disease and cerebrovascular disease pathologies contribute independently to brain functional and structural changes, and cognitive decline. Our study sought to demonstrate the independent contributions of both pathologies to brain functional networks in a longitudinal cohort of mild cognitive impairment patients, often regarded as early stage of the disease. (more…)
Alzheimer's - Dementia, Author Interviews / 20.09.2018

MedicalResearch.com Interview with: Dr Christina Elliott PhD Postdoctoral Researcher Department of Old Age Psychiatry King’s College London MedicalResearch.com: What is the background for this study? Response: Amyloid-beta (Aβ) and its precursor protein, APP have been long implicated in pathogenesis of Alzheimer’s Disease but how they contribute to disease is not fully understood.  This has been further compounded by numerous failed clinical trials which attempted to target Aβ therapeutically. In Alzheimer’s Disease there is an overproduction of Aβ, which can disrupt how neurons communicate at structures called synapses.  It is thought that progressive synapse loss underpins cognitive impairments commonly seen in Alzheimer Disease patients such as memory loss. Our previous work highlighted a central role of the signalling pathway Wnt signalling in Aβ mediated synapse loss through the induction of dickkopf-1 (Dkk1), a well-known modulator of Wnt signalling. The aim of this study was to further investigate the molecular mechanisms of Aβ mediated synapse loss and explore whether this is connected to the overproduction of Aβ.  By dissecting out the key signalling events involved we hoped this would allow us to identify drugs which could be putative therapeutics for Alzheimer’ Disease.   (more…)
Alzheimer's - Dementia, Author Interviews, JAMA, Medical Imaging, Memory / 12.06.2018

MedicalResearch.com Interview with: Arno de Wilde, MD / PhD candidate Department of Neurology & Alzheimer Center Amsterdam Neuroscience VU University Medical Center Amsterdam, the Netherlands MedicalResearch.com: What is the background for this study? What are the main findings? Response: Previous studies assessing the clinical utility of amyloid imaging used very selected research populations, limiting the translatability to clinical practice. In contrast, we used an unselected memory clinic cohort, offering amyloid PET to ALL patients visiting our memory clinic, and for the purpose of this study, we implemented amyloid PET in our routine diagnostic work-up. Our results demonstrate that amyloid PET has important consequences, in terms of diagnosis and treatment changes, for a significant number of patients within a situation that closely resembles clinical practice. I think that these results are an important step in 'bridging the gap' between using amyloid PET in a research setting versus daily clinical practice. (more…)
Annals Internal Medicine, Author Interviews, Biomarkers, Heart Disease / 22.05.2018

MedicalResearch.com Interview with: Prof. Dr. med. Konstantinos Stellos,MD, FAHA, FESC Cardiovascular Research Centre, Institute of Genetic Medicine Newcastle upon Tyne United Kingdom MedicalResearch.com: What is the background for this study?   Response: Risk stratification of patients with a non-ST-segment elevation acute coronary syndrome (NSTE-ACS) remains a major challenge in clinical cardiology. Risk stratification is important to identify patients at high risk, to whom an early coronary intervention with optimal adjunctive medical therapy shall be applied to reduce that risk. Conversely, it is equally important to identify patients at low risk, to whom a potentially hazardous invasive therapy or a multi-drug administration shall be avoided. Current ACC/AHA and ESC guidelines agree in a standardized approach that uses Global Registry of Acute Coronary Events (GRACE) score, a well validated scoring system, to calculate a patient’s risk and guide triage and management decisions. Amyloid-β (Aβ) 1-40 and 1-42 peptides (Aβ40 and Aβ42), are proteolytic fragments of a larger protein, the amyloid precursor protein (APP) cleaved by β- and γ-secretases, found in typical brain amyloid deposits in Alzheimer’s disease. Many lines of evidence support a role of Aβ40 in cardiovascular disease as a peptide with pro-inflammatory and pro-thrombotic properties. Most cardiovascular risk factors seem to affect APP metabolism and thus, Aβ production and its soluble circulating APP770 isoform are elevated in patients with ACS_ENREF_15, suggesting a role for Aβ40 in the triggering and outcome of ACS in stable CAD patients. Although vascular inflammation is considered as a hallmark in the pathophysiologic pathways of coronary artery disease (CAD) and novel mechanisms are continuously recognized in its pathogenesis, no inflammatory marker is currently recommended for risk stratification of patients with NSTE-ACS individually or as a component of the GRACE score. This may partly explain the moderate discriminative ability of GRACE score in some studies, especially in older patients and those after early percutaneous coronary intervention (PCI). In this retrospective study, we used data from two independent prospective cohorts, the Heidelberg study (n=1,145) and the validation multicenter international APACE (Advantageous Predictors of Acute Coronary Syndrome Evaluation, n=734) study and determined the clinical prognostic and reclassification value of baseline circulating Aβ40 levels in the prediction of mortality over the GRACE risk score in patients with NSTE-ACS across a median follow-up of 21.9 ( Heidelberg cohort) and 24.9 months (APACE cohort), respectively. (more…)
Alzheimer's - Dementia, Author Interviews, Merck, NEJM / 02.05.2018

MedicalResearch.com Interview with: Dr. Michael F. Egan MD Merck & Co. North Wales, PA 19454   MedicalResearch.com: What is the background for this study? What are the main findings? Response: A leading theory of Alzheimer's Disease is that it is caused by the buildup of amyloid plaques in the brain. Amyloid is composed of a sticky peptide called Abeta.  Abeta production can be blocked by Inhibiting an enzyme called BACE.  In animal models, BACE inhibtion prevent amyloid accumulation.  We aimed to see if a potent BACE inhibitor would slow clinical decline in Alzheimer's Disease. EPOCH was a Phase 2/3 randomized, placebo-controlled, parallel-group, double-blind study evaluating efficacy and safety of two oral doses of verubecestat an investigational BACE inhibitor, administered once-daily versus placebo in patients with mild-to-moderate AD currently using standard of care treatment. The primary efficacy outcomes of the study are the change from baseline in cognition (assessed using the Alzheimer's Disease Assessment Scale Cognitive Subscale, or ADAS-Cog),  as well as the change from baseline in function (assessed using the Alzheimer's Disease Cooperative Study – Activities of Daily Living, or ADCS-ADL)  after 78 weeks of treatment. Following the recommendation of the external Data Monitoring Committee (eDMC), which assessed overall benefit/risk during  the trial,  the study was stopped early, as there was “virtually no chance of finding a positive clinical effect.” Verubecestat did not reduce cognitive or functional decline in patients with mild-to moderate Alzheimer’s disease and was associated with treatment-related adverse events.  (more…)
Alzheimer's - Dementia, Author Interviews, NIH, PNAS, Sleep Disorders / 19.04.2018

MedicalResearch.com Interview with: Nora D. Volkow MD Senior Investigator Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism National Institutes of Health, Bethesda, MD 20892 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Findings from animal studies had shown that sleep deprivation increased the content of beta-amyloid in brain, which is a risk factor for Alzheimer’s disease.  We wanted to test whether this also happened in the human brain after one night of sleep deprivation. We found that indeed one night of sleep deprivation led to an accumulation of beta amyloid in the human brain, which suggest that one of the reasons why we sleep is to help clean our brain of degradation products that if not removed are toxic to brain cells.  (more…)
Alzheimer's - Dementia, Author Interviews, Biomarkers, JAMA, MRI / 12.01.2018

MedicalResearch.com Interview with: Miguel A. Santos-Santos, MD Department of Neurology, Memory and Aging Center University of California San Francisco Autonomous University of Barcelona, Cerdanyola del Valles, Spain MedicalResearch.com: What is the background for this study? Response: Primary progressive aphasia (PPA) is a clinically and pathologically heterogeneous (generally Frontotemporal lobar degeneration [FTLD, generally tau or tdp proteinopathies] or Alzheimer’s disease [AD] pathology) condition in which language impairment is the predominant cause of functional impairment during the initial phases of disease. Classification of PPA cases into clinical-anatomical phenotypes is of great importance because they are linked to different prevalence of underlying pathology and prediction of this pathology during life is of critical importance due to the proximity of molecule-specific therapies. The 2011 international consensus diagnostic criteria established a classification scheme for the three most common variants (the semantic [svPPA], non-fluent/agrammatic [nfvPPA], and logopenic [lvPPA]) of PPA and represent a collective effort to increase comparability between studies and improve the reliability of clinicopathologic correlations compared to the previous semantic dementia and progressive non-fluent aphasia criteria included in the 1998 consensus FTLD clinical diagnostic criteria. Since their publication, a few studies have reported amyloid imaging and pathological results in PPA, however most of these studies are retrospective in nature and the prevalence of FTLD and Alzheimer’s disease pathological findings or biomarkers in each variant has been inconsistent across the literature, therefore prospective validation with biomarker and autopsy data remains scarce and highly necessary. (more…)
Alzheimer's - Dementia, Author Interviews, JAMA, Mental Health Research / 30.11.2017

MedicalResearch.com Interview with: Willemijn Jansen, PhD Postdoctoral researcher Department of Psychiatry & Neuropsychology Maastricht University Medical Center School for Mental Health and Neuroscience Alzheimer Center Limburg  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Cerebral amyloid-β aggregation is an early pathological event in Alzheimer’s disease (AD), starting decades prior to dementia onset. About 25% of cognitively normal elderly and 50% of patients with mild cognitive impairment (MCI) have biomarker evidence of amyloid pathology. These persons are at increased risk for developing AD-type dementia, but the extent to which amyloid-β aggregation affects cognitive function in persons without dementia is unclear. This is important to know for a better understanding of the course of Alzheimer’s disease and for the design of AD prevention trials. We here investigate the association between amyloid plaques and memory scores, using data from 53 international studies included in the Amyloid Biomarker study. Cognitively healthy elderly people with plaques have a low memory score twice as often as these persons without plaques. MCI patients with plaques had 20% more often low memory and low global cognition scores than MCI patients without plaques. We further observed 10- to 15-year intervals between the onset of amyloid positivity and emergence of low memory scores in cognitively healthy persons. (more…)
Alzheimer's - Dementia, Author Interviews, NYU, Obstructive Sleep Apnea / 15.11.2017

MedicalResearch.com Interview with: Ricardo S Osorio MD Center for Brain Health Department of Psychiatry Center of Excellence on Brain Aging NYU Langone Medical Center New York, NY 10016, USA  MedicalResearch.com: What is the background for this study? What are the main findings? Response: This was a study that was performed in a group of healthy normal elderly from the community that volunteered for studies on memory and aging. The main findings were that sleep apnea was very common, in almost all cases undiagnosed, and that it was associated with a longitudinal increase in amyloid burden which is considered one of the hallmark lesions of Alzheimer's disease (more…)
Author Interviews, Columbia, Heart Disease, Orthopedics / 28.09.2017

MedicalResearch.com Interview with: Dr. Mathew Maurer, Medical Director The Hypertrophic Cardiomyopathy Center NewYork-Presbyterian/Columbia University Medical Center. MedicalResearch.com: What is the background for this study? Response: Transthryretin cardiac amyloidosis (TTR-CA) is an underdiagnosed type of cardiomyopathy in which TTR (transthyretin, also known as prealbumin), a protein that forms amyloid fibrils, deposits in the heart. The deposits cause thickening of the ventricular wall and diastolic as well as systolic dysfunction. It is usually discovered around age 75 and presents more commonly in men than in women. With advances in non-invasive diagnostic modalities and growing awareness, TTR-CA is being diagnosed increasingly more frequently. Additionally, there are several emerging treatments that are under active investigation. Most of these therapies prevent disease progression and don’t address the amyloid already deposited in the heart. Accordingly, it is imperative that we diagnose TTR-CA before patients develop significant amyloid heart disease. However, this presents a great challenge since there are few known clinical predictors that might alert even the most astute physician that a patient is at such risk. With identification of predictors that may appropriately raise the index of clinical suspicion, clinicians may begin to pick up more subtle (and perhaps not yet clinically significant) forms of TTR-CA and initiate treatment before significant damage occurs. The few known clinical predictors of TTR-CA include bilateral carpal tunnel syndrome and lumbar spinal stenosis, and numerous studies found TTR on biopsies and autopsies of other musculoskeletal sites, particularly in hip and knee joints. (Just last week, and also discussed here on MedicalResearch.com, biceps tendon rupture was also shown to occur more frequently in TTR-CA!) We suspected that patients who ultimately develop TTR-CA may first develop clinically significant hip and knee disease, enough to even warrant a hip (THA) or knee (TKA) replacement. (more…)
Author Interviews, Brigham & Women's - Harvard, Heart Disease, JAMA, Orthopedics / 22.09.2017

MedicalResearch.com Interview with: Avinainder Singh, M.B.B.S. Research Fellow Cardiovascular Medicine Brigham & Women's Hospital Harvard Medical School Boston, MA MedicalResearch.com: What is the background for this study? Response: Amyloidosis due to aberrant folding of proteins. These misfolded proteins can deposit in various parts of the body and lead to organ dysfunction. The two most common types of amyloidosis affecting the heart include transthyretin and light chain amyloidosis. Transthyretin is a protein produced by the liver which supports the transport of thyroxine and retinol. Wild-type transthyretin amyloidosis (ATTRwt, previously known as senile amyloidosis) occurs due to deposition of misfolded fibrils derived from transthyretin and primarily affects elderly men. Once considered a rare disease, it is now reported to be responsible for nearly 13% of heart failure with preserved ejected fraction and increased wall thickness. Rupture of the biceps tendon is a rare occurrence in the general population (<1 per 1000). We noticed a ruptured biceps tendon in several patients with wild-type transthyretin amyloidosis and performed this study to further evaluate this finding in a group of patients with wild-type transthyretin amyloidosis and in a control group of age-matched patients with non-amyloid heart failure. (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, 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…)
Author Interviews, Columbia, Heart Disease, JAMA, Medical Imaging / 25.08.2016

MedicalResearch.com Interview with: Adam Castano, M.D., M.S. Division of Cardiology Columbia University Medical Center New York Presbyterian Hospital MedicalResearch.com: What is the background for this study? Response: Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized cause of heart failure with preserved ejection fraction (HFpEF). Traditionally, the gold standard for diagnosis has required an endomyocardial biopsy coupled with either immunohistochemistry or mass spectroscopy. These specialized tests are only performed at centers with experienced satff, do not yield prognostically useful information, may be inadvisable for frail older adults, and often present logistical challenges that lead to delayed care. Fortunately, single center studies have demonstrated excellent diagnostic accuracy using technetium 99m pyrophosphate (Tc99mPYP) cardiac imaging for noninvasively detecting ATTR-CA and differentiating it from another major type of cardiac amyloidosis called light chain (AL). But the diagnostic accuracy of this technique in a multicenter study and the association of Tc99mPYP myocardial uptake with survival were not known prior to this study. Therefore, we assessed in a multicenter study Tc99mPYP cardiac imaging as a diagnostic tool and its association with survival. We conducted a retrospective cohort study of 229 patients evaluated at 3 academic specialty centers for cardiac amyloidosis and also underwent Tc99mPYP cardiac imaging. We measured retention of Tc99mPYP in the heart using a semiquantitative visual score (range 0-3) and a more quantitative heart-to-contralateral (H/CL) ratio calculated as total counts in a region of interest over the heart divided by background counts in an identical size region of interest over the contralateral chest. The outcome measured was time to death after Tc99mPYP imaging. (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, Mental Health Research, NIH, University of Pittsburgh / 01.04.2014

Rosebud O Roberts, M.B., Ch.B. Professor of Epidemiology Professor of Neurology Mayo ClinicMedicalResearch.com Interview with: Rosebud O Roberts, M.B., Ch.B. Professor of Epidemiology Professor of Neurology Mayo Clinic MedicalResearch.com: What are the main findings of the study? Dr. Roberts: We found that among persons 70 years and older, people with type 2 diabetes had a reduced glucose uptake (hypometabolism) in  brain cells.  We also found a similar association for people without type 2 diabetes but who had elevated hemoglobin A1c levels levels at the time of enrollment (HBA1c is a measure of glucose control, and represents the average blood glucose levels over a 3 month period). However, we did not find an association of diabetes with increased brain amyloid accumulation.  Our findings were based on an investigation of the association of type 2 diabetes with markers of brain pathology: brain hypometabolism was assessed by 18F-fluorodeoxyglucose positron emission tomography [PET] and amyloid accumulation was assessed by 11-C Pittsburgh Compound B PET imaging. (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, JAMA, Lipids / 02.01.2014

MedicalResearch.com Interview with: Dr. Bruce Reed PhD Professor of Neurology, Associate Director UC Davis Alzheimer's Disease Center Davis, CA 95616 Dr. Bruce Reed PhD Professor of Neurology, Associate Director UC Davis Alzheimer's Disease Center Davis, CA 95616 MedicalResearch.com: What are the main findings of the study? Dr. Reed: We found that high LDL cholesterol and low HDL cholesterol in blood  were both associated with higher amyloid deposition in the brain.  This is potentially very important because the deposition of amyloid seems to be a critical step that kicks off a whole chain of events that eventually lead to Alzheimer's disease.  It is widely believed (although not proven) that if this deposition of amyloid could be blocked that we could greatly decrease the incidence of Alzheimer's.  The connection to cholesterol is exciting because we know a fair amount about how to change cholesterol levels.  A great deal more research needs to be done, but this does suggest a potential new path toward trying to prevent AD. (more…)