Diagnostic Value of Cerebrospinal Fluid Neurofilament Light Protein in Neurologic Diseases

MedicalResearch.com Interview with:

Charlotte E. Teunissen,

Prof. Teunissen

Charlotte E. Teunissen, PhD
Neurochemistry Laboratory, Department of Clinical Chemistry
VU University Medical Centre, Neuroscience Campus Amsterdam
Amsterdam, the Netherlands

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Several reports have shown increased in NfL in various neurological disorders, separately. We wanted to know how the levels are in these disorders relative to each other. Moreover, some reports showed absence of age effects in Multiple Sclerosis (MS) patients, which is normally present in controls. So, we thought that it would be good to study age effects in a large group of controls, and if these effects are absent in other diseases, similarly as in MS.

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Sleep History as a Predictor For Late-Life Alzheimer’s Disease Later In Life

sleep-alzheimers-dementia-insomniaSleep patterns can predict the increase of Alzheimer’s pathology proteins tau and β-amyloid later in life, according to a June 2019 study published in the Journal of Neuroscience. The findings shed hope on earlier diagnosis of Alzheimer’s and the adoption of preventive measures earlier in life. Researchers found a decrease in sleep spindle synchronization, which is linked to higher tau levels. Reduced amplitude of slow wave activity, meanwhile, is closely related to higher β-amyloid levels. In younger people, both slow oscillations and sleep spindles are synchronized. This changes as people grow older, with less coordination between the two being visible. The researchers also noted that subjects who slept less had a higher chance of having Alzheimer’s proteins when they were older. The findings show that both reduced sleep quantity and quality can serve as important warnings of the onset of Alzheimer’s.

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Amyloid and Tau Biomarkers Help Distinguish Alzheimer’s from Other Forms of Mild Cognitive Impairment

MedicalResearch.com Interview with:
Lauren McCollum, MDCognitive and Behavioral Neurology FellowPenn Memory Center / Cognitive Neurology DivisionLauren McCollum, MD

Cognitive and Behavioral Neurology Fellow
Penn Memory Center / Cognitive Neurology Division

MedicalResearch.com: What is the background for this study?  

Response: Alzheimer’s Disease (AD) is a heterogenous condition, with considerable variability in cognitive symptoms and progression rates.

One major reason for this heterogeneity is “mixed pathology,” – i.e., both AD- and non-AD pathology. Examples of non-AD pathology include cerebrovascular disease (CVD), Lewy Bodies, and TDP-43. Pathologically, Alzheimer’s Disease is defined by characteristic amyloid plaques and neurofibrillary tangles, which can be assessed for in living patients with CSF- or PET-based biomarkers for amyloid and tau, respectively. Classically, amyloid deposition begins years or even decades before pathologic tau accumulation, which is in turn associated with brain atrophy and cognitive decline.

The recently developed NIA-AA “ATN” research framework allows for the classification of individuals with regard to 3 binary biomarkers: Amyloid (A), Tau (T), and Neurodegeneration (N). An individual’s ATN biomarker status indicates where along the “Alzheimer’s Disease continuum” they lie. Additionally, some ATN statuses are on the “typical AD” continuum, while others are not. Research has shown that 15-30% of cognitively normal older adults have elevated amyloid. It stands to reason that some portion of cognitively impaired individuals with elevated amyloid and neurodegeneration have something other than AD driving their neuronal injury. Within the context of the ATN research framework, this subset of people is the A+T-N+ group (i.e., people who have elevated amyloid and neurodegeneration, but are tau-negative), as amyloid alone (that is, amyloid without tau) is not thought to cause significant cognitive impairment or brain atrophy. Our hypothesis was that, compared to A+T+N+ (a set of typical-AD biomarkers), A+T-N+ have cognitive and neuroimaging profiles that deviate from a typical Alzheimer’s Disease pattern – i.e., with less memory loss and less atrophy in AD-signature regions – and may have biomarkers suggestive of alternate non-AD pathologies [e.g., white matter hyperintensities (WMHs), a marker of CVD].

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Some with Elevated Alzheimer’s Biomarkers Interested in Aid-in-Dying Information

MedicalResearch.com Interview with:

Emily Largent, PhD, JD, RNAssistant Professor, Medical Ethics and Health PolicyPerelman School of MedicineLeonard Davis Institute of Health EconomicsUniversity of Pennsylvania

Dr. Largent

Emily Largent, PhD, JD, RN
Assistant ProfessorMedical Ethics and Health Policy
Perelman School of Medicine
Leonard Davis Institute of Health Economics
University of Pennsylvania 

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response:  Public support for aid in dying in the United States is rapidly growing.  As a result, we’re now seeing debates about whether to expand access to aid-in-dying to new populations – such as people with Alzheimer’s disease – who wouldn’t be eligible under current laws.

With those debates in mind, we asked currently healthy people who recently learned about their risk for developing Alzheimer’s disease dementia (i.e., due to the presence of amyloid, an Alzheimer’s disease biomarker) whether they would be interested in aid-in-dying.

Our findings suggest that about 20% of individuals with elevated amyloid may be interested in aid-in-dying if they become cognitively impaired.  

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Verubecestat Failed to Slow Progression of Early Alzheimer’s Disease

MedicalResearch.com Interview with:
Michael F. Egan, MDVice President,  NeuroscienceGlobal Clinical DevelopmentMerck Research LaboratoriesNorth Wales, PAMichael F. Egan, MD
Vice President,  Neuroscience
Global Clinical Development
Merck Research Laboratories
North Wales, PA 

MedicalResearch.com: What is the background for this study?  

Response: Alzheimer’s disease (AD) appears to be due to the gradual accumulation of amyloid over many years (the “amyloid hypothesis”). At some point, it is thought that amyloid triggers abnormalities in tau, which then forms deposits within neurons and leads to progressive neurodegeneration.

Amyloid is made up of  a small, sticky peptide, Abeta, which is produced when the enzyme BACE cleaves a large protein called APP.  In our trial, we tested whether a potent BACE inhibitor, verubecestat, could slow disease progression in subjects with early AD (or prodromal AD) by blocking formation of Abeta.  A previous trial in subjects with dementia due to AD failed to find evidence of efficacy.

One possible reason for this failure is that subjects had too much amyloid in their brain already.

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Criminal and Socially Inappropriate Behaviors Could Be Signs of Dementia

MedicalResearch.com Interview with:

Dr. Madeleine Liljegren

Dr. Madeleine Liljegren
Photo: Ingemar Walldén

Madeleine Liljegren, MD
Division of Oncology and Pathology
Department of Clinical Sciences
Lund University Lund, Sweden

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We know from former studies including patients with a clinical diagnosis of dementia, that criminal and socially inappropriate behaviors can be signs of dementia, sometimes even the first signs of a neurodegenerative disorder.

We wanted to study this relatively large (n=220) cohort of neuropathologically verified Alzheimer disease (AD) and frontotemporal dementia (FTD) patients, who had been followed clinically by specialists in cognitive medicine or geriatric psychiatry during their disease period, to see if we could confirm results from previous studies.

In this paper, we further wanted to study potential differences regarding protein pathology and criminal behavior in frontotemporal dementia patients. This has, to our knowledge, never been done before.

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Long Term Hormone Use May Raise Risk of Alzheimer’s Disease

MedicalResearch.com Interview with:

Tomi Mikkola MDAssociate ProfessorHelsinki University HospitalDepartment of Obstetrics and GynecologyHelsinki, Finland

Dr. Mikkola

Tomi Mikkola MD
Associate Professor
Helsinki University Hospital
Department of Obstetrics and Gynecology
Helsinki, Finland

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In Finland we have perhaps the most comprehensive and reliable medical registers in the world. Thus, with my research group I have conducted various large studies evaluating association of postmenopausal hormone therapy use and various major diseases (see e.g. the references in the B;MJ paper). There has been various smaller studies indicating that hormone therapy might be protective for all kinds of dementias, also Alzheimer’s disease.

However, we have quite recently shown that hormone therapy seems to lower the mortality risk of vascular dementia but not Alzheimer’s disease (Mikkola TS et al. J Clin Endocrinol Metab 2017;102:870-7). Now in this upcoming BMJ-paper we report in a very large case-control study (83 688 women with Alzheimer’s disease and same number of control women without the disease) that systemic hormone therapy was associated with a 9-17% increased risk of Alzheimer’s disease.

Furthermore, this risk increase is particularly in women using hormone therapy long, for more than 10 years. This was somewhat surprising finding, but it underlines the fact that mechanisms behind Alzheimer’s disease are likely quite different than in vascular dementia, where the risk factors are similar as in cardiovascular disease. We have also shown how hormone therapy protects against cardiovascular disease, particularly in women who initiate hormone therapy soon after menopause. Continue reading

Alzheimer Disease Medications: Progression to Nursing Home & Cardiac Side Effects

MedicalResearch.com Interview with:

Alvaro San-Juan-Rodriguez

Alvaro San-Juan-Rodriguez

Alvaro San-Juan-Rodriguez, PharmD
Pharmacoeconomics, Outcomes and Pharmacoanalytics Research Fellow
Pharmacy and Therapeutics
School of Pharmacy
University of Pittsburgh

MedicalResearch.com: What are the main findings?

Response: Currently, there are 4 antidementia drugs approved by the FDA for the treatment of Alzheimer’s disease, including 3 acetylcholinesterase inhibitors (AChEIs)—donepezil, rivastigmine, and galantamine—and the N-methyl-D-aspartic receptor antagonist memantine. On the one hand, evidence about the effect of these drugs at delaying nursing home admission is still sparse and conflicting. On the other, all these antidementia medications have been associated with several cardiovascular side effects, such as bradycardia, ventricular tachycardia, syncope, QT interval prolongation, atrioventricular block or even myocardial infarction.

In this study, we aimed to compare time to nursing home admission and time to cardiovascular side effects across all drug therapies available for the treatment of Alzheimer’s disease. In doing so, we used 2006-2014 medical and pharmacy claims data from Medicare Part D beneficiaries with a new diagnosis Alzheimer’s disease who initiated antidementia drug therapy. Continue reading

Hyperbaric Oxygen Therapy as Potential Therapy for Alzheimer’s Dementia

MedicalResearch.com Interview with:

Dr. Paul Harch MD Clinical Professor and Director of Hyperbaric Medicine LSU Health New Orleans School of Medicine

Dr. Harch

Dr. Paul Harch MD
Clinical Professor and Director of Hyperbaric Medicine
LSU Health New Orleans School of Medicine

MedicalResearch.com: What is the background for this study?

Response: The background is a 30 year clinical experience and investigation in which I explored the effects of low-pressure hyperbaric oxygen therapy (HBOT) on acute, subacute, and chronic neurological conditions.

Beginning with brain-injured Louisiana boxers and commercial divers in the late 1980s I attempted to see if patients with central nervous system disorders could respond to a lower dosing of the drug hyperbaric oxygen therapy than was traditionally used for other wound conditions like diabetic foot wounds, radiation wounds, and decompression sickness (the “bends”).  I was successful with the very first cases after which I expanded this treatment to nearly 90 neurological conditions.  The very first patient was a boxer 23 years after his last bout who was formally diagnosed with dementia pugulistica (dementia from boxing).

Since that time I have treated over 100 patients with cognitive decline or dementia, including 11 Alzheimer’s cases.  Nearly all of the Alzheimer’s and other dementia cases were documented with high-resolution brain blood flow imaging (SPECT).  The present case report was the first Alzheimer’s case that I was able to document with PET metabolic imaging.

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Blood Pressure Control – Good for Heart, Good for the Brain!

MedicalResearch.com Interview with:

Dr-Jeff Douglas Williamson

Dr. Williamson

Jeff D. Williamson, MD
Geriatric Medicine – Sticht Center
Wake Forest Baptist Medical Center

MedicalResearch.com: What is the background for this study?

Response: A growing amount of epidemiologic research has suggested that higher blood pressure is associated with higher risk for dementia, including Alzheimer’s dementia.

MedicalResearch.com: What are the main findings?

Response: More than 9,300 ambulatory, community dwelling persons over age 50, 30% of whom were over the age of 75, were randomly assigned to a blood pressure goal of 120 vs 140.  Persons in the 120 group had a 19% lower risk for developing MCI an transitional stage between normal and dementia (P<.008).  There was a 17% lower risk for developing dementia but this only achieved a p value = 0.10.  The combined risk for both MCI and dementia was 15% lower in the 120 group (p<0.04).  The dementia outcome was the primary outcome but all the outcomes were pre-specified in the protocol at the beginning of the trial.  Unfortunately the blood pressure intervention was stopped after only 3.3 years due to CVD and mortality benefit and this may well have influenced the ability to reach the expected number of dementia cases. 

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Loss of Deep Sleep Associated With Early Alzheimer’s Disease

MedicalResearch.com Interview with:

Brendan P. Lucey, MD, MSCI Assistant Professor of Neurology Director, Sleep Medicine Section Washington University School of Medicine Saint Louis, Missouri 63110

Dr. Lucey

Brendan P. Lucey, MD, MSCI
Assistant Professor of Neurology
Director, Sleep Medicine Section
Washington University School of Medicine
Saint Louis, Missouri 63110

MedicalResearch.com: What is the background for this study?

Response: Alzheimer’s disease and sleep are currently thought to have a two-way or bidirectional relationship.

First, sleep disturbances may increase the risk of developing AD.

Second, changes in sleep-wake activity may be due to Alzheimer’s disease pathology and our paper was primarily focused on this aspect of the relationship.    If sleep changes were a marker for AD changes in the brain, then this would be very helpful in future clinical trials and possibly screening in the clinic.

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Coordinated Care Program For Dementia Patients Reduced Need For Nursing Home Placement

MedicalResearch.com Interview with:

Lee A. Jennings, MD, MSHS Assistant Professor of Medicine Director, Oklahoma Healthy Aging Initiative Reynolds Department of Geriatric Medicine University of Oklahoma Health Sciences Center Oklahoma City, OK 73117

Dr. Jennings

Lee A. Jennings, MD, MSHS
Assistant Professor of Medicine
Director, Oklahoma Healthy Aging Initiative
Reynolds Department of Geriatric Medicine
University of Oklahoma Health Sciences Center
Oklahoma City, OK 73117

MedicalResearch.com: What is the background for this study?

Response: The research study focused on a novel model of care for persons living with Alzheimer’s disease and other types of dementia, the UCLA Alzheimer’s and Dementia Care Program. In the program, people with dementia and their caregivers meet with a nurse practitioner specializing in dementia care for a 90-minute in-person assessment and then receive a personalized dementia care plan that addresses the medical, mental health and social needs of both people. The nurse practitioners work collaboratively with the patient’s primary care provider and specialist physicians to implement the care plan, including adjustments as needs change over time.

The research was designed to evaluate the costs of administering the program, as well as the health care services used by program participants, including hospitalizations, emergency room visits, hospital readmissions and long-term nursing home placement. A total of 1,083 Medicare beneficiaries with dementia were enrolled in the program and were followed for three years. The study compared them to a similar group of patients living in the same ZIP codes who did not participate in the program. Continue reading

Newer MRIs May Predict Alzheimer’s Disease Before Any Symptoms

MedicalResearch.com Interview with:

Cyrus A. Raji, MD PhD Asst Prof of Radiology, Mallinckrodt Institute of Radiology Neuroradiology Faculty and the Neuoimaging Laboratories  Washington University School of Medicine St. Louis

Dr. Raji

Cyrus A. Raji, MD PhD
Asst Prof of Radiology, Mallinckrodt Institute of Radiology
Neuroradiology Faculty and the Neuoimaging Laboratories
Washington University School of Medicine
St. Louis

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Alzheimer’s disease is the most common cause of dementia and every patient suspected of having this disorder receives an MRI scan of the brain.

MRI scans of the brain in dementia are currently limited to evaluating for structural lesions that could be leading to memory loss such as stroke or tumor. What this study sought to accomplish was to determine if a newer type of MRI scan called diffusion tensor imaging (DTI) can predict who will experience cognitive decline and dementia. We found that DTI can predict persons who will demented 2.6 years before the earliest onset of symptoms.

This study was done in 61 individuals, 30 converters and 31 non-converters, from the Alzheimer’s Disease Neuroimaging Initiative and we found that DTI metrics could predict dementia 2.6 years later with 89-95% accuracy.

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Aggression in Dementia: Alternatives to Antipsychotics Also Have Side Effects

MedicalResearch.com Interview with:

Jennifer Watt, PhD Clinical Epidemiology and Health Care Research Institute of Health Policy, Management, and Evaluation University of Toronto

Dr. Watt

Jennifer Watt, PhD
Clinical Epidemiology and Health Care Research
Institute of Health Policy, Management, and Evaluation
University of Toronto

MedicalResearch.com: What is the background for this study?  

Response: Behavioral and psychological symptoms of dementia (e.g. aggression, agitation) are common among persons living with dementia.

Pharmacological (e.g. antipsychotics) and non-pharmacological (e.g. reminiscence therapy) interventions are often used to alleviate these symptoms. However, antipsychotics are associated with significant harm among older adults with dementia (e.g. death, stroke). Regulatory agencies such as the Food and Drug Administration (FDA) and Health Canada issued black box warnings to advise patients and clinicians of this potential for harm. And initiatives were championed to decrease the use of antipsychotics in persons living with dementia.

In response, we have seen a rise in the use of other pharmacological interventions, such as trazodone (an antidepressant). Its potential to cause harm in older adults with dementia is largely unknown. Continue reading

Adults with Down’s Syndrome at High Risk of Alzheimer’s Disease

MedicalResearch.com Interview with:
"A neonate with Down's?" by Sadasiv Swain is licensed under CC BY 2.0Rosalyn Hithersay

LonDowns
Kings College, London 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In our research group, we have been following a large group of adults with Down syndrome in the UK to track changes with ageing in their health and cognitive function. It has been known for some time now that people with Down syndrome are at high risk for developing dementia due to Alzheimer’s disease. This new study has shown the huge impact that this risk has on mortality for these adults.

We found that dementia is now the likely underlying cause of death in more than 70% of adults with Down syndrome aged over 35 years. This is a much bigger proportion of deaths due to Alzheimer’s disease compared to the general population: in England and Wales only 17.5% of deaths past the age of 65 would be related to dementia of any kind.  Continue reading

Can Coffee Protect Against Alzheimer’s and Parkinson’s Disease?

MedicalResearch.com Interview with:
Donald Weaver, PhD, MD, FRCPC, FCAHS
Senior Scientist and Director, Research Institute
Krembil Research Institute
University Health Network
Toronto, Canada

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: First, we are seeking novel molecules that might have usefulness in the treatment of Alzheimer’s disease (AD). Since Mother Nature is a superb chemist, natural products are an ideal place to start looking for possible therapeutics. There is a long history (penicillin, digitalis …) of drugs identified from natural product sources. Moreover, in earlier work by us, we have shown that other natural products extracted from maple syrup have possible therapeutic efficacy against AD.

Therefore, it was logical for us to look at extracts of coffee. We see similarities between maple syrup and coffee. In both of these natural products, the plant derived material (i.e. the coffee bean, or sap from maple syrup) is initially boiled or roasted prior to its use; thus, it is not a direct simple plant product, but one that has been heated (boiled or roasted). We suspect that the heating process “does more chemistry” enabling the generation of new molecules from the plant derived materials. In our study we show that a class of compounds (phenylindanes) from roasted coffee has the ability to inhibit the misfolding of two proteins (beta-amyloid, tau) whose misfolding and aggregation (“clumping”) is implicated in the disease process of AD.

Second, as described below, there is already epidemiological evidence that coffee consumption may offer some protective effects against Alzheimer’s disease and Parkinson’s disease (PD), so by looking at the constituents of coffee for chemicals that might block the clumping of beta-amyloid and/or tau, was an attempt to seek a molecular link explaining the epidemiology. Continue reading

Aortic Stiffness is Associated with Increased Risk of Dementia in Older Adults

MedicalResearch.com Interview with:

Rachel H. Mackey, PhD, MPH, FAHA Assistant Professor of Epidemiology Graduate School of Public Health University of Pittsburgh

Dr. Mackey

Rachel H. Mackey, PhD, MPH, FAHA
Assistant Professor of Epidemiology
Graduate School of Public Health
University of Pittsburgh

MedicalResearch.com: What is the background for this study?

Response: “Hardening,” or stiffening, of the arteries is a risk factor for heart attacks and other cardiovascular disease. Arterial stiffness can be measured by pulse wave velocity (PWV), because the pulse pressure wave travels faster in stiffer arteries. Stiffer arteries transmit increased pulsatile blood flow to the brain and are linked with markers of silent, or subclinical, brain disease, which are related to increased risk of dementia. However, it was not clear whether arterial stiffening would predict risk of dementia, especially in older adults, who often have existing subclinical brain disease. Therefore, a University of Pittsburgh team, led by Chendi Cui, M.S, doctoral student, and Rachel Mackey, PhD, MPH, FAHA, assistant professor of epidemiology at Pitt Public Health, analyzed the association between arterial stiffness and 15-year risk of dementia among 356 older adults, with an average age of 78. Study participants were part of the Cardiovascular Health Study Cognition Study (CHS‐CS), a long‐term study to identify dementia risk factors, led by coauthors Oscar Lopez MD and Lewis Kuller, MD, DrPH. In 1996-2000, study participants had had arterial stiffness measured by pulse wave velocity (PWV), brain imaging by MRI, and had annual follow-up visits for cognitive status.

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Critical Illness Linked To Brain Changes Associated with Cognitive Decline

MedicalResearch.com Interview with:

Keenan Walker, PhD Johns Hopkins University School of Medicine  Baltimore

Dr. Walker

Keenan Walker, PhD
Johns Hopkins University School of Medicine
Baltimore

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: This study was conducted in response to anecdotal accounts and scientific evidence which suggests that major medical conditions, such as critical illness and severe infections, can have a long-term neurological effect on some individuals.

There are quite a few studies to date which have found that critical illnesses, such as severe sepsis, are associated with long-term cognitive impairment. Based on this evidence, we wanted to figure out to what degree critical illness and major infection may affect later brain structure and to determine whether the structural changes associated with these events were similar to those observed in Alzheimer’s disease.

Our main finding was that individuals who had one or more critical illness or major infection major infection during the decades leading up to older adulthood were more likely to have smaller brain volumes in brain regions most vulnerable to Alzheimer’s disease.

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Amyloid Targeting Therapy More Likely To Be Effective Early in Alzheimer’s Disease

MedicalResearch.com Interview with:

Dr Christina Elliott PhD Postdoctoral Researcher Department of Old Age Psychiatry King’s College London

Dr. Elliott

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.   Continue reading

Using Tau PET Scan to Distinguish Alzheimer Disease from Other Neurodegenerative Disorders

MedicalResearch.com Interview with:
PET scanner Wikipedia imageRik Ossenkoppele
PhD
Lund University & VU University Medical Center
Oskar Hansson – Lund University

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: [18F]flortaucipir is a relatively novel PET tracer that can be used to detect tau pathology in the living human brain. Previous studies have shown a robust signal in patients with Alzheimer’s disease, but in patients with other types of dementia the signal was more variable.

We aimed to assess the ability of [18F]flortaucipir PET to distinguish Alzheimer’s disease from other neurodegenerative disease in more than 700 study participants. T

he main finding was that [18F]flortaucipir discriminated Alzheimer’s disease patients from patients with other neurodegenerative diseases with high accuracy. Furthermore, [18F]flortaucipir PET outperformed established MRI markers and showed higher specificity than amyloid-β PET.  Continue reading

Alzheimer’s Disease: Peptide Found in Sea Anemones May Prevent Neuron Destruction

MedicalResearch.com Interview with:

Elena LeychenkoElena Leychenko is a senior research associate at PIBOC (G.B. Elyakov Pacific Institute of Bioorganic Chemistry which is the Far Eastern Branch of the Russian Academy of Sciences), assistant professor, and lecturer at the chair of bioorganic chemistry and biotechnology of the School of Natural Sciences
Far Eastern Federal University 

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Sea anemones are the main object for study in the laboratory for peptide chemistry of PIBOC. These marine dwellers are very interesting for scientists because of a wide range of biologically active compounds, which are the main components of their venom. The development of modern research methods allows us to receive both major and minor components of that poison, and to study their medical properties. Interestingly, inhibitors of Kunitz-type proteinases, which are also content in sea anemones, can be used as anti-inflammatory compounds. In particular, in complex therapy, it could be applied in the treatment of Alzheimer’s disease. 

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Age, Sex and Genetics Can Identify Groups at Higher Risk of Alzheimer’s Disease

MedicalResearch.com Interview with:

Ruth Frikke-Schmidt, Professor, Chief Physician, MD, DMSc, PhD Department of Clinical Biochemistry Rigshospitalet, Blegdamsvej & Deputy Head Department of Clinical Medicine Faculty of Health and Medical Sciences University of Copenhagen

Dr. Frikke-Schmidt

Ruth Frikke-Schmidt, Professor, Chief Physician, MD, DMSc, PhD
Department of Clinical Biochemistry
Rigshospitalet, Blegdamsvej &
Deputy Head
Department of Clinical Medicine
Faculty of Health and Medical Sciences
University of Copenhagen

MedicalResearch.com: What is the background for this study?

 

Response: Alzheimer’s disease and other forms of dementia are devastating, neurodegenerative disorders affecting more than 47 million people in 2015, a number projected to triple by 2050 (1,2). Available curative treatments are lacking, and no useful risk prediction tools exist. The potential for prevention is however substantial, emphasized by the recently observed incidence decline in Western societies, likely caused by improved treatment and prevention of vascular risk factors (1,3,4). Population growth and aging, will however triple dementia prevalence by 2050, if no action is taken. Acting now with ambitious preventive interventions, delaying onset of disease by five years, is estimated to halve the prevalence globally (1,5).

Despite important preventive efforts over the last decades – resulting in decreased smoking, lower blood pressure and lower cholesterol levels in the general population – physical inactivity, overweight, and diabetes remain threats for our health care system, and in particular for cardiovascular disease and dementia. Intensifying preventive efforts in general is thus of crucial importance, and especially for those patients at highest risk who most likely will benefit the most from early and targeted prevention. Risk stratification and specific treatment goals according to the estimated absolute 10-year risk, has been implemented in cardiovascular disease for years (6,7). There is an un-met need for similar strategies in dementia, underscored by the publication of several randomized multicomponent trials that seem to improve or maintain brain function in at-risk elderly people from the general population (8-10) Continue reading

Cardiovascular Risk Factors Also Linked to Dementia

MedicalResearch.com Interview with:

Cécilia Samieri, PhD Université de Bordeaux, INSERM Bordeaux Population Health Research Center Bordeaux, France

Dr. Samieri

Cécilia Samieri, PhD
Université de Bordeaux, INSERM
Bordeaux Population Health Research Center
Bordeaux, France

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Previous research has demonstrated that heart diseases and brain diseases share common risk factors. Favorable health factors (optimal levels of BMI, blood pressure, blood glucose and cholesterol) and behaviors (non smoking, physical activity and diet at optimal levels), which are known to protect the heart, have also been associated with a lower risk of age-related brain diseases (eg, dementia) and lower rate of cognitive decline in some epidemiological studies. However, studies have been controversial and importantly, very limited research has considered risk factors simultaneously. This may be an explanation for the lack of established consensus for recommendations aimed at dementia prevention.

This study adds to previous knowledge by evaluating cardiovascular health factors and behaviors simultaneously in relation to cognitive decline and the risk of dementia in older age. We used the American Heart Association 7-item tool to promote primordial prevention, which aims to prevent the developement of risk factors in a first place as a prevention strategy against cardiovascular diseases.

We found that each additional favorable health factor/behavior was associated with a 10% lower risk to develop dementia in the following decade.

These findings support the promotion if cardiovascular health to prevent the development of risk factors associated with dementia.  

MedicalResearch.com: What should readers take away from your report?

Response: When considering cardiovascular health, each additional improvement of the level of one or several health factors/behaviors is associated with a lower risk opf dementia and less cognitive decline.

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: Evaluate the change in risk factors over time as well was possible differential weighting of the factors in relation to dementia risk. 

Citation:

Samieri C, Perier M, Gaye B, et al. Association of Cardiovascular Health Level in Older Age With Cognitive Decline and Incident Dementia. JAMA. 2018;320(7):657–664. doi:10.1001/jama.2018.11499

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Benzodiazepines Linked to Modest Increased Risk of Alzheimer’s

MedicalResearch.com Interview with:
MedicalResearch.comVesa Tapiainen, MD
School of Pharmacy, University of Eastern Finland
Research Centre for Comparative Effectiveness and Patient Safety
University of Eastern Finland Kuopio, Finland

 MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Alzheimer’s disease is a non-curable dementing disease and a major health concern and thus, identification of potential modifiable risk factors, such as benzodiazepines, is important. Benzodiazepines and related drugs are commonly used among older people as every fourth older people use them.

Benzodiazepines and related drugs were associated with modestly increased risk of Alzheimer’s disease. A dose-response relationship was observed with higher cumulative dose and longer use periods being associated with higher risk of Alzheimer’s disease. The risk associated with larger cumulative doses was partly explained by more common use of other psychotropics among these persons.  Continue reading

Alzheimer’s Disease: Genes Modify Effect of High Fat Diet

MedicalResearch.com Interview with:
The Jackson LaboratoryCatherine Kaczorowski, Ph.D.

Associate Professor and Evnin Family Chair in Alzheimer’s Research
Kristen O’Connell, Ph.D., Assistant Professor
Amy Dunn, Ph.D., Postdoctoral Associate
The Jackson Laboratory


MedicalResearch.com: What is the background for this study? What are the main findings?
 

Dr. Amy Dunn: “Alzheimer’s disease is complex, with both genetic and environmental factors determining symptom onset and disease progression, though our current understanding of how genetic and environmental factors interact to influence disease risk is incomplete. We recently developed a panel of genetically diverse mice carrying human familial AD mutations (AD-BXDs) that better model human AD in order to determine how genetics and diet interact to modify disease onset and severity.

We fed a high fat diet to AD-BXDs and monitored metabolic and cognitive function over the duration of the HFD feeding.  We observed accelerated working memory decline in most of the AD-BXD mouse strains, however, the impact of high fat diet on memory was dependent on individual genetic differences across the panel, with some AD-BXD strains maintaining cognitive function on high fat diet (resilient strains).

Our data suggest that diet and genetic background interact to mediate vulnerability to AD pathogenesis, and that metabolic factors (e.g. obesity, body composition) that may contribute to cognitive decline differentially in normal aging versus AD. “

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Plasma Component Investigated To Reverse Age-Related Cognitive Disorders

MedicalResearch.com Interview with:
alkahestIan Gallager, MS
Scientist at Alkahest Inc.
San Francisco Bay Area 

MedicalResearch.com: What is the background for this study?

Response: Our research is aimed to develop novel therapeutics for age-related disorders from fundamental understandings of blood plasma. This expands upon work initially performed in the Wyss-Coray lab at Stanford utilizing a model of parabiosis. By surgically conjoining the blood supplies between a young and aged mouse, they established that beneficial effects were observed in the aged mouse brain, suggesting that there are proteins in young blood which have enhancing properties.

The research presented at AAIC was the culmination of several years of model and dosing paradigm development utilizing both human plasma and a proprietary fractionated plasma product leading to advances for clinical application.

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Novel Models of Late-Onset Alzheimer’s Disease Based on GWAS

MedicalResearch.com Interview with:

Gregory Carter

Dr. Carter

Gregory Carter, PhD
Associate Professor at The Jackson Laboratory

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Animal models for late-onset Alzheimer’s disease (LOAD) will be of significant benefit for the discovery and characterization of links between specific genetic factors and the molecular pathways associated with the disease. To date, most animal models have been based on rare, early-onset Alzheimer’s disease genes that incompletely capture the complexity of LOAD and have not translated well to therapies. Therefore, developing and utilizing animal models based on genes hypothesized to play a role in LOAD will provide new insights into its basic biological mechanisms.  Continue reading

Metabolic Risk Factors Leading Up to Onset of Dementia

MedicalResearch.com Interview with:

Maude Wagner, PhD Student Biostatistics Team Lifelong Exposures, Health and Aging Team Bordeaux Population Health Research Center Inserm Univ. Bordeaux

Maude Wagner

Maude Wagner, PhD Student
Biostatistics Team
Lifelong Exposures, Health and Aging Team
Bordeaux Population Health Research Center
Inserm
Univ. Bordeaux

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Many studies haves shown associations between cardiometabolic health and dementia in midlife, but associations later in life remain inconclusive.

This study aimed to model concurrently and to compare the trajectories of major cardiometabolic risk factors in the 14 years before diagnosis among cases of dementia and controls.

This study showed that demented persons presented a BMI decline and lower blood pressure (specifically systolic blood pressure) several years before dementia diagnosis that might be a consequence of underlying disease. In contrast, cases presented consistently higher blood glucose levels up to 14 years before dementia suggesting that high glycemia is a strong risk factor for dementia.

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Whole-Exome Analysis of Late-Onset Alzheimer’s Disease Reveals Novel Candidate Genes Involved in Cognitive Function

MedicalResearch.com Interview with:

Dr. Carter

Gregory Carter, PhD
Associate Professor at The Jackson Laboratory

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Late-onset Alzheimer’s disease (LOAD) is the most common form of the disease and the major cause of dementia in the aging population. To date, the complex genetic architecture of LOAD has hampered both our ability to predict disease outcome and to establish research models that effectively replicate human disease pathology.

Therefore, most basic research into Alzheimer’s disease has focused on early-onset forms caused by mutations in specific genes, which has provided key biological insights but to date has not translated to effective disease preventatives or cures.

Our study analyzes both common and rare human genetic variants to identify those significantly associated with .late-onset Alzheimer’s disease, beginning with a large data set from the Alzheimer’s Disease Sequencing Project. We also analyzed RNA sequencing data from post-mortem human and mouse model samples to prioritize candidate genes.

We found a new common coding variant significantly associated with disease, in addition to those in genes previously associated with late-onset Alzheimer’s disease. We also found five candidate genes conferring a significant rare variant burden.  Continue reading

Could Treatment for Herpes Virus Reduce Risk of Alzheimer’s Disease?

MedicalResearch.com Interview with:

This photograph depicts a close-up of the lips of a patient with a herpes simplex lesion on the lower lip, due to the herpes simples virus-1 (HSV-1) CDC image

This photograph depicts a close-up of the lips of a patient with a herpes simplex lesion on the lower lip, due to the herpes simples virus-1 (HSV-1)
CDC image

Prof Ruth Itzhaki
Emeritus Professor
Division of Neuroscience & Experimental Psychology
The University of Manchester

MedicalResearch.com: What is the background for this study?

Response: The background arises from the unexpected discovery, made by my lab almost 30 years ago, that the DNA of the common virus, herpes simplex virus type 1 (HSV1), known as the “cold sore” virus, was present in a high proportion of autopsy brains from elderly humans. Subsequently, we found that HSV1, when in brain of people who have a specific genetic factor, APOE-e4, confers a strong risk of developing Alzheimer’s disease. We found also a parallelism with cold sores in that APOE-e4 is a risk for the sores, which occur in about 25-40% of people infected with HSV1.

We then looked for links between the effects of HSV1 infection of cells in culture and AD, and found some major associations between virus and disease.

Firstly, HSV1 causes an increase in the formation of a small protein called beta amyloid, which is the main component of the abnormal “plaques” seen in Alzheimer’s Disease brains.

Secondly, we discovered that in AD brains, the viral DNA is located precisely within amyloid plaques, which suggests that the virus is responsible for the formation of these abnormal structures. Thirdly, we confirmed the finding of another lab that HSV1 causes the increased formation of an abnormal form of the protein known as tau, which is the main component of the other characteristic abnormality of Alzheimer’s Disease brains – “neurofibrillary tangles”.

All these discoveries suggested that the damage caused by HSV1 leads eventually to the development of AD.

Lastly, we showed that treating HSV1-infected cells in culture greatly reduces the formation of beta amyloid and abnormal tau. This suggests that antiviral agents might be used for treating Alzheimer’s Disease patients.

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