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.

Continue reading

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].

Continue reading

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.  

Continue reading

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.

Continue reading

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.

Continue reading

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.

Continue reading

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.

Continue reading

Herpes Simplex a Major Contributor to Alzheimer’s Disease?

MedicalResearch.com Interview with:
"Herpes" by LEONARDO DASILVA is licensed under CC BY 2.0Prof Ruth Itzhaki PhD
Emeritus Professor
Division of Neuroscience & Experimental Psychology
The University of Manchester

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

Response: Over 30 million people worldwide suffer from Alzheimer’s disease and unfortunately, this figure will rise as longevity increases, so the need for effective treatments is extremely urgent. Current treatments, at best, alleviate symptoms but do not prevent further deterioration. Our research has strongly implicated a common virus in the development of the disease, indicating a direct route to treatment: very effective and safe antiviral agents are available to combat the virus and thus to treat AD patients. They indicate also the future possibility of preventing the disease by vaccination against the virus in infancy.

The virus implicated in Alzheimer’s disease, herpes simplex virus type 1 (HSV1), is the one that causes cold sores. It infects most humans in infancy and thereafter remains lifelong in the body in latent (i.e., dormant) form within the peripheral nervous system (PNS – the part other than the brain and the spinal cord). Occasionally, if the person is stressed, the virus becomes activated and in some people it then causes cold sores.  Continue reading

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.

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

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

Altered Bile Acid Metabolites in Mild Cognitive Impairment and Alzheimer’s Disease

MedicalResearch.com Interview with:

Kwangsik Nho, PhD Assistant Professor of Radiology & Imaging Sciences Indiana University School of Medicine Indianapolis, IN, 

Dr. Kwangsik Nho

Kwangsik Nho, PhD
Assistant Professor of Radiology & Imaging Sciences
Indiana University School of Medicine
Indianapolis, IN

MedicalResearch.com: What is the ADNI (Alzheimer’s Disease Neuroimaging Initiative)?

Response: The initial phase (ADNI-1) was launched in 2003 to test whether serial magnetic resonance imaging (MRI), position emission tomography (PET), other biological markers, and clinical and neuropsychological assessment could be combined to measure the progression of mild cognitive impairment (MCI) and early Alzheimer’s Disease (AD). ADNI-1 was extended to subsequent phases (ADNI-GO, ADNI-2, and ADNI-3) for follow-up for existing participants and additional new enrollments. To our knowledge, the ADNI cohort (370 cognitively normal older adults, 98 patients with significant memory concern, 284 early MCI, 505 late MCI, and 305 patients with AD) uniquely has multi-omics data sets including metabolomics and structural and functional neuroimaging data (MRI, PET) as well as rich clinical and fluid biomarker data on the same participants.

Continue reading

Forgetting To Do Things? Try Acting in Advance

MedicalResearch.com Interview with:

Dr Antonina Pereira - CPsychol, PhD, FHEA, AFBPsS Head of Department of Psychology & Counselling University of Chichester Chichester, West Sussex UK

Dr. Pereira

Dr Antonina Pereira – CPsychol, PhD, FHEA, AFBPsS
Head of Department of Psychology & Counselling
University of Chichester
Chichester, West Sussex UK

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

Response: Prospective memory (PM) is the ability to remember to perform future activities, such as remembering to take medication or remembering to attend an appointment. Prospective memory tasks pervade our daily lives, and PM failures, although sometimes merely annoying (e.g., forgetting an umbrella at home on a rainy day), can have serious and even life-threatening consequences (e.g., forgetting to turn off the stove).

The fulfilment of such delayed intended actions can indeed be an early indicator of Alzheimer’s disease, with prospective memory failures representing one of the most prominent memory concerns in older adulthood and a fundamental requirement for independent living across the lifespan.

We aimed to address this issue by exploring the potential benefits of a purposefully designed technique, encoded enactment, where participants were encouraged to act through the activity they must remember to do.

This particular study was the fruit of an international research collaboration led by the University of Chichester and including members from Radboud University Nijmegen, Sussex Partnership NHS Foundation Trust and the Faculty of Medicine of the University of Lisbon.

Our team has explored the potential benefits of this specific encoding strategy for healthy younger adults, healthy older adults as well as for patients with mild cognitive impairment.

Results were very encouraging: All age groups reported improvement in prospective memory, but this was particularly evident in older patients with mild cognitive impairment, that is, potentially in the early stages of Alzheimer’s disease.

The study suggests that encouraging people in this category to adopt enactment as a means to enhance prospective memory could result in them leading independent, autonomous lives for longer.

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. “

Continue reading

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.

Continue reading

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

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.

Continue reading

Amyloid PET Scan Useful in Memory Evaluation

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.

Continue reading

Alzheimer Study: New Drug Did Not Reduce Cognitive Decline

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.  Continue reading

Lack of Awareness of Cognitive Issues Presages Alzheimer’s Disease

MedicalResearch.com Interview with:
Joseph Therriault

Integrative Program in Neuroscience 

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

Response: Neurologists have known for a long time that Anosognosia, or unawareness of illness, appears in individuals with Alzheimer’s disease. For example, these patients will have diminished awareness of their memory loss, and will also engage in dangerous behaviors, such as leaving the house to go for a walk, without knowing they are at high risk of getting lost.

However, it was not known if decreased awareness of cognitive problems existed in the pre-dementia phase of Alzheimer’s disease. In our study, we compared the ratings of cognitive decline from the patient and their close relative, who also filled out the same questionnaire. When a patient reported having no cognitive problems but the family member reported significant difficulties, the patient was considered to have poor awareness of illness.

We found that patients who are less aware had increased disease pathology, and were nearly three times as likely to progress to dementia within two years, even when taking into account other factors like genetic risk, age, gender and education. The increased progression to dementia was mirrored by increased brain metabolic dysfunction in regions vulnerable to Alzheimer’s disease.

Continue reading

Fragmented Circadian Rhythm Associated with Preclinical Alzheimer’s Disease

MedicalResearch.com Interview with:
“mirror clock” by tourist_on_earth is licensed under CC BY 2.0Yo-El Ju, MD

Assistant Professor of Neurology
Sleep Medicine Section
Washington University School of Medicine

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

Response: The background for this study is that prior studies have shown that people with Alzheimer’s Disease have poor circadian clock function, for example sleeping during the day and being awake or agitated at night. Autopsy studies have shown that people with Alzheimer’s Disease have degeneration in the “clock” part of their brains. In this study, we wanted to examine whether there were any circadian problems much earlier in Alzheimer’s Disease, when people do not have any memory or thinking problems at all.

We measured circadian function in 189 people with an actigraph, which is an activity monitor worn like a watch, for 1-2 weeks. Brain scans and studies of cerebrospinal fluid were used to determine who had preclinical Alzheimer’s Disease, meaning they have the brain changes of Alzheimer’s but do not have symptoms yet.  Continue reading

Personality Changes Can Presage Cognitive Impairment

MedicalResearch.com Interview with:

Richard J. Caselli MD Department of Neurology Mayo Clinic Arizona Scottsdale, AZ 

Dr. Caselli

Richard J. Caselli MD
Department of Neurology
Mayo Clinic Arizona
Scottsdale, AZ  

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

Response: Personality changes are common in patients with a variety of dementing illnesses, and underlie the behavioral disturbances that complicate the course of dementia patients.  We have a been conducting a large longitudinal study of cognitive aging in individuals at genetically defined risk for Alzheimer’s disease (AD) based on their APOE genotype, and have been administering a large battery of neuropsychological tests as well as the gold standard personality questionnaire (the NEO-PI-R) in order to determine whether personality changes during the transition from normal cognition/preclinical AD to mild cognitive impairment.   Continue reading

High Rates of Amyloid Imaging Positivity in Patients With Primary Progressive Aphasia

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

Dr. Miguel A. Santos-Santos

Miguel ASantosSantosMD
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.
Continue reading