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

Aug 21, 2018 @ 5:49 pm 

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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.

Continue reading

Structural Brain Changes in Sleep Apnea Linked to Cognitive Decline

MedicalResearch.com Interview with:
“Woman sleeping” by Timothy Krause is licensed under CC BY 2.0Nathan E. Cross PhD, first author
School of Psychology.
Sharon L. Naismith, PhD, senior author
Leonard P Ullman Chair in Psychology
Brain and Mind Centre
Neurosleep, NHMRC Centre of Research Excellence
The University of Sydney, Australia 

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

Response: Between 30 to 50% of the risk for dementia is due to modifiable risk factors such depression, hypertension, physical inactivity, obesity, diabetes and smoking.

In recent years, multiple longitudinal cohort studies have observed a link between sleep apnoea and a greater risk (1.85 to 2.6 times more likely) of developing cognitive decline and dementia.  Furthermore, one study in over 8000 people also indicated that the presence of obstructive sleep apnoea (OSA) in older adults was associated with an earlier age of cognitive decline, and that treatment of OSA may delay the onset of cognitive impairment.

This study reveals important insights into how sleep disorders such as OSA may impact the brain in older adults, as it is associated with widespread structural alterations in diverse brain regions. We found that reduced blood oxygen levels during sleep are related to reduced thickness of the brain’s cortex in both the left and right temporal areas – regions that are important in memory and are early sites of injury in Alzheimer’s disease. Indeed, reduced thickness in these regions was associated with poorer ability to learn new information, thereby being the first to link this structural change to memory decline. Continue reading

Vision and Cognition Change Together As Older Adults Age

MedicalResearch.com Interview with:
“Old Eyeglasses” by Leyram Odacrem is licensed under CC BY 2.0Diane Zheng MS
NEI F-31 Research Fellow and a Ph.D. candidate in Epidemiology
Department of Public Health Sciences
University of Miami

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

Response: Worsening vision and declining cognitive function are common conditions among older people. Understanding the association between them could be beneficial to alleviate age related cognitive decline.

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Eye Sign of Dementia Risk? Thinning of Retinal Nerve Fiber Layer

MedicalResearch.com Interview with:

Dr. Paul Foster

Dr. Foster

Paul Foster BMedSci(Hons) BMBS PhD FRCS(Ed) FRCOphth FRCS(Eng)
Professor of Glaucoma Studies & Ophthalmic Epidemiology
Research Theme Lead Integrative Epidemiology & Visual Function
UCL Institute of Ophthalmology & Moorfields Eye Hospital
London 

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

Response:  Dementia is the medical challenge of the moment – increasingly common, adversely impacting quality of life for millions, and a great worry for all. Efforts to identify treatments or interventions rely on being able to identify those people at greatest risk. Our motivation was to help identify those people, primarily to aid in the development of treatments through clinical trials.

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Midlife Hypertension Increases Risk of Dementia

MedicalResearch.com Interview with:

Blood pressure monitor reading 120/80 copyright American Heart Association

Blood pressure monitor reading 120/80
copyright American Heart Association

Professor Archana Singh-Manoux, PhD, HDR Epidemiology
Research Director (DR1), INSERM
Honorary Professor, University College London

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

Response: Although there have been previous studies that have linked raised blood pressure in midlife to an increased risk of dementia in later life, the term ‘midlife’ has been poorly defined and ranged from 35 to 68 years.

New findings from the long-running Whitehall II study of over 10,000 civil servants has found 50-year-olds who had blood pressure that was higher than normal but still below the threshold commonly used when deciding to treat the condition, were at increased risk of developing dementia in later life.  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.

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Amyloid PET Scan Can Predict Progression to Alzheimer’s in Patients With Mild Cognitive Impairment

MedicalResearch.com Interview with:

David A. Wolk, MD Associate Professor Department of Neurology Co-Director, Penn Memory Center Associate Director, Alzheimer’s Disease Core Center University of Pennsylvania

Dr. Wolk

David A. Wolk, MD
Associate Professor
Department of Neurology
Co-Director, Penn Memory Center
Associate Director, Alzheimer’s Disease Core Center
University of Pennsylvania

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

Response: Mild Cognitive Impairment (MCI) is a state when individuals have mild memory problems, but not enough to impact day-to-day function.  Many patients with MCI are on the trajectory to developing Alzheimer’s Disease dementia, but about half will not and remain stable.  As such, patients with MCI are often uncertain about the likelihood they should expect to decline in the future which obviously may be associated with considerable anxiety and this may delay opportunities for them to plan for the future or begin therapeutic interventions.

This study examined the degree to which amyloid PET, which detects the amyloid pathology of Alzheimer’s Disease, a measure of shrinkage of the hippocampus with MRI, and cognitive measures predicted development of dementia over 3 years.  We found that each of these measures enhances prediction of whether an individual will or will not develop dementia in the future.  If all of these measures are positive, one has a very high risk of progression whereas if amyloid PET and the MRI measurement are normal, there is very little risk of progression. Continue reading

Vets with Head Injury More Likely To Develop Dementia

MedicalResearch.com Interview with:
Deborah E. Barnes, PhD, MPH Professor, UCSF Weill Institute for Neurosciences Departments of Psychiatry and Epidemiology & Biostatistics University of California, San Francisco: http://profiles.ucsf.edu/deborah.barnes Research Health Sciences Specialist, San Francisco VA Medical Center Senior Investigator, Tideswell at UCSF: http://www.tideswellucsf.org/ Deborah E. Barnes, PhD, MPH

Professor, UCSF Weill Institute for Neurosciences
Departments of Psychiatry and Epidemiology & Biostatistics
University of California, San Francisco: http://profiles.ucsf.edu/deborah.barnes
Research Health Sciences Specialist
San Francisco VA Medical Center

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

  • Previous studies have found a link between moderate to severe head injuries and increased dementia risk.
  • The association between mild head injuries and dementia – especially mild head injury that doesn’t result in loss of consciousness – is less well established
  • We examined the association between mild head injuries with and without loss of consciousness and dementia diagnoses in nearly 360,000 Veterans receiving care in the VA health care system.
  • We found that Veterans with a head injury diagnoses were two to four times more likely to be diagnosed with dementia than those without head injury diagnoses.
  • The risk of dementia diagnosis was doubled in Veterans who experienced head injury without loss of consciousness compared to those with no head injury. 

Continue reading

Some Depression and Overactive Bladder Drugs Linked to Dementia

Medicalresearch.com Interview with:

Professor Phyo Kyaw Myint Chair in Old Age Medicine University of Aberdeen

Prof. Myint

Professor Phyo Kyaw Myint
Chair in Old Age Medicine
University of Aberdeen

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

Response: We have previously studied the potential harmful effects of a group of medications called anticholinergics. They can have side effects on central as well peripheral systems. The link between use of these drugs and dementia is less well understood due to limitations of previous studies.

We used large GP practices data from the UK with long term follow up and examined this association using robust statistical methods.

Medicalresearch.com: What are the main findings?

Response: Key findings are:

  • Drugs with anticholinergic properties which are used to treat depression, urological conditions (e.g. for overactive bladder) and Parkinsonism are linked to development of dementia.
  • Drugs with similar properties which are used to treat gut disorders and heart conditions are not found to be linked to dementia
  • Drugs with low level of anticholinergic effect are not linked to dementia

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

Response: Clinicians should use the drugs with high level of anticholinergic burden cautiously. Also attempts should be made whenever appropriate to reduce or replace with similar drugs but without such properties.

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

Response: We need to ensure confounding effects are minimised by conducting carefully designed prospective studies. Further clinical trial evidence of benefit of deprescribing of these medications (when possible) in at risk populations is also urgently warranted.

Medicalresearch.com: Is there anything else you would like to add? Any disclosures?

Response: In the absence of trial evidence, this study provides best available evidence using robust statistical methods in the largest study of its kind and will help clinicians in making treatment choices for the benefit of the patients.

Citation:

Anticholinergic drugs and risk of dementia: case-control study

BMJ 2018; 361 doi: https://doi.org/10.1136/bmj.k1315 (Published 25 April 2018)Cite this as: BMJ 2018;361:k1315

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

 

 

 

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

Sleep Deprivation Leads to Build Up of Junk Amyloid in Brain

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

Dr. Nora Volkow

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.  Continue reading

Link Between Epilepsy Drugs and Increased Risk of Dementia

MedicalResearch.com Interview with:
Britta Haenisch, PhD

Pharmacoepidemiology in Neurodegenerative Disorders
German Center for Neurodegenerative Diseases,
DZNE 

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

Response: Antiepileptic drugs (AEDs) have been shown to affect cognition by suppressing neuronal excitability and increasing inhibitory neurotransmission. Previous studies suggested that AEDs may be associated with cognitive adverse effects. Therefore, we evaluated the association between AED use and incident dementia and Alzheimer’s disease (AD).

We utilized large longitudinal datasets from Finnish health registers and from German health insurance data. The case-control analyses was adjusted for several potential confounders like comorbidities and polypharmacy. The inclusion of a lag time between . Antiepileptic drugs use and dementia diagnosis allowed minimization of protopathic bias.

Our study provides an association between regular prescription of  antiepileptic drugs with known cognitive adverse effects and the occurrence of dementia and AD in patients aged 65 years and older.  Continue reading

Genetic Overlap Between Some Types of ALS and and Dementia

MedicalResearch.com Interview with:

Celeste Karch, PhD Assistant Professor of Psychiatry Molecular mechanisms underlying tauopathies Washington University School of Medicine St Louis

Dr. Karch

Celeste Karch, PhD
Assistant Professor of Psychiatry
Molecular mechanisms underlying tauopathies
Washington University School of Medicine
St Louis

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

Response: Nearly half of all patients with amyotrophic lateral sclerosis (ALS), a fatal neuromuscular disorder, develop cognitive problems that affect memory and thinking. Why a disease that primarily affects movement also disrupts thinking has been unclear.

Our findings suggest that genetic connections between the two disorders may explain why they share some of the same features and suggest that some drugs developed to treat ALS also may work against frontotemporal dementia and vice versa. We used a statistical method in almost 125,000 individuals with ALS, frontotemporal dementia (FTD), progressive supranuclear palsy, corticobasal degeneration, Alzheimer’s disease and Parkinson’s disease to determine whether there are common genetic variants that increase risk for multiple neurodegenerative diseases.

We found that common variants near the MAPT gene, which makes the tau protein, increases risk for ALS. MAPT has previously had been associated with diseases including frontotemporal dementia and Alzheimer’s disease. But the gene hadn’t been linked to ALS. We also identified variations in a second gene, BNIP1, which normally plays an important role in protecting against cell death, increased the risk of both ALS and frontotemporal dementia. ImportantlyBNIP1 mRNA levels were altered in people who had ALS and in patients with frontotemporal dementia, suggesting the BNIP1 may be a potential therapeutic target for both disorders.

Continue reading

Simple Screening Tool Predicts Parkinson’s Patients At Risk of Dementia

MedicalResearch.com Interview with:

Benjamin Dawson, B.Sc.  MD Candidate 2020

Benjamin Dawson

Benjamin Dawson, B.Sc.
MD Candidate 2020

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

Response: Dementia in Parkinson’s Disease is one of its most feared complications, and may happen eventually to most patients if they reached advanced age. Identifying those at especially high risk of dementia has important potential implications – it would facilitate clinical counselling, it has treatment implications (e.g. knowing a person is likely to get dementia in the near future would probably steer you away from certain medications and towards others).  Most critically, it can help select patients for trials to prevent dementia.

While several factors that show high risk for dementia in Parkinson’s disease have previously been described, these have yet to shape patient-care, either because they are not very strong predictors, or they are not user-friendly.  So, we designed a very simple clinical screening tool, called the Montreal Parkinson’s Risk of Dementia Scale (MoPaRDS).  It took predictors of dementia that were established from large-scale studies and boiled them down into a simple 8-point scale that uses information that you can get in a simple office visit.  The 8 predictors were being over 70, being male, having a blood pressure drop with standing, showing early mild cognitive changes, having a symmetric bilateral disease (that is, one side not clearly worse than the other), experiencing falls or freezing, having experienced hallucinations, and having symptoms of REM sleep behavior disorder (‘acting out’ the dreams at night).

When we tested the scale in a combined cohort of 607 patients with Parkinson’s (of whom 70 developed dementia over mean follow-up of 4.4-years) a positive MoPaRDS screen (≥4 out of 8 items) identified 14-fold increased risk of dementia compared to a negative screen. We recommend dividing the scale into three categories; low-, intermediate- and high-risk. Those in the highest score group (MoPaRDS, 6-8) had a 14.9% risk of developing dementia each year, while those with the lowest scores (MoPaRDS, 0-3) had only 0.6% annual risk.  So, these simple measures can be pretty powerful predictors of dementia. 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