Role Identified for Neuronal Protein in Dementia of Frontotemporal Lobar Degeneration

MedicalResearch.com Interview with:
Shinsuke Ishigaki

Department of Neurology
Department of Therapeutics for Intractable Neurological Disorders
Nagoya University Graduate School of Medicine
Nagoya,Japan

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

Response: Frontotemporal lobar degeneration (FTLD) is a pathological process that
has been characterized by personality changes, abnormal behaviors,
language impairment, and progressive dementia. The genetic and
pathological similarities in fused in sarcoma (FUS), transactive
response (TAR) DNA-binding protein 43 (TDP-43), and C9orf72 in relation
to FTLD and amyotrophic lateral sclerosis (ALS) have recently lead to
the recognition that the two conditions represent points on a spectrum
of a single disease entity. Additionally, Frontotemporal lobar degeneration has also been classified as a tauopathy, characterized by an accumulation of phosphorylated
microtubule-associated protein tau (tau) in affected neurons.

Our study demonstrated a biological link between FUS/SFPQ and the regulation of
tau isoforms involved in the early phase of Frontotemporal lobar degeneration.

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Living Near Major Roads Associated With Increased Dementia Risk

MedicalResearch.com Interview with:

Hong Chen, PhD Scientist, Environmental Health Assessment Public Health Ontario | Santé publique Ontario Assistant Professor, Dalla Lana School of Public Health, University of Toronto Adjunct Scientist, Institute for Clinical Evaluative Sciences (ICES) Toronto, ON

Dr. Hong Chen

Hong Chen, PhD
Scientist, Environmental Health Assessment
Public Health Ontario | Santé publique Ontario
Assistant Professor, Dalla Lana School of Public Health
University of Toronto
Adjunct Scientist, Institute for Clinical Evaluative Sciences
Toronto, ON

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

Response: Over the past several decades, there is unequivocal evidence that living close to major roadways may lead to various adverse health outcomes, such as cardio-respiratory related mortality and mortality. In the past decade, concern is growing that exposures associated with traffic such as air pollution and noise may also have an adverse impact on brain health. Several experimental studies show that air pollutants and diesel exhaust induce oxidative stress and neuroinflammation, activate microglia (which act as the first and main form of immune defense in the central nervous system), and stimulate neural antibodies. There are also a small number of epidemiological studies linking traffic-related noise and air pollution to cognitive decline and increased incidence of Parkinson’s disease and Alzheimer’s disease.

Studies also showed that living near roads was associated with reduced white matter hyperintensity volume and cognition, but its effect on the incidence of dementia, Parkinson’s disease, and multiple sclerosis is unknown. Given hundreds of millions of people worldwide live close to major roads, we conducted this population-based cohort study to investigate the association between residential proximity to major roadways and the incidence of these three neurological diseases in Ontario, Canada.

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Protein Loss in Urine Associated With Increased Risk of Dementia

MedicalResearch.com Interview with:

Kay Deckers, MSc PhD student School for Mental Health and Neuroscience Department of Psychiatry and Neuropsychology Maastricht University The Netherlands

Kay Deckers

Kay Deckers, MSc
PhD student
School for Mental Health and Neuroscience
Department of Psychiatry and Neuropsychology
Maastricht University
The Netherlands

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

Response: In an earlier review (https://www.ncbi.nlm.nih.gov/pubmed/25504093), we found that renal dysfunction was one the new candidate risk factors of dementia and needed further investigation.

MedicalResearch.com: What are the main findings?

Response: Albuminuria is associated with an increased risk of developing cognitive impairment or dementia.

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Access To Two Different Health Care Systems Can Lead To Dangerous Presciption Combinations

MedicalResearch.com Interview with:

Dr-Joshua-M-Thorpe.jpg

Dr. Joshua Thorpe

Joshua M. Thorpe, PhD, MPH
From the Center for Health Equity Research and Promotion
Veterans Affairs Pittsburgh Healthcare System
Pittsburgh Pennsylvania, and
Center for Health Services Research in Primary Care
Department of Pharmacy and Therapeutics
University of Pittsburgh School of Pharmacy

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

Response: Care coordination for persons with dementia is challenging for health care systems under the best of circumstances. These coordination challenges are exacerbated in Medicare-eligible veterans who receive care through both Medicare and the Department of Veterans Affairs (VA). Recent Medicare and VA policy changes (e.g., Medicare Part D, Veteran’s Choice Act) expand veterans’ access to providers outside the VA. While access to care may be improved, seeking care across multiple health systems may disrupt care coordination and increase the risk of unsafe prescribing – particularly in veterans with dementia. To see how expanded access to care outside the VA might influence medication safety for veterans with dementia, we studied prescribing safety in Veterans who qualified for prescriptions through the VA as well as through the Medicare Part D drug benefit.

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Is Depression in Mild Cognitive Impairment a Precursor to Dementia?

MedicalResearch.com Interview with:
Zahinoor Ismail MD FRCPC

Clinical Associate Professor,
Hotchkiss Brain Institute
University of Calgary

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

Response: Depression and depressive symptoms are common in mild cognitive impairment (MCI). Evidence suggests that depression in MCI increases the likelihood of progression from MCI to dementia, compared to non-depressed people with MCI. In the newer construct of mild behavioural impairment (MBI), which describes the relationship between later life onset of sustained and impactful neuropsychiatric symptoms and the risk of cognitive decline and dementia, depression is an important subdomain (in addition to apathy, impulse control, social cognition and psychotic symptoms). Thus, depression and depressive symptoms are a significant risk factor for cognitive, behavioural and functional outcomes in older adults who have at most mild cognitive impairment. As the importance of neuropsychiatric symptoms in older adults emerges, good prevalence estimates are required to inform clinicians and researchers as well as public health policy and decision makers.

We performed a systematic review and meta-analysis to determine the best estimate of prevalence of depression in  mild cognitive impairment. We included 57 studies, representing 20,892 participants in the analysis. While we determined that the omnibus prevalence estimate was 32%, there was significant heterogeneity in this sample based on setting. In community samples, the rate was 25%, but in clinical samples this was higher at 40%. Additionally, different case ascertainment methods for depression (self report, clinician administered or caregiver report) and different MCI criteria didn’t change the prevalence estimates.

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Dementia Risk Raised When Elderly Lose Home During Disaster

MedicalResearch.com Interview with:

Hiroyuki Hikichi, Ph.D. Research Fellow Harvard T.H. Chan School of Public Health Boston, MA 02215

Dr. Hiroyuki Hikichi

Hiroyuki Hikichi, Ph.D.
Research Fellow
Harvard T.H. Chan School of  Public Health
Boston, MA 02215

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

Response: Recovery after major disaster poses potential risks of dementia for the elderly population, such as resettlement in unfamiliar surroundings or psychological trauma. However, no previous studies have demonstrated that experiences of disaster are associated with the deterioration of dementia symptomatology, controlling changes of  risk factors in a natural experimental setting.

We prospectively examined whether experiences of a disaster were associated with incident dementia in the aftermath of the 2011 Great East Japan Earthquake and Tsunami.

MedicalResearch.com: What are the main findings?

Response: The main findings are that major housing damage and home destroyed were associated with cognitive decline: regression coefficient for levels of dementia symptoms = 0.12, 95% confidence interval (CI): 0.01 to 0.23 and coefficient = 0.29, 95% CI: 0.17 to 0.40, respectively.

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

Response: The effect size of destroyed home is comparable to the impact of incident stroke (coefficient = 0.24, 95% CI: 0.11 to 0.36).

From these findings, cognitive decline should be added to the list of health risks of older survivors in the aftermath of disasters.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Hiroyuki Hikichi, Jun Aida, Katsunori Kondo, Toru Tsuboya, Yusuke Matsuyama, S. V. Subramanian, Ichiro Kawachi. Increased risk of dementia in the aftermath of the 2011 Great East Japan Earthquake and Tsunami. Proceedings of the National Academy of Sciences, 2016; 201607793 DOI: 10.1073/pnas.1607793113

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

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At Least Two Genetic Causes For Early Onset Dementia of Leukoencephalopathy

MedicalResearch.com Interview with:

Dr David Lynch MB, MRCPI Leonard Wolfson Clinical Fellow UCL Institute of Neurology Queen Square, London

Dr David Lynch

Dr David Lynch MB, MRCPI
Leonard Wolfson Clinical Fellow
UCL Institute of Neurology
Queen Square, London

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

Response: In 2011 it was discovered that mutations in a gene called CSF1R cause a rare syndrome of early onset dementia often accompanied by movement disorders, spasticity and seizures, which is named adult onset leukoencephalopathy with axonal spheroids (ALSP). The hallmarks of ALSP are a characteristic appearance on MRI imaging and findings in brain pathological specimens – axonal swellings or ‘spheroids’. We manage a multidisciplinary group with expertise in leukoencephalopathies and have previously identified patients with mutations in CSF1R. However, we also found patients with a syndrome typical of ALSP who did not carry mutations in CSF1R.
In this study, we showed that some of these patients carry recessive mutations in a different gene, AARS2. This included a patient with characteristic axonal spheroids in brain tissue and typical ALSP clinical and imaging features.

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Androgen Deprivation For Prostate Cancer Linked to Dementia

MedicalResearch.com Interview with:
Kevin T. Nead, MD, MPhil

Resident, Radiation Oncology
Perelman School of Medicine
Hospital of the University of Pennsylvania.

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

Response: Androgen deprivation therapy is a primary treatment for prostate cancer and works by lowering testosterone levels. There is a strong body of research suggesting that low testosterone can negatively impact neurovascular health and function. We were therefore interested in whether androgen deprivation therapy is associated with dementia through an adverse impact on underlying neurovascular function.

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Mechanical Ventilation Doubles For Persons With Advanced Dementia

MedicalResearch.com Interview with:

Joan M. Teno, MD, MS Department of Gerontology and Geriatrics, Cambia Palliative Care Center of Excellence University of Washington Medicine Seattle, Washington

Dr. Joan Teno

Joan M. Teno, MD, MS
Department of Gerontology and Geriatrics,
Cambia Palliative Care Center of Excellence
University of Washington Medicine
Seattle, Washington

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

Response: An important challenge for our health care system is effectively caring for persons that high-need, high-cost — persons afflicted with advanced dementia and severe functional impairment are among these persons, with substantial need and if hospitalized in the ICU and mechanically ventilated are high cost patients, who are unlikely to benefit from this level of care and our best evidence suggest the vast majority of persons would not want this care. In a previous study, we interviewed families of advance dementia with 96% starting the goals of care are to focus comfort. Mechanical ventilation in some cases may be life saving, but in cases such as those with advanced dementia and severe functional impairment, they may result in suffering without an improvement in survival.

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Early Use of Gene Therapy May Stop Plaques of Alzheimer’s Disease

MedicalResearch.com Interview with:

Dr. Magdalena Sastre PhD Faculty of Medicine, Department of Medicine Senior Lecturer Imperial College London

Dr. Magdalena Sastre

Dr. Magdalena Sastre PhD
Faculty of Medicine, Department of Medicine
Senior Lecturer
Imperial College London

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

Response: Alzheimer’s disease is the most common neurodegenerative disorder, affecting over 45 million people around the world. Currently, there are no therapies to cure or stop the progression of the disease. Here, we have developed a gene therapy approach whereby we delivered a factor called PGC-1α, which regulates the expression of genes involved in metabolism, inflammation and oxidative stress in the brain of transgenic mice. This factor is also involved in the regulation of energy in the cells, because it controls the genesis of mitochondria and in the generation of amyloid-β, the main component of the neuritic plaques present in the brains of Alzheimer’s disease patients.

We have found that the animals with Alzheimer’s pathology treated with PGC-1α develop less amyloid plaques in the brain, perform memory tasks as well as healthy mice and do not have neuronal loss in the brain areas affected by the disease.

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Genetic Mutation Common In Ashkenazi Jews With Lewy Body Dementia

MedicalResearch.com Interview with:

Dr Tamara Shiner MD PhD Specialist in Neurology Neurology Division Tel Aviv Sourasky Medical Centre

Dr Tamara Shiner

Dr Tamara Shiner MD PhD
Specialist in Neurology
Neurology Division
Tel Aviv Sourasky Medical Centre

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

Response: Although in the past believed to be sporadic, there is much emerging evidence for a significant genetic contribution to Dementia with Lewy bodies (DLB). Hetrozygosity for common mutations in the GBA gene have been shown to be more frequent among DLB patients and Parkinson’s disease patients than in the general population.

We found that GBA mutations are in fact exceptionally frequent among Ashkenazi Jewish (AJ) patients with Dementia with Lewy bodies. Our results indicate that one in three of all Ashkenazi DLB patients carry mutations in this specific gene (compared to approximately 6% in the general Ashkenazi Jewish population). We also found that those who carry these mutations have a more severe disease phenotype.

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Inflammatory Biomarkers May Presage Development of Alzheimer’s

MedicalResearch.com Interview with:

Inflammatory Biomarkers May Presage Development of Alzheimer's

Prof. Paul Morgan

Professor B. Paul Morgan
Director, Systems Immunity Research Institute
Institute of Infection and Immunity
School of Medicine
Cardiff University

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

Response: Inflammation is a normal response of the body to infection or injury; however, it is well known that inflammation also has a dark side and when it escapes normal controls can cause disease. Some illnesses, like rheumatoid arthritis, have been known for many years to be caused by rogue inflammation and most of the drugs used to treat work by suppressing the inflammation (anti-inflammatories). More recently, it has become clear that inflammation is behind many other diseases that were previously thought of as diseases of ageing caused by wear and tear and lifestyle – these include heart disease and some brain diseases, notably Alzheimer’s disease the commonest cause of dementia. Evidence that inflammation is one of the drivers of disease has come from many sources, including some where it was noticed that people on long-term anti-inflammatory drugs for other reasons appeared to be protected from developing Alzheimer’s disease.

A problem is that Alzheimer’s disease, despite the name, is not a single disease but rather a group of conditions with similar symptoms, and inflammation is likely to be a cause in only some of the patients; further, most of the inflammation might be occurring very early in the disease, even before symptoms are obvious. So, there is an urgent need for a simple test or set of tests that can be used in individuals with the very earliest hints of Alzheimer’s disease – mild memory loss – that will pick out those who have brain inflammation and are most likely to develop Alzheimer’s disease. It might then be possible to treat this select group with anti-inflammatory drugs that will reduce brain inflammation and slow or stop progression of the disease.

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