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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Hearing Loss Linked To Increased Depression and Dementia Risk

MedicalResearch.com Interview with:

Dr-Frank-Lin.jpg

Dr. Lin

Frank Robert Lin, M.D., Ph.D.
Associate Professor of Geriatric Medicine, Head and Neck Surgery
Johns Hopkins Medicine

MedicalResearch.com Editor’s note: Dr. Lin discussed his research during Cochlear’s Global Research Symposium, which brought together international experts from the audiology community.

MedicalResearch.com: Is there a link between hearing loss and the risk of developing dementia?

Response: In the last few years, we have investigated the link between hearing loss and dementia in large studies of older adults who have been followed for many years. In these studies, we and others have found that those with greater hearing loss have a higher risk of developing dementia even after we account for factors like age, education, medical comorbidities, etc. We think this is because there are some pathways through which hearing loss can directly affect our thinking and memory abilities

MedicalResearch.com: Is there an association between hearing loss and cognitive decline or premature death?

Response: There is a link between hearing loss and accelerated cognitive decline. There is also external research that links hearing loss and premature death (Friburg 2014, Contrera 2015). Hearing loss can also increase a person’s chance of using medical and social services

MedicalResearch.com: How is hearing loss linked to increased social isolation and depression in the elderly?

Response: Older people with hearing loss are at a greater risk of social isolation due to their difficulty communicating with people. These individuals may be less likely to go out, particularly to settings where listening can be difficult (e.g., restaurants), and even if they do go out, they may feel isolated from the conversation and not able to engage with others.

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

Response: Readers should understand that we’re increasingly understanding that hearing loss can detrimentally impact our thinking and memory abilities, risk of dementia, and our ability to remain engaged with others. Ongoing research is now studying to what extent our current hearing loss therapies can reduce and mitigate these risks and promote healthy aging.

MedicalResearch.com: Is there anything else you would like to add?

Response: Readers should know that hearing loss is a growing public health issue. It has been estimated that by 2050 1.2 billion people will suffer from hearing loss, underscoring the need for us to address it and recognize the burden of hearing loss on wider health. To learn more visit,www.linresearch.org and www.nas.edu/hearing

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

Citation:

Cochlear’s Global Research Symposium October 2016

Disclosure:  Symposium supported by Cochlear Limited (ASX: COH), together with Macquarie University and the Australian Hearing Hub

www.cochlear.com

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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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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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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Calcium Supplements May Raise Risk of Dementia in Elderly Women with Cerebrovascular Disease

MedicalResearch.com Interview with:

Silke Kern, MD, PhD Neuropsychiatric Epidemiology Unit and Clinical Neurochemistry Laboratory Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology Sahlgrenska Academy University of Gothenburg Gothenburg, Sweden

Dr. Silke Kern

Silke Kern, MD, PhD
Neuropsychiatric Epidemiology Unit and Clinical Neurochemistry Laboratory
Department of Psychiatry and Neurochemistry
Institute of Neuroscience and Physiology
Sahlgrenska Academy
University of Gothenburg
Gothenburg, Sweden

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

Response: Calcium has an important role in ischemic neuronal cell death and atherosclerosis. Several studies suggest that increased serum calcium increases the risk for vascular events and worsens the outcome after stroke. Widespread ischemic neuronal cell death and atherosclerosis might lead to dementia. We therefore examined if Calcium supplementation is associated with development of dementia. Our study is the first to show a relationship between Calcium supplementation and increased risk for dementia in older women. This risk is mainly confined to women with cerebrovascular disease (history of stroke or presence of white matter lesions).

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