Single Injection of Klotho Gene Protected Animals From Cognitive Decline

MedicalResearch.com Interview with:

Dr Miguel Chillon PhD Department of Biochemistry and Molecular Biology Universitat Autonoma Barcelona Spain

Dr. Chillon

Dr Miguel Chillon PhD
Department of Biochemistry and Molecular Biology
Universitat Autonoma Barcelona
Spain

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

Response: Klotho is a protein with an anti-aging and neuroprotective role. Recent studies show it prevents the development of cognitive problems associated with aging and Alzheimer’s disease. Klotho works mainly by inhibiting the insulin / IGF-1 signaling pathway and decreasing the damage caused by oxidative stress in the brain. One of the latest results revealed that the concentration of Klotho in cerebrospinal fluid is significantly lower in Alzheimer’s patients than in human controls of the same age; and it is lower in the elderly with respect to young adults.

Our study used a gene therapy strategy to introduce the Klotho gene into the Central Nervous System of adult animals. With just a single injection of the Klotho gene, young adult animals were protected over time from the cognitive decline associated with aging in old animals. These exciting results pave the way to further advances in research and the development of a neuroprotective therapy based on Klotho.

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Chronic Inflammation in Midlife May Predispose To Smaller Brain Volumes and Memory Ability In Seniors

MedicalResearch.com Interview with:
Keenan A. Walker, PhD
Johns Hopkins University School of Medicine
Baltimore, MD

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

Response: There is quite a bit of evidence linking immune function with dementia. For example, several of the risk genes for Alzheimer’s disease are known to play a key role in immune functioning and the regulation of inflammation. We conducted the current study to determine whether systemic inflammation earlier in life might be a risk factor for neurodegeneration decades later. This long temporal window allows us to get closer to understanding causality. That is, which comes first – systemic inflammation or brain volume loss.

Using a large community sample, we found that individuals with higher levels of blood inflammatory markers during midlife tended to have smaller brain volumes in select regions and reduced memory ability as older adults. We found the strongest associations between systemic inflammation and brain volume loss in brain regions most vulnerable Alzheimer’s disease.

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Dementia Incidence Lower For Atrial Fibrillation Patients Treated With Anticoagulation

MedicalResearch.com Interview with:

Dr. Leif Friberg MD, PhD Associate professor in cardiology Karolinska Institute Friberg Resarch Stockholm, Sweden 

Dr. Leif Friberg

Dr. Leif Friberg MD, PhD
Associate professor in cardiology
Karolinska Institute
Friberg Resarch
Stockholm, Sweden 

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

Response: I have been doing research on atrial fibrillation and stroke risk for many years and knew that the very common heart arrhythmia is associated with a 40% increased risk of dementia. Considering that that 12-15% of 75 years olds have this arrhythmia, and even more at higher ages, the problem is significant to say the least.

The mechanism behind stroke in atrial fibrillation is that blood clots are formed in the heart. When these are dislodged they travel with the blood stream and may get stuck in the narrow vessels of the brain where they stop blood flow causing brain infarction or stroke. Oral anticoagulant drugs like warfarin or the newer so called NOAC (new oral anticoagulant) drugs are highly efficient in preventing formation of these large blood clots and offer at least 70% risk reduction. Now, blood clots come in different sizes. There are also microscopic clots that do not cause symptoms of stroke but all the same eat away at the brain at a slow but steady pace. Imaging studies shows this after only a few months or even weeks of atrial fibrillation. Our hypothesis was therefore: If anticoagulants are so effective in protecting against large clots, will they not help against the small ones too?

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Dementia Incidence Rates May Be Declining

MedicalResearch.com Interview with:

Carol A. Derby, Ph.D. Research Professor, The Saul R. Korey Department of Neurology Research Professor, Department of Epidemiology & Population Health Louis and Gertrude Feil Faculty Scholar in Neurology Albert Einstein College of Medicine Bronx, NY 10461

Dr. Derby

Carol A. Derby, Ph.D.
Research Professor, The Saul R. Korey Department of Neurology
Research Professor, Department of Epidemiology & Population Health
Louis and Gertrude Feil Faculty Scholar in Neurology
Albert Einstein College of Medicine
Bronx, NY 10461

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

Response: The population over the age of 85 is expected to triple in the coming decades, and with the aging of the population, the number of individuals living with dementia is projected to increase dramatically.

While dementia prevalence rates are driven by demographic shift to older ages, changes in dementia incidence- the rate at which new cases are diagnosed, would also impact the proportion of the population affected in the coming decades.

Recently, studies have suggested that dementia incidence rates may be declining in some populations, although the results have not been consistent. Better understanding trends in dementia rates is important for public health planning.

Our objective was to determine whether there has been a change in the incidence of dementia diagnosis within a community residing group of over older adults followed by the Einstein Aging Study, at the Albert Einstein College of Medicine, in the Bronx, NY between the years 1993 and 2015.

To accurately characterize trends over time in disease rates requires separating the effects of age and the effects of calendar time. Therefore, we conducted a birth cohort analysis in which we examined age specific dementia incidence rates by birth year, for individuals born between 1910 and 1940. The analysis included over 1300 individuals over the age of 70, who were free of dementia when they enrolled in the study. Dementia was diagnosed using identical criteria over the entire study period, and study recruitment was also consistent over the period. We also examined trends in cardiovascular co-morbidities that have been related to dementia risk, as well as trends in education.  Continue reading

Dementia Care Management Improved Quality of Life For Both Caregivers and Patients With Dementia

MedicalResearch.com Interview with:

Jochen René Thyrian, PhD German Center for Neurodegenerative Diseases (DZNE) Greifswald, Germany     

Dr. Thyrian

Jochen René Thyrian, PhD
German Center for Neurodegenerative Diseases (DZNE)
Greifswald, Germany

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

Response: Dementia presents a challenge to the health care systems worldwide. People with dementia (PWD) need comprehensive medical, nursing, psychological and social support to delay the progression of disease and sustain autonomy and social inclusion. Evidence-based interventions alleviate the burden of disease for PwD and their caregivers, as no curative treatment is currently available. Involving caregivers is important because they provide the largest proportion of care for PwD. General physicians in residency have been identified as the first point of contact for PwD and is thus a promising setting for identification, comprehensive needs assessment and initiating dementia-specific treatment and care.

In this study we tested the effectiveness and safety of a model of collaborative care, Dementia Care Management (DCM) on patient-oriented outcomes in n=634 people screened positive for dementia in primary care. DCM is provided by specifically trained nurses, supported by a computerized intervention management system, in close cooperation with the treating physician at the people´s homes. Recommendations for improving treatment and care were based on a comprehensive needs assessment, discussed interprofessionally and their implementation monitored/ adjusted over the course of 6-12 months

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Paper and Digital SAGE Brain Tests Equally Identify Cognitive Impairment and Dementia

MedicalResearch.com Interview with:

Douglas W. Scharre MD Professor of Clinical Neurology and Psychiatry Director Division of Cognitive Neurology, Department of Neurology  Director, Center for Cognitive and Memory Disorders Director, Memory Disorders Research Center Co-Director, Neuroscience Research Institute Ohio State University Wexner Medical Center  Columbus, OH

Dr. Douglas Scharre

Douglas W. Scharre MD
Professor of Clinical Neurology and Psychiatry Director, Division of Cognitive Neurology
Department of Neurology
Director, Center for Cognitive and Memory Disorders
Director, Memory Disorders Research Center
Co-Director, Neuroscience Research Institute
Ohio State University Wexner Medical Center
Columbus, OH

 

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

Response: Self-Administered Gerocognitive Examination (SAGE) is a pen-and paper, valid and reliable cognitive assessment tool for identifying individuals with mild cognitive impairment (MCI) or early dementia. We published age and education normative data on SAGE and determined that one point be added to the scores when age over 79 and one point be added when education level is 12 years or less. We evaluated the identical test questions in digital format (eSAGE) made for tablet use, adjusted with previously published age and education norms, and determined eSAGE’s association with gold standard clinical assessments. eSAGE is commercially known as BrainTest.

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Depressive Symptoms Not Found To Increase Risk of Dementia

MedicalResearch.com Interview with:

Archana Singh-Manoux, PhD Research Professor (Directeur de Recherche) Epidemiology of ageing & age-related diseases INSERM U1018, France Honorary Professor University College London, UK

Dr. Archana Singh-Manoux

Archana Singh-Manoux, PhD
Research Professor (Directeur de Recherche)
Epidemiology of ageing & age-related diseases
INSERM  France
Honorary Professor
University College London, UK 

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

Response: Depressive symptoms are common in dementia patients. Previous studies, based on older adults, show depressive symptoms in late life to be associated with an increased risk of dementia. These studies do not allow conclusions to be drawn on the causal nature of the association between depressive symptoms and dementia.

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No Decrease In Incidence of Dementia Over Past Decades

MedicalResearch.com Interview with:

Emma van Bussel MD, MSc Academic Medical Center | University of Amsterdam Amsterdam | The Netherlands

Dr. Emma van Bussel

Emma van Bussel MD, MSc
Academic Medical Center | University of Amsterdam
Amsterdam | The Netherlands 

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

Response: Dementia forms a high social and economic burden on society. Since there is a growing number of older people, the occurrence of dementia is expected to increase over the years to come. For future planning of care, it is important to have reliable predictions on new dementia cases for the population at large. Studies in Western countries suggested that the incidence per 1000 person years is declining.

We studied the incidence trend of dementia in the Netherlands in primary care registry data, in a population of over 800,000 older people (60 years and over) for the years 1992 to 2014. Our results indicate a small increase of 2.1% (95% CI 0.5% to 3.8%) per year in dementia incidence over the past decades. The trend did not change in the years after 2003, when a national program was developed to support dementia care and research, compared to the years prior to 2003.

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Prostate Cancer: No Association Between Androgen Deprivation Therapy and Dementia

MedicalResearch.com Interview with:
Farzin Khosrow-Khavar, M.Sc. Ph.D. Candidate
Department of Epidemiology, Biostatistics and Occupational Health, McGill University
Center for Clinical Epidemiology – Jewish General Hospital
Montreal, QC 

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

Response: Previous studies have shown an association between androgen deprivation therapy (ADT) and risk of dementia and Alzheimer’s disease. However, these studies had methodological limitations that may account for this positive association. Using appropriate study design and methodology, we found no association between androgen deprivation therapy and risk of dementia (including Alzheimer’s disease) in patients with prostate cancer. These results were consistent by cumulative duration of  androgen deprivation therapy use and by ADT modality.

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Stopping Warfarin in Dementia Patients with Atrial Fib Associated With Increased Risk of Stroke and Death

MedicalResearch.com Interview with:

Ariela Orkaby, MD, MPH Geriatrics & Preventive Cardiology Associate Epidemiologist Division of Aging, Brigham and Women's Hospital Instructor in Medicine, Harvard Medical School

Dr. Ariela Orkaby

Ariela Orkaby, MD, MPH
Geriatrics & Preventive Cardiology
Associate Epidemiologist
Division of Aging, Brigham and Women’s Hospital
Instructor in Medicine, Harvard Medical School

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

Response: Atrial Fibrillation is a common heart rhythm that affects 1 in 25 adults over age 60 and 1 in 10 adults over age 80. The feared consequence of atrial fibrillation is stroke, leading to the prescription of blood thinning medications (anticoagulants such as warfarin) to prevent strokes. However, there is an underutilization of these life-saving medications in older adults, and particularly in those who have dementia. In part, this is due to a lack of research and inclusion of older adults with dementia in prior studies.

In this study, we used clinical Veterans Administration data, linked to Medicare, to follow 2,572 individuals over age 65 who had atrial fibrillation and until a diagnosis of dementia. The average age was 80 years, and 99% were male. We found that only 16% remained on warfarin. We used statistical methods to account for reasons why a patient would or would not be treated with warfarin and found that those who continued to take warfarin had a significantly lower risk of stroke (HR 0.74, 95% Confidence interval 0.54- 0.99, p=0.47) and death (HR 0.72, 95% CI 0.60-0.87, p<0.01) compared to those who did not continue to take warfarin, without an increased risk of bleeding.

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Excessive Sleeping May Be Early Marker of Dementia

MedicalResearch.com Interview with:

Dr. Matthew P. Pase Sidney Sax NHMRC Fellow, Department of Neurology Boston University School of Medicine Investigator, Framingham Heart Study;  Senior Research Fellow, Swinburne University of Technology. Boston MA 02118

Dr. Matthew Pase

Dr. Matthew P. Pase
Sidney Sax NHMRC Fellow, Department of Neurology
Boston University School of Medicine

Investigator, Framingham Heart Study;
Senior Research Fellow, Swinburne University of Technology.
Boston MA 02118

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

Response: Sleep disturbances are common in dementia. However, most studies have focused on patients who already have dementia and so it is unclear whether disturbed sleep is a symptom or a cause of dementia.

We studied 2,457 older participants enrolled in the Framingham Heart Study, a large group of adults sampled from the community in Framingham, Massachusetts. We asked participants to indicate how long they typically slept each night. Participants were then observed for the following 10-years to determine who developed dementia, including dementia due to Alzheimer’s disease. Over the 10 years, we observed 234 cases of dementia. Information on sleep duration was then examined with respect to the risk of developing dementia.
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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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Poor Oral Health in Hospitalized Patients Associated With Dementia and Kidney Disease

MedicalResearch.com Interview with:

Danielle Mairead Maire Ni Chroinin, MB BCh BAO BMedSc MD MRCPI FRACP Staff Specialist in Geriatric Medicine Liverpool Hospital and Senior Conjoint Lecturer UNSW

Dr. Danielle Ni-Chroinin

Danielle Mairead Maire Ni Chroinin,
MB BCh BAO BMedSc MD MRCPI FRACP

Staff Specialist in Geriatric Medicine
Liverpool Hospital and Senior Conjoint Lecturer UNSW

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

Response: Oral disease may have a large impact on older persons’ health and wellbeing, causing pain, impairing speech, adversely affecting nutrition, contributing to systemic infection and harming self-esteem. However, this important issue may be neglected in the acute hospital setting. Our aim was to investigate oral health status and abnormalities in older patients admitted acutely to hospital, exploring the association with medical co-morbidities. We included all individuals aged 70 and older admitted to a geriatric service over 3 months (N=202), and evaluated oral health using a simple bedside tool the Oral Health Assessment Tool (OHAT).

Overall, we found that poor oral health was not uncommon, and was associated with dementia and renal impairment. This association persisted even after adjustment for anticholinergic medication and oral pH, highlighting that patients with these conditions may be particularly vulnerable.

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After Hemorrhagic Stroke, Patients at High Risk of Early and Delayed Dementia

MedicalResearch.com Interview with:

Alessandro Biffi, MD Behavioral Neurology and Neuropsychiatry Departments of Neurology and Psychiatry Massachusetts General Hospital / Harvard Medical School

Dr. Alessandro Biffi

Alessandro Biffi, MD
Behavioral Neurology and Neuropsychiatry
Departments of Neurology and Psychiatry
Massachusetts General Hospital / Harvard Medical School

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

Dr. Biffi: Intracerebral Hemorrhage (ICH) is the most severe form of stroke. It is a form of hemorrhagic (i.e. bleeding) stroke that accounts for ~ 15% of all acute cerebrovascular conditions, affecting ~ 70,000 Americans every year. However, because of its severity it is responsible for almost half of all stroke-related disability worldwide. Survivors of ICH are at very high risk for cognitive impairment (up to and including dementia) following the acute cerebral bleeding event. However, we possess very limited understanding of the time dynamics and risk factors for post-ICH dementia. In particular, prior to our study it was unclear whether the acute cerebral injury due to ICH would be the only mechanism potentially responsible for subsequent development of dementia.

This question is motivated by prior observations suggesting that Intracerebral Hemorrhage represents the acute manifestation of cerebral small vessel disease, a progressive degenerative disorder of small caliber arteries of the central nervous system.

There exist two major subtypes of small vessel disease:

1) cerebral amyloid angiopathy, caused by the deposition of a toxic protein product, beta-amyloid, in the blood vessels (in a process similar to the formation of beta-amyloid plaques that cause Alzheimer’s disease);

2) arteriolosclerosis, caused by long-standing elevated blood pressure. ICH survivors have been previously shown to harbor very severe small vessel disease, which has been linked to dementia in patients without cerebral bleeding.

Our hypothesis was that early-onset dementia (occurring in the first 6 months after ICH) is a manifestation of the acute neurological damage associated with cerebral bleeding, whereas delayed onset dementia (developing beyond 6 months from the acute ICH event) is associated with known markers of small vessel disease, including imaging findings on CT/MRI and genetic markers (such as the APOE gene).

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Elevated Blood Pressure Is Risk Factor For Vascular Dementia

MedicalResearch.com Interview with:

Kazem Rahimi, DM, MSc Oxford Martin School University of Oxford United Kingdom

Dr. Kazem Rahimi

Kazem Rahimi, DM, MSc
Oxford Martin School
University of Oxford
United Kingdom

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

Dr. Rahimi: Vascular dementia is the second most common cause of dementia and is increasing in prevalence worldwide. Vascular dementia often occurs after stroke and can cause apathy, depression, and a decline in cognitive function, and can eventually result in death. High blood pressure (BP) has been identified as a potential risk factor for the development of vascular dementia. However, previous studies, which have been small in size, have reported conflicting results on the relationship between blood pressure and vascular dementia.

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Study Finds Lupus Doubles Risk of Dementia

MedicalResearch.comcom Interview with:
Hui-Wen Lin MD, PHD
Department of Mathematics, Soochow University
Evidence-Based Medicine Center, Wan Fang Hospital, Taipei Medical University
Taipei, Taiwan

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

Dr. Hui-Wen Lin: Systemic lupus erythematosus (SLE) is a systemic autoimmune disorder that affects multiple organ systems and it predominantly affects women aged 20 to 40 years, and clinical symptoms caused by autoantibody deposition that triggers subsequent inflammatory reactions vary between individuals. There were 30~80% of SLE patients present neurological symptoms, and it is referred to as neuropsychiatric SLE (NPSLE). However there is no research about risk of dementia for SLE patients. Therefore we investigated this issue by analyzing the National Health Insurance Research Database in Taiwan.

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Even on Anticoagulation Atrial Fibrillation Contributes to Dementia Risk

MedicalResearch.com Interview with:

T. Jared Bunch, MD Director of Heart Rhythm Research Medical Director for Heart Rhythm Services Intermountain Healthcare system

Dr. T. Jared Bunch

T. Jared Bunch, MD
Director of Heart Rhythm Research
Medical Director for Heart Rhythm Services
Intermountain Healthcare System

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

Dr. Bunch: Approximately 6 years ago we found that patients with atrial fibrillation experienced higher rates of all forms of dementia, including Alzheimers disease.  At the time we started to ask the questions of why this association existed.  We know that atrial fibrillation patients experience higher rates of stroke.  These patients are placed on blood thinners, most commonly warfarin, to lower risk of stroke which at the same time expose that patient to a higher risk of intracranial bleeding.  One possibility to explain the association was that perhaps dementia in the manifestation of many small clots or bleeds in the brain that in total lead to cognitive decline.  If this is the case, then the efficacy and use of anticoagulation is very important in atrial fibrillation patients.

We conducted additional studies that showed this to be the case.  In patients with no history of dementia, managed long-term with warfarin anticoagulation, those that had levels that were frequently too higher or too low that resulted in poor times in therapeutic range, experienced significantly higher rates of dementia.  The risk was highest in younger atrial fibrillation patients that were less than 80 years of age.  We then found that in atrial fibrillation patients that were frequently over anticoagulated and also use an antiplatelet agent, aspirin or plavix, the dementia rates nearly doubled.  At this point we raised the question if atrial fibrillation increased the risk beyond anticoagulation, or does anticoagulation efficacy drive most of the risk.  This question formed the background of the current study.

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Worsening Depression in Older Adults May Be Early Indicator of Dementia

MedicalResearch.com Interview with:

Saira Saeed Mirza, MD, PhD Department of Epidemiology Erasmus MC, Rotterdam

Dr. Saira Saeed Mirza

Saira Saeed Mirza, MD, PhD
Department of Epidemiology
Erasmus MC, Rotterdam

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

Dr. Mirza: Depressive symptoms appearing in late-life have been extensively studied for their relationship with dementia. They not only very frequently occur in demented patients, but also predict dementia. In this context, depressive symptoms have largely been assessed at a single time point only. However, depression is a disorder which remits and relapses, and symptoms do not remain same over the years. Given this pattern of disease progression, it is more important to study the course of depression over time in relation to long-term health outcomes such as dementia, rather than assessing it at a single time-point, which will neglect the course of depression. This is important as people follow different courses of depression, and different courses of depression might carry different risks of dementia.

When we studied the course of depressive symptoms over 11 years in community dwelling older adults in Rotterdam, and the subsequent risks of dementia, we observed that only those who had increasing or worsening depressive symptoms were at a higher risk of dementia. In this group of people, about one in five persons developed dementia. Interestingly, people suffering from high depressive symptoms at a single time point were not at a higher dementia risk than those without depressive symptoms.

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Low Vitamin B12 Associated With Accelerated Brain Aging

MedicalResearch.com Interview with:

Babak Hooshmand, MD, PhD, MPH Center for Alzheimer Research–Aging Research Center Karolinska Institutet Stockholm University, Stockholm, Sweden  Department of Neurology, Klinikum Augsburg Augsburg, Germany

Dr. Babak Hooshmand

Babak Hooshmand, MD, PhD, MPH
Center for Alzheimer Research–Aging Research Center
Karolinska Institutet
Stockholm University, Stockholm, Sweden
Department of Neurology, Klinikum Augsburg
Augsburg, Germany

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

 Dr. Hooshmand: Low and subnormal levels of vitamin B12 as well as high levels of homocysteine (a vascular risk factor and neurotoxic amino-acid associated with B12 deficiency) are common conditions in the elderly and are associated with a variety of disorders, including cardiovascular and cerebrovascular

conditions. Our study showed that over 6-year of follow-up, both low vitamin B12 status and high homocysteine levels are associated with accelerated brain atrophy in older adults, which precedes clinical dementia.

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Older Adults with Chronically High Depressive Symptoms May Be At Higher Risk of Dementia

MedicalResearch.com Interview with:
Allison R. Kaup, PhD
Assistant Adjunct Professor, UCSF Department of Psychiatry
Clinical Research Psychologist / Clinical Neuropsychologist and
Kristine Yaffe MD
Professor of Psychiatry, Neurology and Epidemiology
Chief of Geriatric Psychiatry and Director of the Memory Evaluation Clinic

San Francisco VA Medical Center 

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

Response: Previous research has shown that older adults with depression are more likely to develop dementia.  But, most studies have only examined an older adult’s depressive symptoms at one point in time.  This is an important limitation because we know that depressive symptoms change over time and that older adults show different patterns of depressive symptoms over time.  For the present study, older adults were followed for several years.  We assessed what patterns of depressive symptoms they tended to have during the early years of the study, and then investigated whether these different patterns were associated with who developed dementia during the later years of the study.

MedicalResearch.com: What are the main findings?

Response: Older adults in this study tended to show one of 3 different patterns of depressive symptoms.  Most tended to have few, if any, symptoms over time.  Some tended to have a moderate level of depressive symptoms at the beginning of the study, which increased over time.  And others tended to have a high level of depressive symptoms at the beginning of the study, which increased over time.

We found that older adults with the high-and-increasing depressive symptoms pattern were almost twice as likely to develop dementia than those with minimal symptoms, even when accounting for other important factors.  While older adults with the moderate-and-increasing depressive symptom pattern were also somewhat more likely to develop dementia, this association was not as strong and did not hold up in our statistical models when we accounted for what individuals’ cognitive functioning was like during the early years of the study.

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Is There A Link Between Proton Pump Inhibitors and Dementia?

MedicalResearch.com Interview with:
Dr. Britta Haenisch PhD

German Center for Neurodegenerative Diseases (DZNE) 

Medical Research: What is the background for this study?

Dr. Haenisch: Proton pump inhibitors (PPIs) are widely used for the treatment of gastrointestinal diseases, but have also been shown to be potentially involved in cognitive decline: There were hints from recent other studies that PPIs might affect cognition, e.g. Lam et al. (2013) report a significant association of PPI use with vitamin B12 deficiency in a population-based sample. Vitamin B12 deficiency has been shown to be associated with cognitive decline. In another study, PPIs were observed to enhance amyloid beta peptide (Aβ) levels in mouse brain by affecting the enzymes β- and γ-secretase which leads to increased Aβ levels in mice.

Medical Research: What are the main findings?

Dr. Haenisch: The current study provides a statistical association (applying a time-dependent analysis) between proton pump inhibitors prescription and occurrence of dementia with a focus on long-term regular PPI prescription in patients aged 75 years and older. In our analysis we focused on long-term regular PPI prescription for at least 18 months. It does not prove that proton pump inhibitors cause dementia.

References

-Lam JR, Schneider JL, Zhao W, Corley DA. Proton pump inhibitor and histamine 2 receptor antagonist use and vitamin B12 deficiency. JAMA. 2013;310(22):2435-2442.

-Badiola N, Alcalde V, Pujol A, et al. The proton-pump inhibitor lansoprazole enhances amyloid beta production. PLoS One. 2013;8(3):e58837

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Dementia Incidence Dropping In Those With At Least High School Education

MedicalResearch.com Interview with:

Claudia L. Satizabal, PhD Instructor in Neurology Boston University School of Medicine The Framingham Heart Study Boston, MA 02118-2526

Dr. Claudia Satizabal

Claudia L. Satizabal, PhD
Instructor in Neurology
Boston University School of Medicine
The Framingham Heart Study
Boston, MA 02118-2526

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

 

Dr. Satizabal: Our societies are expected to face an increasing burden of dementia in the next decades due to increasing life expectancies and the aging of a big proportion of the population, the so called “baby boomers”. However, some studies conducted in high-income countries have suggested a decline in the total number of cases (prevalence) as well as new cases (incidence) of dementia at any given age. Yet the findings of these studies were not seen as definitive, either because results were of borderline significance or because they were based on survey data, and stronger evidence was lacking.

We used information collected since 1975 in the Framingham Heart Study to estimate the trends in dementia incidence. One of the strengths of this study is that investigators have been careful to use the same diagnostic criteria for over the past 30 decades, which allows us to provide more robust evidence of dementia trends over time.

We found that there has been a progressive decline in the incidence of dementia at any given age over the past 30 decades. Compared to the late 1970s, we observed a decline of 22% in the late 1980s, 38% in the 1990s and 44% in the 2000s. This beneficial trend was only seen among persons with at least a high school diploma. We also explored trends in vascular risk factors such as blood pressure, smoking, diabetes, and others; however, these trends did not completely explain the decline in dementia incidence. One interesting finding was that the risk of dementia associated with cardiovascular diseases, such as stroke or atrial fibrillation, decreased dramatically over the course of time from the late 1970s to the 2000s.

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Out-of-Pocket Expenses Greatest For Families Caring For Dementia Patient

Amy S. Kelley, MD, MSHS Department of Geriatrics and Palliative Medicine Icahn School of Medicine at Mount Sinai New York, NY

Dr. Kelley

MedicalResearch.com Interview with:
Amy S. Kelley, MD, MSHS
Department of Geriatrics and Palliative Medicine
Icahn School of Medicine at Mount Sinai
New York, NY

Medical Research: Why is it so important to understand the financial burdens families may face in providing end-of-life care for a loved one and why do you think the burdens may be greater for dementia than for other medical conditions?

Dr. Kelley: Understanding the financial risks that older adults face in the last years of life is important for individuals and families, in order to plan and save, if possible. It is also important for our policy makers, in particular, to know about these costs so that this information can help shape health and social policy that will best serve our society. Households of those with dementia face the greatest burden of costs, on average, particularly with regard to out-of-pocket expenses and the costs of caregiving.  Many costs related to daily care for patients with dementia are not covered by health insurance, and these care needs, including everything from supervision, to bathing and feeding, may span several years.

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Orthostatic Hypotension and Blood Pressure Variability Linked to Cognitive Decline

Christine McGarrigle PhD Research Director The Irish Longitudinal Study on Ageing (TILDA) Lincoln Gate Trinity College Dublin Dublin

MedicalResearch.com Interview with:
Christine McGarrigle PhD
Research Director
The Irish Longitudinal Study on Ageing (TILDA)
Lincoln Gate
Trinity College Dublin Dublin

 

Medical Research: What is the background for this study? What are the main findings?
Dr. McGarrigle: Mild cognitive impairment (MCI) is the intermediate state between healthy ageing and dementia and is a stage at which intervention could be effective in reducing conversion to dementia.

Neurocardiovascular instability is an age-related dysregulation of the blood pressure systems manifesting as exaggerated blood pressure variability and orthostatic hypotension (OH). Previous evidence has shown that autonomic dysfunction, blood pressure variation and hypotension are associated with mild cognitive impairment.

Our study found that systolic blood pressure variation was associated with cognitive decline. Mild cognitive impairment participants were more likely to have had OH and more prolonged OH compared to cognitively normal controls. Mild cognitive impairment participants with impaired orthostatic blood pressure responses were twice more likely to convert to dementia than mild cognitive impairment participants without the impaired response over a three year follow-up period.

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Dementia Patients on Cholinesterase Inhibitors Risk Substantial Weight Loss

Meera Sheffrin MD Geriatrics Fellow Division of Geriatrics | Department of Medicine San Francisco VA Medical Center University of California, San Francisco MedicalResearch.com Interview with:
Meera Sheffrin MD
Geriatrics Fellow
Division of Geriatrics | Department of Medicine
San Francisco VA Medical Center
University of California, San Francisco

Medical Research: What is the background for this study? What are the main findings?

Dr. Sheffrin: The main drug treatments for dementia are a class of medications called cholinesterase inhibitors. They have only modest effects on cognition and function in most patients, but since they are one of the few available treatments for dementia and thus very commonly prescribed. However,they are known to cause GI side effects (nausea, vomiting, diarrhea, and anorexia) in many patients when first started. It is plausible they could also caust weight loss, espeically considering they cause nausea and anorexia. However, the data on weight loss from randomized controlled trials is very limited and inconclusive, so we did a very large observational study in a real-world of the VA national healthcare system who were newly started on these medications, to see if they were associated with weight loss.

We found that patient with dementia started on cholinesterase inhibitors had a substantially higher risk of clinically significant weight loss over a 12-month period compared to matched controls.

1,188 patients started on cholinesterase inhibitors were matched to 2,189 similar patients who were started on other new chronic medications. The primary outcome was time to a 10-pound weight loss over a 12-month period, as this represents a degree of loss that would be clinically meaningful – not only noticed by a clinician but would perhaps prompt further action in considering the causes of the weight loss and medical work-up.

We found that starting cholinesterase inhibitors was associated with a 24% greater risk of developing weight loss. Overall, 29% of patients started on cholinesterase inhibitors experienced a weight loss of 10 pounds or more, compared with 23% of the control group. This corresponds to a number needed to harm of 21 over 1 year; meaning only 21 patients need to be treated with a cholinesterase inhibitor over the course of a year for one patient to experience a 10 pound weight loss.

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Diabetic Severity May Predict Risk of Dementia

MedicalResearch.com Interview with:
Wei-Che Chiu, MD, PhD
National Taiwan University College of Public Health,
Cathay General Hospital and Fu Jen Catholic University
Taipei, Taiwan

Medical Research: What is the background for this study?

Response: Diabetes mellitus is a common risk factor for dementia and accounts
for 6–8% of all cases of dementia in older populations. Cognitive
impairment is associated with the presence of diabetic complications
and diabetic severity, but the effects of diabetic severity on
dementia are unclear. Our study was to investigate the association
between the severity and progress of diabetes and the risk of
dementia.

Medical Research: What are the main findings?

Response: The diabetic severity and progression reflected the risk
of dementia, and the early progress in diabetic severity could predict
the risk of dementia in new-onset diabetic patients.

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Defects in DNA Repair Could Underlie Cognitive Decline

Dr. Li-Huei Tsai Ph.D. Professor and Director - Picower Institute For Learning and Memory Department of Brain and Cognitive Sciences Massachusetts Institute of Technology Cambridge, MA MedicalResearch.com Interview with:
Dr. Li-Huei Tsai Ph.D.
Professor and Director – Picower Institute
For Learning and Memory
Department of Brain and Cognitive Sciences
Massachusetts Institute of Technology

Medical Research: What is the background for this study? What are the main findings?

Dr. Tsai: For a while now, we have been interested in observations made by many labs, including our own, that the accumulation of DNA lesions is a hallmark of the aging brain, and that mutations in DNA repair factors manifest in congenital and neurodegenerative disorders. However, the precise contribution of unrepaired DNA lesions to the development of neurological disorders remains poorly understood. A major confounding factor is that the sources that generate DNA lesions in the brain are not well characterized, and it is not known whether damage accumulates non-specifically throughout the genome, or whether there are certain regions that are more prone to accumulate DNA damage.

In this regard, our study reports three major findings:

(1) Physiological neuronal activity itself results in the formation of DNA breaks;

(2) Neuronal activity-induced DNA breaks form at highly specific locations, including within the promoters of a subset of immediate early genes, including Fos, Npas4, and Egr1. These genes are also rapidly expressed in response to neuronal stimulation, and play crucial roles in experience-driven changes to synapses, and learning and memory;

(3) Neuronal activity-induced breaks are generated by a topoisomerase, Topo IIβ, and Topo IIβ-generated DNA breaks facilitate the rapid expression of these immediate early genes following neuronal stimulation. Continue reading

JAMA Study Compares Diagnostic Tests For Dementia

Kelvin TSOI BSc, PhD Research Associate Professor, Stanley Ho Big Data Decision Analytics Research Centre Associate Professor (by Courtesy), School of Public Health and Primary Care Faculty of Medicine The Chinese University of Hong KongMedicalResearch.com Interview with:
Kelvin TSOI BSc, PhD
Research Associate Professor, Stanley Ho Big Data Decision Analytics Research Centre
Associate Professor (by Courtesy), School of Public Health and Primary Care Faculty of Medicine
The Chinese University of Hong Kong

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

Dr. Tsoi: Dementia is a global public health problem afflicting millions of old age population. The Mini-Mental State Examination (MMSE) is the most widely applied test for dementia screening. In fact, there are over 40 tests available for dementia screening and many of them are available for free, but the diagnostic performances of these tests were not yet systematically evaluated. To identify the best alternative in the long list of screening tests, we conducted a systematic review to quantitatively analyze the diagnostic accuracy of these screening tests.

Among 149 eligible studies included over 49,000 participants, we found that the MMSE is a frequently used test for dementia screening. The sensitivity and specificity of MMSE for detection of dementia were combined to be 81.3% and 89.1% respectively. Compared with the other screening tests, the Mini-Cog and the Addenbrooke’s Cognitive Examination Revised (ACE-R) showed the best diagnostic performance which was comparable to that of the MMSE. For mild cognitive impairment (MCI), the Montreal Cognitive Assessment (MoCA) showed comparable performance to the MMSE with 88.9% sensitivity & 74.8% specificity.

MedicalResearch: What should clinicians and patients take away from your report?

Dr. Tsoi: The Mini-Cog and the ACE-R showed better performance than that of the other screening tests for dementia screening. The MoCA showed better performance than the others for MCI screening. Although the MMSE is the only proprietary instrument for dementia screening, the other screening tests were shown to be comparably effective but are easier to perform and freely available.

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

Dr. Tsoi: This study evaluated the existing literature with large sample size, but the screening tests were compared across different populations with various inclusion criteria. The future studies can further verify the test results on the same group of screening subjects.

Citation:

 

MedicalResearch.com Interview with:, Kelvin TSOI BSc, PhD Research Associate Professor, Stanley Ho Big Data Decision Analytics Research Centre, Associate Professor (by Courtesy), School of Public Health and Primary Care, Faculty of Medicine, & The Chinese University of Hong Kong (2015). JAMA Study Compares Dementia Diagnostic Tests MedicalResearch.com

PET Scan Can Detect Amyloid In Alzheimer’s and Other Dementias

Rik Ossenkoppele PhD. Postdoctoral researcher UCSF Memory and Aging CenterMedicalResearch.com Interview with:
Rik Ossenkoppele PhD.
Postdoctoral researcher
UCSF Memory and Aging Center

MedicalResearch: What is the background for this study?

Dr. Ossenkoppele: Since 2004, several PET tracers have been developed that measure fibrillar amyloid-β plaques, a neuropathological hallmark of Alzheimer’s disease (AD). Through visual assessment by a nuclear medicine physician or quantitative cut-points, the presence or absence of amyloid-β pathology can be determined in the living human brain. The FDA, in support of the clinical application of amyloid imaging, has recently approved three of these PET tracers. A proportion of patients with other types of dementia then Alzheimer’s disease that harbor cerebral amyloid-β pathology, however, potentially limits the clinical utility of amyloid imaging. When ordering clinical amyloid PET scans and correctly interpreting the significance of amyloid PET results, clinicians need to understand the prevalence of amyloid-positivity across different types of dementia. It is also important to be aware of the relationships of amyloid-positivity prevalence and demographic (e.g. age and sex), cognitive and genetic (e.g. presence of the AD-risk allele apolipoprotein E [APOE] ε4) factors. Most amyloid PET studies to date come from single centers with modest sample sizes. We therefore conducted a meta-analysis with individual participant data from 29 cohorts worldwide, including 1359 patients with clinically diagnosed Alzheimer’s disease and 538 patients with non-AD dementia. We also included 1849 healthy controls with amyloid PET data, and an independent sample of 1369 AD patients with autopsy data from the NACC database.

MedicalResearch: What are the main findings?

Dr. Ossenkoppele: In patients clinically diagnosed with Alzheimer’s disease, the prevalence of amyloid-positivity decreased from 93% at age 50 to 79% at age 90. The drop in amyloid-positivity was most prominent in older Alzheimer’s disease patients who did not carry an APOE ε4 allele (~1/3 of these patients had a negative amyloid PET scan). This most likely reflects a mix of
1) clinical misdiagnoses (i.e. non-AD pathology causing an AD phenotype),
2) false negative PET scans (i.e. abundance of cerebral amyloid pathology that is not detected by PET), and
3) possibly elder patients need less amyloid pathology (sub-threshold levels for PET) to reach the stage of dementia due to age-related reductions in cognitive resilience (“cognitive reserve theory”) or simultaneous presence of multiple pathologies (“double-hit theory”).
The relatively high rate of amyloid-negative Alzheimer’s disease patients highlights the necessity of biomarker-informed patient selection for Alzheimer’s disease clinical trials.

In most patients clinically diagnosed with non-AD, the prevalence of amyloid-positivity increased with aging and was ~18% higher in APOE ε4 carriers. Presence of amyloid pathology in non-AD dementia may reflect
1) clinical misdiagnosis (i.e. AD pathology is the causative pathology), or
2) comorbid pathologies, where amyloid may be secondary to other pathologies that are actually driving the clinical presentation. Interestingly, patients with a clinical diagnosis of non-AD dementia who harbored cerebral amyloid pathology showed lower Mini-Mental State Examination scores (measure of global cognition), suggesting that amyloid-β is not just an innocent bystander.

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Both Diabetes and Depression Raise Risk of Dementia

MedicalResearch.com Interview with:
Dimitry S. Davydow, MD, MPH
Associate Professor
Department of Psychiatry and Behavioral Sciences
University of Washington School of Medicine
Seattle, WA 98195

Dr, Davydow wishes to acknowledge Dr. Wayne Katon, the lead investigator of the study, who passed away on March 1, 2015.

Medical Research: What is the background for this study?

Dr. Davydow: The medical and public health communities have known for quite a while that diabetes and depression are both potential risk factors for developing dementia later in life. Dr. Wayne Katon previously published two articles detailing the results of two studies of relatively large groups of patients (one with nearly 4,000 patients and the other with 29,000 patients) with diabetes showing that those with diabetes and co-existing depression had a greater risk of developing dementia later in life than those patients with just diabetes. These initial studies were important since patients with diabetes are 3 to 4-times more likely to suffer from depression compared to the general population.

However, it remained unclear when comparing to a population without either diabetes or depression, to what extent each independently raised the risk of developing dementia, and then to what extent having both conditions increased an individual’s subsequent risk of dementia. We sought to answer these questions with this study.

In addition, with the growing obesity epidemic, which carries with it higher burdens of both diabetes and depression, there is reason to be concerned that the risk of dementia could be higher at even younger ages. To address this issue, we also wanted to see if there was a differential impact of the combination of diabetes and co-existing depression on dementia risk among those younger than 65 compared to individuals 65 or older.

We were fortunate to be able to examine health data from all Danish citizens 50 or older over a 6 year period, a population numbering nearly 2.5 million people to be able to answer these questions.

Medical Research: What are the main findings?

Dr. Davydow: We found that compared to individuals without diabetes or depression, those with diabetes alone had about a 15% greater risk of developing dementia, those with depression alone had about an 83% greater risk of developing dementia, and those with both diabetes and co-existing depression had a 107% greater risk of developing dementia compared to those without either condition.

We also found that of all of the cases of dementia diagnosed in Denmark among individuals 50 or older between 2007 through 2013, 6% were potentially due to combination of having both diabetes and depression. This was also true for those 65 or older, where 6% of all diagnosed dementia was potentially attributable to the combination of both diabetes and depression. However, among individuals under age 65, we found that 25% of all cases of dementia may have been directly attributable to the combination of diabetes and co-existing depression.

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B vitamins and Omega-3 May Protect Against Brain Shrinkage

Dr. Fredrik Jernerén PhD Postdoctoral Research Fellow Department of Pharmacology University of Oxford Oxford, United KingdomMedicalResearch.com Interview with:
Dr. Fredrik Jernerén PhD
Postdoctoral Research Fellow
Department of Pharmacology
University of Oxford
Oxford, United Kingdom

Medical Research: What is the background for this study? What are the main findings?

Dr. Jernerén: Development of dementia and Alzheimer’s disease is associated with an accelerated rate of brain shrinkage. Identifying ways to reduce the brain atrophy rate at an early stage may offer new strategies to prevent or delay the onset of dementia. In this study on elderly subjects diagnosed with Mild cognitive impairment (MCI), who are at increased risk of developing dementia, we investigated whether the effect of B vitamin supplementation on reducing the brain atrophy rate was influenced by circulating levels of omega-3 fatty acids. We have found that this indeed was the case. The higher the baseline concentration of the combined omega-3 fatty acids (DHA+EPA), the greater the protective effect of the B vitamin treatment. In subjects with high omega-3 concentrations who at the same time had elevated homocysteine levels (indicating a lack of B vitamins), B vitamin treatment reduced the brain atrophy rate by about 70% compared with the placebo group.  Continue reading

Deep Brain Stimulation Has Potential to Treat Dementia and Memory Loss

Associate Professor Lim Lee Wei (Sunway University, Malaysia) and Assistant Professor Ajai Vyas (Nanyang Technological University, Singapore) discover a new treatment using deep brain stimulation of the Prefrontal Cortex for dementia.

Associate Professor Lim Lee Wei (Sunway University, Malaysia) and Assistant Professor Ajai Vyas (Nanyang Technological University, Singapore) discover a new treatment using deep brain stimulation of the Prefrontal Cortex for dementia.

MedicalResearch.com Interview with: Dr. Lim Lee Wei
School of Biological Sciences, Nanyang Technological University, Singapore;
Department of Biological Sciences, Sunway University, Malaysia

Medical Research: What is the background for this study? What are the main findings?

Response: To date, pharmacological treatments for dementia have limited effects (most of the drugs failed in the second or third clinical trials) and there are no known treatments that cure or delay the progression of this memory impairment. Therefore, a novel non-pharmacological approach such as deep brain stimulation (DBS) is currently considered as an alternative treatment to reduce the symptomatic and progression of this memory deterioration.

Deep brain stimulation for dementia-related disease is currently evaluated as a potential therapy. In line with this development, evidence from recent studies suggests that deep brain stimulation might enhance memory functions when particular brain areas are stimulated. Of particular interest in our study, electrical stimulation of the Prefrontal Cortex induced striking antidepressant activity in both patients and animals studies (see our recent study, Lim et al., 2015 Translational Psychiatry; http://www.nature.com/tp/journal/v5/n3/full/tp201524a.html). However, no studies have shown the putative role of Prefrontal Cortex deep brain stimulation in learning and memory performance. In our finding, we have shown that deep brain stimulation of this region (Prefrontal Cortex) improved the short-term and long-term memory by a very important mechanism, which led to the formation of new brain cells in another region of the brain called the hippocampus, which is also involved in memory. Therefore, our findings suggest that deep brain stimulation of the Prefrontal Cortex has the potential to be developed into a therapy to treat dementia and other conditions that lead to memory loss in humans.

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Antipsychotic Medications Linked To Higher Mortality In Dementia Patients

Donovan Maust, MD, MS Assistant Professor of Psychiatry University of Michigan Research Scientist, Center for Clinical Management Research VA Ann Arbor Healthcare SystemMedicalResearch.com Interview with:
Donovan Maust, MD, MS
Assistant Professor of Psychiatry
University of Michigan
Research Scientist, Center for Clinical Management Research
VA Ann Arbor Healthcare System

Medical Research: What is the background for this study? What are the main findings?

Dr. Maust: From a recent government report, we known that about 1/3 of older adults with dementia in nursing homes and about 14% of those in the community have been prescribed an antipsychotic. While providers focus on what benefit the treatment they offer, it is important to also be aware of the potential harms, particularly when it is death. Prior estimates came from relatively short studies and showed a 1% increase. This paper finds that, over 180 days, the increased mortality comparing antipsychotic users to matched non-users is about 2 to 5 times higher.

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Twin Study Shows Physical Activity May Decrease Dementia Mortality

MedicalResearch.com Interview with:
Paula Iso-Markku, MD,
Department of Clinical Physiology and Nuclear Medicine, 
HUS Medical Imaging Center, 
Helsinki University Central Hospital and University of Helsinki
Helsinki , Finland

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

Dr. Iso-Markku : The social, financial and humane burden of the dementia is extensive as the worldwide prevalence of dementia is estimated around 35.6 million. Finding efficient prevention strategies for dementia is crucial. Within the past decade vascular risk factors have been recognized as very potential risk factors of dementia. As physical activity is known to affect vascular risk factors, it might also be a potential preventive tool against dementia. Few comprehensive epidemiological studies on physical activity in middle age and dementia occurrence later in life have been conducted.

The comprehensive Finnish Twin Study offers a unique approach to the subjects as the shared growing up environment and genes can be taken into account. The study population is extensive and a good representation of the Finnish population. In this study the association of physical activity in adulthood and dementia mortality was investigated in a 29-year follow-up.

The main finding in this study was that persistent vigorous (i.e. more strenuous than walking) physical activity was significantly associated with lower dementia mortality. The results in the paired analysis, comparing twins to co-twins, were similar but remained non-significant. The analyses of the volume of physical activity were, however, controversial.

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Community Based Memory Testing Provides Useful Screening Information

dr-peter-bayleyMedicalResearch.com Interview with:
Peter Bayley PhD
War Related Illness and Injury Study Center
Veteran Affairs Palo Alto Health Care System
Palo Alto, California

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

Dr. Bayley: There is currently widespread interest and debate surrounding the topic of screening for Alzheimer’s disease and other types of dementia The study describes results from National Memory Screening Day in 2010, an annual community event sponsored by the Alzheimer Foundation of America. Face-to-face screening takes place in a private setting; only the individual being tested and the screener are present. The memory screening consists of one of seven validated cognitive tests: the GPCOG (General Practitioner Assessment of Cognition), MINI-COG, MIS (Memory Impairment Screen), the BAS (Brief Alzheimer’s Screening), Kokmen Short Test of Mental Status, Mini-Mental State Examination, Montreal Cognitive Assessment, or the Saint Louis University Mental Status Examination.  Participants with scores below cutoff for possible dementia are encouraged to bring the results to their healthcare professional for follow-up and/or inclusion in medical files.

We report the results from a subset of 3,064 participants. Overall, 11.7% failed one of the memory screening tests. As expected, failure rates were higher in older and less-educated participants (P’s < .05). Subjective memory concerns were associated with a 40% greater failure rate for persons of similar age and education but no memory concerns (odds ratio = 1.4, 95% confidence interval = 1.07–1.78). However, most individuals who expressed concern about their memories passed the screening tests (54-96%, depending on age and education).

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Anticholinergic Medications May Increase Dementia Risk

Shelly L. Gray, PharmD, MS Professor of Pharmacy School of Pharmacy, University of Washington, SeattleMedicalResearch.com Interview with:
Shelly L. Gray, PharmD, MS
Professor of Pharmacy
School of Pharmacy, University of Washington, Seattle

Medical Research: What is the background for this study? What are the main findings?

Dr. Gray: Many medications have anticholinergic effects such as those used to treat overactive bladder, seasonal allergies, and depression.  The general view is that anticholinergic-induced cognitive impairment is reversible, however, emerging evidence suggests that these medications may be associated with increased dementia risk.  We conducted a prospective population-based cohort study in 3434 older adults to examine whether cumulative anticholinergic medication use is associated with increased risk of incident dementia.  Using automated pharmacy data, we found that higher 10-year cumulative dose was associated with increased risk for dementia and Alzheimer disease over an average of 7.3 years of follow-up.  In particular, people with the highest use (e.g. taking the equivalent of oxybutynin 5 mg/day or chlorpheniramine 4 mg/day for longer than 3 years) were at greatest risk.
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Traumatic Brain Injury Raises Dementia Risk in Elderly

Raquel C. Gardner, MD, Research Fellow San Francisco VA Medical Center Clinical Instructor Memory and Aging Center, Department of Neurology University of California, San FranciscoMedicalResearch.com Interview with:
Raquel C. Gardner, MD, Research Fellow
San Francisco VA Medical Center
Clinical Instructor
Memory and Aging Center, Department of Neurology
University of California, San Francisco

Medical Research: What are the main findings of the study?

Dr. Gardner: We found that people who experience a  traumatic brain injury (TBI )when they are 55 or older have a 26% higher chance of getting dementia over the next 5 to 7 years compared to people who experience bodily trauma.

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Memory Complaints May Presage Increased Risk Of Dementia

Richard J. Kryscio, PhD, Professor Sanders-Brown Center on Aging University of KentuckyMedicalResearch.com Interview with:
Richard J. Kryscio, PhD, Professor
Sanders-Brown Center on Aging
University of Kentucky

Medical Research: What are the main findings of the study?

Dr. Kryscio:  We followed 531 elderly over time assessing their cognition annually; of these 105 (about 20%) eventually were diagnosed with a serious cognitive impairment (either a mild cognitive impairment or a dementia) and 77% of the latter declared a subjective memory complaint prior to the diagnosis of the impairment.  In brief, declaration of a memory problem put a subject at three times the risk of a future impairment.
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Sleep Difficulties Linked To Shrinking Brain

Dr. Claire Sexton Ph.D. University of OxfordMedicalResearch.com Interview with:
Dr. Claire Sexton Ph.D.
University of Oxford

Medical Research: What are the main findings of the study?

Dr. Sexton: We found that sleep difficulties (which can include trouble falling asleep, waking up during the night, or waking up too early) were associated with an increased rate of decline in brain volumes over 3-5 years.

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